| Project/Area Number |
12671139
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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 |
General surgery
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| Research Institution | GUNMA UNIVERSITY FACULTY OF MEDICINE |
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Principal Investigator |
HORIGUCHI Jun (2001) GUNMA UNIVERSITY FACULTY OF MEDICINE ASSISTANT PROFESSOR, 医学部, 助手 (70272242)
武井 寛幸 (2000) 群馬大学, 医学部, 助手 (40261846)
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| Co-Investigator(Kenkyū-buntansha) |
KURABAYASHI Masahiko GUNMA UNIVERSITY FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (00215047)
堀口 淳 群馬大学, 医学部, 助手 (70272242)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ANTIANGIOGENIC AGENT / TNP-470 / APOPTOSIS / MDA-MB-231 TUMOR / UFT / VEGF / TAMOXIFEN / DORMANCY THERAPY / 血管新生 / MDA-MB-231 / 乳癌 / Vascular endothelial growth factor / Apoptosis / 5-fluorouracil |
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| Research Abstract |
Angiogenesis is one of the key mechanisms of tumor development, invasion and metastasis. Suppression of tumor growth by antiangiogenic agent (TNP-470) is induced by apoptosis of cancer cells. Combination therapy of TNP-470 with UFT suppressed growth of MDA-MB-231 tumor compared to TNP-470 alone. The 5-FU concentration was higher in MDA-MB-231 tumors treated by TNP-470 plus UFT than TNP-470 alone. It was suggested that TNP-470 might increase 5-FU concentration in MDA-MB-231 tumors. Suppression of tumor growth by combination therapy of UFT with TNP-470 may be owing to the increase of 5-FU in the tumors. VEGF is one of growth factors with strong angiogenesis. VEGF production in cancer cells is suppressed by some chemo- and/or endocrine therapy. Tamoxifen inhibited VEGF production of ER-positive MCF-7 cells. Similarly, combination therapy of UFT with TNP-470 decreased VEGF concentration in MDA-MB-231 tumors. VEGF production was not suppressed by TNP-470 alone. Combination therapy of UFT with TNP-470 inhibited VEGF production of MDA-MB-231 tumors, which might be induced by increase of intra-tumoral concentration of 5-FU. Combination therapy of chemo-endocrine and antiangiogenic agents may induce breast cancer to tumor dormancy.
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