Asbestos Research Today is a free monthly online journal that collates and summarizes the latest research about Asbestos, including details on mesothelioma, lung disease, dangers, effects, risks. | ||||||||
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Susceptibility of mesothelioma cell lines to adeno-associated virus 2 vector-based suicide gene therapy.Berlinghoff S, Veldwijk MR, Laufs S, Maser HP, Jauch A, Wenz F, Jens Zeller W, Fruehauf S German Cancer Research Center, INF 280, D-69120 Heidelberg, Germany. Although great efforts have been made to improve conventional therapy for diffuse malignant pleural mesothelioma, the median survival time of the patients after appearance of clinical symptoms remains poor. Due to confinement of the primary tumor to the pleural space, locoregional approaches are attractive strategies to improve the clinical outcome. In this context locoregional gene therapy using the recombinant adeno-associated virus 2 (rAAV-2) may be a new approach. Vectors were constructed containing a fusion gene, consisting of the Herpes simplex virus thymidine kinase (HSV-TK) and the green fluorescent protein (GFP) genes; the former serving as suicide gene by converting the prodrug ganciclovir (GCV) into a toxic agent, thereby killing infected cells. Among a number of different tumor cell lines, rAAV-2 achieved high GFP expression levels in three mesothelioma cell lines (H-Meso-1, MSTO-211H, NCI-H28). A variety of rAAV-2-constructs containing different promoters were tested. The vector with the elongation factor-1alpha (EF-1alpha) promoter showed the highest expression rates. Expression could be further increased by addition of the tyrosine kinase inhibitor genistein. Using the rAAV-2-based suicide system, a nearly complete eradication of transduced and GCV-treated mesothelioma cells was observed. rAAV-2-based suicide gene therapy may be a new approach for locoregional treatment of mesothelioma. Published 11 October 2004 in Lung Cancer, 46(2): 179-86.
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