• About
  • Policies
  • What is openaccess
  • Library
  • Contact
Advanced search
      View Item 
      •   BUIR Home
      • University Library
      • Bilkent Theses
      • Theses - Department of Molecular Biology and Genetics
      • Dept. of Molecular Biology and Genetics - Ph.D. / Sc.D.
      • View Item
      •   BUIR Home
      • University Library
      • Bilkent Theses
      • Theses - Department of Molecular Biology and Genetics
      • Dept. of Molecular Biology and Genetics - Ph.D. / Sc.D.
      • View Item
      JavaScript is disabled for your browser. Some features of this site may not work without it.

      Hepatocellular carcinoma viral etiology and molecular mechanisms

      Thumbnail
      View / Download
      2.4 Mb
      Author
      Yıldız, Esra
      Advisor
      Öztürk, Mehmet
      Date
      2003
      Publisher
      Bilkent University
      Language
      English
      Type
      Thesis
      Item Usage Stats
      80
      views
      23
      downloads
      Abstract
      Hepatocellular carcinoma (HCC) is one of the most frequent carcinomas throughout the world, being responsible for more than 1 million deaths annually and has a strong association with several etiological factors including aflatoxinB1, alcohol and Hepatitis virus B and C. Several studies suggested that HCV subtype 1b causes more severe liver diseases including HCC in a high manner and resistance to antiviral therapy. So, it is important to know genotype and some characteristics of HCV which are unique for the countries to develop better strategies regarding public health. By using direct sequencing information from 5`UTR and NS5B regions we identified subtype 1b as a predominant hepatitis C virus genome in Turkey. Next, the full genome sequence of a Turkish 1b isolate (HCV-TR1) was obtained by cloning of polypeptide-encoding region into 7 overlapping fragments. Although major structural and functional motifs of HCV proteins were maintained in HCV-TR1, it displayed amino acid substitutions in 6 out of 9 major cytotoxic T-cell epitopes. Several HCV proteins have been reported to contribute hepatocellular malignancy by interaction with critical cellular proteins involved in hepatocyte proliferation and survavil. Such studies often use HCC-derived cell lines as experimental models. As a prerequisite to future studies about the Turkish HCV 1b isolate in term of its contribution to HCC developments we investigated on phenotypic characterization of HCC cell lines. We provide experimental evidence that α-fetoprotein-producing HCC lines display in vitro liver stem cell-like properties with self-renewing capability and multi-lineage differentiation potential, even after single-cell cloning. However, their ability to generate fully differentiated normal progeny was disrupted, even if they modulate their differentiation program in response to external factors. These features qualify AFP-producing HCCs as “mis-specified” liver stem cell cancers whose cellular programs are deviated from repopulating liver to forming malignant tumors. Interestingly, stem-like cells described here have been used extensively to study the role HCV proteins. Our observations offer new opportunities for addressing the potential role of HCV in the misspecification of liver stem cells in relation with viral hepatocellular carcinogenesis.
      Permalink
      http://hdl.handle.net/11693/29332
      Collections
      • Dept. of Molecular Biology and Genetics - Ph.D. / Sc.D. 70
      Show full item record

      Browse

      All of BUIRCommunities & CollectionsTitlesAuthorsAdvisorsBy Issue DateKeywordsTypeDepartmentsThis CollectionTitlesAuthorsAdvisorsBy Issue DateKeywordsTypeDepartments

      My Account

      Login

      Statistics

      View Usage StatisticsView Google Analytics Statistics

      Bilkent University

      If you have trouble accessing this page and need to request an alternate format, contact the site administrator. Phone: (312) 290 1771
      Copyright © Bilkent University - Library IT

      Contact Us | Send Feedback | Off-Campus Access | Admin | Privacy