1997 Fiscal Year Final Research Report Summary
Basic and Clinical Research of p53 Gene Therapy for Human Cancer
| Project/Area Number |
08671529
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Okayama University |
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Principal Investigator |
INOUE Fumiyuki Okayama University Medical School, First Department of Surgery, Assistant Professor, 医学部・附属病院, 講師 (90223271)
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| Co-Investigator(Kenkyū-buntansha) |
YASUDA Tatsuji Okayama University Medical School, Department of Cell Biology, Institute of Cell, 医学部, 教授 (30092357)
FUJIWARA Toshiyoshi Okayama University Medical School, First Department of Surgery, Instructor, 医学部, 助手 (00304303)
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| Project Period (FY) |
1996 – 1997
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| Keywords | p53 Gene / Antiangiogenesis / Lung Cancer / Gene Therapy |
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| Research Abstract |
Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor p53 gene is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here we investigated the antiangiogenic effect of the wild-type p53 gene transfer on a human non-small-cell lung cancer cell line. Mutant p53-expressing H226Br NSCLC cells were transduced with the wild-type p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semi-quantitative reverse transcription-polymerase chain reactions to detect altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system subcutaneously transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by subcutaneously inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1 (BAI1), resulting in the reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wild-type p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wild-type p53 gene is antiangiogenic, which may explain in part the mechanism of the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells.
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Research Products
(4 results)
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[Publications] Bouvet, M., Ellis, L.M., Nishizaki, M., Fujiwara, T., Liu, W., Bucana, C.D., Fang, B,Lee, J.J., Roth, J.A.: "Adenovirus-mediated Wild-type p53 gene transfer downregulates vascular endotherial growth factor expression and inhibits angiogenesis in human colon cancer." Cancer Research. 58. 2288-2292 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nishizaki, M., Fujiwara, T., Tanida, T., Hizuta, A., Nishimori, H., Tokino, T., Nakamura, Y., Bouvet, M., Roth, J.A., Tanaka, N.: "Antiangiogenic effect of recombinant adenovirus expressing the wild-type p53 gene : proposed mechanism for bystander effect." Clinical Cancer Research. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
