Molecular Studies on Endometrial and Ovarian Carcinogenesis
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Molecular Studies on Endometrial and Ovarian Carcinogenesis

Molecular Studies on Endometrial and Ovarian Carcinogenesis


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About the Book

This dissertation, "Molecular Studies on Endometrial and Ovarian Carcinogenesis" by 陳君怡, Kwan-yi, Queeny, Chan, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Molecular studies on endometrial and ovarian carcinogenesis" submitted by Chan Kwan Yi, Queeny for the Degree of Doctor of Philosophy at the University of Hong Kong in August 2007 Endometrial and ovarian cancers are the most common and the most lethal malignancies of female genital tract, respectively. The pathogenesis of these cancers was studied with three approaches. Firstly, single nucleotide polymorphisms of cytochrome P4501A1 (CYP1A1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were evaluated using the Sequenom MassARRAY system. Secondly, the expression of stem cell-related genes including STAT3, SOX2, FOXD3, OCT4, and NANOG was studied by quantitative real-time PCR and immunohistochemistry. Bisulfite sequencing and methylation-specific PCR (MS-PCR) was performed to determine the methylation status of the 5'-flanking regions of STAT3, OCT4, and NANOG. Effect of demethylating 5'-aza-2'-deoxycytidine and acetylating trichostatin-A treatments was also studied. Thirdly, annealing control primer(TM)-based RT-PCR was performed to identify novel differentially expressed genes. Down-regulation of follistatin-like 1 (FSTL1) was identified in 73.3% of endometrial and 91.7% of ovarian cancers. Full length FSTL1 cDNA was cloned and transiently transfected into Ovca420 for a series of in vitro functional analyses. Significant difference in CYP1A1 Ile462Val genotypes was demonstrated between the endometrial cancers and controls (P=0.022) with higher risk in valine-carriers (P=0.012). Increased risk was confined to oestrogen dependent endometrioid carcinoma (P=0.006) and in patients with high body mass index (OR=3.600; 95% CI=1.118-11.594; P=0.027). Regarding the NQO1 Pro187Ser polymorphism, 187Ser-carriers carried reduced risk of developing the endometrioid and clear cell ovarian carcinomas (OR=0.320, 95% CI=0.179-0.571, P=0.001), the latter was significantly associated with endometriosis (OR=3.793, 95% CI=1.739-8.272; P=0.001) and poor survival (P=0.004). Significantly reduced expression of STAT3, SOX2, FOXD3, and NANOG (Psignificantly inversely with expression level of NANOG (P=0.032, R =-0.798), 2 2 STAT3 (Pmethylated and new CpG sites were identified in STAT3 and OCT4, respectively. MS-PCR finding concurred with results of bisulfite sequencing and correlated with OCT4 expression. Demethylation and acetylation treatments demonstrated changes in STAT3 and SOX2 expression with a dosage-dependent pattern. Functional assays including MTT and cell count proliferation assays demonstrated significantly slower proliferation rate in FSTL1-transfected cells. By TUNEL and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G1 cell population was observed in the transfected cells. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells. Subsequent cDNA and protein expression analysis suggested that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor sign


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Product Details
  • ISBN-13: 9781374665989
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 334
  • Weight: 776 gr
  • ISBN-10: 1374665983
  • Publisher Date: 27 Jan 2017
  • Binding: Paperback
  • Language: English
  • Spine Width: 18 mm
  • Width: 216 mm


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