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Identification and Characterization of Cancer-Related Genes in Esophageal Squamous Cell Carcinoma: (English)

Identification and Characterization of Cancer-Related Genes in Esophageal Squamous Cell Carcinoma: (English)

          
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About the Book

This dissertation, "Identification and Characterization of Cancer-related Genes in Esophageal Squamous Cell Carcinoma" by Li, Fu, 付利, 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 Identification and characterization of cancer-related genes in esophageal squamous cell carcinoma Submitted by Fu Li For the degree of Doctor of Philosophy at The University of Hong Kong in June 2007 Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer death worldwide and the fourth most common malignancies in China. Previous studies have shown that ESCC is a lethal disease caused by a combination of environmental and genetic risk factors. However, the genetic steps involved in carcinogenesis of ESCC are still unclear. This study aims to identify more ESCC-related genes and to characterize their roles in the tumorigenesis of ESCC. Deletion of chromosome 3p is common in ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs) at this region. Single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG), was applied to investigate loss of heterozygosity (LOH) on 3p in 100 primary ESCC cases with 386 SNP markers. The accuracy of LOH frequency detected by SMSG was further validated by quantitative real-time PCR in five selected SNP loci and the results demonstrated that SMSG is a reliable tool for LOH screening. Four minimal deleted regions (MDRs) at 3p26.3, 3p22, i3p21.3 and 3p14.2 were identified. Absent and down-regulated expression of candidate TSGs from MDRs and other frequent LOH loci, including CHL1, APG7L, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. Deletions of MDR-1, 2 and 4 correlated with both advanced tumor stage and poor differentiation in ESCC further strengthened the clinical relevance to these deleted regions. A potential TSG located at 3p22, Phospholipase C-δ1 (PLCD1), was subsequently characterized. Absent expression of PLCD1 was detected in 26/50 (52%) primary ESCCs and 4/9 (44.4%) ESCC cell lines, which was significantly associated with DNA- copy-number loss and promoter hypermethylation (P The majority of ESCC patients presented with advanced/metastatic disease upon diagnosis let us to identify new biomarkers for molecular tumor staging and prognostic evaluation. Differentially expressed proteins among different stages of primary ESCCs and their paired nontumorous tissues were compared by proteomics-based technology. Among 18 differentially expressed proteins, the expression levels of alpha-actinin 4 ii(ACTN4) and 67 kDa laminin receptor (67LR) progressively increased from stage I to III. Clinicopathological correlation study using TMA revealed that ACTN4 overexpression was significantly associated with advanced clinical stage and lymph node metastasis while 67LR overexpression was significantly correlated with advanced clinical stage. In summary, this study provided evidence that more ESCC-associated 3p


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Product Details
  • ISBN-13: 9781361429976
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 166
  • Spine Width: 11 mm
  • Width: 216 mm
  • ISBN-10: 1361429976
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Language: English
  • Series Title: English
  • Weight: 680 gr


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