| Project/Area Number |
18591466
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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 | The University of Tokushima |
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Principal Investigator |
NISHIOKA Masanori The University of Tokushima, University Medical and Dental Hospital, Assistant Professor (50398020)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Kentaro The University of Tokushima, Institute of Health Bioscience, Guraduate School, researcher (20403727)
HORI Hitoshi The University of Tokushima, Institute of Technology and science, Guraduate School, Professor (90119008)
NAGASAWA Hideko Gifu Pharmaceutical Univesity, Facully of Pharmaceutical Science, Professor (90207994)
UTO Yoshihiro The University of Tokushima, Institute of Technolog and science, Guraduate School, Associate Professor (20304553)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Colorectal cancer / Radiation / Hypoxia / Sensitivity / Sensitizer / Anviogenesis / Metastasis / Surgery |
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| Research Abstract |
[Introduction and Purpose]
The resistance to radiation treatment caused by tumor hypoxia, basic surroundings of cancer, is a major complicating factor in cancer therapy. TX-l877 with a function like oxygen mimic is reported to be more potent radiosensitizer than etanidazole and have many additional biological activities such as antimetastatic and antiangiogenesis activity. Purpose is to reveal pathophysiologic facts of tumor hypoxia and to improve hipoxic cancer therapy.
[Methods and Results]
1. The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity by antiangiogenesis and inhibits liver metastasis-on pancreatic cancer.
In an orthotopic model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-1877 and irradiation showed significant reduction in volume. Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that treatment with TX-1877 alone or with TX-I877 and irradiation inhibited expression of the angiogenic molecules, vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8 and matrixmetalloproteinase 9 more than control or did treatment with irradiation alone. These treatments also induced apoptosis in cancer cells. These date show that treatment of TX-1877 and irradiation decreased growth of human pancreatic cancer, suppressed angiogenesis and inhibited liver metastasis, leading to prolonged survival.
2. The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity and inhibits lymph nodes metastasis on colorectal cancer In an orthotopic model, tumors from nude mice injected with colon cancer cells and treated with TX-1877 and irradiation showed significant reduction in volume. Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that treatment with TX-1877 and irradiation inhibited expression of the matastatic molecules, uPA and matrixmetalloproteinase 9 more than control or did treatment with irradiation alone.
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