DEPT OF OBSTETRICS & GYNAECOLOGY
| Researcher : Chai J |
| Project Title: | A pilot study of pre-operative misoprostol in reducing operative blood loss during hysterectomy |
| Investigator(s): | Chai J, Yeung WSB, Ho PC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 08/2008 |
| Completion Date: | 01/2010 |
| Abstract: |
| Uterine fibroid is the commonest benign tumour affecting women in their reproductive age. Around 20-50% can cause symptoms that warrant treatment (Stovall et al, 2001; Farquhar C et al 2001). Different medical therapies, including prostaglandins releasing hormone analogues (GnRHa), mifepristone, progestins and androgens have been tried (Chavez et al, 2001). However, most of the medical therapy have significant side-effects that would only allow a short-term treatment. Surgery in the form of total abdominal hysterectomy (TAH) is the definitive treatment for large, symptomatic fibroids. Operative mortality of TAH is rare. However the operation may be associated with significant morbidities (Guarnaccia MM et al, 2001). Significant operative blod loss that required blood transfusion and oral iron supplement is not uncommon. Various methods have been tried to reduce the operative morbidity of TAH, mainly blood loss during surgery. A course of few months hormonal therapy (GnRHa and mifepristone) before operation to shrink the fibroid and reduce vascularity is the commonest approach (Lethaby A et al, 2001; Lethaby A et al, 2002; Eisinger SH et al 2003). Although it is effective, there are significant side effects. The cost of GnRHa is high. Intramyometrial vasopression injection has been reported. However, serious complications have been reported (Okin et al 2001). Misoprostol, a prostaglandin E1 analogous, has been used widely in clinical practice in Obstetrics and Gynaecology. It stimulates uterine contractions (Danielsson KG et al 1998) and this increase in myometrial contraction will lead to contraction of the vessels supplying blood to the leiomyomas. Misoprostol has been shown to increase the uterine artery resistance and reduce the blood flow to the uterine fibroid (Celik et al 2003). It has been shown that pre-operative misoprostol can reduce intra-operative blood loss and need for post-operative blood transfusion after abdominal myomectomy (Celik et al 2003). As the misoprostol can stimulate the uterine contraction and reduce the uterine blood flow, it is possible that pre-operative misoprostol can “squeeze” the blood from the diseased uterus back to the circulation, therefore reducing the blood loss during TAH. It is therefore the aim of our study is to see whether a single dose of sublingual misoprostol before total abdominal hysterectomy +/- salpingo-oophorectomy for uterine fibroid can reduce operative blood loss and need for post-operative blood transfusion. References: Celik H, Sapmaz E. Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myoectomy . Fertility Sterility 2003;79(5):1207-1210. Celik H. Sapmaz E, Serhatlioglu S, Parmaksiz C, Altingul A. Effect of intravaginal misoprostol use on uterine artery blood flow in patients with myoma uteri. Fertility Sterility 2003;80(6):1526-1528. Chavez NF, Stewart EA. Medical treatment of uterine fibroids. Clin Obstet Gynecol 2001;44:372-384. Danielsson KG, Marions L, Rodriguez A, Spur BW, Wong PY, Bygdeman M. Comparison between oral and vaginal administration of misoprostol on uterine contractility. Obstet Gynecol 1998;93:275-280. Eisiger SH, Meldrum S, Fiscella K, Guzick DS. Low dose mifepristone for uterine leiomyomata. Obstet Gynecol 2003;101:243-250. Farquhar C, Arroll B, Ekeroma A, Fentiman G, Lethaby A, Rademaker L. An evidence-based guideline for the management of uterine fibroids. Aust N Z J Obstet Gynaecol 2001;41:125-140. Guarnaccia MM, Rein MS. Traditional surgical approaches to uterine fibroids: abdominal myomectomy and hysterectomy. Clin Obstet Gynecol 2001;44:385-400. Lethaby A, Vollenboven B, Sowter M. Efficacy of pre-operative gonadotrophins hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systemic review. BJOG 2002;109:1097-1108. Lethaby A, Vollenboven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001;2:CD000547. Okin CR, Guido RS, Meyn LA, Ramanathan S. Vasopressin during abdominal hysterectomy: a randomized controlled trial. Obstet Gynecol 2001;97:867-872. Stovall DW. Clinical symptomatology of uterine leiomyomas. Clin Obstet Gynecol 2001;44:364-371. |
| Researcher : Chan DW |
| Project Title: | Functional characterization of AMPKgamma 2 in ovarian cancer |
| Investigator(s): | Chan DW, Ngan HYS, Liu VWS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2008 |
| Completion Date: | 08/2009 |
| Abstract: |
| PURPOSE OF PROPOSED INVESTIGATION The purpose is to investigate the roles of AMPKgamma2 in AMPK activity and its effects on AICAR treatment and tumorigenicity of ovarian cancer. HYPOTHESIS Despite advances in diagnosis and treatment, the incidence of ovarian cancer is rising and it is within the top ten causes of cancer deaths in Hong Kong women (DOH statistics 2003). Therefore, discovery of novel targets for therapies will improve the quality of life of patients. Recent studies have shown that AMPK may be used as a therapeutic target and some AMPK activator agents such as 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) mediates anti-proliferative and pro-apoptotic effects on human cancer cells. However, the effect of AICAR varies in different cancer cells and the reasons remain unknown. One possible reason is the binding efficiency of AMP/ZMP to the gamma subunit of AMPK. Therefore, this project is aimed at investigating the roles of AMPKgamma2 subunit in AMPK system and particularly to the effects of AICAR and tumorigenicity on ovarian cancer. AMPK activity and human cancer AMPK signaling pathway plays a crucial role in the regulation of cell proliferation and cancer development because sustain AMPK activation is able to inhibit cell proliferation, cell growth and also regulate cell apoptosis (Hardie, 2007; Meisse et al., 2002). These findings are not surprising given that the upstream regulator of AMPK, LKB1, is a well know tumor suppressor (Hardie, 2004a; Hardie, 2005). Besides, the general effects of AMPK activation on biosynthesis, such as inhibition on fatty acid synthesis (Zhou et al., 2007) and the mTOR pathway (Kimura et al., 2003) inhibit cell proliferation of cancer cells. Therefore, AMPK is an important therapeutic target and may be used for cancer treatment. The role of AMPK has been studied in a number of cancer cell types, including prostate cancer cells (Xiang et al., 2004), gastric cancer cells (Saitoh et al., 2004), liver cancer cells (Imamura et al., 2001), and neuroblastoma cells (Garcia-Gil et al., 2003). However, its role in ovarian cancer has not been reported yet. Regulation and activation of AMPK AMPK is activated in response to a rising AMP:ATP ratio within the cell caused by metabolic stresses such as hypoxia, glucose deprivation and heat shock (Long & Zierath, 2006). Structurally, AMPK is a heterotrimeric complex comprising a catalytic subunit and regulatory betaand gamma subunits (Hardie, 2007). Each subunit is encoded two or three isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3) leading to a diverse combinations of heterotrimeric complexes (Hardie, 2004b; Hardie, 2007). The regulation of AMPK involves direct allosteric activation by AMP and phosphorylation by upstream kinase. In the absence of AMP, AMPK exists in inactive conformation due to the interaction between the kinase domain and the auto-inhibitory domain on alpha subunit which blocks the phosphorylation of the kinase domain (Cheung et al., 2000a). Upon metabolic stresses, there is a rise in AMP:ATP ratio and AMP is known to activate AMPK in three ways. AMPK activation requires conformation change induced by AMP binding to CBS domains of gamma subunit, which in turns promotes alpha subunit phosphorylation (Thr-172)/activation by the upstream protein kinase LKB1, as well as inhibits dephoshphorylation of Thr-172 by protein phosphatses (Hardie, 2004b; Hardie, 2007). The effects of AMP may be antagonized by high concentration of ATP, probably by competing for the same binding site (Hardie, 2004c). AICAR treatment in human cancer AICAR, a widely used AMPK activation agent, converted to the monophosphorylated form, ZMP, inside the cell by an adenosine kinase (Corton et al., 1995a). ZMP mimicks the effects of AMP on AMPK without any changes in the AMP/ATP ratio (Corton et al., 1995b). Similarly, ZMP activates AMPK and its upsteam kinase LKB1 by binding to CBS domains of gammasubunit and activate AMPK as same as above mechanism (Corton et al., 1995a). Therefore, the gamma subunit of AMPK system plays important role to sense the amount of AMP or ZMP in cells and is critically to determine the activity of AMPK. However, the roles and functions of AMPK gamma subunits in AMPK system and particularly to the effects of AICAR mediated anti-proliferative and pro-apoptotic effects in human cancers are still unclear. PROJECT OBJECTIVES The aims of the proposed work are to fully characterize AMPKgamma2, its roles on AMPK activity, and its functions on AICAR mediated cell proliferation inhibition in ovarian cancer as follows: (1) To investigate the expression status of AMPKgamma2 in ovarian cancer samples by real-time quantitative RT-PCR and immunohistochemical staining. (2) To delineate the functions and regulatory mechanism of AMPKgamma2 in AMPK activity. (3) To examine the roles of AMPKgamma2 in AICAR mediated cell proliferation inhibition in ovarian cancer cells. (4) To investigate the roles of AMPKgamma2 in tumroigenicity of ovarian cancer. KEY ISSUES AND PROBLEMS BEING ADDRESSED Despite advances in diagnosis and treatment, the incidence of ovarian cancer is rising and it is within the top ten causes of cancer deaths in Hong Kong women (DOH statistics 2003). The current main treatment strategy is chemotherapy which causes significant side effects with major implications on the quality of life. Understanding the roles of AMPKgamma2 in AMPK activity and its effects on AICAR mediated cell proliferation inhibition would give a better insight into the development and tumor progression of ovarian cancer. This would provide a scientific basis for future development of novel treatment options. |
| Project Title: | Functional characterization of GRB7 and its variant, GRB7v, in ovarian cancer |
| Investigator(s): | Chan DW, Ngan HYS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2009 |
| Completion Date: | 08/2010 |
| Abstract: |
| Purpose of proposed investigation The purpose is to characterize the functions of GRB7 and GRB7v in the tumorigenisis of ovarian cancer, and to investigate the differetial roles of GRB7 and GRB7v in the modulation of signaling pathways. Key issues and problems being addressed Ovarian cancer is one of the most lethal gynecological malignancies. Most of ovarian cancer cases are poor prognosis and many patients died at late stage. Therefore, understanding the molecular mechanisms in the development of ovarian cancer through identification and characterization of oncogenes and tumor suppressor genes will help discovery of novel targets for therapies. Growth factor receptor bound protein 7 (GRB7) is an adaptor protein which plays an important role on mediating signal transduction from multiple cell surface receptors to various downstream signaling pathways. GRB7 consists of a PR (proline-rich) region, a GM (shared by GRB and Mig) region with PH (pleckstrin homologue), and the most important carboxyl-terminal SH2 (src-homology) region which has been found to associate with a large number of receptor tyrosine kinases and other signaling molecules. One of GRB7 variant with deletion of SH2 domain, GRB7v, was also found in mammalian cells. Accumulating studies have documented that overexpression of GRB7 and GRB7v was frequently observed in a wide variety of human cancers. We have recently found that both GRB7 and GRB7v mRNA transcripts overexpressed in ovarian cancer cells and clinical samples. Moreover, the overexpression of GRB7 and GRB7v was significantly associated with high graded human ovarian cancer cells. Intriguingly, ectopic expression of GRB7 and GRB7v in ovarian cancer cells found that GRB7 promoted cell migration/invasion, wheareas GRB7v enhanced cell proliferation, suggesting that these two proteins have distinct functions. However, the regulatory mechanisms of GRB7 and GRB7v in mediating different cellular functions, and their tumorigenic roles in ovarian cancer remain unknown. Therefore, the present project will investigate the molecular mechanisms of GRB7 and GRB7v, examine the functions of GRB7 and GRB7v in the tumorigenicity of ovarian cancer cells, and evaluate the clinicopathological correlation by their protein expression status in ovarian cancer. Possible outcome, relevance, significance and value of research project Ovarian cancer is one of the most common cancers in female and high mortality is usually associated with high grade tumors. The understanding of the molecular mechanisms in high grade ovarian cancer will assist in improving therapeutic intervention of this disease. GRB7 is an emerging family of cytosolic adaptor mediating of various cell surface receptors with specific downstream signalling pathways. Our proposed work on characterization of the underlying mechanism and roles of GRB7 and its variant GRB7v in mediating differential signalling pathways will shed insight into the distinct functions of GRB7 and GRB7v in the pathogenesis of high grade ovarian cancer. We will provide evidence of how GRB7 and GRB7v mediated diverse cellular functions through delineating the importance of SH2 domain in GRB7, the different signalling pathways regulated by GRB7 and GRB7v, the relationship between the altered expression levels of GRB7 and GRB7v with cellular behaviours. Moreover, using immunohistochemical analysis analysis to evaluate the expression status of GRB7 and GRB7v in a larger pool of clinical ovarian cancer samples will provide clinicopathological relevance of GRB7 and GRB7v in ovarian cancer. We believe the comprehensive characterization of the mechanism and functions of GRB7 and GRB7v will significantly advance our understanding of ovarian cancer development and may present a promising target for therapeutic intervention in ovarian cancer. Objectives (1) To delineate the molecular mechanism of GRB7 and GRB7v in signaling transduction. (2) To assess the functions of GRB7 and GRB7v in the tumorigenicity of ovarian cancer cells. (3) To confirm the clinicopathological significance of GRB7 and GRB7v in ovarian cancer samples. |
| Project Title: | 22nd Lorne Cancer Conference Loss of Sox7 is involved in the pathogenesis of Endometrial Cancer |
| Investigator(s): | Chan DW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 02/2010 |
| Completion Date: | 02/2010 |
| Abstract: |
| N/A |
| Project Title: | Identification of putative miRNAs involved in chemoresistance of ovarian cancer |
| Investigator(s): | Chan DW, Ngan HYS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 04/2010 |
| Abstract: |
| Purpose of proposed investigation The purpose is to identify the putative miRNAs involved in the development of chemoresistance in ovarian cancer. Key issues and problems being addressed Ovarian cancer is one of the most lethal gynecological malignancies. Most of ovarian cancer cases are poor prognosis and many patients died at late stage. Platinum-based drugs, e.g. Cisplatin, are the most potent anti-tumor agents commonly used in advanced ovarian cancers. However, the major limitation of using these drugs is the acquisition of resistance to initially responsive tumors. Therefore, understanding the molecular mechanisms in the development of chemoresistance in ovarian cancer through identification and characterization of genetic/epigenetic alterations will help discovery of novel targets for diagnosis, prognosis and therapeutic improvement in this disease. There are two possibilities leading to chemoresistance in human cancers; it may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. In this proposal, we will mainly focus on analyzing the molecular mechanisms in the development of acquired chemoresistance in human ovarian cancer cells. We hypothesize that the acquired chemoresistance of ovarian cancer cells may be induced due to genetic/epigenetic alterations during prolonged treatment with platinum-based drugs. MicroRNAs (miRNAs) are a class of ~22 nucleotide non-coding RNAs that regulate gene expression by post-transcriptionally silencing large number of target messenger RNA (mRNA). Emerging evidence suggests that the deregulation of miRNAs expressions is involved in the initiation, progression, and metastasis of human cancers. However, studies on the expression status of miRNAs associated with chemoresistance in ovarian cancer are rare. In the present study, we have studied the miRNA expression profiling of 2 pairs of genetically identical cell models cisplatin-sensitive (OV2008 and A2780s) and cisplatin-resistant (C13* and A2780cp) using Exiqon LNA™ miRNAs profiling system. The next steps will systematically evaluate the expression status of each putative miRNAs, examine their functional roles in chmoresistance, and delineate their putative protein targets. Objectives (1) To evaluate the expression status of each putative miRNAs using a high-throughput quantitative RT-PCR analysis. (2) To examine the function of these miRNAs by over-expression or gene silencing approach in cell culture system with platinum-based drugs treatment. (3) To delineate the putative protein-coding target(s) regulated by these miRNA(s) using bioinformatics approach and their validation by Western blot analysis. |
| List of Research Outputs |
| Chan D.W., Liu V.W.S. and Ngan H.Y.S., Loss of Sox7 is involved in the pathogenesis of endometrial Cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Li C., Liu V.W.S., Chan D.W. and Ngan H.Y.S., Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer, AACR 101st Annual Meeting 2010, USA. 2010. |
| Liu V.W.S., Li C., Chan D.W. and Ngan H.Y.S., Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer, Association for International Cancer Research (AICR) 30th Anniversary Conference, St. Andrews, UK, April 7-9, 2010 . 2010. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, 16th HKICC 6th Annual Meeting. 2009. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, In: AACR 101st Annual Meeting 2010, AACR 101st Annual Meeting. USA. 2010. |
| Wang Y., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Differential functions of GRB7 and its variant, GRB7v in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Wang Y., Chan D.W., Liu V.W.S., Chiu P.M. and Ngan H.Y.S., Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis, Clinical Cancer Research. AACR, 2010, 16: 2529-39. |
| Researcher : Chan KKL |
| Project Title: | Relationship between placental ratio and placental function |
| Investigator(s): | Chan KKL, Lao TTH |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding for New Staff |
| Start Date: | 01/2003 |
| Abstract: |
| To examine the relationship between PR and placental function in terms of fetal acid- base balance, haematology and biochemiatry; to determine if there is a cut-off in the PR for the detection of fetal growth restriction (FRG) as reflected by changes in placental function in newborns with birthweigth within the normal range. |
| Project Title: | The effect of fulvestrant in epithelial ovarian cancer with differential estrogen receptor status in mice |
| Investigator(s): | Chan KKL, Liu S, Tam KF, Ngan HYS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2008 |
| Abstract: |
| Objectives: To test the hypothesis that Fulvestrant, a pure estrogen antagonist, would reduce the growth of ovarian tumour transplanted in mice, regardless of the estrogen receptor status of the tumour Primary outcome: Difference in size of tumour in mice transplanted with ovarian cancer with or without treatment with Fulvestrant. Secondary outcome: Any difference in the response in tumours with or without ER receptors Key issues and problems being addressed: Ovarian Cancer is the 4th commonest cancer in women in the western countries and is within the top 10 causes of cancer deaths in women in Hong Kong. About 90% of ovarian cancers arise from the ovarian surface epithelium. The mainstay of current treatment is cytoreductive surgery followed by combination chemotherapy. Despite optimal primary treatment, majority would develop recurrences. Salvage chemotherapy regimes are much less effective, giving an average of 20% response but are associated with significant toxicities. Ovarian cancer, like breast cancer, expresses oestrogen receptors (1) and is hormone sensitive. Oestrogen regulates the expression of many genes that are important for cell proliferation, inhibition of apoptosis, stimulation of invasion and metastasis and promotion of angiogenesis. Most of the effects of oestrogen are medicated by oestrogen receptors (ER). ER has at least 2 functions. Apart from being a transcription factor for oestrogen related genes, it also functions outside the nucleus and in the plasma membrane to active growth factor signalling. Therefore, oestrogen can potentially affect ovarian cancer cell growth (5,8). Hormonal therapy is an attractive option in the treatment of ovarian cancer because of its better side effect profile compared to standard chemotherapy regimes. Tamoxifen, an anti-estrogen used in the treatment of breast cancer, has also been used in the treatment of ovarian cancer. However, overall response rate is only about 13% (7). This low response rate may be partly due to Tamoxifen being a partial oestrogen agonist, with both anti -oestrogen and oestrogenic activities which may confuse the overall response. A clearer role of hormonal treatment of ovarian cancer may be provided by Fulvestrant ( FVT ), a newly developed pure anti-oestrogen. This new drug has been found to be effective in the treatment of breast cancer (2-4) , but the information for the use of FVT in ovarian cancer is limited. In vitro studies suggested that FVT reduced ovarian cancer cell growth, even in estrogen receptor negative cell lines (7). Our laboratory studies using ovarian cancer cell lines with different ER receptor combinations also demonstrated that Fulvestrant would reduce proliferation of ovarian epithelial cancer cells, regardless of the tumour receptor status. References 1. Rao B.R. and Slotman B.J., Endocrine factors in common epithelial ovarian cancer. Endocr. Rev. 12 (1991), pp. 14–26. 2. Osborne CK, Pippen J, Jones SE, et al: A double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant with anastrozole in post-menopausal women with advanced breast cancer progressing on prior endocrine therapy: Results of a North American trial. J Clin Oncol 20:3386-3395, 2002 3. Howell A. Robertson JF. Abram P. Lichinitser MR. Elledge R. Bajetta E. Watanabe T. Morris C. Webster A. Dimery I. Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Journal of Clinical Oncology. 22(9):1605-13, 2004 May 1 4. Bross PF. Baird A. Chen G. Jee JM. Lostritto RT. Morse DE. Rosario LA. Williams GM. Yang P. Rahman A. Williams G. Pazdur R. Fulvestrant in postmenopausal women with advanced breast cancer. Clinical Cancer Research. 9(12):4309-17, 2003 Oct 1. 5. Langdon S.P., Hirst G.L., Miller E.P., Hawkins R.A.,. Tesdale A.L, Smyth J.F. et al., The regulation of growth and protein expression by estrogen in vitro: a study of 8 human ovarian carcinoma cell lines. J. Steroid Biochem. Mol. Biol. 50 (1994), pp. 131–135. 6. Ercoli A. Battaglia A. Raspaglio G. Fattorossi A. Alimonti A. Petrucci F. Caroli S. Mancuso S. Scambia G. Activity of cisplatin and ICI 182,780 on estrogen receptor negative ovarian cancer cells: cell cycle and cell replication rate perturbation, chromatin texture alteration and apoptosis induction. International Journal of Cancer. 85(1):98-103, 2000 Jan 1. 7. Perez-Gracia JL. Carrasco EM. Tamoxifen therapy for ovarian cancer in the adjuvant and advanced settings: systematic review of the literature and implications for future research. Gynecol Oncol. 2002; 84:201-9 |
| Project Title: | The role of PDCD4 gene in ovarian carcinogenesis |
| Investigator(s): | Chan KKL, Liu S, Ngan HYS, Leung THY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 06/2009 |
| Abstract: |
| The purpose of the present study is to investigate the expression and the role of PDCD4 gene in ovarian carcinogenesis. Among the gynecologic malignancies, ovarian cancer has the highest mortality rate and is the 4th commonest cancer in women in western countries, and is within the top 10 causes of cancer deaths in women in Hong Kong. Ovarian cancer is a disease difficult to detect in early stages due to nonspecific symptoms and lack of reliable biomarkers for early detection, and resulting in the diagnosis of many new patients with advanced ovarian cancer with poor prognosis. It also has a rapid progression with frequent relapses after radical surgical procedure. Understanding the molecular mechanism underlying the progression of ovarian cancer may provide insights into new therapeutic targets. Human programmed cell death 4 (PDCD4) is a newly described tumour suppressor (1). It was first cloned from a human glioma library and expressed ubiquitously in normal tissues (2). Loss of PDCD4 expression has been found in several types of human cancer cell lines (3) and some primary tumours such as gliomas (4), lung cancer (5), hepatocellular carcinomas (6) and colon cancer (7). PDCD4 was shown to be a tumour suppressor in skin tumour carcinogenesis both in cell culture and animal models (1,8). It inhibits oncogenesis by suppressing gene transcription and translation (1). PDCD4 expression in some tumour cells resulted in their apoptotic death or sensitized them to anti-cancer agents (3,6), and PDCD4 protein was shown to be an important component of apoptotic machinery (6,9). In addition, markedly decrease of PDCD4 expression has been found to be correlated with the invasiveness of breast and colon cancers (10,11). The significance of PDCD4 suppression for tumour progression was also demonstrated in lung cancer where loss of PDCD4 correlated with poor prognosis and survival (5). Despite demonstrated role of PDCD4 for apoptotic cell death and its ability to suppress tumourigenic potential, these properties of PDCD4 are conditional rather than universal. In some studies, overexpression of PDCD4 did not lead to apoptotic changes in cells (12,13), but was subjected to regulation. PDCD4 activity was found to be inhibited by Akt protein kinase phosphorylation, and the level of PDCD4 protein was controlled by S6K1 and betaTRCP through an ubiquitination-dependent mechanism (14,15). In addition, epigenetic modification of PDCD4 at transcription level has been recently demonstrated in human gliomas (16). PDCD4 has also been shown to involve in modulation of cell sensitivity to hormonal / chemo treatment. It has also been observed that antiestrogen and the HER-2/neu antagonist, Herceptin (Trastuzumab), induced PDCD4 expression in T-47D cells, which may result from intracellular signaling crosstalk that exists between RAR, ER and Her-2/neu, and suggesting that PDCD4 may play a central role in growth inhibition in breast cancer cells (9). Stable expression of antisense PDCD4 significantly reduced the sensitivity of MCF-7 breast cancer cells to geldanamycin and to tamoxifen (3). However, the mechanisms of function and regulation of PDCD4 are still largely unknown and its potential function in ovarian cancer has not been investigated. We hypothesize that the tumour suppressor PDCD4 may play a role in the development and progression of ovarian cancer. Objectives: 1, To determine and compare the expression of PDCD4 in normal ovary and malignant ovarian samples. 2, To explore the potential role of PDCD4 in the regulation of ovarian cancer cell growth and progression. 3, To assess the involvement of epigenetic modification in silencing the PDCD4 expression in ovarian cancer. 4, To assess the significance of PDCD4 expression and methylation as potential diagnostic and prognostic markers in ovarian cancer. References 1 Cmarik JL, et al: Differentially expressed protein Pdcd4 inhibits tumour promoter-induced neoplastic transformation. Proc Natl Acad Sci U S A 1999;96:14037-14042. 2 Matsuhashi S, et al: Isolation of a novel gene from a human cell line with Pr-28 Mab which recognizes a nuclear antigen involved in the cell cycle. Res Commun Biochem Cell Mol Biol. 1997; 1: 109–20. 3 Jansen AP, et al: Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity. Mol Cancer Ther 2004;3:103-110. 4 Gao F, et al: Frequent loss of PDCD4 expression in human glioma: possible role in the tumourigenesis of glioma. Oncol Rep 2007;17:123-128. 5 Chen Y, et al: Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J Pathol 2003;200:640-646. 6 Zhang H, et al: Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Oncogene 2006;25:6101-6112. 7 Mudduluru G, et al: Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 2007;110:1697-1707. 8 Jansen AP, et al: Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumourigenesis. Cancer Res 2005;65:6034-6041. 9 Afonja O, et al: Induction of PDCD4 tumour suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis. Oncogene 2004;23:8135-8145. 10 Wen YH, et al: Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep 2007;18:1387-1393. 11 Wang Q, et al: Downregulation of tumour suppressor Pdcd4 promotes invasion and activates both beta-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells. Oncogene 2008;27:1527-1535. 12 Shibahara K, et al: Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene 1995;166:297-301. 13 Lankat-Buttgereit B, et al: The action of Pdcd4 may be cell type specific: evidence that reduction of dUTPase levels might contribute to its tumour suppressor activity in Bon-1 cells. Apoptosis 2008;13:157-164. 14 Palamarchuk A, et al: Akt phosphorylates and regulates Pdcd4 tumour suppressor protein. Cancer Res 2005;65:11282-11286. 15 Dorrello NV, et al: S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 2006;314:467-471. 16 Gao F, et al: PDCD4 gene silencing in gliomas is associated with 5'CpG island methylation and unfavorable prognosis. J Cell Mol Med 2008. |
| Project Title: | Selective hormonal treatment in ovarian cancer |
| Investigator(s): | Chan KKL, Leung THY, Ngan HYS, Liu S |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 01/2010 |
| Abstract: |
| Ovarian cancer cells are hormone responsive. Tamoxifen , an anti-estrogen, is used for treatment for ovarian cancer recurrence. Hormonal treatment is an attractive option in cancer therapy because it lacks significant side effects. However, the overall response rate is only about 10-15%. One of the key issues is how to improve its effectiveness. For many years, estrogen is known to act through estrogen receptors . In 1996, a new estrogen (ERβ) was discovered and was found to be genetically distinct from the classical ER (ERα) (1) . Since then, ERβ was found in most estrogen –target tissues such as the prostate (2) and the ovary (3) . More interestingly, the two receptors are found to have opposing functions on cell growth in breast cancer cell lines (4) . In the presence of ERα, estrogen leads to proliferation but in the presence of ERβ, it inhibits proliferation. Furthermore, reduced levels of ERβ mRNA expression were found in malignant tissues compared to normal tissues in various estrogen dependent tumors such as breast ,prostate cancers (5-7), suggesting that the loss of ERβ expression may be involved in carcinogenesis. This is further supported by the findings that exogenous expression of ERβ in breast and prostate led to increased apoptosis and inhibits motility and invasion of cells (8, 9). However, the mechanisms involved are still unclear. Estrogen receptors classically mediate the effects by the genomic pathway where the receptors dimerise and translocate into the nucleus and binds to the estrogen response elements which then result in gene transcription. In addition to this classical mechanism, ER is also known to have non-genomic effects where membrane ER can activate different cytoplasmic signaling pathways. In lung cancer cells, ERB was found to have mainly non genomic actions where ERB was found to be in the cytoplasm and failed to translocate to the nucleus in the presence of estrogen (10). The role of ERβ appeared to be tissue specific, eg in colon cancer, selective ERβ agonists has an inhibitory effect (11) whereas in lung cancer, increased cell proliferation was seen (10). The action of ERβ in ovarian cancer is largely unknown. Our previous study demonstrated that ERβ expression was significantly higher in normal tissues compared with borderline tumors and malignant tissues. ERβ expression was significantly higher in stage I disease compared with stage II-IV disease . A high ERβ expression was also found to be significantly associated with a longer disease free survival as well as overall survival (12). This suggests that ERβ may play a role in ovarian carcinogenesis. In this project, we aim to further investigate the effect of ERβ in ovarian cancer cells as follow : Objectives : 1. To determine the effects of ERβ selective agonists and antagonists on cell proliferation, apoptosis and cell migration. 2. To investigate whether ERβ mediates its effects by non-genomic actions by studying the possible cytoplasmic signaling pathways associated with ERβ including the MAPK and PI3K/AKT pathways 3. To investigate whether ERβ translocate to the nucleus upon ligand binding. References 1. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proceedings of the National Academy of Sciences of the United States of America 1996;93(12):5925-30. 2. Weihua Z, Makela S, Andersson LC, Salmi S, Saji S, Webster JI, et al. A role for estrogen receptor beta in the regulation of growth of the ventral prostate. Proceedings of the National Academy of Sciences of the United States of America 2001;98(11):6330-5. 3. Brandenberger AW, Tee MK, Jaffe RB. Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ovarian serous cystadenocarcinoma and ovarian cancer cell lines: down-regulation of ER-beta in neoplastic tissues. Journal of Clinical Endocrinology & Metabolism 1998;83(3):1025-8. 4. Strom A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson JA. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D.[erratum appears in Proc Natl Acad Sci U S A. 2006 May 23;103(21):8298]. Proceedings of the National Academy of Sciences of the United States of America 2004;101(6):1566-71. 5. Skliris GP, Munot K, Bell SM, Carder PJ, Lane S, Horgan K, et al. Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model. J Pathol 2003 Oct;201(2):213-20. 6. Iwao K, Miyoshi Y, Egawa C, Ikeda N, Noguchi S. Quantitative analysis of estrogen receptor-beta mRNA and its variants in human breast cancers. Int J Cancer 2000 Dec 1;88(5):733-6. 7. Horvath LG, Henshall SM, Lee CS, Head DR, Quinn DI, Makela S, et al. Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res 2001 Jul 15;61(14):5331-5. 8. Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F. ER beta inhibits proliferation and invasion of breast cancer cells. Endocrinology 2001;142(9):4120-30. 9. Cheng J, Lee EJ, Madison LD, Lazennec G. Expression of estrogen receptor beta in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis. FEBS Letters 2004;566(1-3):169-72. 10. Zhang G, Liu X, Farkas AM, Parwani AV, Lathrop KL, Lenzner D, et al. Estrogen receptor beta functions through nongenomic mechanisms in lung cancer cells. Molecular Endocrinology 2009;23(2):146-56. 11. Motylewska E, Stasikowska O, Melen-Mucha G. The inhibitory effect of diarylpropionitrile, a selective agonist of estrogen receptor beta, on the growth of MC38 colon cancer line. Cancer Letters 2009;276(1):68-73. 12. Chan KK, Wei N, Liu SS, Xiao-Yun L, Cheung AN, Ngan HY. Estrogen receptor subtypes in ovarian cancer: a clinical correlation. Obstetrics & Gynecology 2008;111(1):144-51. |
| List of Research Outputs |
| Chan K.K.L., Editorial Board, Journal of Paediatrics, Obstetrics and Gynaecology. 2010. |
| Hu Y., Chan K.K.L. and Ngan H.Y.S., Preventing Cervical Cancer: Primary And Secondary Measures, Journal Of Paediatrics, Obstetrics And Gynaecology. 2009, 35: 213. |
| Kwan T.T.C., Tam K.F., Lee P.W.H., Lo S.S.T., Chan K.K.L. and Ngan H.Y.S., De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial, Psycho-Oncology. 2010, 1-11. |
| Liu S., Leung C.Y., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping assay by comparison with Roche Linear Array HPV genotyping assay, Journal of Clinical Microbiology. 2010, 48(3): 758-64. |
| Ngan H.Y.S., Cheung A.N.Y., Tam K.F., Chan K.K.L., Tang H.W., Bi D., Descamps D. and Bock H.L., Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong, Hong Kong Med J.. 2010, 16(3): 171-9. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Wong C.S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers, 16th HKICC 6th Annual Meeting and The 14th Research Postgraduate Symposium, HKU, November 4-6, 2009. |
| Researcher : Chan RWS |
| Project Title: | 25th Annual Meeting European Society of Human Reproduction and Embryology Human Endometriotic Cells Exhibit Stem-like Cell Properties |
| Investigator(s): | Chan RWS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 06/2009 |
| Completion Date: | 07/2009 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Chan R.W.S., Endometrial Stem Cells, 1st International Stem Cell Biology and Regenerative Medicine Course . 2009. |
| Chan R.W.S., Ng E.H.Y., Lee C.K.F. and Yeung W.S.B., Human Endometriotic Cells Exhibit Stem-like Cell Properties. , 25th European Soceity of Human Reproduction and Embryology, 28 Jun - 1 Jul, Amsterdam, Netherlands. Oxford Journal, 2009, 24: i97. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Researcher : Cheong AWY |
| List of Research Outputs |
| Cheong A.W.Y., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., aracrine regulation of the complement component-3 (C3) and the C3 receptor in the preimplantation embryos developed in vivo and in vivo., P.6.01. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Researcher : Cheong KB |
| List of Research Outputs |
| Leung K.Y., Cheong K.B., Lee C.P., Chan V.N.Y., Lam Y.H. and Tang M.H.Y., Ultrasonographic prediction of homozygous ao-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination? , Ultrasound in Obstetrics & Gynecology. 2010, 35: 149-154. |
| Researcher : Cheong WYA |
| List of Research Outputs |
| Cheong W.Y.A., Lee C.Y.L., Liu W., Yeung W.S.B. and Lee C.K.F., Oviductal Microsomal Epoxide Hydrolase (EPHX1) Reduces Reactive Oxygen Species (ROS) Level and Enhances Preimplantation Mouse Embryo Development. , Biology of Reproduction. 2009, 81: 126-32. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., Paracrine regulation of the production of embryotrophic oviductal complement componenet-3 and the expression of embryonic complement receptor-3 in a human oviductal cells-mouse embryo coculture system. , P312. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., The oviductal embryotrophic factor complement componenet-3 modulates its receptor expression in the pre-implantation embryos co-cultured with human oviductal epithelial cells. , OR-01. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong. . 2009. |
| Lee C.K.F., Lee C.Y.L., Cheong W.Y.A. and Yeung W.S.B., Roles of Oviductal proteins on preimplantation embryo development. , MS.58. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Researcher : Cheung TM |
| List of Research Outputs |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Researcher : Cheung VYT |
| List of Research Outputs |
| Cheung V.Y.T., A 10-year experience in removing Chinese intrauterine devices, International Journal of Gynecology and Obstetrics. Elsevier, 2010, 109: 219-22. |
| Cheung V.Y.T., Accessory ovary, Journal of Obstetrics and Gynaecology Canada. 2010, 32: 107. |
| Cheung V.Y.T., Best Oral Presentation Award (Gynaecology) , 6th International Society of Ultrasound in Obstetrics & Gynecology Outreach Course, Singapore. 2010. |
| Cheung V.Y.T., Electrosurgery in Gynaecology, Postgraduate Study Day, Department of Obstetrics & Gynaecology, the University of Hong Kong. 2010. |
| Cheung V.Y.T., Yang F. and Leung K.Y., Lower uterine segment thickness measurement in women with previous cesarean section: comparison of 2-D versus 3-D transabdominal sonography, 6th International Society of Ultrasound in Obstetrics & Gynecology Outreach Course, Singapore . 2010. |
| Cheung V.Y.T., Sonographic appearances of Chinese intrauterine contraceptive devices, 6th International Society of Ultrasound in Obstetrics & Gynecology Outreach Course, Singapore . 2010. |
| Researcher : Chiu CN |
| Project Title: | Identification of zona pellucida protein receptors in human spermatozoa |
| Investigator(s): | Chiu CN, Yeung WSB, Pang RTK, Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2008 |
| Completion Date: | 02/2010 |
| Abstract: |
| KEY ISSUES: -Mechanism of spermatozoa-ZP binding is unclear Fertilization starts with the carbohydrate-mediated binding of the spermatozoa to the zona pellucida (ZP) of the oocyte. The mechanism of spermatozoa-ZP binding is unclear partly due to the paucity of ZP glycoproteins, inability to produce recombinant ZP glycoproteins with correct glycosylation and to identify the ZP receptor on spermatozoa. -Knowledge of spermatozoa-ZP binding from mouse may not be applicable Much of the research on ZP is done in mouse. The mouse ZP composes of three glycoproteins: mouse ZP glycoprotein 1 (mZP1), mZP2, and mZP3. The initial sperm-binding activity resides on mZP3 [1]. In addition, mZP3 induces acrosome reaction (AR) [2], a crucial event in fertilization resulting in the release of enzymes from the acrosome of ZP-bound spermatozoa to facilitate ZP penetration. After AR, mZP2 binds to the acrosome-reacted spermatozoa [3]. mZP1 is not involved directly in spermatozoa–ZP interactions but serves as a crosslinking protein for stability of the ZP matrix [2]. In contrast to mouse ZP, human ZP (hZP) composes of four glycoproteins, hZP1-4 [4]. Little is known on the functions of these glycoproteins due to their limited availability. The glycosylation of ZP glycoproteins is important in spermatozoa-ZP interaction [5,6]. The binding of mouse but not human spermatozoa to oocytes from mZP2- and mZP3-deficient transgenic mice expressing hZP2 and hZP3 [7,8] is consistent with species-specific recognition of ZP mediated by the mouse-specific glycosylation irrespective of the protein core. -Sperm receptor for ZP glycoproteins may involved multi-molecular species Most of the previous studies assumed that the sperm ZP receptor is a single molecular species. Several carbohydrate-binding proteins have been proposed to be the sperm ZP receptors [9]. However, none of these proteins is solely responsible for mediating spermatozoa-ZP binding [9] as mouse deficient in these proteins is fertile. The exact identity of the sperm receptor(s) remains unclear. Accumulated evidence suggested that spermatozoa–ZP binding involved multiple receptors on spermatozoa [9-11]. For instance, β1,4-galactosyltransferase is a potential mZP3 receptor [12]. Spermatozoa from β1,4-galactosyltransferase-deficient mouse do not respond to mZP3-induced AR, though still bind to the oocyte [13], suggesting that other molecule is involved in spermatozoa-mouse ZP binding. Consistent with this, fucosyltransferase-5 on human spermatozoa binds to hZP but its agonists do not affect the AR [14]. Thus spermatozoa-hZP binding is likely to involve at least one molecule for binding to hZP and another molecule for induction of AR. It has been demonstrated that spermatozoa-ZP binding involves a series of binding events [15], and that the zona receptor may be a multimeric complex consisting of several molecular species [10]. However, direct evidence for these suggestions is lacking. PRELIMINARY WORK DONE BY INVESTIGATORS: -Identification of fucosyltransferase is a ZP receptor in spermatozoa With the combined use of chemical cross-linker, immunoprecipitation and mass spectrometry analysis, we show that fucosyltransferase-5 is a receptor of hZP on human spermatozoa [14]. -Purification of ZP glycoproteins from unfertilized human oocytes We have successfully purified native hZP2-4 for the first time by immunoaffinity columns [16]. The specific monoclonal antibodies (kind gift from Prof. S.K. Gupta, National Institute of Immunology, India) used enabled the isolation of hZP glycoproteins with high purities (88-93%). -The purified human ZP glycoproteins are biologically active Native hZP3 and hZP4 bound to the acrosome region of the capacitated human spermatozoa. The binding lost after AR. Native hZP2 bound to the same region only in acrosome-reacted spermatozoa. The three native hZP glycoproteins had differential binding to the post-acrosomal region and the mid-piece of spermatozoa, and induced AR in a time- and concentration-dependent manner to different extents. They inhibited spermatozoa-hZP binding. hZP3 also induced hyperactivation. These biological activities of the glycoproteins were dependent partly on their glycosylation [16,17]. -Human sperm membrane complex can be separated by Blue native gel electrophoresis The hZP-binding protein complexes in human sperm plasma membrane were separated by two-dimensional blue native-gel/sodium dodecyl sulphate- polyacrylamide gel electrophoresis BNG/SDS-PAGE (Figure 1 and see below). Twelve components (arrows) of the complexes were resolved by the denaturing SDS-PAGE in the second dimension and provisionally identified by mass spectrometric analyses. These components include nicotinic acetylcholine receptor, acrosomal vesicle protein-1, tyrosine-protein kinase-JAK1, calreticulin and fucosyltransferase-5. HYPOTHESIS We hypothesize that the hZP receptors exist as receptor complex. This is based on (1) β1,4-galactosyltransferase deficient mouse spermatozoa bind to mouse ZP, but do not respond to mZP3-induced AR; (2) Mouse ZP glycoproteins binds to more than one binding sites of mouse spermatozoa; (3) sperm fucosyltransferase-5 binds to hZP but its agonists do not affect the AR; (4) our detection of hZP glycoproteins-bound large sized molecular entities from solubilized human sperm membrane. OBJECTIVES 1.To identify hZP-binding complexes on human spermatozoa; 2.To study the role of the complexes in spermatozoa-hZP interaction; 3.To investigate the effect of capacitation on the organization of zona receptor complexes. REFERENCES 1.Florman HM, Wassarman PM. Cell. 1985; 41:313-24. 2.Wassarman PM. J Cell Physiol. 2005; 204:388-91. 3.Bleil JD, Greve JM, Wassarman PM. Dev Biol. 1988; 128:376-85. 4.Lefievre L, Conner SJ, Salpekar A et al. Hum Reprod. 2004; 19:1580-6. 5.Wassarman PM, Jovine L, Litscher ES. Nat. Cell Biol. 2001; 3, E59-64. 6.Topfer-Petersen E. Hum. Reprod. Update. 1999; 5:314-329. 7.Rankin TL, Tong ZB, Castle PE et al. Development. 1998; 125:2415-2424. 8.Rankin TL, Coleman JS, Epifano O et al. Dev. Cell. 2003; 5:33-43. 9.Wassarman PM. Cell. 1999; 96:175-83. 10.Nixon B, Asquith KL, Aitken RJ. Mol Cell Endocrinol. 2005; 240:1-10. 11.Castle PE. Reproduction. 2002; 124:29-32. 12.Nixon B, Lu Q, Wassler MJ et al. Cells Tissues Organs. 2001; 168:46-57. 13.Lu Q, Shur BD. Development. 1997; 124:4121-31. 14.Chiu PC, Chung MK, Koistinen R et al. J Cell Sci. 2007; 120:33-44. 15.Thaler CD, Cardullo RA. Biol Chem. 1996; 71:23289-97. 16.Chiu PC, Wong BS, Lee CL et al. Native human ZP glycoproteins: Purification and binding properties. 2007; SUBMITTED. 17.Chiu PC, Wong BS, Chung MK et al. Native human ZP glycoproteins II: Effects on acrosomal exocytosis and sperm-ZP interaction. 2007; SUBMITTED. |
| Project Title: | Control of human trophoblast invasion by glycodelin-A |
| Investigator(s): | Chiu CN, Lao TTH, Pang RTK, Yeung WSB |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 01/2009 |
| Abstract: |
| (1) As the project is funded only HK$804,125 for 2 years, the experiments using primary trophoblast cells cannot be performed because of (1) lack of resource to recruit staff for collection, preparation and characterization of the primary trophoblast cells; and (2) constraint of shorter funding period. Only experiment using trophoblast cell lines will be performed. The change is unlikely to affect the overall result and conclusion of the project; (2) As the project is funded only HK$804,125 for 2 years, the experiments using primary trophoblast cells cannot be performed because of (1) lack of resource to recruit staff for collection, preparation and characterization of the primary trophoblast cells; and (2) constraint of shorter funding period. Only experiment using trophoblast cell lines will be performed. The change is unlikely to affect the overall result and conclusion of the project; (3) As the project is funded only HK$804,125 for 2 years, the experiments using primary trophoblast cells cannot be performed because of (1) lack of resource to recruit staff for collection, preparation and characterization of the primary trophoblast cells; and (2) constraint of shorter funding period. Only experiment using trophoblast cell lines will be performed. The change is unlikely to affect the overall result and conclusion of the project; (4) As the project is funded only HK$804,125 for 2 years, the experiments using primary trophoblast cells cannot be performed because of (1) lack of resource to recruit staff for collection, preparation and characterization of the primary trophoblast cells; and (2) constraint of shorter funding period. Only experiment using trophoblast cell lines will be performed. The change is unlikely to affect the overall result and conclusion of the project. |
| Project Title: | The role of sperm fucosyltransferase-5 on sperm-oviductal epithelial cell interaction |
| Investigator(s): | Chiu CN, Lee CL, Yeung WSB |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2010 |
| Abstract: |
| BACKGROUND - Sperm reservoir in oviduct In mammals, including human, oviduct functions as a sperm reservoir which is created by binding of the spermatozoa to the epithelial lining in the isthmic region of the oviduct [1,2]. Human spermatozoa may reside in the oviduct up to a few days [3] until after ovulation. In the oviductal reservoir, spermatozoa bind to the oviductal epithelium. Such interaction maintains/improves the motility, preserves the viability and fertilizing ability, improves fertilization rates in infertile males, reduces sperm chromatin damage and regulates capacitation of spermatozoa in vivo and in vitro [1,2,4-7]. - Mechanism controlling the binding of spermatozoa to the oviduct Sperm binding to the oviductal epithelium involves carbohydrate recognition; various monosaccharides, oligosaccharides or glycoproteins inhibit the binding of spermatozoa to the oviductal epithelial cells or explants in different species [8]. In contrast to other mammalian species, the mechanism controlling the binding of spermatozoa to the oviductal epithelium in human is not clear because of the difficulty in obtaining human oviductal cells. - In vitro assays for studying the spermatozoa-oviduct interaction Different in vitro assays have been developed to study the spermatozoon-oviduct interaction in non-primate animal species. Most of these methods are based on co-incubation of a defined number of spermatozoa with oviduct explants or scrapped oviductal epithelium contaminated with the underlying stroma with [9-11]. The possible differential actions of epithelial cells and stromal cells on sperm functions cannot be dissected in these systems. Therefore, other studies use co-incubation with oviductal vesicles [9], primary oviductal cell monolayers [12] or apical membranes of oviductal cells [13] to study spermatozoa-oviductal epithelial cell interaction. While the use of these latter models in animal is feasible, their use in human is difficult because of ethical and technical limitations in obtaining sufficient primary oviductal epithelial cells. Thus there is no well accepted model for studying spermatozoa-oviduct interaction in humans. - Sperm fucosyltransferase-5 (sFUT5) Glycodelin-A is abundant in the secretory endometrium [14]. It is the first endogenous glycoprotein found to inhibit spermatozoa-zona pellucida binding [15]. We identified sFUT5 as a surface glycodelin-A receptor locating on the acrosomal region of human spermatozoa [16]. Biologically active sFUT5 has been purified from human spermatozoa, and is further shown to be a receptor of zona pellucida glycoproteins [16]. Recently, our unpublished data demonstrated that affinity-purified sFUT5 bound to the epithelial lining of human oviduct and to an immortalized human oviductal epithelial cell line, OE-E6/E7 [17]. PRELIMINARY WORK DONE BY INVESTIGATORS - sFUT5 is a human sperm receptor for glycodelin-A and zona pellucida With the combined use of chemical cross-linker, immunoprecipitation and mass spectrometry analysis, we showed that sFUT5 was a receptor of glycodelin-A and zona pellucida in spermatozoa [16]. sFUT5 is a carbohydrate binding protein. It has been located to the plasma membrane overlying the acrosomal region of human spermatozoa [16], where spermatozoa bind to the oviductal epithelium [1,8]. - Generation of immortalized human oviductal epithelial cell line We are the first group in the field to generate an immortalized human oviductal epithelial cell line [17]. The cell line maintains many of the characteristics of oviductal epithelial cells including the production of oviduct-specific glycoproteins. - sFUT5 is responsible for adhesion of human spermatozoa to the oviductal epithelium Our preliminary data demonstrated binding of human spermatozoa to an immortalized oviductal cell line, OE-E6/E7 (Figure 1; Appendix 1). Moreover, affinity-purified sFUT5 bound to the epithelial lining of human oviduct and to the immortalized human oviductal epithelial cell line, OE-E6/E7 [17] (Figure 2; Appendix 1). - Oviductal cell membrane proteins enhances the fertilizing ability of human spermatozoa Human spermatozoa retained motility and viability longer when incubated with membrane proteins extracted from OE-E6/E7 (Figure 3; Appendix 1). HYPOTHESIS Based on the above preliminary work and the knowledge on the presence of oligosaccharides on the cell surface of the human oviductal epithelial cells that are recognized by the carbohydrate-binding proteins on sperm surface [8,18], we hypothesize that FUT5 mediates spermatozoa-oviductal epithelial cells interaction and the beneficial effects of such interaction on the fertilizing ability of human spermatozoa. OBJECTIVES OF THE PROPOSAL To test the above hypothesis, studies with the following objectives will be performed: 1. To optimize a coculture model for human spermatozoa-oviductal epithelial cells interaction; 2. To study the role of sFUT5 on spermatozoa-oviductal epithelial cell interaction; 3. To investigate the effect of oviductal epithelial cell membrane proteins on sperm functions and their possible relationships with sFUT5; 4. Identification of the sFUT5-interacting proteins in oviductal epithelial cells membrane. REFERENCES 1. Suarez SS, Pacey AA. Hum Reprod Update. 2006;12:23-37. 2. Yao Y, Ho P, Yeung WS. Fertil Steril. 2000;73:479-86. 3. Wilcox AJ, Weinberg CR, Baird DD. N Engl J Med. 1995;333:1517-21. 4. Ellington JE, Evenson DP, Wright RW Jr, Jones AE, Schneider CS, Hiss GA, Brisbois RS. Fertil Steril. 1999;71:924-29. 5. Kervancioglu ME, Saridogan E, Atasü T, Camlibel T, Demircan A, Sarikamis B, Djahanbakhch O. Hum Reprod. 1997;12:1253-58. 6. Lyons RA, Saridogan E, Djahanbakhch O. Hum Reprod Update. 2006;12:363-72. 7. Yeung WS, Ng VK, Lau EY, Ho PC. Hum Reprod. 1994;9:656-660. 8. Suarez, S.S. Cells Tissues Organs. 2001:168:105-12. 9. Gwathmey TM, Ignotz GG, Mueller JL, Manjunath P, Suarez SS. Biol Reprod. 2006;75:501-07 10. Ignotz, G. G., Lo, M., Perez, C., Gwathmey, T. M., and Suarez, S. S. Biol. Reprod. 2001;64:1806–11. 11. Tollner, T.L., Yudin, A.I., Tarantal, A.F., Treece, C.A., Overstreet, J.W., Cherr, G.N. Biol. Reprod. 2008:78:400-12 12. Green, C.E., Bredl, J., Holt, W.V., Watson, P.F., Fazeli, .A. Reprod. 2001;122: 305-15. 13. Boilard, M., Bailey, J., Collin, S., Dufour, M., Sirard, M.A. Biol. Reprod. 2002;67:1125-32. 14. Seppälä M, Koistinen H, Koistinen R, Chiu PC, Yeung WS. Hum Reprod Update. 2007;13:275-87. 15. Chiu PC, Koistinen R, Koistinen H, Seppala M, Lee KF, Yeung WS. J Biol Chem. 2003;278:13570-7. 16. Chiu PC, Chung MK, Koistinen R, Koistinen H, Seppala M, Ho PC, Ng EH, Lee KF, Yeung WS. J Cell Sci. 2007;120:33-44. 17. Lee YL, Lee KF, Xu JS, Wang YL, Tsao SW, Yeung WS. Mol Reprod Dev. 2001;59:400-9. 18. Schulte, B.A., Rao, K.P., Kreutner, A., Thomopoulos, G.N., Spicer, S.S. Lab. Invest. 1985;52:207-19. |
| Project Title: | 26th Annual Meeting of the European Society of Human Reproduction and Embryology The role of adrenomedullin in regulating human sperm motility |
| Investigator(s): | Chiu CN |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 06/2010 |
| Completion Date: | 06/2010 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Chiu C.N., Liao S., Lam K.W., Tang F., Ho J.C.M., Ho P.C., O W.S., Yao Q.Y. and Yeung W.S.B., Adrenomedullin regulates sperm motility and oviductal ciliary beat via cyclic adenosine 5'-monophosphate/protein kinase A and nitric oxide, Endocrinology. 2010, 151(7): 3336-3347. |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Hong S.J., Chiu C.N., Lee C.K.F., Tse J.Y., Ho P.C. and Yeung W.S.B., Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass, Fertil Steril. 2009, 92: 971-8. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Li R.H.W., Chiu C.N., Cheung M.P.L., Yeung W.S.B. and O W.S., Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa, International Journal of Andrology. 2009, 32: 687-694. |
| Li R.H.W., Liao S., Chiu C.N., Tam W.W., Ho J.C.M., Ng E.H.Y., Ho P.C., Yeung W.S.B., Tang F. and O W.S., Expression of adrenomedullin in human oviduct, its regulaton by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium, Journal of Clinical Endocrinology and Metabolism. 2010, 95(9): E18-E25. |
| O W.S., Liao S., Sun J.Z., Ho J.C.M., Chiu C.N., Ng E.H.Y., Yeung W.S.B., Li R.H.W. and Tang F., Adrenomedullin and oviduct function in human and rats, Biology of Reproduction. 2009, 81: 99. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Wong S.T., Chiu C.N., Lee C.K.F. and Yeung W.S.B., Effect of adrenomedullin on extravillous cytotrophoblast invasion. , P-10. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Yeung W.S.B., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Chiu C.N., Effects of glycodelins on functional competence of spermatozoa, J Reprod Immunol. 2009, 83: 26-30. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., Excellent Poster Presentation: MicroRNA-34c is important for the first cell division in mouse embryos, First SKLAB Symposia on Frontiers in Preimplantation Biology 8-12 May 2010, Beijing. 2010. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., MicroRNA-34c is important for the first cell division in mouse embryos, The First SKLAB Symposia on Frontiers in Periimplantation Biology, Beijing China. 2010, 55. |
| Researcher : Chiu PM |
| List of Research Outputs |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Wang Y., Chan D.W., Liu V.W.S., Chiu P.M. and Ngan H.Y.S., Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis, Clinical Cancer Research. AACR, 2010, 16: 2529-39. |
| Researcher : Chow JFC |
| List of Research Outputs |
| Chow J.F.C., Yeung W.S.B., Lau E.Y.L., Lam S.T.S., Tong T., Ng E.H.Y. and Ho P.C., Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification, Fertility and Sterility. 2009, 92(2): 828, e7-e10. |
| Researcher : Chow WN |
| List of Research Outputs |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Researcher : Chung MK |
| List of Research Outputs |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Researcher : Fong SW |
| List of Research Outputs |
| Lee C.Y.L., Peng Q., Fong S.W. and Yeung W.S.B., THE EXPRESSION AND REGULATION OF SIRT1 IN HUMAN EMBRYONIC STEM CELLS, International Society for Stem Cell Research 8th Meeting, 16-19 June, San Francisco, 2010. |
| Researcher : Fung FKC |
| List of Research Outputs |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Researcher : Ho PC |
| Project Title: | A retrospective analysis of maternal serum anti-Mullerian hormone level in Down’s syndrome pregnancies |
| Investigator(s): | Ho PC, Li RHW, Lau ETK, Ng EHY, Tang MHY, Yeung WSB, Hui PW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2009 |
| Completion Date: | 12/2009 |
| Abstract: |
| • To demonstrate the difference in maternal serum AMH level between normal pregnancy and pregnancy affected by fetal Down’s syndrome. • To evaluate the predictive value of maternal serum AMH level in Down’s screening either alone or in combination with other common biological (e.g. maternal age, nuchal translucency measurement) and biochemical markers (e.g. maternal serum levels of AFP, beta-HCG and PAPP-A). • To compare the predictive value of maternal serum AMH level in Down’s screening in women below and above age of 35. • To compare the predictive value of maternal serum AMH level in Down’s screening in natural and assisted conceptions. |
| Project Title: | Combined use of letrozole and misoprostol for medical termination of pregnancy |
| Investigator(s): | Ho PC, Lee CKF, Ng EHY, Yeung WSB |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 01/2009 |
| Abstract: |
| (1) To determine the mechanisms of action of combined use of letrozole and misoprostol for the second trimester medical termination; (2) To investigate the efficacy of combined use of letrozole and misoprotsol for the first trimester medical termination; (3) To study the effect of letrolzole on the function of the corpus luteum during early pregnancy in humans. |
| List of Research Outputs |
| Chan C.H., Tiwari A.F.Y., Fong D.Y.T. and Ho P.C., Post-traumatic stress disorder among Chinese women survivors of intimate partner violence: A review of the literature, International Journal of Nursing Studies. 2010, 47: 918-925. |
| Chan E.K.L., Brownridge D.A., Tiwari A.F.Y., Fong D.Y.T., Leung W.C. and Ho P.C., Associating pregnancy with partner violence against Chinese women, Journal of Interpersonal Violence. 2010. |
| Chan E.K.L., Tiwari A.F.Y., Leung W.C., Fong D.Y.T., Brownridge D.A. and Ho P.C., Cost Measures for the Economic Impact of Domestic Violence, paper presented in the First Asia-Pacific Conference on Health Promotion and Education (APHPE), organized by the Northern Part of Western Pacific Region of International Union of Health Promotion and Education (NPWP/IUHPE) & Japanese Society of Health Education and Promotion (JSHEP), Makuhari Messe, Japan, July 18-20, 2009.. 2009. |
| Chiu C.N., Liao S., Lam K.W., Tang F., Ho J.C.M., Ho P.C., O W.S., Yao Q.Y. and Yeung W.S.B., Adrenomedullin regulates sperm motility and oviductal ciliary beat via cyclic adenosine 5'-monophosphate/protein kinase A and nitric oxide, Endocrinology. 2010, 151(7): 3336-3347. |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Chow J.F.C., Yeung W.S.B., Lau E.Y.L., Lam S.T.S., Tong T., Ng E.H.Y. and Ho P.C., Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification, Fertility and Sterility. 2009, 92(2): 828, e7-e10. |
| Ho P.C., Antimullerian hormone in reproductive medicine, The Annual Scientific Meeting of the Fertility and Sterility Society of Republic of China, May 29-30, 2010 in Taiwan. 2010. |
| Ho P.C., Associate Editor, Human Reproduction. 2009. |
| Ho P.C., Director of Editorial Board in Obstetrics and Gynaecology, Journal of Paediatrics, Obstetrics and Gynaecology, 1997 till now. 2009. |
| Ho P.C., Does ovarian hyperstimulation impairs endometrial receptivity?, The 3rd Asia Pacific Congress on Controversies in Obstetrics, Gynaecology and Infertility, November 12-15, 2009 in Beijing, China. 2009. |
| Ho P.C., First trimester medical abortion, The Session of Termination of Pregnancy in FIGO 2009 World Congress, October 4-9, 2010 in Cape Town, South Africa. 2009. |
| Ho P.C., Infertility treatment and multiple pregnancies, The World Congress on Recent Advances in Obstetrics abd Gynaecology, September 11-13, 2009, Mumbai, India. 2009. |
| Ho P.C., Management of poor responders, The Symposium on "Updates on Assisted Reproduction" on June 5, 2010 in Hong Kong. 2010. |
| Ho P.C., Management of subfertility in endometriosis, The 7th Conference of The Pacific Rim Society for Fertility and Sterility 2009 and Annual Meeting of Taiwanese Society for Reproductive Medicine 2009, August 20-23, 2009 in Taipei, Taiwan. 2009. |
| Ho P.C., Medical Abortions, Singapore Journal of Obstetrics and Gynaecology. 2009, 40(2): 67. |
| Ho P.C., Medical abortion in the second trimester, The 25th AICC RCOG Conference, February 26-27, 2010 in Kolkata, India. 2010. |
| Ho P.C., Medical abortions (S15.1), The 7th Singapore International Conference of Obstetrics and Gynaecology, 26-29 August, 2009, Marina Mandarin Singapore. 2009. |
| Ho P.C., Member of Editorial Board, "Hospital Practice and Infection Control", 1989 till now. 2010. |
| Ho P.C., Member of Editorial Board, Chinese Journal of Obstetrics and Gynaecology. 2009. |
| Ho P.C., Member of Editorial Board, Clinical Obstetrics and Gynaecology (Bailliere Tindall). 2009. |
| Ho P.C., Member of Editorial Board, Journal of Assisted Reproduction and Genetics. 2009. |
| Ho P.C., Member of Editorial Board, Journal of Practical Obstetrics and Gynaecology. 2009. |
| Ho P.C., Member of Editorial Board, Journal of Reproductive Medicine (China). 2009. |
| Ho P.C., Member of the Advisory Editorial Board, Asia Oceania Journal of Obstetrics and Gynaecology, 1994 till now. 2010. |
| Ho P.C., Misoprostol - an essential drug in Obstetrics and Gynaecology, The 11th National Conference of Nepal Society of Obstetricians and Gynaecologists, April 13, 2010 in Nepal. 2010. |
| Ho P.C., Optimization of ovarian stimulation in assisted reproduction, The Taiwan Association of Obstetrics and GYnaecology 2010 Annual Meeting, March 13-14, 2010 in Taipei. 2010. |
| Ho P.C., Liu Y., Lee C.K.F., Ng E.H.Y. and Yeung W.S.B., Ovarian stimulation and endometrial receptivity. , The 7th Conference of the Pacific Rim Society for Fertility and Sterility & Annual Meeting of the Taiwanese Society for Reproductive Medicine, 20-23 Aug, Taipei.. 2009. |
| Ho P.C., Ovarian stimulation protocol: The best is still to come, 3rd Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2010), Bangkok, Thailand, April 9-11, 2010. 2010. |
| Ho P.C., Ovarian stimulation: Challenges and opportunities, The Annual Scientific Meeting of the Fertility and Sterility Society of Republic of China, May 29-30, 2010 in Taiwan. 2010. |
| Ho P.C., Reviewer for "American Journal of Obstetrics and Gynaecology". 2010. |
| Ho P.C., Reviewer for "Biology of Reproduction". 2010. |
| Ho P.C., Reviewer for "Obstetrics and Gynaecology". 2010. |
| Hong S.J., Chiu C.N., Lee C.K.F., Tse J.Y., Ho P.C. and Yeung W.S.B., Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass, Fertil Steril. 2009, 92: 971-8. |
| Kodithuwakku K.S.P.K., Yeung W.S.B., Ho P.C. and Lee C.K.F., In vitro modeling of tubal ectopic implantation of embryos: A study on the role of olfactomedin 1 (Olfm1) in tubal ectopic pregnancy. , P-06. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Lee C.K.F., Liu Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Excessive ovarian stimulation affects endometrial receptivity in IVF patients. , The 5th Huaxia Congress of endocrinology, 4-9 Dec, Taipei.. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Lee V.C.Y., Ng E.H.Y. and Ho P.C., Issues in second trimester induced abortion (medical/surgical methods), Best Practice and Research Clinical Obstetrics and Gynaecology. 2010, 24: 517-527. |
| Li R.H.W., Liao S., Chiu C.N., Tam W.W., Ho J.C.M., Ng E.H.Y., Ho P.C., Yeung W.S.B., Tang F. and O W.S., Expression of adrenomedullin in human oviduct, its regulaton by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium, Journal of Clinical Endocrinology and Metabolism. 2010, 95(9): E18-E25. |
| So W.S., Ng E.H.Y., Wong Y.Y., Yeung W.S.B. and Ho P.C., Accupuncture for frozen-thawed embryo transfer cycles: A double-blind randomized controlled trial, Reproductive BioMedicine Online. 2010, 20: 814-821. |
| Tang F.O.S., Schweer H., Lee W.H. and Ho P.C., Pharmacokinetics of repeated doses of misoprostol, Human Reproduction. 2009, 24(8): 1862-1869. |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Researcher : Hou YCD |
| List of Research Outputs |
| Lee C.Y.L., Hou Y.C.D., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Study of extracellular matrix for the culture of human embryonic stem cells., International Society For Stem Cell Research, 7th Annual Meeting, 8-11 July, Spain. 2009. |
| Researcher : Hu Y |
| List of Research Outputs |
| Hu Y., Chan K.K.L. and Ngan H.Y.S., Preventing Cervical Cancer: Primary And Secondary Measures, Journal Of Paediatrics, Obstetrics And Gynaecology. 2009, 35: 213. |
| Researcher : Huang W |
| List of Research Outputs |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Researcher : Hui PW |
| Project Title: | 31st British International Congress of Obstetrics & Gynaecology 2007 A rare cause of Thrombocytopenia in Pregnancy-EDTA-dependent Pseudothrombocytopenia |
| Investigator(s): | Hui PW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 07/2007 |
| Abstract: |
| N/A |
| Researcher : Kodithuwakku KSPK |
| List of Research Outputs |
| Kodithuwakku K.S.P.K., Yeung W.S.B., Ho P.C. and Lee C.K.F., In vitro modeling of tubal ectopic implantation of embryos: A study on the role of olfactomedin 1 (Olfm1) in tubal ectopic pregnancy. , P-06. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Researcher : Kwan TTC |
| List of Research Outputs |
| Kwan T.T.C., Tam K.F., Lee P.W.H., Lo S.S.T., Chan K.K.L. and Ngan H.Y.S., De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial, Psycho-Oncology. 2010, 1-11. |
| Researcher : Lam KW |
| List of Research Outputs |
| Chiu C.N., Liao S., Lam K.W., Tang F., Ho J.C.M., Ho P.C., O W.S., Yao Q.Y. and Yeung W.S.B., Adrenomedullin regulates sperm motility and oviductal ciliary beat via cyclic adenosine 5'-monophosphate/protein kinase A and nitric oxide, Endocrinology. 2010, 151(7): 3336-3347. |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Researcher : Lam KW |
| List of Research Outputs |
| Chiu C.N., Liao S., Lam K.W., Tang F., Ho J.C.M., Ho P.C., O W.S., Yao Q.Y. and Yeung W.S.B., Adrenomedullin regulates sperm motility and oviductal ciliary beat via cyclic adenosine 5'-monophosphate/protein kinase A and nitric oxide, Endocrinology. 2010, 151(7): 3336-3347. |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Researcher : Lam YH |
| Project Title: | 11th World Congress on Ultrasound in Obstetrics and Gynecology Integrated First and Second Trimester Screening for Down Syndrome |
| Investigator(s): | Lam YH |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 10/2001 |
| Abstract: |
| N/A |
| Researcher : Lao TTH |
| Project Title: | The First Congress on Obstetrics, Gynecology & Infertility Does Impaired Glucose Tolerance Impact on Pregnancy Outcome? |
| Investigator(s): | Lao TTH |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 10/1999 |
| Abstract: |
| N/A |
| Project Title: | Dietary caloric intake and the development of gestational diabetes mellitus in at-risk Chinese women |
| Investigator(s): | Lao TTH, Leung WC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2002 |
| Abstract: |
| To determine the relationship between daily total caloric intake in the third trimester and the development of gestational diabetes mellitus in at-risk pregnant Chinese women; to compare the roles of toal caloric intake versus the carbohydrate: protein: fat ratio in the daily diet and development of gestational diabetes mellitus in the at-risk Chinese women. |
| Project Title: | The role of adiponectin in the development of gestational diabetes mellitus and its effect on pregnancy outcome |
| Investigator(s): | Lao TTH, Lam KSL, Chan KKL |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To determine if plasma adiponectin concentration is reduced, at the time of the oral glucose tolerance test (OGTT), in women who develop GDM in the latter half of pregnancy versus women with normal OGTT; to determine, following the diagnosis of GDM, whether the subsequent changes in adiponectin concentration is associated with obstetric complications and perinatal morbidity; to correlate circulatory concentration of adiponectin with polymorphisms and mutations in the apM1 gene in high risk women with and without GDM, and with the expression of adiponectin in subcutaneous and omental fat cells obtained from biopsy at the time of caesarean delivery for obstetric indications; to correlate antenatal adiponectin concentration and result of the genetic study with the postnatal glucose tolerance status in the women who have developed GDM. |
| Project Title: | Elevated TNF-α in gestational diabetes mellitus-cause or consequence? |
| Investigator(s): | Lao TTH, Leung WC, Ngai CSW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To determine and compare the serial changes in maternal blood level of TNF-α and its receptors, C-reactive protein (CRP) , and ferritin in relation to the development of gestational diabetes mellitus (GDM) in Chinese pregnant women with singleton and twin pregnancies; to determine the relationship between changes in maternal blood level of TNF-α and its receptors, CRP and ferritin with the occurrence of complicantions in Chinese pregnant women with and with and without GDM, and whether there is any difference between singleton and twin pregnancies. To correlate the levels of TNF-α and its receptors between maternal blood with cord blood, and between these two compartments with placental size and the placental expression of TNF-α and its receptors. To correlate maternal and cord blood, and placental TNF-α and its receptors with the infant birthweight and development of perinatal complications, and the determine if there is any difference between singleton and twin pregnancies. |
| Project Title: | The relationship between the antioxidant defense system with the development of gestational diabetes mellitus and its complications in the Chinese population. |
| Investigator(s): | Lao TTH |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 12/2005 |
| Abstract: |
| Gestational diabetes mellitus (GDM) has become the leading medical complication in pregnancy in the local Chinese population, and despite satisfactory glycaemic control, maternal and perinatal complications cannot be eliminated. One of the metabolic disturbances now documented with diabetes mellitus in non-pregnant subjects is an increased oxidative stress. The standard approach in the management of GDM is to normalize blood glucose level with dietary and insulin treatment, but this may not be sufficient to counter the increased oxidative stress, and the persistent risk of maternal and perinatal complications could be related to inadequate defense against the increased oxidative stress in GDM. There has been minimal information about the natural antioxidant defense systems, such as the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and especially thioredoxin reductase (TRx), in pregnancy with and without GDM, and there is no information on these systems in the infant at the time of birth. These enzyme systems are present in the placenta and can also be measured in peripheral blood. The present study is designed to investigate (1) the maternal antioxidant defense systems at the time of diagnosis of GDM, comparing between women with normal and abnormal glucose tolerance; (2) and its subsequent changes in relation to treatment and glycaemic control, (3) the changes in relation to pregnancy complications in women with and without GDM; and (4) the changes in the fetal compartment as reflected in cord blood and placental tissue. |
| Researcher : Lau EYL |
| List of Research Outputs |
| Chow J.F.C., Yeung W.S.B., Lau E.Y.L., Lam S.T.S., Tong T., Ng E.H.Y. and Ho P.C., Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification, Fertility and Sterility. 2009, 92(2): 828, e7-e10. |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Researcher : Lee CKF |
| Project Title: | Functional characterization of VAD1.3, a novel acrosome-specific protein by conditional tissue-specific gene inactivation |
| Investigator(s): | Lee CKF, Cheah KSE, Yeung WSB, Luk JMC, Lee NPY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 01/2006 |
| Abstract: |
| To generate VAD1.3 knockout targeting construct; to generate VAD1.3 knockout mice; to produce antibodies against mouse VAD1.3; to analysis the VAD1.3 knockout mice. |
| Project Title: | Functional characterization of a testis-specific Trs4 gene on spermatogenesis by tissue-specific conditional inactivation |
| Investigator(s): | Lee CKF, Yeung WSB, Cheah KSE |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | NSFC/RGC Joint Research Scheme |
| Start Date: | 01/2007 |
| Abstract: |
| To characterize monoclonal antibodies against TRS4; to determine the interacting partners of TRS4; to generate TRS4 conditional knockout targeting construct; to generate TRS4 conditional knockout mice; to phenotype the TRS4 knockout mice. |
| Project Title: | Understanding Human Endometrial Stem Cell Proliferative and Differentiation Potential |
| Investigator(s): | Lee CKF, Yeung WSB, Chan RWS, Ng EHY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 04/2008 |
| Completion Date: | 09/2009 |
| Abstract: |
| The Endometrium The human endometrium in the female is known for its remarkable regenerative capacity in the reproductive years (Okulicz, 2002). The endometrium regenerates from the lower basalis layer which persists after each menstruation and gives rise to the new upper functionalis containing mature endometrial epithelial and stromal cells. This cyclical regeneration is regulated by sex steroid hormones (Ferenczy et al., 1979). Even before menstruation is completed, endometrial regeneration commences as epithelial cells migrate from the exposed mouths of basal glands to cover the endometrial surface. Stromal tissue begins to grow only when the endometrial wound is completely re-epithelialized (Ferenczy, 1976; McLennan and Rydell, 1965). The ability to undergo cyclical rapid regrowth has led to speculation of the presence of stem cells in the endometrium (Padykula, 1991). Somatic Stem Cells Somatic stem cells are found in many adult regenerative tissues (Fuchs et al., 2004; Slack, 2000). The key functions of the somatic stem cells are self renewal and differentiation. The stem cells undergo self-renewal to produce identical daughter cells so as to maintain the stem cell pool in the tissues. They may also undergo asymmetric cell division to form an identical daughter cell and a committed progenitor cell (Morrison et al., 1997). The progenitors proliferate to produce more differentiated, rapidly proliferating transit amplifying cells (TA), which eventually differentiate into the functional mature cells with no proliferative capacity. These unique properties allow the stem cells to produce identical daughter cells and at the same time differentiate down one or more lineages to produce mature functional progenies (Watt and Hogan, 2000). Stem cells types share common core functionalities, such as self-renewal and multipotency. It had once been thought that these are the outcomes of selective expression of a common set of genes, which is often referred to as stemness genes or stem cells molecular signature (Cai et al., 2004). To identify such genetic elements, a series of DNA microarray experiments have been performed on neural stem cells and skin epithelial stem cells (Aiba et al., 2006; Cai et al., 2006; Tumbar et al., 2004). These attempts have led to the identification of molecular entity specific for each stem cell type. The properties of somatic stem cells have been investigated in several ways. The pluripotent nature of the stem cells has been examined in vitro using clonogenic assays, where stem cells are seeded at very low density resulting in the formation of clones (Morrison et al., 1999). The label retaining technique (LRC) (Lehrer et al. 1998), making use of the property of slow-cycling cells in retaining 5-bromo-2’-deoxyuridine (BrdU) label in the nucleus of the stem/progenitor cells, allows the identification of stem/progenitor cells in tissues. The long-term proliferative capacity of stem cells has been studied by counting the total cell output from serially passaged cells cultured at the same initial density (Li et al., 1998). Their self renewing capacity has been examined by transplanting the stem cells into an immuno-compromised animal and examining for tissue reconstitution (Booth et al., 1999). Endometrial stem/progenitor cells Our group was the first to use a functional approach (clonogenic assay) to identify epithelial and stromal stem/progenitor cells in human endometrium (Chan et al., 2004). We showed that 0.22±0.07% of endometrial epithelial cells and 1.25±0.18% of stromal cells formed colonies when single endometrial cell suspensions were cultured at very low cloning densities. Two types of colonies formed from endometrial epithelial and stromal cells: large colonies, comprising densely packed small cells of high proliferative potential initiated by putative/stem progenitor cells, and small colonies comprising loosely arranged, large cells of low proliferative potential initiated by putative tissue proliferating cells (Gargett, 2004). Using the LRC technique, we were the first to demonstrate LRC in the epithelial and stromal compartments, suggesting that epithelial and stromal stem cells exist in mouse endometrium (Chan and Gargett, 2006). Our results indicated that 2.75±0.03% (n=4) of epithelial LRCs were found after 8 weeks chase and 6.33±0.03% (n=3) of stromal LRCs after 12 weeks. Phenotypic characterization of LRCs showed that many stromal LRCs were found in a perivascular location i.e. adjacent to endothelial cells of blood vessels. These results suggest that epithelial LRCs proliferate more frequently than stromal LRCs suggesting a shorter cell-cycle time. Stem cell niches Increasing evidence indicates that stem cells have a defined location and that the one or several neighboring cells (niche cells) provide specialized microenvironment (niches) regulating self renewal and differentiation of the somatic stem cells (Spradling et al., 2001; Watt and Hogan, 2000). The stem cell niche protects the stem cells and holds them in position by preventing their loss through non-self renewing cell divisions. In addition, the niche cells communicate with stem cells in a paracrine manner when they need to undergo self renewing cell divisions to replace themselves. This essential function of niche cells allows stem cells to respond to environmental cues, especially tissue damage when replacement cells are required (Spradling et al., 2001; Zhang et al., 2003). At present, epithelial stem cell niches are being characterized in a number of mammalian tissues. However, nothing is known about the stromal stem cell niche. Our knowledge on the niches for endometrial stem/progenitor is relatively primitive. Our data (Chan and Gargett, 2006) in mouse showed that stromal LRC were also in close proximity to glandular and luminal epithelium and that these LRC co-expressed estrogen receptor- alpha (ERα). Epithelial LRCs were mainly located in the surface epithelium and appear not to co-express ERα. The expression of ERα in some stromal LRCs indicates that these cells are capable of responding to estrogen and that they may transmit paracrine signals to epithelial cells to stimulate regeneration of the endometrial epithelium. Hypothesis We hypothesize that estrogen and regenerating endometrial cells affect the gene expression of endometrial stem/progenitor cells. This hypothesis predicts that estrogen and regenerating endometrial cells enhance the transformation of the large colonies to the small colonies with change in the expression of genes associated with loss of stemness involving the stem cells’ proliferative and differentiation potential. Due to the funding limitation of the scheme, we will only test the hypothesis on endometrial epithelial colonies. Objectives: 1. To compare the mRNA expression profiles between large and small endometrial clones. 2. To identify specific genes which are differentially expressed in large and small colonies, and determine their effected by estrogen treatment and/or coculture with regenerating endometrial cells. 3. To study the effect of changes in the expression of genes identified in Objective 2 on production and differentiation of large clones. |
| Project Title: | A Study of Oviductal Epoxide Hydrolase on reducing Reactive Oxygen Species (ROS) in an Embryo Co-culture System |
| Investigator(s): | Lee CKF, Yeung WSB, Lee CYL |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2008 |
| Completion Date: | 04/2010 |
| Abstract: |
| In mammals, fertilization and early embryonic development begin in the oviduct [1]. In order to cope with the changing needs of the developing embryos, the mother actively modifies the internal environment of her reproductive tract [2-4]. Studies from our laboratory and others have demonstrated that the oviductal epithelial cells produce growth factors, cytokines and other embryotrophic factors of unknown identities to support embryo development in vitro (reviewed in [3]). Indeed, it is generally accepted that coculture with oviductal epithelial cells enhances embryo development in vitro. Yet, the underlying molecular mechanism of this coculture effect remains obscure. Apart from producing embryotrophic compounds, oviductal cells may also modify the culture environment for better embryo development by removing deleterious substances. It has been suggested that an imbalance between the production of toxic compounds, such as oxygen free radicals and lipid peroxidase, and the detoxification and scavenging of harmful molecules in vivo may affect preimplantation embryo development [5]. Evidence is accumulating that the embryo modulates the production of embryotrophic factors from the female reproductive tract [6-8]. Epoxide hydrolases (EH or Ephx) are a class of enzymes important in detoxifying genotoxic compounds, catabolism and regulation of signaling molecules. In microorganisms, EHs seems to be important in the catabolism of specific carbon sources from tartaric acid or limonene, and environmental contaminants such as epichlorohydrin [9]. In plant, EHs seems to be important in cuticle formation, responses to stresses and pathogen defenses. In mammals, there are several EHs, including cholesterol epoxide hydrolase (chEH), microsomal epoxide hydrolase (mEH or Ephx1) and soluble epoxide hydrolase (sEH or Ephx2). chEH mainly hydrates the 5,6-oxide of cholesterol and other 5-epoxy steroids and hepoxilin hydrolase [9]. The latter two enzymes were first distinguished by their subcellular localization. Later, they were also found to have distinct and complementary substrate specificity. Human epoxide hydrolases catalyze the formation of dihydrodiols from the corresponding epoxides by addition of water molecules [10]. This hydration process is essentially irreversible and produces mainly less reactive metabolites that can readily be excreted. Ephx1 possesses a strong hydrophobic trans-membrane domain of approximately 20 residues anchoring the protein to cellular membranes. In liver, Ephx1 resides in both the smooth endoplasmic reticulum and the plasma membrane. Ephx1 and Ephx2 shared 39% amino acids homology at the C-terminal. Interestingly, recent findings suggested that Ephx2 was involved in the regulation of blood pressure and inflammation, and that Ephx1 in xenobiotic metabolism and the onset of several diseases [9]. Previously, we demonstrated that human oviductal epithelial cells affect the gene expression of developing embryos in vitro [11, 12] partly via complement C3 derivatives [12, 13]. The developing embryos, in turn, altered the gene expression of the oviduct [5, 14, 15]. By comparing the gene expression profiles in the oocyte-containing oviduct with that of the embryo-containing oviduct, we had isolated more than a dozen of genes differentially expressed in the embryo-containing oviduct [5, 14]. Yet, the functions of these genes on embryo development are largely unknown. One of these up-regulated genes in the embryo-containing oviduct shared high sequence homology with microsomal epoxide hydrolase (mEH/Ephx1). The role of ephx1 on pre-implantation embryo development remains unknown. Hypothesis We hypothesize that Ephx1 improves in vitro embryo development by removing of deleterious substances (e.g. ROS) from the medium, and thereby improved the developmental potential of mouse embryos. To characterize and study the roles of Ephx1 on pre-implantation embryo development, we proposal to study the expression and regulation of Ephx1 gene in vivo and use in vitro mouse embryo-human oviductal epithelial cells (OE-E6/E7) co-culture with or without an Ephx1 competitive inhibitor, cyclohexene oxide (CHO) to investigate the underlying molecular mechanism that somatic cells support embryo culture in vitro. Objectives 1. To study the mRNA and protein expression profiles of Ephx1 in mouse tissues. 2. To evaluate the intra-cellular and extra-cellular reactive oxygen species levels in human oviductal epithelial (OE-E6/E7) cells with or without Ephx1 inhibitor (cyclohexene oxide). 3. To study the co-culture effect (OE-E6/E7) with or without CHO on mouse embryo development. |
| Project Title: | Environmental Screening, Computational and Biological Characterization of Endocrine Disruptors, in Respect to Receptor Binding, Embryo and Gonad Physiology |
| Investigator(s): | Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Collaborative Research Fund (CRF) - Group Research Project |
| Start Date: | 06/2009 |
| Abstract: |
| 1) The reveal the “structure-activity” relationship of food contaminants, using chemical characterization and biological assays. 2) To reveal the direct estrogenic and/or dioxin-like activities of the contaminant using both computational modeling and ligand-binding assay with ligand-binding domains of estrogen receptors and aryl hydrocarbon receptor. 3) To investigate the effect of endocrine-disruptor exposure on the growth and the implantation of mouse embryos. 4) To investigate the feasibility of using proteomic techniques as an assessment tool to decipher the molecular fingerprints in the gonads of in utero exposed embryos. |
| Project Title: | The 42nd Annual Meeting of the Society for the Study of Reproduction Roles of oviductal proteins on preimplantation embryo development |
| Investigator(s): | Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 07/2009 |
| Completion Date: | 07/2009 |
| Abstract: |
| N/A |
| Project Title: | Functional Role of acrosome-expressing protein 2 (AEP2/VAD1.2) in Spermatogenesis and Fertility |
| Investigator(s): | Lee CKF, Yeung WSB |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2010 |
| Abstract: |
| Spermatogenesis, the generation of spermatozoa, involves meiosis of the diploid spermatogonia to form the haploid spermatids and spermiogenesis to transform the round spermatids into spermatozoa (Abou-Haila & Tulsiani, 2000). Severe defective spermatogenesis is one of the important causes of infertility, affecting more than 5% of human couples. Effective treatment for spermatogenic dysfunction is lacking due to our incomplete knowledge of the regulation of spermatogenesis. Normal fertilization requires the release of enzymes from the acrosome at the anterior region of the sperm head. The success rate of conventional assisted reproduction treatment for men with acrosomeless spermatozoa only (globozoospermia) is low. Although direct injection of acrosomeless spermatozoon into an oocyte by intracytoplasmic sperm injection technique can help these men, the success rate is still lower than using normal spermatozoon (Iammarrone et al., 2003). Recent data indicate that spermatogenesis is regulated by unique mechanisms with testis-specific components (Maclean, 2005). Therefore, knowledge of these unique components is important to the understanding of spermatogenesis. VAD1.2 was first isolated as a 934 bp cDNA fragment (Luk et al., 2003). VAD1.2 transcript was detected in the postnatal rat testes from Day 25-32 onwards and in vitamin A-deficient (VAD) rat testes from Day 25 after re-initiation of spermatogenesis by vitamin A administration, coinciding with the appearance of round spermatids in these testes (Fig. 1; Lee et al., 2004). VAD1.2 cDNA has an open reading frame of 1.5-kb encoding a protein with 348 amino acid residues. Bioinformatics analysis reveals the genomic locations of rat (NM_001005531), mouse (NM_177801), and human (NM_152343) VAD1.2 on chromosome 18, 11E1, and 17, respectively. The amino acid sequence of rat VAD1.2 (NP_001005531) shares 74%, 53%, 39%, 50%, 48% amino acid sequence similarity with the mouse (NP_808469), cow (AAI12606), human (NP_689556), monkey (XP_001103721), dog (XP_848282) counterparts. Structurally, VAD1.2 contains a histidine-rich region (a.a. 26-35) in conjunction with a neighboring glutamic acid-rich region (a.a. 36–109) at proximal site of the mouse and rat sequences. VAD1.2 expression is testis- and spermatogenic stage-specific. It is expressed only in germ cells. Northern blot analysis identified a band of 1.5-kb in size in testis RNA (Fig. 1). In situ hybridization localized VAD1.2 mRNA at the seminiferous tubules of testis at stages VIII-XII of the spermatogenic cycle in rats and mice. The signal was concentrated in the central portion of these tubules with the round spermatids as the predominant cell type. Using affinity-purified antibody specific to VAD1.2, we localized VAD1.2 immunoreactivity to the acrosome of round spermatids in Day 25-32 of postnatal testis and at stages VIII-XII of the spermatogenic cycles in adult rats (Fig. 2). No immunostaining was observed with the pre-absorbed antibody. Similar immunoreactivities were found in the acrosome region of mouse, pig, monkey and human spermatids. Importantly, the expression of VAD1.2 protein in human testis diminished in patients with hypospermatogenesis, maturation arrest, undescended testis and Sertoli cell-only syndrome (Lee et al., 2008). VAD1.2 protein was not detected in mature spermatozoa isolated from caudal epididymis, suggesting that they may not be directly involved in fertilization and early embryonic development. The interaction of VAD1.2 with other proteins was studied by in vitro co-immunoprecipitation studies. Antibody against VAD1.2 peptide was used to immunoprecipitate VAD1.2 protein and its interacting partners from mouse, rat and human testis lysates. Western blotting confirmed the interaction between VAD1.2 and syntaxin 1 and b-actin (Fig. 2). Moreover, mass spectrometric analysis on the SDS-PAGE separated proteins identified b-actin and myosin heavy chain as interacting partners of VAD1.2 in the testicular lysates (Lee et al., 2008). We hypothesize that VAD1.2 has a functional role in acrosome formation. This project aims to identify the function(s) of VAD1.2 in the mouse testis using molecular and biological approaches. Importantly, chimeric mice carrying conditional VAD1.2 allele will be generated. If VAD1.2 is important for acrosome formation in the round spermatids, the lack of VAD1.2 expression will lead to the deformation of the heads of elongate spermatids and spermatozoa. As such, infertility will result. The project has two objectives: 1. to study the interaction of VAD1.2 with its binding protein(s) on acrosome formation; 2. to generate VAD1.2 targeted ES cells and chimeric mice for functional study. |
| List of Research Outputs |
| Chan R.W.S., Ng E.H.Y., Lee C.K.F. and Yeung W.S.B., Human Endometriotic Cells Exhibit Stem-like Cell Properties. , 25th European Soceity of Human Reproduction and Embryology, 28 Jun - 1 Jul, Amsterdam, Netherlands. Oxford Journal, 2009, 24: i97. |
| Cheong A.W.Y., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., aracrine regulation of the complement component-3 (C3) and the C3 receptor in the preimplantation embryos developed in vivo and in vivo., P.6.01. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Liu W., Yeung W.S.B. and Lee C.K.F., Oviductal Microsomal Epoxide Hydrolase (EPHX1) Reduces Reactive Oxygen Species (ROS) Level and Enhances Preimplantation Mouse Embryo Development. , Biology of Reproduction. 2009, 81: 126-32. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., Paracrine regulation of the production of embryotrophic oviductal complement componenet-3 and the expression of embryonic complement receptor-3 in a human oviductal cells-mouse embryo coculture system. , P312. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., The oviductal embryotrophic factor complement componenet-3 modulates its receptor expression in the pre-implantation embryos co-cultured with human oviductal epithelial cells. , OR-01. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong. . 2009. |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Harlow C.R., Leyden J.V., Waterfall M., Horne A.W., Lee C.K.F., Hillier S.G. and Morley S.D., Side populations in ovarian cancer, normal ovarian surface and oviduct epithelium cell lines exhibit markers characteristic of adult stem cells., Adult Stem cells in Regenerative Medicine and Disease. 26-27 August, Newcastle upon Tyne, UK.. 2009. |
| Ho P.C., Liu Y., Lee C.K.F., Ng E.H.Y. and Yeung W.S.B., Ovarian stimulation and endometrial receptivity. , The 7th Conference of the Pacific Rim Society for Fertility and Sterility & Annual Meeting of the Taiwanese Society for Reproductive Medicine, 20-23 Aug, Taipei.. 2009. |
| Hong S.J., Chiu C.N., Lee C.K.F., Tse J.Y., Ho P.C. and Yeung W.S.B., Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass, Fertil Steril. 2009, 92: 971-8. |
| Kodithuwakku K.S.P.K., Yeung W.S.B., Ho P.C. and Lee C.K.F., In vitro modeling of tubal ectopic implantation of embryos: A study on the role of olfactomedin 1 (Olfm1) in tubal ectopic pregnancy. , P-06. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Kodithuwakku S.P., Yeung W.S.B. and Lee C.K.F., Olfactomedin 1 (Olfm1): A novel protein modulates the embryo like trophoblastic spheroids attachment to the endometrial cells in vitro. , P.6.03. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lee C.K.F., Liu Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Excessive ovarian stimulation affects endometrial receptivity in IVF patients. , The 5th Huaxia Congress of endocrinology, 4-9 Dec, Taipei.. 2009. |
| Lee C.K.F., Ovarian stimulation and endometrial receptivity, Updated on ART, 5 June 2010, Hong Kong. 2010. |
| Lee C.K.F., Lee C.Y.L., Cheong W.Y.A. and Yeung W.S.B., Roles of Oviductal proteins on preimplantation embryo development. , MS.58. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Lee C.K.F., Understanding spermatogenesis by gene targeting in mice, Frontiers in Biomedical Research, HKU 2009, 4 Dec, Hong Kong. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Lee C.Y.L., Hou Y.C.D., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Study of extracellular matrix for the culture of human embryonic stem cells., International Society For Stem Cell Research, 7th Annual Meeting, 8-11 July, Spain. 2009. |
| Leung O.N., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Aberrant expression of microRNA-135a is involved in the progression of cervical cancer. , P-07. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., Basic Science Award: MicroRNA-135a regulates early embryo development through mediating expression of E3 Ubiquitin Ligase Seven In Absentia Homolog 1 (SIAH1), 26th Annual Meeting of European Society for Reproduction and Embryology, 27-30 June 2010, Rome. 2010. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA-135a regulates early embryo development through mediating expression of E3 ubiquitin ligase seven in absentia homolog 1 (SIAH1)., The European Society of Human Reproduction & Embryology 26th Annual Meeting, 27th -30th June, Rome, Italy.. 2010. |
| Liu W., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Best Abstract Award: MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine 21 January 2010. 2010. |
| Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine . 2010. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Shi Y.Q., Li Y.C., Hu X.Q., Liu T., Liao S.Y., Guo J., Huang L., Hu Z.Y., Tang A.Y., Lee C.K.F., Yeung W.S.B., Han C.S. and Liu Y.X., Male germ cell-specific protein Trs4 binds to multiple proteins, Biochem Biophys Res Commun. 2009, 388: 583-8. |
| Tang Y.B.A., Liu Y.X., Yeung W.S.B. and Lee C.K.F., Molecular and functional characterization of a testis-specific TRS4 gene in spermatogenesis. , O23. The Society for Reproduction and Fertility annual Conference 2009, 12-14 July, Oxford, UK.. 2009. |
| Wong S.T., Chiu C.N., Lee C.K.F. and Yeung W.S.B., Effect of adrenomedullin on extravillous cytotrophoblast invasion. , P-10. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., An in vitro system for mouse implantation study. , P-11. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Identification of endometrial proteins responsible for embryo implantation using comparative proteomic study. , O.2.21. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Yeung W.S.B., Lee C.Y.L. and Lee C.K.F., Coculture and assisted reproduction, In: Edited by William L. Ledger, Seang Lin Tan, Adil O.S. Bahathiq, The Fallopain Tube in Infertility and IVF Practice. 2010, II: 8-17. |
| Yeung W.S.B., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Chiu C.N., Effects of glycodelins on functional competence of spermatozoa, J Reprod Immunol. 2009, 83: 26-30. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., Excellent Poster Presentation: MicroRNA-34c is important for the first cell division in mouse embryos, First SKLAB Symposia on Frontiers in Preimplantation Biology 8-12 May 2010, Beijing. 2010. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., MicroRNA-34c is important for the first cell division in mouse embryos, The First SKLAB Symposia on Frontiers in Periimplantation Biology, Beijing China. 2010, 55. |
| Researcher : Lee CL |
| List of Research Outputs |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Lee C.L., Jiang P., Sit W.H., Yang X. and Wan J.M.F., Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes., Journal of Pharmacy and Pharmacology . 2010, 62(8): 1028-36. |
| Researcher : Lee CP |
| List of Research Outputs |
| Leung K.Y., Cheong K.B., Lee C.P., Chan V.N.Y., Lam Y.H. and Tang M.H.Y., Ultrasonographic prediction of homozygous ao-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination? , Ultrasound in Obstetrics & Gynecology. 2010, 35: 149-154. |
| Zayts O.A., Schnurr S. and Lee C.P., Prenatal genetic screening in Hong Kong as a site for activity analysis: Re-establishing the importance of participant structure in intercultural encounters , 8th Interdisciplinary Conference: Communication, Medicine & Ethics; Boston University School of Public Health & College of Health & Rehabilitation Sciences. 2010. |
| Researcher : Lee CYL |
| Project Title: | Study of Fibulin 5 in human endometrium and mouse uterus |
| Investigator(s): | Lee CYL, Yeung WSB, Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2008 |
| Abstract: |
| The human endometrium is one of the few adult tissues with regular angiogenesis. Endometrial angiogenesis is under the control of ovarian estrogen and progesterone [1]. Successful embryo implantation requires the development of a receptive endometrium with enormous morphological and physiological changes in the vascular bed [2]. Abnormal angiogenesis not only leads to reproductive failure, it is also associated with other diseases including dysfunctional uterine bleeding, endometriosis, endometrial cancer and intrauterine growth retardation [3]. Extracellular Matrix (ECM) is an essential component of the vasculature. It forms a physical scaffold supporting the endothelial cells, the surrounding pericytes and smooth muscle cells. It interacts with integrins on the surface of vascular cells for signal transduction [4]. ECM remodeling is under hormone regulation and is critical for endometrial receptivity [5-7]. Fibulin is a family of ECM proteins widely expressed and secreted in the blood vessel, basement membrane and stroma of most tissues. Its members were suggested to participate in the formation and stabilization of basement membrane, elastic fibers, and loose connective tissues [8;9]. Fibulin-5 (FBLN-5) is a recently identified multifunctional family member of fibulin. It is also known as UP50 (Urine Protein 50), EVEC (embryonic vascular EGF-like repeat-containing protein) [10] and DANCE (developmental arteries and neural crest epidermal growth factor-like) [11]. Mice deficient in FBLN-5 had elastinopathy of the skin, lung and vasculature, demonstrating the importance of FBLN-5 in scaffolding of cells to elastic fibers [12;13]. Unlike other fibulins, FBLN-5 binds integrins (alpha v beta 3, alpha v beta 5 and alpha 9 beta 1) and mediates endothelial cell adhesion through its RGD motif [11;13], suggesting that the molecule may have a more active role in angiogenesis. FBLN-5 has been implicated in cell proliferation and motility in a context dependent manner. It stimulates DNA synthesis and motility of fibroblasts and fibrosarcoma cells, but inhibits these processes in the epithelial and endothelial cells [14;15]. FBLN-5 reduces the response of mouse brain microvascular endothelial cells to vascular endothelial growth factor (VEGF), and induces the expression of an anti-angiogenic factor, thrombospondin-1 [14]. FBLN-5 has been suggested to be a tumor suppressor in a number of tumors because of its ability in interfering tumor cell invasion and angiogenesis [15]. There is no study on the role of FBLN-5 in endometrium. The objectives of the present study are to study the expression of FBLN-5 in human endometrium and to investigate its potential function by correlating its expression with different normal and pathological conditions, including natural menstrual cycle, endometriosis and endometrial carcinoma. In addition, the effect of steroids/embryos on the expression of FBLN-5 will be studied in the mouse models during early pregnancy, after ovariectomy with or without steroid administration, and after estrogen injection in delayed implantation. Reference List [1] Smith SK. Regulation of angiogenesis in the endometrium. Trends Endocrinol Metab 2001; 12: 147-151. [2] Carson DD, Bagchi I, Dey SK, Enders AC, Fazleabas AT, Lessey BA, Yoshinaga K. Embryo implantation. Dev Biol 2000; 223: 217-237. [3] Geva E, Jaffe RB. Role of angiopoietins in reproductive tract angiogenesis. Obstet Gynecol Surv 2000; 55: 511-519. [4] Davis GE, Senger DR. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 2005; 97: 1093-1107. [5] Aplin JD, Lacey H, Haigh T, Jones CJ, Chen CP, Westwood M. Growth factor-extracellular matrix synergy in the control of trophoblast invasion. Biochem Soc Trans 2000; 28: 199-202. [6] Bischof P, Campana A. Molecular mediators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 801-814. [7] Sillem M, Prifti S, Neher M, Runnebaum B. Extracellular matrix remodelling in the endometrium and its possible relevance to the pathogenesis of endometriosis. Hum Reprod Update 1998; 4: 730-735. [8] Timpl R, Sasaki T, Kostka G, Chu ML. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 2003; 4: 479-489. [9] Argraves WS, Greene LM, Cooley MA, Gallagher WM. Fibulins: physiological and disease perspectives. EMBO Rep 2003; 4: 1127-1131. [10] Kowal RC, Richardson JA, Miano JM, Olson EN. EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature. Circ Res 1999; 84: 1166-1176. [11] Nakamura T, Ruiz-Lozano P, Lindner V, Yabe D, Taniwaki M, Furukawa Y, Kobuke K, Tashiro K, Lu Z, Andon NL, Schaub R, Matsumori A, Sasayama S, Chien KR, Honjo T. DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J Biol Chem 1999; 274: 22476-22483. [12] Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA, Olson EN. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 2002; 415: 168-171. [13] Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, Cheng CF, Kobuke K, Dalton N, Takada Y, Tashiro K, Ross JJ, Honjo T, Chien KR. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 2002; 415: 171-175. [14] Albig AR, Schiemann WP. Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells. DNA Cell Biol 2004; 23: 367-379. [15] Schiemann WP, Blobe GC, Kalume DE, Pandey A, Lodish HF. Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J Biol Chem 2002; 277: 27367-27377. |
| Project Title: | 7 th Annual Meeting of International Society of Stem Cell Research STUDY OF EXTRACELLULAR MATRIX FOR THE CULTURE OF HUMAN EMBRYONIC STEM CELLS |
| Investigator(s): | Lee CYL |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 07/2009 |
| Completion Date: | 07/2009 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Cheong A.W.Y., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., aracrine regulation of the complement component-3 (C3) and the C3 receptor in the preimplantation embryos developed in vivo and in vivo., P.6.01. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Liu W., Yeung W.S.B. and Lee C.K.F., Oviductal Microsomal Epoxide Hydrolase (EPHX1) Reduces Reactive Oxygen Species (ROS) Level and Enhances Preimplantation Mouse Embryo Development. , Biology of Reproduction. 2009, 81: 126-32. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., Paracrine regulation of the production of embryotrophic oviductal complement componenet-3 and the expression of embryonic complement receptor-3 in a human oviductal cells-mouse embryo coculture system. , P312. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., The oviductal embryotrophic factor complement componenet-3 modulates its receptor expression in the pre-implantation embryos co-cultured with human oviductal epithelial cells. , OR-01. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong. . 2009. |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Lee C.K.F., Lee C.Y.L., Cheong W.Y.A. and Yeung W.S.B., Roles of Oviductal proteins on preimplantation embryo development. , MS.58. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Lee C.Y.L., Hou Y.C.D., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Study of extracellular matrix for the culture of human embryonic stem cells., International Society For Stem Cell Research, 7th Annual Meeting, 8-11 July, Spain. 2009. |
| Lee C.Y.L., Peng Q., Fong S.W. and Yeung W.S.B., THE EXPRESSION AND REGULATION OF SIRT1 IN HUMAN EMBRYONIC STEM CELLS, International Society for Stem Cell Research 8th Meeting, 16-19 June, San Francisco, 2010. |
| Peng Q., Lee C.Y.L., Ng E.H.Y. and Yeung W.S.B., Expression and regulation of connexin 43 in human embryonic stem cells, International Society for Stem Cell Research, 8th Meeting, 16-19 June San Francisco, 2010. |
| Yeung W.S.B., Lee C.Y.L. and Lee C.K.F., Coculture and assisted reproduction, In: Edited by William L. Ledger, Seang Lin Tan, Adil O.S. Bahathiq, The Fallopain Tube in Infertility and IVF Practice. 2010, II: 8-17. |
| Researcher : Lee VCY |
| List of Research Outputs |
| Lee V.C.Y., Ng E.H.Y. and Ho P.C., Issues in second trimester induced abortion (medical/surgical methods), Best Practice and Research Clinical Obstetrics and Gynaecology. 2010, 24: 517-527. |
| Researcher : Lee WH |
| List of Research Outputs |
| Tang F.O.S., Schweer H., Lee W.H. and Ho P.C., Pharmacokinetics of repeated doses of misoprostol, Human Reproduction. 2009, 24(8): 1862-1869. |
| Researcher : Lee YW |
| List of Research Outputs |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Researcher : Leung CY |
| List of Research Outputs |
| Liu S., Leung C.Y., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping assay by comparison with Roche Linear Array HPV genotyping assay, Journal of Clinical Microbiology. 2010, 48(3): 758-64. |
| Liu S., Chan Y.K., Leung C.Y., Luk H.M., Lo S.T., Fong D.Y.T., Cheung A.N.Y., Lin Z.Q. and Ngan H.Y.S., Human papillomavirus infection in Southern Chinese women – a population-based study , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010. |
| Researcher : Leung KY |
| List of Research Outputs |
| Chan C.Y., Lee A.M., Lam S.K., Leung K.Y., Chung K.F., Koh Y.W. and Tang C.S.K., Psychological abuse experiences are independently associated with disordered eating symptoms among pregnant women, Paper presented at the Hong Kong Psychological Society Annual Conference 2010 "Development challenges across Life Stages", Hong Kong, June 12, 2010. |
| Cheung V.Y.T., Yang F. and Leung K.Y., Lower uterine segment thickness measurement in women with previous cesarean section: comparison of 2-D versus 3-D transabdominal sonography, 6th International Society of Ultrasound in Obstetrics & Gynecology Outreach Course, Singapore . 2010. |
| Koh Y.W., Lee A.M., Leung K.Y., Chan C.Y., Tang C.S.K. and Chung K.F., Identifying Psychosocial Risk Factors for Mental Health and Psychosomatic Problems Among Expectant Fathers During Transition to Fatherhood, Paper presented at the American Psychological Science Annual Convention, Boston, May 27-30, 2010. |
| Leung K.Y., Cheong K.B., Lee C.P., Chan V.N.Y., Lam Y.H. and Tang M.H.Y., Ultrasonographic prediction of homozygous ao-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination? , Ultrasound in Obstetrics & Gynecology. 2010, 35: 149-154. |
| Li T.K.T., Leung K.Y., Lam Y.H., Tang M.H.Y. and Chan V.N.Y., Does in-utero transfusion for homozygous ao-thalassemia depend on hemoglobin level alone? , 19th World Congress on Ultrasound in Obstetrics and Gynecology, Hamburg, Germany, September 13–17 2009.. 2009. |
| Researcher : Leung ON |
| List of Research Outputs |
| Leung O.N., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Aberrant expression of microRNA-135a is involved in the progression of cervical cancer. , P-07. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., Basic Science Award: MicroRNA-135a regulates early embryo development through mediating expression of E3 Ubiquitin Ligase Seven In Absentia Homolog 1 (SIAH1), 26th Annual Meeting of European Society for Reproduction and Embryology, 27-30 June 2010, Rome. 2010. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA-135a regulates early embryo development through mediating expression of E3 ubiquitin ligase seven in absentia homolog 1 (SIAH1)., The European Society of Human Reproduction & Embryology 26th Annual Meeting, 27th -30th June, Rome, Italy.. 2010. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Researcher : Leung THY |
| Project Title: | Characterization of BCA3, a novel binding partner of p73 in cervical cancer |
| Investigator(s): | Leung THY, Ngan HYS, Liu S |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 12/2008 |
| Completion Date: | 05/2010 |
| Abstract: |
| Objectives and Significance The purpose of this study is to characterize the putative tumor suppressor gene p73 and its protein binding partner, Breast Cancer Associated 3 gene (BCA3), functionally in cervical cancer. Cervical cancer is a common genital tract cancer in women in Hong Kong. Molecular and epidemiologic studies have shown that a persistent infection with high-risk human papillomavirus (HPV) is the most important risk factor for both cervical cancer and its precursor lesions, low-grade or high-grade squamous intraepithelial lesions (LSIL and HSIL respectively). Our previous finding has indicated that the expression of p73 is associated with the radiosensitivity in cervical cancer. In this study, we aimed to investigate the novel mechanistic pathway contributing by p73 in cervical cancer. Yeast two hybrid screening has been applied and a novel protein BCA3 is identified as a binding partner of p73. Objectives: 1. To delineate the underlying mechanism of p73 in cervical cancer 2. To identify and characterize the novel protein binding partner of p73: Breast Cancer Associated 3 gene (BCA3) 3. To characterize the function of BCA3 in cervical cancer and the relation with the two different forms of p73 (TAp73 and DNp73) Key issues and problems being addressed: Cervical cancer is one of the major women malignancy in the world and is particularly prevalent in Southeast Asia including Hong Kong. Radiotherapy is the mainstay of treatment, especially in advanced cervical cancer. The survival rate of the patients can be determined by their responsiveness to radiotherapeutic treatment. However, radioresistance can be induced by genetic and epigenetic alterations in cancer cell while the molecular pathways contributing to the radioresistance in cervical cancer remain largely to be elucidated. New adjuvant treatment modalities for cervical cancer are much awaited. In this regard, knowledge of the molecular and cellular targets underlying the development and progression of cervical cancer is of importance as this can provide novel opportunities for therapeutic interventions for this cancer. In studying the molecular pathways that p73 participates in the cervical cancer carcinogenesis, we found that the differential expression of TAp73 and DNp73 is related to the radiosensitvity in cervical cancer. However, the detail mechanisms on how p73 contributes to the radiosensitivity remain unclear. Therefore, searching for the novel protein binding partners of p73 is curial in studying the detail function of p73 in cervical cancer diagnosis and proagnosis. Using yeast two hybrid screening, we have recently identified a Beast Cancer Associated gene (BCA3) as a novel binding partner of p73. BCA3 gene is a novel protein which plays an important role in substrate localization, transcriptional regulation as well as actin cytoskeleton remodeling. Although the functional roles of BCA3 may be implicated in human cancers, the underlying mechanisms are not fully understood. It will be of interest in studying the significance of the interaction between BCA3 and p73. BCA3 is localized in the nucleus but little is known about its functions. Furthermore, BCA3 is considered as a tumor suppressor when it is neddylated. In our study, we hypothesize that p73 may work together with BCA3 in the regulation of gene transcription which ultimately suppresses tumor formation. |
| List of Research Outputs |
| Leung T.H.Y., Yam J.W.P., Chan L.K., Ching Y.P. and Ng I.O.L., DLC2 (Deleted in liver cancer 2) suppresses cell growth via regulation of Raf-1-ERK1/2-p70S6K signaling pathway. (accepted), Liver International. 2010. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis. AACR Scholar-in-Training Award, AACR Special conference: Cell death mechanism and cancer therapy, 2010 (San Diego, USA). 2010. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis. (accepted), Cancer Research. 2010. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis., AACR Special conference: Cell death mechanism and cancer therapy, 2010. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Wong C.S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers, 16th HKICC 6th Annual Meeting and The 14th Research Postgraduate Symposium, HKU, November 4-6, 2009. |
| Yau T.O., Leung T.H.Y., Lam S.G.S., Cheung O.F., Tung K.K., Khong P.L., Lam A.K.M., Chung S.K. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) was dispensable for development and its deficiency did not aggravate hepatocarcinogenesis., PLoS One. 2009, 4(8): e6566. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |
| Researcher : Leung WC |
| List of Research Outputs |
| Chan E.K.L., Brownridge D.A., Tiwari A.F.Y., Fong D.Y.T., Leung W.C. and Ho P.C., Associating pregnancy with partner violence against Chinese women, Journal of Interpersonal Violence. 2010. |
| Chan E.K.L., Tiwari A.F.Y., Leung W.C., Fong D.Y.T., Brownridge D.A. and Ho P.C., Cost Measures for the Economic Impact of Domestic Violence, paper presented in the First Asia-Pacific Conference on Health Promotion and Education (APHPE), organized by the Northern Part of Western Pacific Region of International Union of Health Promotion and Education (NPWP/IUHPE) & Japanese Society of Health Education and Promotion (JSHEP), Makuhari Messe, Japan, July 18-20, 2009.. 2009. |
| Researcher : Li C |
| List of Research Outputs |
| Li C., Liu V.W.S., Chan D.W. and Ngan H.Y.S., Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer, AACR 101st Annual Meeting 2010, USA. 2010. |
| Liu V.W.S., Li C., Chan D.W. and Ngan H.Y.S., Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer, Association for International Cancer Research (AICR) 30th Anniversary Conference, St. Andrews, UK, April 7-9, 2010 . 2010. |
| Researcher : Li C |
| List of Research Outputs |
| Li C., Liu V.W.S., Chan D.W. and Ngan H.Y.S., Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer, AACR 101st Annual Meeting 2010, USA. 2010. |
| Liu V.W.S., Li C., Chan D.W. and Ngan H.Y.S., Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer, Association for International Cancer Research (AICR) 30th Anniversary Conference, St. Andrews, UK, April 7-9, 2010 . 2010. |
| Researcher : Li RHW |
| List of Research Outputs |
| Li R.H.W., Chiu C.N., Cheung M.P.L., Yeung W.S.B. and O W.S., Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa, International Journal of Andrology. 2009, 32: 687-694. |
| O W.S., Liao S., Sun J.Z., Ho J.C.M., Chiu C.N., Ng E.H.Y., Yeung W.S.B., Li R.H.W. and Tang F., Adrenomedullin and oviduct function in human and rats, Biology of Reproduction. 2009, 81: 99. |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Researcher : Li TKT |
| List of Research Outputs |
| Li T.K.T., Leung K.Y., Lam Y.H., Tang M.H.Y. and Chan V.N.Y., Does in-utero transfusion for homozygous ao-thalassemia depend on hemoglobin level alone? , 19th World Congress on Ultrasound in Obstetrics and Gynecology, Hamburg, Germany, September 13–17 2009.. 2009. |
| Researcher : Liu S |
| List of Research Outputs |
| Liu S., Leung C.Y., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping assay by comparison with Roche Linear Array HPV genotyping assay, Journal of Clinical Microbiology. 2010, 48(3): 758-64. |
| Liu S., Chan Y.K., Leung C.Y., Luk H.M., Lo S.T., Fong D.Y.T., Cheung A.N.Y., Lin Z.Q. and Ngan H.Y.S., Human papillomavirus infection in Southern Chinese women – a population-based study , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |
| Researcher : Liu VWS |
| Project Title: | Exploring the potential uses of metformin and LY294002 in controlling ovarian cancer cell growth |
| Investigator(s): | Liu VWS, Ngan HYS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 04/2009 |
| Completion Date: | 03/2010 |
| Abstract: |
| Ovarian cancer is a lethal disease because it is usually asymptomatic until the very late stage of development (Jemal et al., 2008). Conventional cisplatin treatment is hindered by the acquisition of or intrinsic chemoresistance in cells of advanced ovarian tumours (Siddik, 2003). Thus, new treatment to reduce its mortality is urgently needed. Metformin is a widely used drug for treatment of type II diabetes with little side effect (Strack, 2008). Epidemiological studies indicate that metformin may lower the risk of cancer development in diabetic patients (Evens et al., 2005). Metformin can activate AMP-activated protein kinase (AMPK), which is a master sensor of cellular energy balance (Kahn et al., 2005) (Fig. 1). Its upstream kinase is the tumour suppressor gene, LKB1 (Woods et al., 2003). Recent studies indicate that AMPK may also be a potential target for cancer therapy. Activation of AMPK can inhibit cell proliferation through activation of its downstream target, the TSC1/TSC2 tumour suppression complex. TSC1/TSC2 can inhibit cellular protein synthesis by down-regulating the mTOR signaling activity (Inoki et al., 2002; Inoki et al., 2003). Furthermore, AMPK can also up-regulate p53 expression to induce p21 expression to arrest cell growth (Rattan et al., 2005) (Fig. 1). The PI3K/Akt/mTOR signaling pathway is frequently activated in human cancers including ovarian cancer (Engelman et al., 2006). Ovarian cancer cells with up-regulated PI3K/Akt signaling are usually resistant to cisplatin (Ohta et al., 2006). In contrast to AMPK, Akt is an inhibitor of the TSC1/TSC2 tumour suppression complex (Manning et al., 2002; Tee et al., 2003) (Fig. 1). Suppression of TSC1/TSC2 releases the mTOR signaling which enhances cell growth (Tee et al., 2002; Fingar et al., 2004). Since constitutively activated in many types of human cancer, the PI3K/Akt/mTOR pathway is also a potential target for cancer therapy (LoPiccolo et al., 2008). Small molecule inhibitors of the pathway have been developed. LY294002 is a well-known PI3K inhibitor and can inhibit cancer cell growth. Although the LKB1/AMPK and PI3K/Akt pathways have a common target, there is no report thus far for studying the application of AMPK activator and PI3K/AKT inhibitor in solving the chemoresistance of ovarian cancer cells. In our preliminary study, we sought to investigate the anti-proliferation effects using metformin (AMPk activator) and LY294002 (PI3K inhibitor) on ovarian cancer cells. Our preliminary data demonstrate that metformin or LY294002 could inhibit the cell growth rate of ovarian cancer cells; A2780s, A2780cp, OV2008 and C13*, by more than 50% (Fig. 2). Intriguingly, the cell growth inhibitory effect was further increased up to 80% by co-treatment of metformin and LY294002 (Fig. 2). This indicates that both drugs could work synergistically to inhibit ovarian cancer cell growth. Western blotting analysis demonstrated that the anti-proliferation effect by metformin was due to AMPK activation mediated elevation of phospho-AMPK-alpha, reduction of phospho-P70S6K (downstream target of mTOR) and induction of p21. Notably, co-treatment of LY294002 further increased Metformin induced p21 expression. Thus, metformin and LY294002 can synergistically inhibit ovarian cancer cell growth. We postulated that the application of metformin and LY294002 may assist in solving the chemoresistance and increasing the efficacy of cisplatin in ovarian cancer treatment. In addition, understanding the modes of action of metformin and LY294002 in inhibiting cancer cell growth may be beneficial to the long term development of effective treatment. References 1. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606-19. 2. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304-5. 3. Fingar DC, Richardson CJ, Tee AR, Cheatham L, Tsou C, Blenis J. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol. 2004;24:200-16. 4. Inoki K, Li Y, Zhu T, Wu J, Guan KL.TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4:648-57. 5. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003;115:577-90. 6. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. 7. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1:15-25. 8. LoPiccolo J, Blumenthal GM, Bernstein WB, Dennis PA. Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat. 2008;11:32-50. 9. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell. 2002;10:151-62. 10. Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, Takahashi K, Igarashi H, Du B, Doshida M, Mirei IG, Motoyama T, Tasaka K, Kurachi H. Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models. Endocrinology. 2006;147:1761-9. 11. Rattan R, Giri S, Singh AK, Singh I. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J Biol Chem. 2005;280:39582-93. 12. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22:7265-79. 13. Strack T. Metformin: a review. Drugs Today (Barc). 2008;44:303-14. 14. Tee AR, Anjum R, Blenis J. Inactivation of the tuberous sclerosis complex-1 and -2 gene products occurs by phosphoinositide 3-kinase/Akt-dependent and -independent phosphorylation of tuberin. J Biol Chem. 2003;278:37288-96. 15. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002;99:13571-6. 16. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol. 2003;13:2004-8. |
| Project Title: | AICR 30th Anniversary Conference Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer |
| Investigator(s): | Liu VWS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 04/2010 |
| Completion Date: | 04/2010 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Chan D.W., Liu V.W.S. and Ngan H.Y.S., Loss of Sox7 is involved in the pathogenesis of endometrial Cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Li C., Liu V.W.S., Chan D.W. and Ngan H.Y.S., Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer, AACR 101st Annual Meeting 2010, USA. 2010. |
| Liu V.W.S., Li C., Chan D.W. and Ngan H.Y.S., Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer, Association for International Cancer Research (AICR) 30th Anniversary Conference, St. Andrews, UK, April 7-9, 2010 . 2010. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, 16th HKICC 6th Annual Meeting. 2009. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, In: AACR 101st Annual Meeting 2010, AACR 101st Annual Meeting. USA. 2010. |
| Miller F., Nagley P., Mariani J.A., Ou R., Liu V.W.S., Zhang C., Linnane A.W., Pepe S. and Rosenfeldt F., Age-related decline in stress responses of human myocardium may not be explained by changes in mtDNA., Mech Ageing Dev. 2009, 130: 742-747. |
| Wang Y., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Differential functions of GRB7 and its variant, GRB7v in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Wang Y., Chan D.W., Liu V.W.S., Chiu P.M. and Ngan H.Y.S., Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis, Clinical Cancer Research. AACR, 2010, 16: 2529-39. |
| Researcher : Liu W |
| Project Title: | 中国动物学会第十六届会员代表大会暨学术讨论会 miR34-c is required for early embryo development in mice |
| Investigator(s): | Liu W |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 10/2009 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Cheong W.Y.A., Lee C.Y.L., Liu W., Yeung W.S.B. and Lee C.K.F., Oviductal Microsomal Epoxide Hydrolase (EPHX1) Reduces Reactive Oxygen Species (ROS) Level and Enhances Preimplantation Mouse Embryo Development. , Biology of Reproduction. 2009, 81: 126-32. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., Basic Science Award: MicroRNA-135a regulates early embryo development through mediating expression of E3 Ubiquitin Ligase Seven In Absentia Homolog 1 (SIAH1), 26th Annual Meeting of European Society for Reproduction and Embryology, 27-30 June 2010, Rome. 2010. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA-135a regulates early embryo development through mediating expression of E3 ubiquitin ligase seven in absentia homolog 1 (SIAH1)., The European Society of Human Reproduction & Embryology 26th Annual Meeting, 27th -30th June, Rome, Italy.. 2010. |
| Liu W., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Best Abstract Award: MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine 21 January 2010. 2010. |
| Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine . 2010. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., Excellent Poster Presentation: MicroRNA-34c is important for the first cell division in mouse embryos, First SKLAB Symposia on Frontiers in Preimplantation Biology 8-12 May 2010, Beijing. 2010. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., MicroRNA-34c is important for the first cell division in mouse embryos, The First SKLAB Symposia on Frontiers in Periimplantation Biology, Beijing China. 2010, 55. |
| Researcher : Liu Y |
| List of Research Outputs |
| Ho P.C., Liu Y., Lee C.K.F., Ng E.H.Y. and Yeung W.S.B., Ovarian stimulation and endometrial receptivity. , The 7th Conference of the Pacific Rim Society for Fertility and Sterility & Annual Meeting of the Taiwanese Society for Reproductive Medicine, 20-23 Aug, Taipei.. 2009. |
| Lee C.K.F., Liu Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Excessive ovarian stimulation affects endometrial receptivity in IVF patients. , The 5th Huaxia Congress of endocrinology, 4-9 Dec, Taipei.. 2009. |
| Researcher : Lok TM |
| List of Research Outputs |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, 16th HKICC 6th Annual Meeting. 2009. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, In: AACR 101st Annual Meeting 2010, AACR 101st Annual Meeting. USA. 2010. |
| Researcher : Ng EHY |
| Project Title: | The 17th IFFS World Congress on Fertility and Sterility 1) Measurement of Serum CA-125 Concentrations Does not Improve the Value of Chlamydia Trachomatis Antibody (CAT) in Predicting Tubal Pathology at Laparoscopy 2) A Comparison of the Pain Levels During Egg Collection and Postoperative Side Effects Using Paracervical Block with and without Conscious Sedation |
| Investigator(s): | Ng EHY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 11/2001 |
| Abstract: |
| N/A |
| Project Title: | Comparison of the prevalence of polycystic ovary only and polycystic ovary syndrome between two different ethnic populations |
| Investigator(s): | Ng EHY, Chan CW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2005 |
| Abstract: |
| The objective of this study is To define the prevalence of polycystic ovary only and polycystic ovary syndrome and its associated hormonal and biochemical profiles in Chinese and Indian populations. |
| Project Title: | The role of anti-Müllerian hormone in the prediction of livebirth rate and cumulative livebirth rate during in vitro fertilization treatment |
| Investigator(s): | Ng EHY, Yeung WSB, Ho PC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2006 |
| Abstract: |
| To determine and compare the predictive values of serum FSH, serum AMH and AFC in livebirth and cumulative livebirth rates following in vitro fertilization treatment. This study will provide information on these predictive values and help in counselling patients with regard to the livebirth rate prior to the IVF treatment. |
| Project Title: | The significance of serum anti-Mullerian hormone level in pregnancy and livebirth rates of the controlled ovarian stimulation and intrauterine insemination |
| Investigator(s): | Ng EHY, Yeung WSB, Ho PC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2008 |
| Completion Date: | 08/2009 |
| Abstract: |
| The aim of this study is to evaluate the role of serum anti-Mullerian hormone level (AMH) level in predicting pregnancy and livebirth rates of ovarian stimulation and intrauterine treatment. The hypothesis is that a higher early follicular serum AMH level is associated with higher pregnancy and livebirth rates. |
| List of Research Outputs |
| Chan R.W.S., Ng E.H.Y., Lee C.K.F. and Yeung W.S.B., Human Endometriotic Cells Exhibit Stem-like Cell Properties. , 25th European Soceity of Human Reproduction and Embryology, 28 Jun - 1 Jul, Amsterdam, Netherlands. Oxford Journal, 2009, 24: i97. |
| Chow J.F.C., Yeung W.S.B., Lau E.Y.L., Lam S.T.S., Tong T., Ng E.H.Y. and Ho P.C., Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification, Fertility and Sterility. 2009, 92(2): 828, e7-e10. |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Ho P.C., Liu Y., Lee C.K.F., Ng E.H.Y. and Yeung W.S.B., Ovarian stimulation and endometrial receptivity. , The 7th Conference of the Pacific Rim Society for Fertility and Sterility & Annual Meeting of the Taiwanese Society for Reproductive Medicine, 20-23 Aug, Taipei.. 2009. |
| Lee C.K.F., Liu Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Excessive ovarian stimulation affects endometrial receptivity in IVF patients. , The 5th Huaxia Congress of endocrinology, 4-9 Dec, Taipei.. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Lee V.C.Y., Ng E.H.Y. and Ho P.C., Issues in second trimester induced abortion (medical/surgical methods), Best Practice and Research Clinical Obstetrics and Gynaecology. 2010, 24: 517-527. |
| Li R.H.W., Liao S., Chiu C.N., Tam W.W., Ho J.C.M., Ng E.H.Y., Ho P.C., Yeung W.S.B., Tang F. and O W.S., Expression of adrenomedullin in human oviduct, its regulaton by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium, Journal of Clinical Endocrinology and Metabolism. 2010, 95(9): E18-E25. |
| Ng E.H.Y., The application of three-dimensional ultrasonography in predicting the IVF outcome, The 3rd International Seminar on ART: Laboratory strategies and clinical management for repeated IVF-ET failure organized by Sothern Medical University, Guangzhou, P.R. China, November 6-8, 2009.. 2009. |
| Ng E.H.Y., The role of acupuncture in IVF, Roundtable Luncheon Discussion in The American Society for Reproductive Medicine's Annual Meeting, Atlanta, Georgia, U.S.A., October 17-21, 2009. 2009. |
| Ng E.H.Y., What can be achieved by acupuncture in assisted reproduction?, The 3rd Asia Pacific Congress on Controversies in Obstetrics, Gynecology and Infertility, Beijing, P.R. China, November 12-15, 2009. 2009. |
| O W.S., Liao S., Sun J.Z., Ho J.C.M., Chiu C.N., Ng E.H.Y., Yeung W.S.B., Li R.H.W. and Tang F., Adrenomedullin and oviduct function in human and rats, Biology of Reproduction. 2009, 81: 99. |
| Peng Q., Lee C.Y.L., Ng E.H.Y. and Yeung W.S.B., Expression and regulation of connexin 43 in human embryonic stem cells, International Society for Stem Cell Research, 8th Meeting, 16-19 June San Francisco, 2010. |
| So W.S., Ng E.H.Y., Wong Y.Y., Yeung W.S.B. and Ho P.C., Accupuncture for frozen-thawed embryo transfer cycles: A double-blind randomized controlled trial, Reproductive BioMedicine Online. 2010, 20: 814-821. |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Researcher : Ng TY |
| Project Title: | A propective randomised controlled trial: prevention of lymphedema by omentoplasty after pelvic lymphadenectomy |
| Investigator(s): | Ng TY, Ngan HYS |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Low Budget High Impact Programme |
| Start Date: | 11/2001 |
| Abstract: |
| To see whether these preliminary results are validated in a prospective randomised comparison. |
| Researcher : Ngai CSW |
| Project Title: | Vaginal misoprostol for first trimester termination of pregnancy prior to 9 weeks of gestation |
| Investigator(s): | Ngai CSW, Tang FOS, Chan YM, Ho PC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Health Services Research Fund - Full Grants |
| Start Date: | 05/1999 |
| Abstract: |
| To compare the effectiveness of vaginal misoprostol (water vs no water added) in first trimester termination of pregnancy. |
| Project Title: | Cervical assessment in prediction of preterm labour: is three-dimensional ultrasonography a better choice? |
| Investigator(s): | Ngai CSW, Lao TTH, Chen M, Leung KY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To compare the usefulness of 3D versus 2D US in prediction of preterm labour. |
| Project Title: | Multiple pregnancy and gestational diabetes: a physiological response or a pathologic condition? |
| Investigator(s): | Ngai CSW, Lao TTH, Leung WC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To investigate the incidence of gestational disbetes mellitus in twin pregnancy; to investigate the changes of glucose metabolism throughout pregnancy in multiple pregnancy; to evaluate the diagnostic criteria of gestational diabetes mellitus in twin pregnancy. |
| Project Title: | The XIXth Asian and Oceanic Congress of Obstetrics & Gynaecology Should We Screen Sexually Transmitted Diseases for Women Requesting for Termination of Pregnancy? |
| Investigator(s): | Ngai CSW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 10/2005 |
| Abstract: |
| N/A |
| Researcher : Ngan HYS |
| Project Title: | High dose cis-platinum and cyclophosphamide vs taxol in ovarian cancer |
| Investigator(s): | Ngan HYS, Wong RLC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Other Funding Scheme |
| Start Date: | 07/1994 |
| Abstract: |
| To study high dose cis-platinum and cyclophosphamide vs taxol in ovarian cancer. |
| Project Title: | Differential expression of DeltaNp73 controlling the radiotherapeutic response in cervical cancers |
| Investigator(s): | Ngan HYS, Cheung ANY, Leung THY, Liu S |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 04/2008 |
| Abstract: |
| The purpose of this proposed investigation is to study the role of the p73 isoform, DNp73, in irradiation-induced apoptosis and in relation to the radiosensitivity of cervical cancer. Cervical cancer is a common genital tract cancer in women. Its treatment includes mainly radical hysterectomy and/or radiotherapy. Radiotherapy is the mainstay of treatment, especially in advanced cervical cancer. The patients’ survival rate can be determined by their responsiveness to radiotherapeutic treatment. Response of cancers to ionizing radiation varies widely, and this may be explained by differences in cancer cell death-inducing effectors. Multiple genetic and epigenetic changes in the cancer cell may contribute to radioresistance. p73, a homolog of p53 tumor suppressor, has been suggested to be an alternative p53-independent apoptotic pathway, in particular, in cervical cancer. This is because cervical cancer is strongly linked to infection by high-risk human papillomavirus (HPV) types of which the viral oncoprotein E6 has the ability to inactivate the function of p53 by promoting degradation. Our previous study has demonstrated an association between p73 expression and radiosensitivity of cervical cancers and suggested that p73 might play an important role in controlling cellular radiosensitivity (Liu et al., 2004). p73 has been identified as a structural and functional homologue of the tumour suppressor protein p53 (Kaghad et al., 1997; Zhu et al., 1998). Despite their similarities, these two proteins are likely to display distinct functions, particularly in tumour formation and progression (Melino et al., 2002; Moll et al., 2001; Yang et al., 2000). Mutations of p73 in human tumours are extremely rare, and p73-deficient mice lack a spontaneous tumour phenotype (Moll et al., 2001). One possible explanation for the different roles of p53 and p73 in tumorigenesis possibly lies within their different genomic organization. While p53 encodes one protein, p73 gives rise to multiple protein isoforms due to alternative promoter utilization and alternative mRNA splicing (Irwin and Kaelin, 2001; Melino et al., 2002; Yang and McKeon, 2000). The full length wild-type TA isoform of p73 (TAp73) containing an N-terminal transactivation domain (TA) can activate downstream target genes and induce apoptosis. In contrast, the N-terminal truncated form (DNp73) lacking the transactivation domain acts as “dominant inhibitors” of the wild-type TAp73 and p53 and has anti-apoptotic function. This suggested p73 holds dual roles where the TAp73 isoform harbors pro-apoptotic characteristic while DNp73 holds anti-apoptotic property. DNp73, acting as a dominant-negative inhibitor, can interfere with p53 from binding to the p53-responsive elements and also inhibit the transcription of the TAp73 isoforms. Both isoforms could co-express in the cells, and their relative expression levels might be important in tumor formation and cell death. Our recent study has demonstrated that the expression level of these two p73 isoforms was inversely correlated, and increase of DNp73 expression was associated with tumor radioresistance and the adverse outcome of cervical cancer patients (Liu et al., 2006a). We hypothesize that DNp73 expression may contribute to the radioresistance of the cervical cancer by its dominant-negative effect. In this study, the effect of DNp73 expression on radiosensitivity will be investigated by overexpression (by expression vector) and underexpression (by siRNA) of DNp73 expression in the cancer cell lines and its relationship with TAp73 expression. Since the high-risk HPV infection and viral oncogene E6 and E7 expression are responsible for cervical carcinogenesis, HPV E6 and E7 expression will also be assessed in clinical specimens and correlated with DNp73 expression. Objectives 1 To study the response of cervical cancer cells to radiation treatment by in vitro manipulation of DNp73 expression. 2 To study the relationship between DNp73 and HPV E6 and E7 expression in cervical cancer. |
| Project Title: | Regulation of TP73 functions by BCA3 and clinical significance of BCA3 gene in cervical cancer. |
| Investigator(s): | Ngan HYS, Liu S, Leung THY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 05/2009 |
| Abstract: |
| The purpose of this proposed investigation is to study the newly identified protein binding partner of p73 isoform, DNp73, Breast Cancer Associated gene (BCA3), in relation to the p73 function in cervical cancer. Cervical cancer is a common genital tract cancer in women. Its treatment includes mainly radical hysterectomy and/or radiotherapy. Radiotherapy is the mainstay of treatment, especially in advanced cervical cancer. The patients’ survival rate can be determined by their responsiveness to radiotherapeutic treatment. Response of cancers to ionizing radiation varies widely, and this may be explained by differences in cancer cell death-inducing effectors. Multiple genetic and epigenetic changes in the cancer cell may contribute to radioresistance. p73, a homolog of p53 tumor suppressor, has been suggested to be an alternative p53-independent apoptotic pathway, in particular, in cervical cancer. This is because cervical cancer is strongly linked to infection by high-risk human papillomavirus (HPV) types of which the viral oncoprotein E6 has the ability to inactivate the function of p53 by promoting degradation. Our previous study has demonstrated an association between p73 expression and radiosensitivity of cervical cancers and suggested that p73 might play an important role in controlling cellular radiosensitivity (Liu et al., 2004). The candidate tumor suppressor gene, p73 was identified by Kaghad et al in 1997 (Kaghad et al., 1997). It was predicted to encode a protein with significant similarity to p53. It was mapped the minimal region of 1p36 that is recurrently deleted in many types of cancers such as neuroblastoma (Ichimiya et al., 2001), breast cancer (Dominguez et al., 2001), squamous cell carcinoma (Araki et al., 2002) and B-cell lymphoma (Martinez-Delgado et al., 2002). Unlike the p53, somatic mutation of p73 gene is extremely rare. The p73 exists in two forms: the N-terminal transactivation domain containing form (TAp73) and the isoforms lacking the transactivation domain (DNp73) (including N, N’, exon2, and exon2/3). The TAp73 exhibits growth inhibitory, tumor suppressive and pro-apoptotic functions while the DNp73 promotes oncogenic activity and abolishes the functions of TAp73. The absent of the transactivation domain is due to transcription started at an alternative promoter (P2) which is located in intron 3 (resulting Np73 and N’p73) and alternative splicing variants (p73/exon2 and p73/exon2/3) (Ishimoto et al., 2002). In normal tissue, the expression of p73 is very low (Kovalev et al., 1998). The balance between the expression level of TAp73 and DNp73 has been shown to play an important role in the development of cancer. Overexpression of the oncogenic DNp73 was found in various types of cancers including breast, ovarian, liver, prostate, colon, and neuroblastoma cancers (Concin et al., 2004; Dominguez et al., 2006; Douc-Rasy et al., 2002; Guan and Chen, 2005; Putzer et al., 2003; Zaika et al., 2002). Elevated expression of DNp73 is associated with poor prognosis in cancer patients as DNp73 inhibits the suppressive functions exerted by p53 and TAp73 which resulted in decreased apoptosis response and chemoresistance (Casciano et al., 1999; Concin et al., 2005; Dominguez et al., 2006). BCA3, also known as A-kinase-interacting protein 1 (AKIP1), was cloned by PCR subtractive hybridization using library matched breast tumor and normal breast cell lines mRNAs (Kitching et al., 2003). It contains a number of putative functional domains including a nuclear localization signal, a proline-rich sequence, five src homology 2 (SH2) binding motifs and a PZD binding motif. The protein expression of AKIP1 is higher in the breast cancer cell lines but is much lower in normal breast tissue (Kitching et al., 2003). Immunostaining of AKIP1 in breast tumor tissue section revealed that AKIP1 is expressed in breast tumor cell but not in the surrounding stroma cells (Kitching et al., 2003). Study has shown that neddylated modified BCA3 represses the NFB-dependent transcription by recruiting the class III histone deaceylase SIRT1 (Gao et al., 2006). Furthermore, recent study has indicated that BCA3 promotes the nuclear retention and phosphorylation of p65 which resulted in enhancing the NFB-dependent gene expression (Gao et al., 2008). These result suggest that posttranslational modification of BCA3 protein play an important role on its function. We hypothesize that BCA3 regulates p73 activity via the binding to p73 and oligomerization of p73 might influence its binding with BCA3. From our preliminary study, the binding affinity of BCA3-DNp73 was stronger than BCA3-TAp73. Since TAp73 and DNp73 play an opposite role in cancer cell development as well as cancer treatment, it will be interesting to study the effects on BCA3-TAp73 and BCA3-DNp73 binding in carcinogenesis. In this study, we will elucidate the effects of BCA3 expression on p73 tumor suppressor function. Objectives 1 To elucidate the binding activity of BCA3 and p73 isoforms and p53 family protein 2 To delineate the functional significance of the binding between BCA3 and p73 3 To address BCA3, TAp73 and DNp73 expression and clinical significance in cervical cancer Reference List 1. Araki D, et al (2002). Int J Oncol 20: 355-60. 2. Casciano I, et al (1999). . Cell Death Differ 6: 391-3. 3. Concin N, et al (2004). Cancer Res 64: 2449-60. 4. Concin N, et al (2005). . Clin Cancer Res 11: 8372-83. 5. Dominguez G, et al (2006). J Clin Oncol 24: 805-15. 6. Dominguez G, et al (2001). . Breast Cancer Res Treat 66: 183-90. 7. Douc-Rasy S, et al (2002). Am J Pathol 160: 631-9. 8. Gao F, et al (2006). Nat Cell Biol 8: 1171-7. 9. Gao N, et al (2008). J Biol Chem 283: 7834-43. 10. Guan M, Chen Y (2005). J Clin Pathol 58: 1175-9. 11. Ichimiya S, et al (2001). Med Pediatr Oncol 36: 132-4. 12. Ishimoto O, et al (2002). Cancer Res 62: 636-41. 13. Kaghad M, et al (1997). Cell 90: 809-19. 14. Kitching R, et al (2003). Biochim Biophys Acta 1625: 116-21. 15. Kovalev S, et al (1998). Cell Growth Differ 9: 897-903. 16. Liu SS, ... Ngan HY (2004). Clin Cancer Res 10: 3309-16. 17. Martinez-Delgado B, et al (2002). Int J Cancer 102: 15-9. 18. Putzer BM, et al (2003). Cell Death Differ 10: 612-4. 19. Zaika AI, et al (2002). J Exp Med 196: 765-80. 20. Zaika A, et al (2001). J Biol Chem 276: 11310-6 |
| Project Title: | Functional characterization and clinical significance of C35-DNp73 in ovarian cancer. |
| Investigator(s): | Ngan HYS, Leung THY, Liu S |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2010 |
| Abstract: |
| The purpose of this proposed study is to investigate the newly identified protein binding partner of p73, C35, in relation to the p73 function in ovarian cancer. Ovarian cancer is one of the commonest causes of cancer deaths in women in western countries as well as Hong Kong. The mainstay of treatment includes aggressive surgical cytoreduction and administration of platinum-based cytotoxic drugs. Despite optimal primary treatment, recurrences are common and the overall prognosis is poor. The development of novel ovarian cancer diagnostic tests as well as treatment is urgently required. Therefore, understanding of the molecular mechanisms that contribute to the ovarian cancer development is crucial. The candidate tumor suppressor gene, p73 was identified by Kaghad et al in 1997 1. It was predicted to encode a protein with significant similarity to p53. It was mapped to the minimal region of 1p36 that is recurrently deleted in many types of cancers such as neuroblastoma 2, breast cancer 3, squamous cell carcinoma 4 and B-cell lymphoma 5. Unlike p53, somatic mutation of p73 gene is extremely rare. In normal tissue, the expression of p73 is very low 6. The balance between the expression level of TAp73 and DNp73 has been shown to play an important role in the development of cancer. Functionally, TAp73 exhibits growth inhibitory, tumor suppressive and pro-apoptotic functions while the DNp73 promotes oncogenic activity and abolishes the functions of TAp73. Overexpression of the oncogenic DNp73 was found in various types of cancers including breast, ovarian, liver, prostate, colon, and neuroblastoma cancers 7-12. Elevated expression of DNp73 is associated with poor prognosis in cancer patients as DNp73 inhibits the suppressive functions exerted by p53 and TAp73 which ultimately resulted in decreased apoptotic response and chemoresistance 9,13-14. C35, also known as C17ORF37, was identified by substructive hybridization using library matched breast tumor and normal breast cell lines mRNAs 15. It encoded a 12kDa protein and was abunduntly expressed in breast cancer with distant metastases. Low level of C35 was found in normal human tissue. It was reported that C35 was highly expressed in prostate cancer cell lines and clinical prostate cancer tissue. Ectopic expression of C35 enhanced the ability of prostate cancer cell migration and invasion by up-regulating the expression of matrix metallopeptidase 9 (MMP-9), urokinase plasminogen activator (uPA) and vascular endothelial growth factor (VEGF). Down-regulation of C35 by siRNA could also reduce the DNA binding activity of NF-KappaB 16. These results suggest that C35 protein may play an oncogenic in cancer development. We hypothesize that C35 cooperates with DNp73 to promote oncogenesis in ovarian cancer. From our preliminary study, the binding affinity of C35-DNp73 was strong. Since DNp73 play an oncogenic role in cancer development, it will be interesting to study the effects on C35-DNp73 binding in carcinogenesis. In this study, we will elucidate the functional significance of C35-DNp73. Objectives 1 To elucidate the binding activity of C35 and p73 isoforms and p53 family protein 2 To delineate the functional significance of the binding between C35 and p73 3 To address C35 expression and clinical significance in ovarian cancer Reference List 1. Kaghad, M., et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90, 809-819 (1997). 2. Ichimiya, S., et al. Downregulation of hASH1 is associated with the retinoic acid-induced differentiation of human neuroblastoma cell lines. Med Pediatr Oncol 36, 132-134 (2001). 3. Dominguez, G., et al. Wild type p73 overexpression and high-grade malignancy in breast cancer. Breast Cancer Res Treat 66, 183-190 (2001). 4. Araki, D., et al. Frequent allelic losses on the short arm of chromosome 1 and decreased expression of the p73 gene at 1p36.3 in squamous cell carcinoma of the oral cavity. Int J Oncol 20, 355-360 (2002). 5. Martinez-Delgado, B., et al. Frequent inactivation of the p73 gene by abnormal methylation or LOH in non-Hodgkin's lymphomas. Int J Cancer 102, 15-19 (2002). 6. Kovalev, S., Marchenko, N., Swendeman, S., LaQuaglia, M. & Moll, U.M. Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines. Cell Growth Differ 9, 897-903 (1998). 7. Zaika, A.I., et al. DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J Exp Med 196, 765-780 (2002). 8. Concin, N., et al. Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo. Cancer Res 64, 2449-2460 (2004). 9. Dominguez, G., et al. DeltaTAp73 upregulation correlates with poor prognosis in human tumors: putative in vivo network involving p73 isoforms, p53, and E2F-1. J Clin Oncol 24, 805-815 (2006). 10. Douc-Rasy, S., et al. DeltaN-p73alpha accumulates in human neuroblastic tumors. Am J Pathol 160, 631-639 (2002). 11. Guan, M. & Chen, Y. Aberrant expression of DeltaNp73 in benign and malignant tumours of the prostate: correlation with Gleason score. J Clin Pathol 58, 1175-1179 (2005). 12. Putzer, B.M., Tuve, S., Tannapfel, A. & Stiewe, T. Increased DeltaN-p73 expression in tumors by upregulation of the E2F1-regulated, TA-promoter-derived DeltaN'-p73 transcript. Cell Death Differ 10, 612-614 (2003). 13. Casciano, I., Ponzoni, M., Lo Cunsolo, C., Tonini, G.P. & Romani, M. Different p73 splicing variants are expressed in distinct tumour areas of a multifocal neuroblastoma. Cell Death Differ 6, 391-393 (1999). 14. Concin, N., et al. Clinical relevance of dominant-negative p73 isoforms for responsiveness to chemotherapy and survival in ovarian cancer: evidence for a crucial p53-p73 cross-talk in vivo. Clin Cancer Res 11, 8372-8383 (2005). 15. Evans, E.E., et al. C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer. Mol Cancer Ther 5, 2919-2930 (2006). 16. Dasgupta, S., et al. Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells. Oncogene 28, 2860-2872 (2009). |
| List of Research Outputs |
| Au C.W., Siu M.K., Liao X., Wong E.S., Ngan H.Y.S., Tam K.F., Chan D.C., Chan Q.K. and Cheung A.N.Y., Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome, Cancer Lett. 2009 Aug 28;281(2):151-61. 2009. |
| Basu P., Ngan H.Y.S. and Hseon T.E., HPV vaccination in women over 25 years of age: Asian Cervical Cancer Prevention Advisory Board recommendations. , J Obstet Gynaecol Res. 2009, 35(4): 712-716. |
| Chan D.W., Liu V.W.S. and Ngan H.Y.S., Loss of Sox7 is involved in the pathogenesis of endometrial Cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Cheung A.N.Y., Tsun O.K.L., Ng K.M., Szeto E.F., Siu K.Y., Wong E.S.Y. and Ngan H.Y.S., P634A4 and TAp73 immunocytochemistry in liquid-based cervical cytology—potential biomarkers for diagnosis and progress prediction of cervical neoplasia, Modern Pathology. 2010, 23: 559-66. |
| Chow S.N., Soon R., Park J.S., Pancharoen C., Qiao Y.L., Basu P. and Ngan H.Y.S., Knowledge, attitudes, and communication around human papillomavirus (HPV) vaccinatin amongst urban Asian mothers and physicians, Vaccine, 25 Mar,. 2010. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Fung F.K.C., Chan D.W., Liu V.W.S. and Ngan H.Y.S., PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer, 22nd Lorne Cancer Conference, Australia. 2010. |
| Hu Y., Chan K.K.L. and Ngan H.Y.S., Preventing Cervical Cancer: Primary And Secondary Measures, Journal Of Paediatrics, Obstetrics And Gynaecology. 2009, 35: 213. |
| Klug S.J., Ressing M., Koenig J., Abba M.C., Agorastos T., Brenna S.M., Ciotti M., Das B.R., Del Mistro A., Dybikowska A., Giuliano A.R., Gudleviciene Z., Gyllensten U., Haws A.L., Helland A., Herrington C.S., Hildesheim A., Humbey O., Jee S.H., Kim J.W., Madeleine M.M., Menczer J., Ngan H.Y.S., Nishikawa A., Niwa Y., Pegoraro R., Pillai M.R., Ranzani G., Rezza G., Rosenthal A.N., Roychoudhury S., Saranath D., Schmitt V.M., Sengupta S., Settheetham-Ishida W., Shirasawa H., Snijders P.J., Stoler M.H., Suárez-Rincón A.E., Szarka K., Tachezy R., Ueda M., van der Zee A.G., von Knebel Doeberitz M., Wu M.T., Yamashita T., Zehbe I. and Blettner M., TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies, Lancet Oncol. 2009 Aug;10(8):772-84. Epub 2009 Jul 20. 2009. |
| Kwan T.T.C., Tam K.F., Lee P.W.H., Lo S.S.T., Chan K.K.L. and Ngan H.Y.S., De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial, Psycho-Oncology. 2010, 1-11. |
| Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., Report on the Survey of Family Planning Knowledge, Attitude and Practice in Hong Kong 2007. Hong Kong, Family Planning Association of Hong Kong, 2009, pp 87. |
| Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., The report of youth sexuality study 2006. Hong Kong, Family Planning Association of Hong Kong, 2009, 208pp. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis. AACR Scholar-in-Training Award, AACR Special conference: Cell death mechanism and cancer therapy, 2010 (San Diego, USA). 2010. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis. (accepted), Cancer Research. 2010. |
| Leung T.H.Y. and Ngan H.Y.S., Interaction of TAp73 and BCA3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis., AACR Special conference: Cell death mechanism and cancer therapy, 2010. |
| Li C., Liu V.W.S., Chan D.W. and Ngan H.Y.S., Functional analysis of the β1 subunit of AMP-activated protein kinase in ovarian cancer, AACR 101st Annual Meeting 2010, USA. 2010. |
| Liu S., Leung C.Y., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping assay by comparison with Roche Linear Array HPV genotyping assay, Journal of Clinical Microbiology. 2010, 48(3): 758-64. |
| Liu S., Chan Y.K., Leung C.Y., Luk H.M., Lo S.T., Fong D.Y.T., Cheung A.N.Y., Lin Z.Q. and Ngan H.Y.S., Human papillomavirus infection in Southern Chinese women – a population-based study , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010. |
| Liu V.W.S., Li C., Chan D.W. and Ngan H.Y.S., Functional analysis of the alpha-2 subunit of AMP-activated protein kinase in ovarian cancer, Association for International Cancer Research (AICR) 30th Anniversary Conference, St. Andrews, UK, April 7-9, 2010 . 2010. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, 16th HKICC 6th Annual Meeting. 2009. |
| Lok T.M., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Overexpression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells, In: AACR 101st Annual Meeting 2010, AACR 101st Annual Meeting. USA. 2010. |
| Monk B.J., Herzog T.J., Kaye S.B., Krasner C.N., Vermorken J.B., Muggia F.M., Pujade-Lauraine E., Lisyanskaya A.S., Makhson A.N., Rolski J., Gorbounova V.A., Ghatage P., Bidzinski M., Shen K., Ngan H.Y.S., Vergote I.B., Nam J.H., Park Y.C., Lebedinsky C.A. and Poveda A.M., Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer, J Clin Oncol.. 2010. |
| Ngan H.Y.S., "The management of cervical cancer" & "Knowledge and psychosocial reaction to cervical cancer and HPV vaccine”, XIX FIGO World Congress, Cape Town, South Africa, 4-9 October. 2009. |
| Ngan H.Y.S., Beyond Staging and Classification in Gestational Trophoblastic Neoplasia, 15th World Congress on Gestational Trophoblastic Diseases, Cochin, India, November 12-15. 2009. |
| Ngan H.Y.S., Editorial Boaed Member - Journal of Paediatrics, Gynaecology and Obstetrics since 1997. 2009. |
| Ngan H.Y.S., Editorial Board Member - Journal of Medical Association of Thailand. 2010. |
| Ngan H.Y.S., Editorial Board Member of 实用婦產科雜誌(編 委) 2008. 2010. |
| Ngan H.Y.S., Editorial Member - 中華婦產科雜誌. 2010. |
| Ngan H.Y.S., Editorial Member - 國際婦產科學雜誌第七屆編輯委員會. 2009. |
| Ngan H.Y.S., Gestational Trophoblastic Disease (GTD), The 41st Annual Meeting for Women’s Cancer organized by the Society of Gynecologic Oncologist (SGO) of USA, March 17. 2010. |
| Ngan H.Y.S., Gynaecologic Cancer Clinical Trials in Hong Kong, The IGOG Founding Meeting, Bangalore, India, May 30. 2010. |
| Ngan H.Y.S., Cheung A.N.Y., Tam K.F., Chan K.K.L., Tang H.W., Bi D., Descamps D. and Bock H.L., Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong, Hong Kong Med J.. 2010, 16(3): 171-9. |
| Ngan H.Y.S., Journal of Gynecologic Oncology (JGO). 2010. |
| Ngan H.Y.S., Robotic radical hysterectomy, The 4th Biennial Conference of Asia Oceania Research organization on Genital Infections and Neoplasia (AOGIN), New Delhi, India, March 26-29. 2010. |
| Ngan H.Y.S., Treatment Paradigm in Ovarian & Cervical Cancer, Female Cancer Symposium of Hong Kong College of Radiologists, Aug 8. 2009. |
| Ngan H.Y.S., Updates on management of endometrial cancer, Women’s Health Suite of Asian Oncology Summit 2010, Bali, Indonesia, April 9-11. 2010. |
| Ngan H.Y.S., 宮頸癌的防治, 第十屆全國現代婦產科學新進展學術會, Shenzhen, 20 Sep, 2009. |
| Siu K.Y., Wong E.S.Y., Kong S.H., Wong G.W., Tam K.F., Ngan H.Y.S., Le X.F. and Cheung A.N.Y., Dysregulated expression of stem cell transcription factor Nanog in development and progress of ovarian cancers. , The 101st Annual Meeting of the American Association for Cancer Research, Washington DC, U.S.A., 17 - 21 April 2010.. 2010. |
| Siu K.Y., Yeung C.W., Zhang H., Kong S.H., Ho W.K.J., Ngan H.Y.S., Chan D.C. and Cheung A.N.Y., p21-activated kinase 1 promotes aggressive phenotype, cell proliferation and invasion in gestational trophoblastic disease. , Am J Pathol.. 2010, 176: 3015-22. |
| Wang Y., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Differential functions of GRB7 and its variant, GRB7v in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Wong C.S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers, 16th HKICC 6th Annual Meeting and The 14th Research Postgraduate Symposium, HKU, November 4-6, 2009. |
| Wong G.W., Siu K.Y., Ngan H.Y.S. and Cheung A.N.Y., Dysregulated expression and function of Plexin-B1 in ovarian cancers , The 101st Annual Meeting of the American Association for Cancer Research, Washington DC, U.S.A.. 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |
| Researcher : Ong CYT |
| Project Title: | To determine the correlation of changes in maternal levels of pregnancy-associated plasma protein A (PAPP-A) and free [beta] human chorionic gonadotrophin (F[beta]-hCG) with placental development and fetal outcomes |
| Investigator(s): | Ong CYT, Lao TTH, Leung WC, Leung KY, Lam HSW |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To correlate the serial changes of maternal serum PAPP-A and free [beta]-hCG concentrations with placental volume and vascular indices, swell as fetal size, as assessed by 3-D/4-D ultrasonographic studies throughout pregnancy; to determine whether different patterns in the changes of PAPP-A and free [beta]-hCG in different trimesters will be predictive of different patterns of placental development and fetal growth, and whether this can help to identify specifically the eventual complications through the association with the various growth and developmental patterns. |
| Project Title: | Assessment of the interrelationship among the angiogenic growth factors and topological properties of placental villous capillaries with fetal growth, development of the placenta and its vasculature progressively throughout the course of pregnancy, and pregnancy outcomes |
| Investigator(s): | Ong CYT |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Incentive Award for RGC GRF Fundable But Not Funded Projects |
| Start Date: | 07/2004 |
| Abstract: |
| N/A |
| Project Title: | First trimester prediction of fetal α-thalassaemia-1 with maternal serum markers, nuchal translucency measurement and three dimentional ultrasound measurement of placental volume |
| Investigator(s): | Ong CYT, Chen M, Leung KY, Tang MHY, Lee CP |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To measure 3D ultrasound placental and fetal volume at 10-14 weeks of gestation, and to determine whether different changes in the placental volume is predictive of fetuses affected by α-thalassaemia-1; to measure maternal serum PAPP-A and free β-hCG concentrations in fetuses affected and unaffected by β-thalassaemia-1 at 10-14 weeks of gestation, and determine the predictive value of these markers along with or without NT measurement in diagnosis of fetuses affected by α-thalassaemia-1. |
| Project Title: | Maternal serum level of ADAM 12 as an early marker of trisomy 21, trisomy 13 and trisomy 18 |
| Investigator(s): | Ong CYT, Lee CP, Lau ETK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2007 |
| Abstract: |
| Objectives 1. To investigate the use of maternal serum ADAM 12 concentration in the first trimeter as a marker of trisomy 21, trisomy 18 and trisomy 13. 2. To correlate maternal serum with pregnancy outcomes Brief background and significance The ADAMs (A disintegrin and metalloprotease) constitute a glycoprotein family with proteolytic and cell-adhesion activities (Wolfsberg et al., 1995; Primakoff and Myles, 2000; Seals and Courtneidge, 2003). Human ADAM12 exists in two forms, ADAM12-L (long) and ADAM12-S (short), the latter being the secreted form of ADAM12. ADAM12-S differs from ADAM12-L at the C-terminal end in that it does not contain the transmembrane and cytoplasmatic domains (Gilpin et al., 1998). ADAM12-S binds to and has proteolytic activity against insulin-like growth factor binding protein (IGFBP)-3 and, to a lesser extent, IGFBP-5. Insulin growth factors (IGFs) I and II are proinsulin-like polypeptides that are produced in nearly all foetal and adult tissues. Lack of IGF I and II causes foetal growth retardation in mice (Powel-Braxton et al., 1993). The cleavage of IGFBPs into smaller fragments with reduced affinity for the IGFs reverses the inhibitory effects of the IGFBPs on the mitogenic and DNA stimulatory effects of the IGFs (Blat et al., 1994). ADAM12-S is an important indicator of foetal growth because ADAM12-S is an IGFBP-3 protease and IGFBP-3 is the most abundant IGFBP in serum. The proteolysis of IGFBP-3 would stimulate growth by increasing levels of bioavailable IGF I and II. Previous study (Laigaard et al. 2003) has reported that in 18 first trimester Down syndrome pregnancies versus 136 healthy controls, maternal serum concentration of ADAM12 was decreased with the median multiple of mean (MoM) value of 0.14 (0.01-0.76). This results in a detection rate of 82% for a false positive rate of 3.2% (using 1:400 risk as cut-off) for fetal Down syndrome. In another study (Laigaard et al. 2005), maternal serum ADAM 12-S concentrations were found to be lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (MoM) of 0.28 (p < 0.001). These findings suggest that maternal serum ADAM 12-S may be a novel marker for trisomy 21, trisomy 18 and perhaps trisomy 13 in the first trimester of pregnancy. Pregnancy associated plasma protein-A (PAPP-A) and ADAM12-S are both IGFBP-5 proteases synthesised by the placenta. Low concentrations of maternal serum PAPP-A are associated with fetal trisomy 21 (Brambati et al. 1993, Macintosh et al. 1994, Spencer et al. 1999) and pregnancy adverse outcomes (Ong et al. 2000). Therefore ADAM12 can be a worthwhile marker for investigation as an indicator of foetal well-being. References: Blat C, Villaudy J, Binoux M. 1994. In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. J Clin Invest 93: 2286–2290. Brambati B, Macintosh MC, Teisner B, Maguiness S, Shrimanker K, Lanzani A, Bonacchi I, Tului L, Chard T, Grudzinskas JG 1993. Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype. Br J Obstet Gynaecol 100(4):324-6. Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM. 1998. A novel secreted form of human ADAM12 (meltrin alpha) provokes myogenesis in vivo. J Biol Chem 273: 157–166. Laigaard J, Christiansen M, Frohlich C, Pedersen BN, Ottesen B, Wewer UM 2005. The level of ADAM12-S in maternal serum is an early first-trimester marker of fetal trisomy 18. Prenat Diagn. 25(1):45-6. Laigaard J, Sorensen T, Frohlich C, Pedersen BN, Christiansen M, Schiott K, Uldbjerg N, Albrechtsen R, Clausen HV, Ottesen B, Wewer UM 2003. ADAM12: a novel first-trimester maternal serum marker for Down syndrome. Prenat Diagn 30;23(13):1086-91. Macintosh MC, Iles R, Teisner B, Sharma K, Chard T, Grudzinskas JG, Ward RH, Muller F 1994. Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A, markers for fetal Down syndrome at 8-14 weeks. Prenat Diagn 14(3):203-8. Ong CYT, Liao AW, Spencer K, Munim S, Nicolaides KH 2000.First trimester maternal serum free human chorionic gonadotrophin & pregnancy associated plasma protein A as predictors of pregnancy complications. Br J Obstet Gynaecol 107: 1265-1270. Powel-Braxton L, Hollingshead P, Warburton C, et al. 1993. IGF-I is required for normal embryonic growth in mice. Genes Dev 7: 2609–2617. Primakoff P, Myles DG. 2000. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet 16: 83–87. Seals DF, Courtneidge SA. 2003. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 17: 7–30. Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH 1999. A screening program for trisomy 21 at 10-14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 13(4):231-7. Wolfsberg TG, Primakoff P, Myles DG, White JM. 1995. ADAM, a novel family of membrane proteins containing a disintegrin and metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J Cell Biol 131: 275–278. |
| Researcher : Pang RTK |
| Project Title: | A comparative study of the extracellular matrix molecules from feeder cells supporting the growth of human embryonic stem cells |
| Investigator(s): | Pang RTK, Yeung WSB, Lee CYL |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2007 |
| Abstract: |
| Key issues and problems being addressed Human embryonic stem cells are cells derived from the inner cell mass at the blastocyst-stage of preimplantation embryos. In appropriate condition, these cells undergo self-renewal and divide continuously with a stable karyotype for prolong period. More importantly, they can differentiate into different cell types of the body. This pluripotent property of the human embryonic stem cells has cast a lot of hope on their possible use in regenerative medicine and in establishment of disease models for the study of metabolic and life-threatening disorders. To maintain human embryonic stem cells in an undifferentiated state in vitro, the cells are usually grown on feeder cells. Apart from mouse fetal fibroblast cells, a variety of cell types of human origin have been used as feeder cells including fibroblasts from fetus (Richards et al., 2002, 2003), adult skin (Amit et al., 2003; Hovatta et al., 2003) and placenta (Genbacev et al., 2005), adult marrow cells (Cheng et al., 2003), uterine endometrial cells (Lee et al., 2005), muscle and lung epithelial cells (Richards et al., 2003). Recently, human embryonic stem cells had been grown on established fibroblast cell line (Park et al., 2003; Inzunsa et al., 2005) and embryonic stem cell-derived cells (Xu et al., 2004; Stojkovic et al., 2005a). The use of feeder cells has raised concerns on transmission of contaminant from the feeder cells to the embryonic stem cells. Indeed, it was demonstrated that human embryonic stem cells cultured on mouse feeder cells contained molecule(s) with sialic acid of non-human origin (Martin et al., 2005). In addition, the use of feeder cells also complicates studies on differentiation, pluripotency and self-renewal of human embryonic stem cells (Amit et al., 2004). Effort has been made to culture human embryonic cells without feeder cells through the use of extracted basement membrane from mouse sarcoma cells, matrigel (Xu et al., 2001; Amit et al., 2004; Ludwig et al., 2006) or purified extracellular matrix molecules, laminin and fibronectin (Amit et al., 2004; Beattie et al., 2005; Li et al., 2005), and use of spent media after culture of mouse embryonic fibroblast cultures (Xu et al., 2001; Amit et al., 2004; Stojkovic et al., 2005b). Hypothesis: The hypothesis of this project is that the feeder cells produce matrix molecules that are important to the development of human embryonic stem cells. Objectives: 1. To compare the matrix molecules of feeder cells with different capacity of supporting the growth of human embryonic stem cells. 2. To develop a culture system for the collection of matrix molecules from feeder cells in large scale. References Amit M, Shariki C, Margulets V et al. 2004 Feeder layer- and serum-free culture of human embryonic stem cells. Biology of Reproduction 70, 837–845. Amit M, Margulets V, Segev H et al. 2003 Human feeder layers for human embryonic stem cells. Biology of Reproduction 68, 2150–2156. Beattie GM, Lopez AD, Bucay N et al. 2005 Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells 23, 489–495. Cheng L, Hammond H, Ye Z et al. 2003 Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells 21, 131–142. Genbacev O, Krtolica A, Zdravkovic T et al. 2005 Serum-free derivation of human embryonic stem cell lines on huma n placental fibroblast feeders. Fertility and Sterility 83, 1517–1529. Hovatta O, Mokkola M, Gertow K et al. 2003 A culture system using human foreshin fibroblasts as feeder cells allows production of human embryonic stem cells. Human Reproduction 18, 1404–1409. Inzunza J, Gertow K, Stromberg et al. 2005 Derivation of human embryonic stem cell lines in serum replacement medium using postnatal human fibroblasts as feeder cells. Stem Cells 23, 544–549. Li Y, Powell S, Brunette E et al. 2005 Expansion of human embryonic stem cells in defined serum-free medium devoid of animal-derived products. Biotechnology and Bioengineering 91, 688–698. Ludwig TE, Bergendahl V, Levenstein ME et al. 2006 Feeder-independent culture of human embryonic stem cells. Nature Methods 3, 637-46 Martin MJ, Muotri A, Gage F et al. 2005 Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nature Medicine 11, 228–232. Park JH, Kim SJ, Oh EJ et al. 2003 Establisment and maintenance of human embryonic stem cells on STO, a permanently growing cell line. Biology of Reproduction 69, 2007–2014. Richards M, Fong CY, Chan WK et al. 2002 Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cells. Nature Biotechnology 20, 933–936. Richards M, Tan S, Fon CY et al. 2003 Comparative evaluation of various human feeders for prolonged undifferentiated frowth of human embryonic stem cells. Stem Cells 21, 546–556. Stojkovic P, Lako M, Stewart R et al. 2005a An autogenic feeder cell system that efficiently supports growth of undifferentiated human embryonic stem cells. Stem Cells 23, 306–314. Stojkovic P, Lako M, Przyborski S et al. 2005b Human-serum matrix supports unidfferentiated growth of human embryonic stem cells. Stem Cells 23, 895–902. Xu C, Inokuma MS, Denham J et al. 2001 Feeder-free growth of undifferentiated human embryonic stem cells in vitro. Nature Biotechnology 19, 971–974. Xu C, Jiang J, Sottile V et al. 2004 Immortalized fibroblast-like cells derived from human embryonic stem cells support undifferentiated cell growth. Stem Cells 22, 972–980. |
| List of Research Outputs |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Lee C.Y.L., Hou Y.C.D., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Study of extracellular matrix for the culture of human embryonic stem cells., International Society For Stem Cell Research, 7th Annual Meeting, 8-11 July, Spain. 2009. |
| Leung O.N., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Aberrant expression of microRNA-135a is involved in the progression of cervical cancer. , P-07. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., Basic Science Award: MicroRNA-135a regulates early embryo development through mediating expression of E3 Ubiquitin Ligase Seven In Absentia Homolog 1 (SIAH1), 26th Annual Meeting of European Society for Reproduction and Embryology, 27-30 June 2010, Rome. 2010. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA-135a regulates early embryo development through mediating expression of E3 ubiquitin ligase seven in absentia homolog 1 (SIAH1)., The European Society of Human Reproduction & Embryology 26th Annual Meeting, 27th -30th June, Rome, Italy.. 2010. |
| Liu W., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Best Abstract Award: MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine 21 January 2010. 2010. |
| Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine . 2010. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., An in vitro system for mouse implantation study. , P-11. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Identification of endometrial proteins responsible for embryo implantation using comparative proteomic study. , O.2.21. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., Excellent Poster Presentation: MicroRNA-34c is important for the first cell division in mouse embryos, First SKLAB Symposia on Frontiers in Preimplantation Biology 8-12 May 2010, Beijing. 2010. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., MicroRNA-34c is important for the first cell division in mouse embryos, The First SKLAB Symposia on Frontiers in Periimplantation Biology, Beijing China. 2010, 55. |
| Researcher : Peng Q |
| List of Research Outputs |
| Lee C.Y.L., Peng Q., Fong S.W. and Yeung W.S.B., THE EXPRESSION AND REGULATION OF SIRT1 IN HUMAN EMBRYONIC STEM CELLS, International Society for Stem Cell Research 8th Meeting, 16-19 June, San Francisco, 2010. |
| Peng Q., Lee C.Y.L., Ng E.H.Y. and Yeung W.S.B., Expression and regulation of connexin 43 in human embryonic stem cells, International Society for Stem Cell Research, 8th Meeting, 16-19 June San Francisco, 2010. |
| Researcher : So WS |
| List of Research Outputs |
| So W.S., Ng E.H.Y., Wong Y.Y., Yeung W.S.B. and Ho P.C., Accupuncture for frozen-thawed embryo transfer cycles: A double-blind randomized controlled trial, Reproductive BioMedicine Online. 2010, 20: 814-821. |
| Researcher : Tam KF |
| List of Research Outputs |
| Au C.W., Siu M.K., Liao X., Wong E.S., Ngan H.Y.S., Tam K.F., Chan D.C., Chan Q.K. and Cheung A.N.Y., Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome, Cancer Lett. 2009 Aug 28;281(2):151-61. 2009. |
| Kwan T.T.C., Tam K.F., Lee P.W.H., Lo S.S.T., Chan K.K.L. and Ngan H.Y.S., De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial, Psycho-Oncology. 2010, 1-11. |
| Ngan H.Y.S., Cheung A.N.Y., Tam K.F., Chan K.K.L., Tang H.W., Bi D., Descamps D. and Bock H.L., Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong, Hong Kong Med J.. 2010, 16(3): 171-9. |
| Siu K.Y., Wong E.S.Y., Kong S.H., Wong G.W., Tam K.F., Ngan H.Y.S., Le X.F. and Cheung A.N.Y., Dysregulated expression of stem cell transcription factor Nanog in development and progress of ovarian cancers. , The 101st Annual Meeting of the American Association for Cancer Research, Washington DC, U.S.A., 17 - 21 April 2010.. 2010. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Researcher : Tang FOS |
| Project Title: | A prospective randomized comparison of sublingual and vaginal misoprostol in termination of pregnancy in the second trimester |
| Investigator(s): | Tang FOS, Ho PC |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Other Funding Scheme |
| Start Date: | 10/2000 |
| Abstract: |
| To compare the efficacy of sublingual and vaginal misoprostol in termination of second trimester pregnancy. |
| List of Research Outputs |
| Tang F.O.S., Schweer H., Lee W.H. and Ho P.C., Pharmacokinetics of repeated doses of misoprostol, Human Reproduction. 2009, 24(8): 1862-1869. |
| Researcher : Tang GWK |
| Project Title: | A cross sectional health care study of Chinese perimenopausal women in Hong Kong |
| Investigator(s): | Tang GWK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Other Funding Scheme |
| Start Date: | 01/1993 |
| Abstract: |
| To study Chinese women in Hong Kong on: 1) their perception and understanding of the menopause; 2) their symptoms expressed and experienced before, during and after the menopause; 3) bone density in various age groups ranging from adolescence to postmenopause and to correlate such values with biophysical parameters and diet; 4) how best health care strategies can be planned based on the findings in the study so that women's needs are met most cost effectively. |
| Project Title: | Fracture incidence reduction and safety of TSE-424 (Bazedoxifene Acetate) compared to placebo and Raloxifene in osteoporotic postmenopausal women / Endomentrial Safety Substudy |
| Investigator(s): | Tang GWK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Wyeth Austral PTY Ltd - General Award |
| Start Date: | 02/2002 |
| Abstract: |
| (A) This reduction in the circulating levels of oestrogen during menopause is associated with a number of changes, including osteoporosis. Osteoporosis is characterized by a loss of bone mass and micro architectural deteroration of bones tissue, with a consequent increase in bone fragility and susceptibility to bone fracture. (B) Bazedoxifene acetate is a selective oestrogen receptor modulator (SERM). It has been designed to exhibit the positive effects of an oestrogen agonist on the skeletal and cardiovascular systems, while acting as an antagonist on the uterus and the breast. SERMs have 2 principal indications in the clinic: the prevenetion and treatment of postmenopausal osteoporsis(raloxifene) and the prevention and treatment of breast cancer (tamoxifen), mainly in postmenopausal women. (C) Pre-clinical studies suggest that bazedoxifene acetate protects bone at a lower dose than currently marketed SERMs with no uterine agonist effect, a low potentional to induce flushes, and an improvement in the serum lipid profile. Pre-clinical data has also demonstrated that bazedoxifene acetate effectively suppress the proliferation of breast cancer cell lines, which suggests that it may exhibit antagonist activity on breast cell proliferation. (D) This is a multi-centre, double-blind, randomised, placebo and active comparator controlled phase 3 trial that will involve approximately four thousand patients. There will be about 180 sites participating in the study, which will be conducted globally. Of the four thousand patients recrutied into the study, 1000 patients will be recruited to one of the following four study groups: 1. bazedoxifence acetate 20mg, 2. bazedoxifence acetate 40mg, 3. raloxifece 60mg, 4. placebo. |
| Project Title: | Main Study (013-01)- A study to Evaluate the Efficacy of Quadrivalent HPV (Types 6,11,16 and 18) L1 Virus-Like Particle (VLP) Vaccine in Reducing the Incidence of HPV 6/11-, 16- and 18- Related CIN, and HPV 16 and 18-Related AIS and Cervical Cancer, and HPV 6/11-, 16-, and 18-Related External Genital Warts, VIN and VaIN, and HPV 16 and 18-Related Vulvar and Vaginal Cancer in 16- to 23- Year-Old Women -- The F.U.T.U.R.E. I Study (Females United to Unilaterally Reduce Endo/Ectocervical disease). Substudy (012-01)- Immunogenicity and Safety of Quadrivalent HPV (Types 6,11,16,18)L1 Virus-Like Particle (VLP) Vaccine in 16- to 23-Year-Old Women With an Immunogenicity Bridge Between the HPV 16 Component of the Qualdrivalent Vaccine and the Monovalent HPV 16 Vaccine Pilot Manufacturing Material - The F.U.T.U.R.E. I Study (Females United to Unilaterally Reduce Endo/Ectocervical Disease) |
| Investigator(s): | Tang GWK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Merck, Sharp and Dohme (Asia) Ltd. - General Award |
| Start Date: | 08/2002 |
| Abstract: |
| To demonstrate that a 3-dose regimen of quadrivalent HPV (Types 6,11,16,18) L1 VLP vaccine is generally well tolerated; to demonstrate that quadrivalent HPV vaccine is generally well tolerated. |
| List of Research Outputs |
| Dillner J., Kjaer S., Wheeler C., Sigurdsson K., Iversen O., Hernandez-Avila M., Perez G., Brown D.R., Koutsky L., Tay E., Garcia P.J., Ault K., Garland S.M., Leodolter S., Olsson S., Tang G.W.K., Ferris D., Paavonen J., Lehtinen M., Steben M., Bosch F.X., Joura E.A., Majewski S., Munoz N., Myers E.R., Villa L.L., Taddeo F.J., Roberts C.C., Tadesse A.S., Bryan J.T., Maansson R., Lu S., Vuocolo S., Hesley T.M., Barr E. and Haupt R., Four year efficacy of prophylactic human papillomavirus (types 6,11,16 and 18) L1 virus-like-particle vaccine against low-grade cervical, vulvar, and vaginal intraepithelial neoplasia and condylomata acuminata, BMJ. 2010, 341. |
| Kjaer S.K., Sigurdsson K., Iversen O.E., Hernandez-Avila M., Wheeler C.M., Perez G., Brown D.R., Koutsky L.A., Tay E.H., Garcia P., Ault K.A., Garland S.M., Leodolter S., Olsson S.E., Tang G.W.K., Ferris D.G., Paavonen J., Lehtinen M., Steben M., Bosch F.X., Dillner J., Joura E.A., Majewski S., Munoz N., Myers E.R., Villa L.L., Taddeo F.J., Roberts C., Tadesse A., Bryan J., Maansson R., Lu S., Vuocolo S., Hesley T.M., Saah A., Barr E. and Haupt R.M., A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against ghigh-grade cervical and external genital lesions, Cancer Prev Res (Phila Pa). 2009, 2(10): 868-878. |
| Munoz N., Kjaer S.K., Sigurdsson K., Iversen O.E., Hernandez-Avila M., Wheeler C.M., Perez G., Brown D.R., Koutsky L.A., Tay E.H., Garcia P.J., Ault K.A., Garland S.M., Leodolter S., Olsson S.E., Tang G.W.K., Ferris D.G., Paavonen J., Steben M., Bosch F.X., Dillner J., Huh W.K., Joura E.A., Kurman R.J., Majewski S., Myers E.R., Villa L.L., Taddeo F.J., Roberts C., Tadesse A., Bryan J.T., Lupinacci L.C., Giacoletti K.E.D., Sings H.L., James M.K., Hesley T.M., Barr E. and Haupt R.M., Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women, Journal of the National Cancer Institute. Oxford Journals, 2010, 102(5): 325-339. |
| Olsson S.E., Kjaer S.K., Sigurdsson K., Iversen O.E., Hernandez-Avila M., Wheeler C.M., Perez G., Brown D.R., Koutsky L.A., Tay E.H., Garcia P., Ault K.A., Garland S.M., Leodolter S., Tang G.W.K., Ferris D.G., Paavonen J., Lehtinen M., Steben M., Bosch F.X., Dillner J., Joura E.A., Majewski S., Munoz N., Myers E.R., Villa L.L., Taddeo F.J., Roberts C., Tadesse A., Bryan J., Maansson R., Vuocolo S., Hesley T.M., Saah A., Barr E. and Haupt R.M., Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection., Hum Vaccin. 2009, 5(10): 696-704. |
| Tang G.W.K., Consensus statement on cardiovascular disease and menopause, The Obstetrical and Gynaecological Society of Hong Kong / Hong Kong Menopause Society, Joint Scientific Meeting, July 28, 2009, Hong Kong. 2009. |
| Tang G.W.K., Establishing the Link between CPD and Enhanced Physician Competence and Performance in Practice, 2nd International Forum on CPD, Accreditation Sydney, Australia. 2010. |
| Tang G.W.K., Medical Council of Hong Kong and Ethical Issues, HKU Faculty of Medicine. 2010. |
| Tang G.W.K., Outstanding Contribution Award, 女醫師傑出貢獻獎, China Medical Women Association 2010. 北京 中國女醫師協會, 2010. |
| Tang G.W.K., Recent Development on the Use of Hormones in the Management of Climacteric Problems, HKU, Faculty of Medicine / Hong Kong Public Libraries. 2010. |
| Researcher : Tang MHY |
| List of Research Outputs |
| Leung K.Y., Cheong K.B., Lee C.P., Chan V.N.Y., Lam Y.H. and Tang M.H.Y., Ultrasonographic prediction of homozygous ao-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination? , Ultrasound in Obstetrics & Gynecology. 2010, 35: 149-154. |
| Li T.K.T., Leung K.Y., Lam Y.H., Tang M.H.Y. and Chan V.N.Y., Does in-utero transfusion for homozygous ao-thalassemia depend on hemoglobin level alone? , 19th World Congress on Ultrasound in Obstetrics and Gynecology, Hamburg, Germany, September 13–17 2009.. 2009. |
| Researcher : Tang YBA |
| List of Research Outputs |
| Tang Y.B.A., Liu Y.X., Yeung W.S.B. and Lee C.K.F., Molecular and functional characterization of a testis-specific TRS4 gene in spermatogenesis. , O23. The Society for Reproduction and Fertility annual Conference 2009, 12-14 July, Oxford, UK.. 2009. |
| Researcher : To MY |
| List of Research Outputs |
| Chan D.W., Liu V.W.S., To M.Y., Chiu P.M., Lee Y.W., Yao K.M., Cheung A.N.Y. and Ngan H.Y.S., Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21(WAF1/CIP1) expression in ovarian cancer, Briitish Journal of Cancer. 2009, 101: 1433-1443. |
| Researcher : Wang Y |
| List of Research Outputs |
| Wang Y., Chan D.W., Liu V.W.S. and Ngan H.Y.S., Differential functions of GRB7 and its variant, GRB7v in the tumorigenicity of ovarian cancer, 16th HKICC 6th Annual Meeting. 2009. |
| Wang Y., Chan D.W., Liu V.W.S., Chiu P.M. and Ngan H.Y.S., Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis, Clinical Cancer Research. AACR, 2010, 16: 2529-39. |
| Researcher : Wei N |
| List of Research Outputs |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |
| Researcher : Wei N |
| List of Research Outputs |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Function and modulation of Pdcd4 in ovarian cancer, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009 . 2009. |
| Wei N., Liu S., Leung T.H.Y., Tam K.F., Liao X., Cheung A.N.Y., Chan K.K.L. and Ngan H.Y.S., Loss of programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer , Molecular Cancer. 2009, 8: 70. |
| Wei N., Liu S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer , American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |
| Researcher : Wong BPC |
| List of Research Outputs |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Researcher : Wong CS |
| List of Research Outputs |
| Wong C.S., Leung T.H.Y., Chan K.K.L. and Ngan H.Y.S., Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers, 16th HKICC 6th Annual Meeting and The 14th Research Postgraduate Symposium, HKU, November 4-6, 2009. |
| Researcher : Wong ST |
| List of Research Outputs |
| Wong S.T., Chiu C.N., Lee C.K.F. and Yeung W.S.B., Effect of adrenomedullin on extravillous cytotrophoblast invasion. , P-10. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Researcher : Wong YY |
| List of Research Outputs |
| So W.S., Ng E.H.Y., Wong Y.Y., Yeung W.S.B. and Ho P.C., Accupuncture for frozen-thawed embryo transfer cycles: A double-blind randomized controlled trial, Reproductive BioMedicine Online. 2010, 20: 814-821. |
| Researcher : Yang F |
| List of Research Outputs |
| Cheung V.Y.T., Yang F. and Leung K.Y., Lower uterine segment thickness measurement in women with previous cesarean section: comparison of 2-D versus 3-D transabdominal sonography, 6th International Society of Ultrasound in Obstetrics & Gynecology Outreach Course, Singapore . 2010. |
| Researcher : Ye T |
| List of Research Outputs |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., An in vitro system for mouse implantation study. , P-11. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Identification of endometrial proteins responsible for embryo implantation using comparative proteomic study. , O.2.21. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Researcher : Yeung WSB |
| Project Title: | The mechanism of action of a novel glycodelin isoform from cumulus matrix on stimulating spermatozoa-zona pellucida binding |
| Investigator(s): | Yeung WSB, Chiu CN, Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 09/2006 |
| Completion Date: | 02/2010 |
| Abstract: |
| To determine the effect of glycodelin-C treatment on zona pellucida protein binding; to determine the intracellular signalling pathway of glycodelin-C in human spermatozoa; to study the mechanisms of action of glycodelin-C in increasing spermatozoa-zona binding. |
| Project Title: | Validation of an in vitro model for implantation |
| Investigator(s): | Yeung WSB, Pang RTK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 12/2008 |
| Abstract: |
| Infertility affects 15% of the couples worldwide. Although effort has been made in improving assisted reproduction treatment, the success rate is still low, which could be partly due to the transfer of embryos into a suboptimal uterine cavity (Wang and Dey, 2006). The implantation of blastocyst onto the maternal endometrium is crucial to reproduction. A mutual interaction between the blastocyst and the receptive uterus within a restricted period of the reproductive cycle (implantation window) is critical for the success of implantation. Estrogen and progesterone are essential in preparing a receptive endometrium for implantation (Wang and Dey 2006). In mice, blastocyst attachment onto the uterine luminal epithelium occurs between 2200–2300h on Day 4 of pregnancy. The embryos induce the epithelium and the subepithelial stromal cells around the embryos to express cyclooxygenase-2 (Cox-2) on Day 4 and Day 5 (Chakraborty et al., 1996). The enzyme is required for decidualization of the stromal cells surrounding the implanting embryos (Lim et al., 1997, 1999). Decidualization involves initial increase in proliferation and subsequent differentiation of the stromal cells to form the primary decidual zone between Day 5 afternoon and Day 6 morning of pregnancy. The cells within this zona then undergo apoptosis, and most of them disappear by Day 8 to create room for the implanting embryos. The stromal cells adjacent to the pdz continue to proliferate and differentiate into polyploid cells to form the secondary decidual zone (Tan et al., 2002). During decidualization, the stromal cells hypertrophy and express alkaline phosphatase and a panel of signaling molecules (Paria et al., 2001). The cells provide nutritional support to the developing embryo Researches on the molecular mechanism of implantation in vivo is challenging for several reasons. First, the number of implanted embryos is limited. Second, it is difficult to locate the newly implanted embryos in vivo because of their small size. Third, experiment has to be performed within the short window when the endometrium is receptive to blastocyst implantation (Paria et al., 1993). Fourth, implantation is affected by a number of endocrine and paracrine factors making researchers difficult to dissect the contribution of these factors. Fifth, although knockout models can be used to study these implantation-related genes, they are difficult to prepare. There are in vitro models for implantation to solve some of the above problems. These involve co-culturing of embryos or clumps of trophoblast cells (spheroids) with monolayer culture of either the endometrial epithelial or stromal cells. During implantation, the blastocysts interact with both the endometrial epithelium and stroma. The physiology of the stroma is affected by the epithelium and vice versa (Cooke et al., 1997; Kurita et al., 1998). Therefore, these models using monolayer endometirial cell culture are inadequate on their own, lack involvement of stroma-epithelial interaction, and cannot be used for embryo penetration studies. A three-dimensional tissue culture model has recently been reported (Tan et al., 2005), in which mouse endometrial tissue composing of both epithelial and stromal cells is cultured on lens paper. The cultured tissue expresses endometrial receptivity markers and blastocysts attach to and begin to invade the cultured tissue within 24 hours. We have repeated the model in the laboratory and found that the tissue showed signs of degeneration after 24 hours. Thus the model could not be used to study later event of implantation i.e. penetration and decidualization. Factors that regulate embryo attachment in such model have not been reported. We have modified the condition for the tissue culture model by culturing the tissue on the extracellular matrix from human amniotic membrane. This modification enables the endometrial tissue to be cultured for 48 hours without significant change in cellular morphology (Figure 1) probably as a result of better stromal cell growth. The extended culture period potentially allows us to study decidualization in implantation. Blastocysts attached to the tissue even after 24 hours of culture (Figure 2). We hypothesize that the model can be used to study the attachment, penetration and decidualization in implantation. Therefore the objectives of this proposal are to characterize these processes in the model and to compare with that obtained in vivo. References: Chakraborty I, Das SK, Wang J, Dey SK (1996). Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroid. J Mol Endocrinol 16:107-22s Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, Taylor J, Lubahn DB, Cunha GR (1997). Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium, Proc. Natl. Acad. Sci. U S A. 94:6535–6540. Kurita T, Young P, Brody JR, Lydon JP, O'Malley BW, Cunha GR (1998), Stromal progesterone receptors mediate the inhibitory effects of progesterone on estrogen-induced uterine epithelial cell deoxyribonucleic acid synthesis, Endocrinology 139:4708–4713. Lim H, Paria BC, Das SK, Dinchuk J, Langenbach R, Trzaskos JM, Dey SK (1997) Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91:197–208. Lim H, Gupta RA, Ma W, Paria BC, Moller DE, Morrow JD, DuBois RN, Trzaskos JM, Dey SK (1999) Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev. 13:1561–1574. Paria BC, Huet-Hudson YM, Dey SK (1993). Blastocyst’s state of activity determines the ‘window’ of implantation in the receptive mouse uterus. Proc. Natl. Acad. Sci. USA 90:10159–10162. Paria BC, Ma W, Tan J, Raja S, Das SK, Dey SK, Hogan BL (2001) Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. PNAS 98:1047–1052. Tan J, Raja S, Davis MK, Tawfik O, Dey SK, Das SK (2002). Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation. Mech. Dev. 111, 99– 113. Tan Y, Tan D, He M, Gu M, Wang Z, Zeng G, Duan E (2005). A model for implantation: coculture of blastocysts and uterine endometrium in mice. Biol Reprod. 72:556-61. Wang H, Dey SK (2006). Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet. 7:185-99. |
| Project Title: | A study on glycodelin-A induced differentiation of trophoblast cells |
| Investigator(s): | Yeung WSB, Lee CKF, Pang RTK |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 01/2009 |
| Abstract: |
| (1) To determine the temporal expression pattern of Notch signaling components and miR-34a during BeWo cell differentiation; (2) To investigate the functional role of Notch signaling components in BeWo cell differentiation; (3) To study the role of miR-34a in BeWo cell differentiation. 4 To compare hCG and glycodelin-A induced BeWo cell differentiation. |
| Project Title: | The role of microRNA-34 c in zygotic development |
| Investigator(s): | Yeung WSB, Liu W, Pang RTK, Lee CKF |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 12/2009 |
| Abstract: |
| MicroRNAs (miRNAs) are endogenous non-coding RNAs that bind to mRNA 3’UTRs to induce cleavage and/or inhibit translation of specific target mRNAs (Ambros, 2004; Bartel, 2004; Giraldes et al 2006). MiRNA genes are transcribed into primary transcripts (pri-miRNAs) of several kilobases long. In the nucleus, Drosha RNase III enzyme and its associated proteins excise the stem-loop of pri-miRNAs to form the precursor of miRNAs (pre-miRNA) of 60-70 nucleotides long, which are transported by exportin-5 to the cytoplasm, where Dicer RNase III enzyme and its double-stranded RNA-binding domain protein partner cut the pre-miRNA to generate the mature miRNA (Hutvagner et al., 2001; Ketting et al., 2001) of ~22 nucleotides in length. MiRNAs have been implicated in development of Caenorhabditis elegans, Drosophila, fish and mammals. There is a growing belief that miRNAs are critical in key developmental events in vertebrates and invertebrates (Johnson et al., 2005; Brennecke et al., 2003). In zebrafish, mutation of Dicer affects morphogenesis of embryos (Giraldez et al., 2005) and miR-430 promotes clearance of maternal mRNAs in early embryos (Giraldez et al., 2006). In mammals, most of the studies are on the involvement of miRNAs in post-implantation development. Many miRNAs are expressed in a temporal- and spatial-specific manner during post-implantation embryo development (Mineno et al., 2006) and report has demonstrated a role of miRNAs in limb development in mice (Harfe et al., 2005). There is only one circumstantial evidence suggesting that miRNAs are also involved in mammalian preimplantation embryo development i.e. Dicer is active in mammalian oocytes and early embryos. The dicer-deficient mouse oocytes have minimal amount of miRNAs, maternal mRNA expression different from wildtype oocytes, disorganized spindle formation, their resulting zygotes cannot pass through the first cleavage and express higher levels of H1foo and SCP3 (Tang et al., 2007). The development of preimplantation embryo encompasses a period from fertilization to implantation, and is marked by 3 waves of gene activation. In mouse, these occur at the 2-cell, after 4-cell stage and at morula-blastocyst transition (Wang et al., 2004; Hamatani et al., 2004). Apart from gene activation, fertilization triggers the degradation of maternal transcripts, and 90% of them are degraded by the 2-cell stage in mice (Nothaias et al., 1995). Degradation of maternal miRNAs and synthesis of embryonic miRNAs up to the 8-cell stage have recently been reported (Tang et al., 2007). We have used the stem-loop amplification-reverse transcription-polymerase chain reaction method (Chen et al., 2005; Tang et al., 2006) to perform mature miRNA profiling in mouse oocyte, zygote, 2-cell, 4-cell, 8-cell embryos, morula and blactocysts. Hierarchical clustering identifies a number of genes with distinct expression patterns and k-means clustering further identifies 6 differential expression (p<0.05) patterns. The expression of selected mature miRNAs including miR-34c, -135a, -143, -145 and -196b are subsequently validated by the two-step TaqMan® MicroRNA Assay. In particular, a group of 16 miRNAs is found upregulated in the pronucelated zygotes but decreased thereafter. One of these miRNAs is miR-34c. Injection of inhibitor of miR-34c inhibits first cleavage division in 70% of the pronucleated zygotes while over 97% of the zygotes injected with control inhibitor proceed to the 2-cell stage (Liu WM and Yeung WSB, unpublished observation). Hypothesis: MiR-34c is important for first cleavage division in mouse zygotes Objectives: 1. To study the production of miR-34c after fertilization 2. To confirm Bcl-2 as a target gene of miR-34c in mouse zygotes 3. To determine the functional role of Bcl-2 in mouse zygotic development. References: Ambros V (2004) The functions of animal microRNAs. Nature, 431:350-355. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116:281-297. Brennecke J, Hipfner DR, Stark A et al. (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113:25-36 Chen C, Ridzon DA, Broomer AJ et al. (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179. Giraldez AJ, Cinalli RM, Glasner ME et al. (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science, 308:833-838. Giraldez AJ, Mishima Y, Rihel J et al. (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science, 312:75-79. Hamatani T, Carter MG, Sharov AA et al. (2004) Dynamics of global gene expression changes during mouse preimplantation development. Dev Cell, 6, 117-131. Harfe BD, McManus MT, Mansfield JH et al. (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A, 102:10898-10903. Hutvagner G, McLachlan J, Pasquinelli AE et al. (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834-838. Johnson SM, Grosshans H, Shingara J et al. (2005) RAS is regulated by the let-7 microRNA family. Cell, 120:635-647. Ketting RF, Fischer SE, Bernstein E et al. (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 15:2654-2659. Mineno J, Okamoto S, Ando T et al. (2006) The expression profile of microRNAs in mouse embryos. Nucleic Acids Res, 34:1765-1771. Nothias JY, Majumder S, Kaneko KJ et al. (1995) Regulation of gene expression at the beginning of mammalian development. J Biol Chem, 270, 22077-22080. Tang F, Hajkova P, Barton SC et al. (2006) 220-plex microRNA expression profile of a single cell. Nature Protocol 1:1154-1159. Tang F, Kaneda M, O'Carroll D et al. (2007) Maternal microRNAs are essential for mouse zygotic development. Genes Dev, 21:644-648. Wang QT, Piotrowska K, Ciemerych MA et al. (2004) A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell, 6, 133-144. |
| Project Title: | Characterization of Stem/Progenitor Cells in Human Endometriosis |
| Investigator(s): | Yeung WSB, Chan RWS, Lee CKF, Luk JMC, Ng EHY |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 01/2010 |
| Abstract: |
| 1) To compare endometrial stem/progenitor cells from eutopic endometrium, ectopic endometriotic tissue and shed endometrium of menstruating women; 2) To examine the effect of estrogen on epithelial-stromal interactions; 3) To examine the effect of cytokines of peritoneal fluid of women with and without endometriosis on clonogeneic cells from eutopic and ectopic endometrium. The objective was to study the role of cytokines in peritoneal fluid on proliferation of the endometrial stem cells. Because the amount of funding granted is less than that requested, the use of antibody array to detect the cytokines in the peritoneal fluid of our patients will not be performed. Instead, the cytokines to be studied will be selected from relevant literature. Therefore the objective is slightly revised; 4) To demonstrate the involvement of stem/progenitor cells in the formation of endometriotic lesions using a mouse transplantation model in vivo. |
| List of Research Outputs |
| Chan R.W.S., Ng E.H.Y., Lee C.K.F. and Yeung W.S.B., Human Endometriotic Cells Exhibit Stem-like Cell Properties. , 25th European Soceity of Human Reproduction and Embryology, 28 Jun - 1 Jul, Amsterdam, Netherlands. Oxford Journal, 2009, 24: i97. |
| Cheong A.W.Y., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., aracrine regulation of the complement component-3 (C3) and the C3 receptor in the preimplantation embryos developed in vivo and in vivo., P.6.01. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Liu W., Yeung W.S.B. and Lee C.K.F., Oviductal Microsomal Epoxide Hydrolase (EPHX1) Reduces Reactive Oxygen Species (ROS) Level and Enhances Preimplantation Mouse Embryo Development. , Biology of Reproduction. 2009, 81: 126-32. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., Paracrine regulation of the production of embryotrophic oviductal complement componenet-3 and the expression of embryonic complement receptor-3 in a human oviductal cells-mouse embryo coculture system. , P312. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Cheong W.Y.A., Lee C.Y.L., Yeung W.S.B. and Lee C.K.F., The oviductal embryotrophic factor complement componenet-3 modulates its receptor expression in the pre-implantation embryos co-cultured with human oviductal epithelial cells. , OR-01. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong. . 2009. |
| Chiu C.N., Liao S., Lam K.W., Tang F., Ho J.C.M., Ho P.C., O W.S., Yao Q.Y. and Yeung W.S.B., Adrenomedullin regulates sperm motility and oviductal ciliary beat via cyclic adenosine 5'-monophosphate/protein kinase A and nitric oxide, Endocrinology. 2010, 151(7): 3336-3347. |
| Chiu C.N., Lam K.W., Lee C.L., Chung M.K., Huang W., O W.S., Tang F., Ho P.C. and Yeung W.S.B., The role of adrenomedullin in regulating human sperm motility , In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30, 2010. ESHRE, P-059. |
| Chow J.F.C., Yeung W.S.B., Lau E.Y.L., Lam S.T.S., Tong T., Ng E.H.Y. and Ho P.C., Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification, Fertility and Sterility. 2009, 92(2): 828, e7-e10. |
| Chow W.N., Lee C.Y.L., Wong B.P.C., Chung M.K., Lee C.K.F. and Yeung W.S.B., Complement 3 deficiency impairs early pregnancy in mice. , Molecular Reproduction and Development. 2009, 76: 647-55. |
| Chung M.K., Chiu C.N., Lee C.L., Pang R.T.K., Ng E.H.Y., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Yeung W.S.B., Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix, Hum Reprod. 2009, 24(11): 2856-67. |
| Ho P.C., Liu Y., Lee C.K.F., Ng E.H.Y. and Yeung W.S.B., Ovarian stimulation and endometrial receptivity. , The 7th Conference of the Pacific Rim Society for Fertility and Sterility & Annual Meeting of the Taiwanese Society for Reproductive Medicine, 20-23 Aug, Taipei.. 2009. |
| Hong S.J., Chiu C.N., Lee C.K.F., Tse J.Y., Ho P.C. and Yeung W.S.B., Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass, Fertil Steril. 2009, 92: 971-8. |
| Kodithuwakku K.S.P.K., Yeung W.S.B., Ho P.C. and Lee C.K.F., In vitro modeling of tubal ectopic implantation of embryos: A study on the role of olfactomedin 1 (Olfm1) in tubal ectopic pregnancy. , P-06. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Kodithuwakku S.P., Yeung W.S.B. and Lee C.K.F., Olfactomedin 1 (Olfm1): A novel protein modulates the embryo like trophoblastic spheroids attachment to the endometrial cells in vitro. , P.6.03. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A suppresses human trophoblast invasion through modulating extracellular signal regulated kinase (ERK) activities. , P-12. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Lee C.L., Lee C.K.F., Yeung W.S.B. and Ho P.C., Glycodelin-A as a modulator of trophoblast invasion. , O.2.09. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Lam K.W., Chiu C.N., Chung M.K., Lee C.L., Lee C.K.F., Koistinen R., Koistinen H., Seppala M., Ho P.C. and Yeung W.S.B., Glycodelin-A as a modulator of trophoblast invasion, Hum Reprod. 2009, 24(9): 2093-103. |
| Lam K.W., Chiu C.N., Lee C.L., Yeung W.S.B. and Ho P.C., Glycodelin-A suppressed trophoblast invasion by down-regulating urokinase plasminogen activator and extracellular signal regulated kinases activities., In: European Society of Human Reproduction and Embryology, 26th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology Rome, Italy, Jun 27-30. 2010. ESHRE, P-132. |
| Lee C.K.F., Liu Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Excessive ovarian stimulation affects endometrial receptivity in IVF patients. , The 5th Huaxia Congress of endocrinology, 4-9 Dec, Taipei.. 2009. |
| Lee C.K.F., Lee C.Y.L., Cheong W.Y.A. and Yeung W.S.B., Roles of Oviductal proteins on preimplantation embryo development. , MS.58. The society for the study of reproduction 42nd Annual Meeting. 18-22 July, Pittsburgh, Pennsylvania, USA.. 2009. |
| Lee C.K.F., Lee C.Y.L., Chan R.W.S., Cheong A.W.Y., Ng E.H.Y., Ho P.C. and Yeung W.S.B., Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue, Fertility and Sterility. 2010, 93(4): 1052-1060. |
| Lee C.Y.L., Hou Y.C.D., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Study of extracellular matrix for the culture of human embryonic stem cells., International Society For Stem Cell Research, 7th Annual Meeting, 8-11 July, Spain. 2009. |
| Lee C.Y.L., Peng Q., Fong S.W. and Yeung W.S.B., THE EXPRESSION AND REGULATION OF SIRT1 IN HUMAN EMBRYONIC STEM CELLS, International Society for Stem Cell Research 8th Meeting, 16-19 June, San Francisco, 2010. |
| Leung O.N., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Aberrant expression of microRNA-135a is involved in the progression of cervical cancer. , P-07. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., Basic Science Award: MicroRNA-135a regulates early embryo development through mediating expression of E3 Ubiquitin Ligase Seven In Absentia Homolog 1 (SIAH1), 26th Annual Meeting of European Society for Reproduction and Embryology, 27-30 June 2010, Rome. 2010. |
| Leung O.N., Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA-135a regulates early embryo development through mediating expression of E3 ubiquitin ligase seven in absentia homolog 1 (SIAH1)., The European Society of Human Reproduction & Embryology 26th Annual Meeting, 27th -30th June, Rome, Italy.. 2010. |
| Li R.H.W., Chiu C.N., Cheung M.P.L., Yeung W.S.B. and O W.S., Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa, International Journal of Andrology. 2009, 32: 687-694. |
| Li R.H.W., Liao S., Chiu C.N., Tam W.W., Ho J.C.M., Ng E.H.Y., Ho P.C., Yeung W.S.B., Tang F. and O W.S., Expression of adrenomedullin in human oviduct, its regulaton by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium, Journal of Clinical Endocrinology and Metabolism. 2010, 95(9): E18-E25. |
| Liu W., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Best Abstract Award: MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine 21 January 2010. 2010. |
| O W.S., Liao S., Sun J.Z., Ho J.C.M., Chiu C.N., Ng E.H.Y., Yeung W.S.B., Li R.H.W. and Tang F., Adrenomedullin and oviduct function in human and rats, Biology of Reproduction. 2009, 81: 99. |
| Pang R.T.K., Liu W., Lee C.K.F. and Yeung W.S.B., MicroRNA let-7 is important in embryo implantation, Annual Scientific Meeting of the Hong Kong Society for Reproductive Medicine . 2010. |
| Pang R.T.K., Leung O.N., Ye T., Liu W., Chiu C.N., Lam K.W., Lee C.K.F. and Yeung W.S.B., MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells, Carcinogenesis. 2010, 31 (6): 1037-1044. |
| Peng Q., Lee C.Y.L., Ng E.H.Y. and Yeung W.S.B., Expression and regulation of connexin 43 in human embryonic stem cells, International Society for Stem Cell Research, 8th Meeting, 16-19 June San Francisco, 2010. |
| Shi Y.Q., Li Y.C., Hu X.Q., Liu T., Liao S.Y., Guo J., Huang L., Hu Z.Y., Tang A.Y., Lee C.K.F., Yeung W.S.B., Han C.S. and Liu Y.X., Male germ cell-specific protein Trs4 binds to multiple proteins, Biochem Biophys Res Commun. 2009, 388: 583-8. |
| Siu S.O., Lam P.Y., Lau E., Yeung W.S.B., Cox D.M. and Chu I.K., N-Linked Glycoprotein Analysis Using Dual-Extraction Ultrahigh-Performance Liquid Chromatography and Electrospray Tandem Mass Spectrometry , Functional Glycomics: Methods and Protocols . 2009, 5: 133-143. |
| So W.S., Ng E.H.Y., Wong Y.Y., Yeung W.S.B. and Ho P.C., Accupuncture for frozen-thawed embryo transfer cycles: A double-blind randomized controlled trial, Reproductive BioMedicine Online. 2010, 20: 814-821. |
| Tang Y.B.A., Liu Y.X., Yeung W.S.B. and Lee C.K.F., Molecular and functional characterization of a testis-specific TRS4 gene in spermatogenesis. , O23. The Society for Reproduction and Fertility annual Conference 2009, 12-14 July, Oxford, UK.. 2009. |
| Wong S.T., Chiu C.N., Lee C.K.F. and Yeung W.S.B., Effect of adrenomedullin on extravillous cytotrophoblast invasion. , P-10. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Wu R., Fung Y.S. and Yeung W.S.B., Microfluidic-chip Capillary Electrophoresis for Analysis of Clinical Urinary Protenis , Abstract, 25th International Symposium on Microscale Bioseparations (MSB 2010), March 21-25, 2010, Prague, Czech Republic . 2010, P136, pp129. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., An in vitro system for mouse implantation study. , P-11. The Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, 22 Nov, Hong Kong.. 2009. |
| Ye T., Pang R.T.K., Lee C.K.F. and Yeung W.S.B., Identification of endometrial proteins responsible for embryo implantation using comparative proteomic study. , O.2.21. The 14th Research Postgraduate Symposium, HKU. 2 & 3 Dec, Hong Kong.. 2009. |
| Yeung W.S.B., Lee C.Y.L. and Lee C.K.F., Coculture and assisted reproduction, In: Edited by William L. Ledger, Seang Lin Tan, Adil O.S. Bahathiq, The Fallopain Tube in Infertility and IVF Practice. 2010, II: 8-17. |
| Yeung W.S.B., Lee C.K.F., Koistinen R., Koistinen H., Seppala M. and Chiu C.N., Effects of glycodelins on functional competence of spermatozoa, J Reprod Immunol. 2009, 83: 26-30. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., Excellent Poster Presentation: MicroRNA-34c is important for the first cell division in mouse embryos, First SKLAB Symposia on Frontiers in Preimplantation Biology 8-12 May 2010, Beijing. 2010. |
| Yeung W.S.B., Li R.H.W., Cheung T.M., Ng E.H.Y., Lau E.Y.L. and Ho P.C., Frozen-thawed embryo transfer cycles, Hong Kong Medical Journal. 2009, 15(6): 420-426. |
| Yeung W.S.B., Liu W., Pang R.T.K., Chiu C.N., Lao K. and Lee C.K.F., MicroRNA-34c is important for the first cell division in mouse embryos, The First SKLAB Symposia on Frontiers in Periimplantation Biology, Beijing China. 2010, 55. |
| Yeung W.S.B., Preimplantation Genetic Diagnosis - past, present and future, 11th AGM and Scientific Seminar of the Hong Kong Society of Medical Genetics. 2010. |
| Researcher : Zhang P |
| List of Research Outputs |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, American Association for Cancer Research (AACR) 101th annual meeting, Washington DC, USA, April 17-21, 2010 . 2010. |
| Zhang P., Liu S., Wei N., Leung T.H.Y. and Ngan H.Y.S., TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells, The 16th Hong Kong International Cancer Congress, Hong Kong, Nov. 4-6, 2009. |