| Project/Area Number |
16590584
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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 |
Gastroenterology
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| Research Institution | Gifu University |
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Principal Investigator |
SHIRATORI Yoshimune GIFU UNIVERSITY, UNIVERSITY HOSPITAL, ASSOCIATE PROFESSOR, 医学部附属病院, 助教授 (20313877)
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| Co-Investigator(Kenkyū-buntansha) |
MORIWAKI Hisataka GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学系研究科, 教授 (50174470)
KINOSADA Yasutomi GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学系研究科, 教授 (50161526)
HANDA Hiroshi TOKYO INSTITUTE OF TECHNOLOGY, GRADUATE SCHOOL OF BIOSCIENCE AND BIOTECHNOLOGY, AND INTEGRATED RESEARCH INSTITUTE, PROFESSOR, フロンティア創造共同研究センター, 教授 (80107432)
SHIDOJI Yoshihiro SIEBOLD UNIVERSITY, CELLULAR BIOCHEMISTRY SECTION, PROFESSOR, 看護栄養学部, 教授 (00111518)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | CANCER CHEMOPREVENTION / HEPATOCELLULAR CARCINOMA / RETINOID / NUCLEAR RECEPTOR / MEMBREN RECEPTOR / MOLECUAR TARGET |
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| Research Abstract |
We have conducted investigations of chemoprevention of hepatocellular carcinoma (HCC) by retionoids and confirmed the clinical effects of acyclic retionid on second primary hepatocarcinogenesis. Acyclic retinoid prevents hepatocarcinogenesis by eradicating premalignant and latent malignant clones of transformed cells from the liver. We demonstrate the mechanism of this clonal deletion at the cellular level. We revealed that acyclic retinoid not only binds to nuclear receptors, but also affects membrane receptors. Acyclic retinoid enhanced anti-tumor effects of not only interferon (IFN)-β but also IFN-α, however, natural retinoic acid (all-trans and 9-cis retinoic acid) failed to exert such effect. This combination effect was likely due to enhanced apoptosis induction as characterized by DNA fragmentation and chromatin condensation. Pretreatment of the HCC cells with acyclic retinoid followed by IFN-β, but not the converse, induced such cytotoxic effect. Acyclic retinoid increased the expression of type 1 IFN receptor (IFNR) and inclusion with anti-type 1 IFNR antibody abolished the synergistic growth suppression by the combination.
The hospital information system brings substantial benefits to clinical study. We also demonstrate that the hospital information system is useful for translational study of cancer chemoprevention.
We evaluate these results as very important to establish cancer chemoprevention with retionids and to develop novel cancer chemopreventive agents.
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