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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.

Research Project

Project/Area Number 13671305
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKobe University

Principal Investigator

TOMINAGA Masahiro  Kobe University, Graduate School of Medicine, Associate Professor, 医学部附属病院, 講師 (70188796)

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)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsHepatocellular carcinoma / Percutaneous Isolated Hepatic Perfusion / Interferon / 肝細胞癌 / C型肝炎
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 具 英成: "多発進行肝癌に対する集学的治療戦略:外科切除と経皮的肝灌流の合併療法"手術. 55. 1945-1951 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 具 英成: "高度進行肝細胞癌に対する外科集学的治療;原料切除と経皮的肝灌流によるDual Treatment"消火器外科. 26. 587-595 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 具 英成: "Interventional radiologyを活用した進行肝細胞癌に対する経皮的肝灌流化学療法"外科. 65. 1158-1167 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 具 英成: "進行多発肝細胞癌に対する減量切除と経皮的肝灌流(PIHP)の合併療法による新治療体系の確立"消化器科. 37. 419-426 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 具 英成: "原発性・転移性進行肝癌に対する経皮的肝灌流化学療法"外科. 65. 1293-1298 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 富永正寛: "切除不能肝細胞癌に対する減量肝切除と経皮的肝再灌流による集学的治療"臨床外科. 59. 293-301 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ku Y., Tominaga M., Iwasaki T., Fukumoto T., Kuroda Y.: "Isolated hepatic perfusion chemotherapy for unresectable malignant hepatic tumors."Int J Clin Oncol. 7. 82-90 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ku Y, Tominaga M, Iwasaki T, Fukumoto T, Kusunoki N, Ogata S, Kuroda Y: "Regional treatment for unresectable malignant hepatic tumors : An overview of isolated hepatic perfusion"Chir Gastroenterol. 19. 370-376 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 具 英成: "高度進行肝細胞癌に対する外科集学的治療;減量切除と経皮的肝灌流によるDual Treatment"消化器外科. 26. 587-595 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 具 英成: "Interventional radiologyを活用した進行肝細胞癌に対する経皮的肝灌流化学療法"外科. 65(10). 1158-1167 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 具 英成: "進行多発肝細胞癌に対する減量切除と経皮的肝灌流(PIHP)の合併療法による新治療体系の確立"消化器科. 37(4). 419-426 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 具 英成: "原発性・転移性進行肝癌に対する経皮的肝灌流化学療法"外科. 65(11). 1293-1298 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yonson Ku: "Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma"Annals of Surgery. 239(1). 53-60 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 富永正寛: "切除不能肝細胞癌に対する減量肝切除と経皮的肝灌流による集学的治療"臨床外科. 59(3). 293-301 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 具英成, 富永正寛, 岩崎武他: "多発進行肝癌に対する集学的治療戦略:外科切除と経皮的肝灌流の合併療法"手術. 55. 1945-1951 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ku Y., Tominaga M., Iwasaki T., Fukumoto T., Kuroda Y.: "Isolated hepatic perfusion chemotherapy for unresectable malignant hepatic tumors"Int J Clin Oncol. 7. 82-90 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takamastu M., Fukumoto T, Ku Y., Tominaga M, et al.: "HCV core protein modulate drug resistance through P-glycoprotein mediated mechanism"Hepatology. (印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋徹也: "肝癌に対する経皮的肝灌流(PIHP)と末梢造血幹細胞移植(PBSCT)の併用による超高用量化学療法の第1相臨床試験"癌と化学療法. 27(12). 1801-1804 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kusunoki N: "Effect or sodium thiosulfate on cisplatin removal with complete hepatic venous isolation and extracorporeal charcoal hemoperfusion A pharmacokinetic evaluation"Annals of Surgical Oncology. 8(5). 449-457 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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