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Anti-Angiogenic Gene Therapy of Hepatocellular Carcinoma by Aav-Mediated Expression of Kallistatin and Vasostatin: (English)

Anti-Angiogenic Gene Therapy of Hepatocellular Carcinoma by Aav-Mediated Expression of Kallistatin and Vasostatin: (English)

          
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About the Book

This dissertation, "Anti-angiogenic Gene Therapy of Hepatocellular Carcinoma by AAV-mediated Expression of Kallistatin and Vasostatin" by Lai-yin, Tse, 謝禮賢, 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 Anti-angiogenic gene therapy of hepatocellular carcinoma by AAV-mediated expression of kallistatin and vasostatin submitted by Tse Lai Yin for the degree of Doctor of Philosophy at the University of Hong Kong in May 2005 Despite recent medical advances, the present curative treatments for hepatocellular carcinoma (HCC) are restricted to surgical resection and orthotopic liver transplantation (OLT). Since only a limited number of patients are suitable for surgical resection and OLT is limited by the supply of compatible donor livers, development of new treatment modalities is essential. Angiogenesis is an important hallmark in development of hepatocellular carcinoma. An anti-angiogenic approach was, therefore, undertaken to test its effect on HCC. Kallistatin and vasostatin are potent angiogenic inhibitors and they are the candidate genes used in this study. Here, we had successfully established an anti-angiogenic gene therapy method for treatment of ectopic HCC in mice. In this study, we investigated the efficacy of two angiogenic inhibitors, kallistatin and vasostatin, in treatment of ectopic hepatocellular carcinoma (HCC) by means of adeno-associated virus (AAV) serotype-2 transduction of liver. Normal BALB/c mice were inoculated subcutaneously with mouse BNL 1ME A.7R.1 cell, a chemically-transformed mouse HCC cell line. The target organ, liver, was transduced by recombinant AAV (rAAV) constructs with either kallistatin or vasostatin or control virus of rAAV-EGFP via hepatic portal vein injection. The size of tumour was monitored and recorded regularly for approximately 60 days. Livers, hearts, kidneys, livers, lungs, skeletal muscles, small intestines, spleens and stomachs were harvested and RNA was extracted. CD34 staining indicated that continuous release of kallistatin and vasostatin in livers successfully suppressed angiogenesis in HCC in comparison to control group injected with only rAAV-EGFP. Growth of HCC was also significantly retarded by the two proteins. Proliferative index by Ki-67 staining showed also a significant reduction in cell proliferation. Most importantly, long-term in situ liver expression of the exogenous genes was demonstrated after 1, 2 and 6 months post-transduction by PCR. The expression of transgenes was liver-specific, with RT-PCR revealing that RNA transcripts in hearts, kidneys, livers, lungs, skeletal muscles, small intestines, spleens and stomachs after viral transduction remained undetectable. In short, anti-angiogenic gene therapy of HCC by AAV-mediated expression of kallistatin and vasostatin is promising in HCC treatment. The present study provides valuable information and lays important foundation for development of anti-angiogenic gene therapy applicable to treatment of HCC. DOI: 10.5353/th_b3204566 Subjects: Protease inhibitors Gene therapy Neovascularization Liver - Cancer - Treatment Transgenic mice


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Product Details
  • ISBN-13: 9781361055816
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 178
  • Spine Width: 10 mm
  • Width: 216 mm
  • ISBN-10: 1361055812
  • Publisher Date: 26 Jan 2017
  • Binding: Paperback
  • Language: English
  • Series Title: English
  • Weight: 426 gr


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