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An Experimental Study Of HTERT Promoter On Targeting Therapy For Lung Cancer With Suicide Gene HSV-TK

Posted on:2007-04-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:X J TangFull Text:PDF
GTID:1104360185494590Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background and Objective Suicide gene therapy is an importantstrategy of gene therapy for cancer, and it is one of the focus fields of cancer research. It has been proved that HSV-TK/GCV was the most representative suicide gene therapy system. Previous laboratory studies and clinical trials demonstrated its promising prospect. However, application of HSV-TK/GCV in clinical cancer therapy is greatly restricted because of its toxicities to normal cells, attributed to lack of tumor-selectivity of therapeutic effect. Targeting gene therapy may be the effective approach to resolve this problem, which can be realized by targeting transfection and targeting expression of therapeutic gene. Because of more knowledge in structure, function and regulatory mechanism ofgene, as well as progress in theories and techniques of molecular biology in recent years, targeting gene expression looks like more feasible and reliable approach for targeting gene therapy for cancer. Tissue-specific or tumor-specific gene transcriptional control element is necessary for targeting gene expression, and an ideal transcriptional control element should have powful transcriptional activity, high speciality and wide applicability. Telomerase is a wide-spectrum tumor marker, which is positive in more than 85% of malignant tumors while negative in almost all mature somatic cells. Human telomerase reverse transcriptase (hTERT) is the determinant component of human telomerase for its activity. Expression of hTERT is predominantly regulated at transcriptional level by its promoter. So, transcriptional activity of hTERT promoter should be highly tumor specific and might be ideal transcriptional control element in targeting gene therapy for cancer. The results of early studies in this area are encouraging. The goal of present study is to explore the feasibility and approach of targeting gene therapy for lung cancer with suicide gene HSV-TK driven by hTERT promoter.
Keywords/Search Tags:hTERT promoter, suicide gene, targeting expression, lung cancer, gene therapy
PDF Full Text Request
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