2003 Fiscal Year Final Research Report Summary
Effect of chemotherapy to the liver with pretreatment of interferon for hepatocellular carcinoma to aim at the acquisition of the sensitivity for anti-cancer drugs.
| Project/Area Number |
13671305
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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 | Kobe University |
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Principal Investigator |
TOMINAGA Masahiro Kobe University, Graduate School of Medicine, Associate Professor, 医学部附属病院, 講師 (70188796)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMOTO Takumi Kobe University, Graduate School of Medicine, Medical Staff, 医学部附属病院, 医員
IWASAKI Takeshi Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助手 (90324912)
KU Yonson Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40195615)
KURODA Yoshikazu Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70178143)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Hepatocellular carcinoma / Percutaneous Isolated Hepatic Perfusion / Interferon |
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| Research Abstract |
We have detected hepatitis C virus (HCV) core protein induced the tolerance against the anti-cancer drugs. Interferon (IFN) is well known to decrease viral load of HCV. Percutaneous Isolated Hepatic Perfusion (PIHP) is a high dose chemotherapy to the liver, while reducing the systemic exposure of the cytotoxic drugs. We investigate the efficacy of the chemotherapy to the liver using PIHP with pretreatment of IFN for patients who has hepatocellular carcinoma (HCC) with HCV.
(A)Basic study
1)Analysis of the mechanism in the acquirement of the tolerance against anti-cancer drugs.
We cultured HCV core protein expression cells and controlled cells in the medium including Actinomycin D (Act.D) or Doxorubicin (Doxo). CyclosporinA, which is a inhibitor of P-glycoprotein, suppress the survival of HCV core protein expression cells (Act.D ; 151%→10.2%, Doxo ; 86%→2.4%). P-glycoprotein is one of the mediators relating to the mechanism in the acquirement of the tolerance against anti-cancer drugs in the HCV core protein expression cells.
(B)Clinical study
1)Retrospecthe study : Patients treated by PIHP who had HCC with HCV were categorized into two groups according to the HCV-RNA levels. Group I ; HCV-RNA<3x10^2Kcopy/ml, GroupII ; HCV-RNA≧3x10^2Kcopy/ml. We compared the tumor effect between group I and II. Local tumor control was significantly effective in group I compared with group II. CR+PR ; 86% in group I vs 25% in group II
2)Prospective study : We produced the protocol of the pretreatment of IFN-α (IFN-α 300 x 10^4 IU/day, everyday, 1week). PIHP was performed in 2 cases after pretreatment of IFN. These 2 cases has partial response after 1 month of PIHP. Based on these results, pretreatment of IFN increases the sensitivity of anti-tumor drugs in HCC patients with HCV However, pancytopenia which is a side effect of IFN is the most problem to be improved.
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[Publications] Ku Y, Iwasaki T, Tominaga M, Fukumoto T, Takahashi T, Kido M, Ogata S, Takahashi M, Kuroda Y, Matsumoto S, Obara H.: "Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma."Ann.Surg.. 239. 53-60 (2004)
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