2004 Fiscal Year Final Research Report Summary
A novel capacity for diagnosis and treatment with survivin targeting in colorectal carcinomas
| Project/Area Number |
15591454
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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 |
Digestive surgery
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| Research Institution | Osaka Medical College |
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Principal Investigator |
YAMAMOTO Tetsuhisa Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 助手 (50330072)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGAWA Nobuhiko Osaka Medical College, Medical, Professor, 医学部, 教授 (00111956)
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| Project Period (FY) |
2003 – 2004
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| Keywords | survivin / gene therapy / variants / promoter |
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| Research Abstract |
Background. Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, has been markedly overexpressed in most human carcinomas, and been recognized as a novel tumor marker and a potential target in anticancer therapy. Methods. In this study we have evaluated the transcription levels of survivin mRNA and its splice variants (survivin-2B and survivin-deltaEx3) in tumor samples, and a survivin targeting adenoviral vector for the cytoreductive effects in human colorectal carcinoma cells. Transcription levels were measured by performing quantitative RT-PCR using primer pairs specific for survivin and either of variants. The correlation between transcription levels and pathological findings, as well as the chemosensitivity of tumor samples to the expression levels of survivin, were analyzed. Results. The transcription levels of survivin and variants were significantly higher in the tumor samples, while extremely lower in the normal ones. Comparing the histological disease stages (I+II vs. III+IV),there were no significant differences in the expression levels of survivin and variants. The expression level of survivin-2B/survivin for stage III+IV was lower than the one for stage I+II. In addition, higher expression level of survivin-2B/survivin significantly correlated with better prognosis in the present series. As a result of the chemosensitivity test, higher expression of survivin tended to be more sensitive to irinotecan in vitro. Adenoviral infection caused potential for spontaneous apoptosis in tumor cells, and suppressed tumor formation, as well as decreased the tumor volumes compared with the controls. Furthermore, this anti-tumor efficacy was enhanced in combination with drugs. Conclusions. These findings demonstrate high expression of survivin and its variants is relatively specific in tumor tissue and suggest their important roles in progression and targeting therapy of colorectal carcinomas.
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