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Analysis of CTL targeted on hepatoma transfected with HIV gene Innovation of vaccine against hepatitis C virus.

Research Project

Project/Area Number 14570473
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKagawa University(Faculty of Medicine)

Principal Investigator

KUROKOHCHI Kazutaka  Kagawa University, school of Medicine, Research Assistant, 医学部, 助手 (10294753)

Co-Investigator(Kenkyū-buntansha) WATANABE Seishiro  Kagawa University, school of Medicine, Assistant Professor, 医学部, 助教授 (00158635)
MASAKI Tsutomu  Kagawa University, school of Medicine, Research Assistant, 医学部, 助手 (30335848)
KURIYAMA Shigeki  Kagawa University, school of Medicine, Professor, 医学部, 教授 (50244710)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHepatitis C / Hepatitis C virus / Cytotoxic T lymphocytes / Immunology / Costimulatory molecule / Hepatocellular carcinoma / Radiofrequency ablation (RFA) / 制御性T細胞 / T細胞受容体(TCR)
Research Abstract

The pathogenic mechanism for hepatocellular damage in HCV infection has not been clearly understood. Peripheral blood mononuclear cells (PBMCs) and liver infiltrating mononuclear cells (LIMCs) isolated from the HCV-infected patients were analyzed with antibodies directed against a variety of co-stimulatory molecules by flow cytometry. PBMCs expressing CD8,CD28,CD80 or CD154 were significantly reduced in HCV-infected patients compared with the healthy controls. CD28(+)CD8(+)PBMCs in the patients inversely correlated with ALT levels. Conversely, levels of CD28(-)CD8(+)LIMCs correlated with ALT levels. HCV-specific CTL activity was blocked by the treatment with anti-CB8 antibody, but not with anti-CD4 or anti-CD28 antibody. Immunohistochemical analysis revealed the accumulation of CD28(+) cells around the portal area in the liver of a patient with chronic active hepatitis C. These results suggest that CD28(+)CD8(+) T cells leave the circulation, move to the livers and are activated in the portal area in proportion to the extent of liver diseases. CD28(-)CD8(+) T cells may finally function as effector T cells causing the hepatocellular damage in HCV infection.
Radiofrequency ablation (RFA) is currently used for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the usefullness of combination therapy of percutaneous ethanol injection (PEI) and RFA (PEI-RFA). Patients with biopsy-proven HCC and liver cirrhosis underwent RFA after a bolus injection of ethanol into HCC (PEI-RFA). The volume of coagulated necrosis was estimated and compared with that in the group treated with RFA alone. Significantly larger coagulated necrosis areas were observed in patients treated with PEI-RFA compared with those treated with RFA alone. In the PEI-RFA group, the volume of coagulated necrosis was significantly correlated with the amounts of ethanol injected into HCC. No major complications were observed during and after the PEIRFA treatment.

Report

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

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Kurokohchi K, Masaki T, Miyauchi Y, 9 Others.: "Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma."Int J Oncol. 24. 381-387 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokohchi K, Masaki T, Arima K, 8 Others.: "CD28-negative CD8-positive cytotoxic T lymphocytes mediate Hepatocellular damage in hepatitis C virus infection."J Clin Immunol. 23. 518-527 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kobara H, Uchida N, Tsutsui K, 4 Others (1^<st>): "Abnormal bile flow in patients with achalasia"J Gastroenterol. 38. 327-331 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki T, Shiratori Y, Rengifo Wand, 9 Others (3^<rd>).: "Cyclins and cyclin-dependent kinases : comparative study of hepatocellular carcinoma versus cirrhosis."Hepatology. 37. 534-543 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki T, Igarashi K, Tokuda M, 11 Others (10^<th>).: "pp60c-src activation in lung adenocarcinoma."Eur J Cancer. 39. 1447-1455 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iihara N, Kurokohchi K, Tsukamoto T, 5 Others (2^<nd>).: "Hypoglycaemia in patients with liver diseases administered levothyroxine"Journal Clin Phar Ther. 28. 355-361 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morishita A, Murota M, Fujita J, 6 Others (2^<nd>).: "Autoreactive helper T cells specific for cytokeratin 19 in patients with autoimmune hepatitis."Hepatol Res. 25. 415-422 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murota M, Watanabe S, Fujita J, 10 Others (7^<th>).: "Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis."Hepatol Res. 25. 271-280 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe S, Uchida N, Masaki, 7 Others(1^<st>).: "Measurement of left portal vein blood flow velocity by doppler sonograph in a patient with acute fatty liver of pregnancy."J Med Ultrasound. 30. 57-61 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 正木 勉, 黒河内和貴, 舟木利治ほか14名: "肝細胞癌におけるmyristoylated alanine-rich C kinase substrate (MARCKS)の局在とリン酸化"医学と薬学. 49. 208-210 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wu F, 正木 勉, 室田将之ほか6名(4番目): "TNF-αで誘導される肝細胞癌のアポトーシスにおけるCYFRA 21-1の発現"MINOPHAGEN MEDICAL REVIEW. 48. 187-190 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 栗山茂樹, 吉治仁志, 正木 勉ほか12名(2番目): "AFP遺伝子の制御領域を含むキメラ制御因子を用いた肝癌細胞選択的遺伝子発現の誘導. In:臨床応用を目指した消化器分子生物学(小俣政男編)"アークメディア、東京. 93-99 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokohchi K, Masaki T, Miyauchi Y, 9 Others.: "Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma."Int J Oncol. 24. 381-387 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokohchi K, Masaki T, Arima K, 8 Others.: "CD28-negative CD8-positive cytotoxic T lymphocytes mediate Hepatocellular damage in hepatitis C virus infection."J Clin Immunol. 23. 518-527 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kobara H, Uchida N, Tsutsui K, 4 Others(1^<st>): "Abnormal bile flow in patients with achalasia."J Gastroenterol. 38. 327-331 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki T, Shiratori Y, Rengifo W, 9 Others(3^<rd>): "Cyclins and cyclin-dependent kinases : comparative study of hepatocellular carcinoma versus cirrhosis."Hepatology. 37. 534-543 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki T, Igarashi K, Tokuda M, 11 Others(10^<th>): "pp60c-src activation in lung adenocarcinoma."Eur J Cancer. 39. 1447-1455 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iihara N, Kurokohchi K, Tsukamoto T, 5 Others(2^<nd>): "Hypoglycaemia in patients with liver diseases administered levothyroxne."Journal Clin Phar Ther. 28. 355-361 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morishita A, Murota M, Fujita J, 6 Others(2^<nd>): "Autoreactive helper T cells specific for cytokeratin 19 in patients with autoimmune hepatitis."Hepatol Res. 25. 415-422 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murota M, Watanabe S, Fujita J 10 Others(7^<th>): "Measurement of left portal vein blood flow velocity by doppler sonography in a patient with acute fatty liver of pregnancy."J Med Ultrasound. 30. 57-61 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki T, Kurokohchi K, Funaki T, 14 Others: "Location and phosphorylation of myristoylated alanine-rich C kinase substrate (MARKS) in hepatocellular carcinoma."Medicine and Pharmacology. 49. 208-210 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wu F, Masaki T, Murota M, 6 Others(4^<nd>): "Expression of CYFFRA21-1 on hepatoma cell induced by TNF-α"MENOPHAGEN MEDICAL REVIEW. 48. 187-190 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuriyama S, Yoshiji H, Masaki T, 12 Others(2^<nd>): "ARCHMEDIA (Tokyo) Induction of hepatoma specific gene expression using the chimera regulatory factor including AFP promoter."Arcmedium Tokyo. 93-99 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurokohchi K, Masaki T, Miyauchi Y, 9 Others.: "Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma."Int J Oncol. 24. 381-387 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurokohchi K, Masaki T, Arima K, 8 Others.: "CD28-negative CD8-positive cytotoxic T lymphocytes mediate Hepatocellular damage in hepatitis C virus infection."J Clin Immunol. 23. 518-527 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobara H, Uchida N, Tsutsui K, 4 Others (4^<th>).: "Abnormal bile flow in patients with achalasia"J Gastroenterol. 38. 327-331 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaki T, Shiratori Y, Rengifo W, 9 Others (6^<th>).: "Cyclins and cyclin-dependent kinases : comparative study of hepatocellular carcinoma versus cirrhosis."Hepatology. 37. 534-543 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaki T, Igarashi K, Tokuda M, 11 Others (13^<th>).: "pp60c-src activation in lung adenocarcinoma."Eur J Cancer. 39. 1447-1455 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iihara N, Kurokohchi K, Tsukamoto T, 5 Others.: "Hypoglycaemia in patients with liver diseases administered levothyroxine"Journal Clin Phar Ther. 28. 355-361 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morishita A, Murota M, Fujita J, 6 Others (5^<th>).: "Autoreactive helper T cells specific for cytokeratin 19 in patients with autoimmune hepatitis."Hepatol Res. 25. 415-422 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murota M, Watanabe S, Fujita J, 10 Others (10^<th>).: "Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis."Hepatol Res. 25. 271-280 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe S, Uchida N, Masaki T, 7 Others (4^<th>).: "Measurement of left portal vein blood flow velocity by doppler sonography in a patient with acute fatty liver of pregnancy."Med Ultrasound. 30. 57-61 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 正木 勉, 黒河内和貴, 舟木利治ほか14名: "肝細胞癌におけるmyristoylated alanine-rich C kinase substrate (MARCKS)の局在とリン酸化"医学と薬学. 49. 2058-210 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mu F, 正木 勉, 室田将之ほか6名(7番目): "TNF-αで誘導される肝細胞癌のアポトーシスにおけるCYFRA 21-1の発現"MINOPHAGEN MEDICAL REVIEW. 48. 187-190 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 栗山茂樹, 吉治仁志, 正木勉ほか12名(5番目): "AFP遺伝子の制御領域を含むキメラ制御因子を用いた肝癌細胞選択的遺伝子発現の誘導.In:臨床応用を目指した消化器分子生物学(小俣政男 編)"アークメディア、東京. 93-99 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida S, Kurokohchi K, Arima K, 7 Others: "Clinical significance of lens culinaris agglutinin-reactive fraction of serum α-fetoprotein in patients with hepatocellular carcinoma"Int J Oncol. 20. 305-309 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakai S, Masaki T, Shiratori Y, 5 Others (6th): "Expression of p57^<KIP2> in hepatocellular carcinoma : relationship between tumor differentiation and patient survival"Int J Oncol. 20. 769-775 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Deguchi A, Arima K, Masaki T, 7 Others (8th): "Enhanced expression of bcl-2 in lymphocytes infiltrating into the liver of patients with primary biliary cirrhosis"Int J Mol Med. 9. 571-577 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe S, Sasahara K, Kinekawa F, 8 Others (6th): "Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer"Oncol Rep. 9. 1063-1068 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurokohchi K, Watanabe S, Masaki T, 8 Others: "Combination therapy of percutaneous ethanol injection and radiofrequency ablation against hepatocellular carcinomas difficult to treat"Int J Oncol. 21. 611-615 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurokohchi K, Watanabe S, Masaki T, 6 Others: "Combined use of percutaneous ethanol injection and radiofrequency ablation for the effective treatment of hepatocellular carcinoma"Int J Oncol. 21. 841-846 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohgi T, Masaki T, Nakal S, 8 Others (9th): "Expression of p33^<ING1>in hepatocellutar carcinoma : relationships to tumor differentiation and cyculin E kinase activity"Scand J Gastroenterol. 37. 1440-1448 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morishita A, Murota M, Fujita J, 6 Others (5th): "Autoreactive helper T cells specific for cytokeratin 19 in patients with autoimmune hepatitis"Hepatol Res. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murota M, Watanabe S, Fujita J, 10 Others (4th): "Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis"Hepatol Res. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobara H, Uchida N, Tsutsui K, 4 Others (4th): "Abnormal bile flow in patients with achalasia"J Gastroenterol. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 黒河内和貴, 栗山茂樹: "肝細胞癌に対するエタノール注入併用ラジオ波凝固療法(PEI-RFA)"遺伝子医学. 6. 645-649 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 黒河内和貴, 栗山茂樹: "抗結核剤リファンピシンのチトクロームP450に与える影響"消化器科. 35. 655-659 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 渡辺精四郎, 黒河内和貴, 森田翼ほか8名: "表在性および肝外突出型肝細胞癌の局所療法について-ラジオ波焼灼療法、マイクロ波凝固療法、エタノール注入療法の比較-"医学と薬学. 47. 232-235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 黒河内和貴, 渡辺精四郎, 栗山茂樹: "エタノール注入併用RFA(PEI-RFA). In:肝癌ラジオ波熱凝固療法の実際「治療のコツと工夫」(國分茂博, 森安史典編)"南江堂、東京. 128-132 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 栗山茂樹, 黒河内和貴: "肝細胞癌に対するエタノール注入ラジオ波凝固療法(PEI-RFA). In:肝疾患診療のコツと落とし穴(井廻道夫編)"中山書店、東京. 108-109 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 栗山茂樹, 辻之上裕久, 美登路昭ほか7名(8番目): "肝癌に対する疫遺伝子治療-多発性肝癌に対するアジュバント療法の可能性-In:再生・増殖・分化と消化器病(小俣政男編)"アークメディア、東京. 150-156 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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