Monday, August 8, 2011

Adenoviral Gene Transfer and Mesothelioma Cancer Cell Lines



Another interesting study called "adenovirus-mediated Bak gene transfer causes apoptosis in mesothelioma cell lines" by Abujiang Pataer, MD, PhD, W. Roy Smythe, Dr. Robert Yu, MS, Bingliang Fang, MD, PhD . sc, Tim McDonnell, MD, PhD, Jack A. Roth, Dr. Stephen G. Swisher, MD - from the Department of Thoracic Molecular Oncology, Department of Thoracic and cardiovascular surgery, and Institute of Molecular Pathology, University of Texas MD. Anderson Cancer Center, Houston, Texas - General Thoracic Surgery, J Thorac Cardiovasc Surg 2001; 121:0061-0067 Here is an excerpt: "Objective: Conventional treatment for mesothelioma is largely ineffective, therefore, evaluated the new approach. By adenoviral gene transfer of proapoptotic Bcl-2 family Bak in mesothelioma cancer cell lines, which are sensitive and resistant to adenoviral p53.

Methods: Binary adenoviral Bak (Ad / GT-Bak and Ad/GV16) and Laczi (Ad / GT-Laczi and Ad/GV16) vectors were used to convert from mesothelioma cell lines I-45 (p53-resistant ) and REN (p53-sensitive). Protein levels are determined by Western blotting. Apoptosis was assessed morphological changes, caspase-3 cleavage, and fluorescence-activated cell sorting analysis of subdiploid populations. Cell viability was determined by XTT assay. Statistical analysis was performed with analysis of variance and Student test.

Results: High levels of Bak gene transfer were seen after coadministration Ad / GT-Bak and Ad/GV16 in both mesothelioma cell lines. Apoptosis is induced 24 hours after Bak but not Laczi gene transfer ([Bak: I-45, 36%, Ren, 25%] vs [Laczi: I-45, 1%, Ren, 3%], p <0 , 05]) in p53-sensitive (REN) and p53-resistant (I-45) cell lines. The cell viability was significantly reduced by 48 to 72 hours after Bak gene transfer compared with the control vector in both cell lines (72 hours: Bak I-45, 1.4% ± 1.0%, and Bak REN, 4.7% ± 1%, vs Lac-Z-45, 83% ± 3%, and Lac-Z REN, 100% ± 1%, P <0.05 ).


Conclusion: adenovirus-mediated overexpression of Bak gene causes apoptosis and decreased cell viability in p53-sensitive and p53-resistant mesothelioma cells. These data suggest that gene transfer of proapoptotic Bcl-2 family members may represent a novel strategy for gene therapy for treatment of mesothelioma.

Conclusion: adenovirus-mediated overexpression of Bak gene causes apoptosis and decreased cell viability in p53-sensitive and p53-resistant mesothelioma cells. These data suggest that gene transfer of proapoptotic Bcl-2 family members may represent a novel strategy for gene therapy for treatment of mesothelioma.

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