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lüll Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy Mhashilkar AM; Schrock RD; Hindi M; Liao J; Sieger K; Kourouma F; Zou-Yang XH; Onishi E; Takh O; Vedvick TS; Fanger G; Stewart L; Watson GJ; Snary D; Fisher PB; Saeki T; Roth JA; Ramesh R; Chada SMol Med 2001[Apr]; 7 (4): 271-82BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.|*Interleukins[MESH]|*Oxazines[MESH]|*Xanthenes[MESH]|Adenoviridae/genetics[MESH]|Annexin A5/metabolism[MESH]|Blotting, Western[MESH]|Cell Division/drug effects[MESH]|Cell Line[MESH]|Cell Separation[MESH]|Chromosome Mapping[MESH]|Chromosomes, Human, Pair 1[MESH]|Coloring Agents/pharmacology[MESH]|Dose-Response Relationship, Drug[MESH]|Exons[MESH]|Flow Cytometry[MESH]|Genes, Tumor Suppressor/genetics[MESH]|Genetic Therapy/*methods[MESH]|Growth Substances/*genetics/*metabolism[MESH]|Humans[MESH]|In Situ Nick-End Labeling[MESH]|Microscopy, Confocal[MESH]|Microscopy, Fluorescence[MESH]|Neoplasms/*therapy[MESH]|Propidium/pharmacology[MESH]|Thymidine/metabolism[MESH]|Time Factors[MESH]|Transduction, Genetic[MESH]|Trypan Blue/pharmacology[MESH]|Tumor Cells, Cultured[MESH] |