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Combination therapy of apoptosis induction and molecular targeting for hepatocellular carcinoma. -Transgenic mice study-

Research Project

Project/Area Number 15590619
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionGunma University

Principal Investigator

TAKAGI Hitoshi  Gunma University, Department of Medicine and Molecular Science, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20251093)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordshepatocellular carcinoma / EGF receptor / PPAR-ganma / ZD1839 / pioglitazone / rosiglitazone / 肝臓 / EGF recepter / Apoptosis
Research Abstract

Hepatocellular carcinoma is one of the most intractable cancers in the world. Recent progress of molecular targeting enables the specific growth inhibition of cancer cells by the receptor agonist or antagonist. EGF-receptor is abundant in liver cancer cell but the effect of EGF receptor antagonist on hepatoma has not been proved to be effective. On the other hand, we have clarified the three-hepatocellular carcinoma cell lines including PLC/PRF/5, Huh7 and HepG2 were induced apoptosis by PPAR ganma agonist, rosiglitazone and pioglitazone. Furthermore anticancer drugs epirubicine more enhanced the apoptosis than 5FU and CDDP. Then we tested the collaborative effect of EGF-receptor antagonist on the PPAR agonist. As a result, pioglitazone enhanced the effect of ZD1839. The expression of EGF-R assayed by real time PCR was decreased in HepG2 compared with the other two lines but it was not correlated the effect of ZD1839.
Further study using nude mice and TGFalpha transgenic mice bearing liver cancer are on schedule.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (33 results)

All 2005 2004 2003 Other

All Journal Article (25 results) Book (2 results) Publications (6 results)

  • [Journal Article] Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels2005

    • Author(s)
      Sohara N, et al.
    • Journal Title

      Liver Int 25

      Pages: 28-32

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term outcome of interferon alpha induced autoimmune thyroid disorders in chronic hepatitis C.2005

    • Author(s)
      Honda F, et al.
    • Journal Title

      Liver Int 25

      Pages: 242-246

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Efficient formation of vesicular stomatitis virus pseudotypes bearing the negative forms of hepatitis C virus envelope proteins detected after sonication.2005

    • Author(s)
      Tamura K, et al.
    • Journal Title

      Microbes Infect 7

      Pages: 29-40

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels.2005

    • Author(s)
      Sohara N, Takagi H, Kakizaki S, Sato k, Mori M.
    • Journal Title

      Liver Int. 25

      Pages: 28-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Orthodox sometimes generates paradox.2005

    • Author(s)
      Takagi H.
    • Journal Title

      Internal Med. 44

      Pages: 163-164

    • NAID

      10015566954

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term outcome of interferon alpha induced autoimmune thyroid disorders in chronic hepatitis C.2005

    • Author(s)
      Honda F, Kakizaki S, Takagi H, Murakami M, Sohara N, Otsuka T, Abe T, Mori M.
    • Journal Title

      Liver International 25

      Pages: 242-246

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Efficient formation of vesicular stomatitis virus pseudotypes bearing the negative forms of hepatitis C virus envelope proteins detected after sonication.2005

    • Author(s)
      Tamura K, Oue A, Tanaka A, Shimizu N, Takagi H, Kato N, Morikawa A, Hoshino H.
    • Journal Title

      Microbes Infect 7

      Pages: 29-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tretament of the bone metastasis of liver cancer.2005

    • Author(s)
      Takagi H, et al.
    • Journal Title

      Treand in Bone Cancer Research(Nova Publishers)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Short-term complication of retrograde transvenouse obliteration of gastric varices in patients with portal hypertension : effect of obliteration of major portosystemic shunts.2005

    • Author(s)
      Shimoda R, Takagi H, et al.
    • Journal Title

      Abdominal Imaging 29・1(Epub)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin level.2005

    • Author(s)
      Sohara N, Takagi H, et al.
    • Journal Title

      Liver International 25・1

      Pages: 28-32

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metastasis of hepatocellular carcinoma to the maxilla and right ventricle.2004

    • Author(s)
      Arai R, et al.
    • Journal Title

      HepatoGastroenterology 51

      Pages: 1159-1161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatocellular carcinoma developed 12 years after serologic clearance of HBs antigen.2004

    • Author(s)
      Yoshino S, et al.
    • Journal Title

      Acta Hepatologica Jpn. 45

      Pages: 206-210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of small focal nodular hyperplasia involved in portal vein abnormality.2004

    • Author(s)
      Nakajima Y, et al.
    • Journal Title

      Liver Cancer. 10

      Pages: 9-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of hepatocellular carcinoma accompanied with non-alcoholic steatohepatitis.2004

    • Author(s)
      Sakamoto N, et al.
    • Journal Title

      Liver Cancer. 10

      Pages: 126-131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Metastasis of hepatocellular carcinoma to the maxilla and right ventricle.2004

    • Author(s)
      Arai R, Otsuka T, Mori K, Kobayashi R, Tomizawa Y, Sohara N, Kakizaki S, Hirokawa T, Kanda D, Nakayama H, Nakajama T, Takagi H, Mori M.
    • Journal Title

      Hepato Gastroenterol 51

      Pages: 1159-1161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of focal nodular hyperplasia coexisted with hemangioma of the liver.2004

    • Author(s)
      Sato K, et al.
    • Journal Title

      Liver Cancer. 10

      Pages: 198-205

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] HBs抗原陰性化後12年経過し発見された肝細胞癌の1例2004

    • Author(s)
      吉野 聡 他
    • Journal Title

      肝臓 45・4

      Pages: 206-210

    • Related Report
      2004 Annual Research Report
  • [Journal Article] NASHに合併した肝細胞癌の1例2004

    • Author(s)
      坂本直美 他
    • Journal Title

      Liver Cancer 10・2

      Pages: 126-131

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 肝血管腫を合併した肝限局性結節性過形成の1例2004

    • Author(s)
      佐藤 賢 他
    • Journal Title

      Liver Cancer 10・2

      Pages: 198-205

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis.2003

    • Author(s)
      Takagi H, et al.
    • Journal Title

      Int J Vitam Nutr Res 73

      Pages: 411-415

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Primary biliary cirrhosis complicated with sigmoid colonic varices ; the usefulness of computed tomographic angiography2003

    • Author(s)
      Kakizaki s, et al.
    • Journal Title

      Abd Imaging 28

      Pages: 831-834

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis.2003

    • Author(s)
      Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago Y, Konaka K, Kabeya K, Kaneko M, Takayama H, Hashimoto Y, Yamada T, Takahashi H, Shimojo H, Nagamine T, Mori M.
    • Journal Title

      Int J Vitam Nutr Res 73

      Pages: 411-415

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Primary biliary cirrhosis complicated with sigmoid colonic varices ; the usefulness of computed tomographic angiography.2003

    • Author(s)
      Kakizaki S, Ishikawa T, Koyama Y, Yamada H, Kobayashi R, Sohara N, Otsuka T, Takagi H, Mori M.
    • Journal Title

      Abdom Imaging. 28

      Pages: 831-384

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A case of hepatocellular carcinoma complicated with multiple extrahepatic metastases resembling a cholangiocellular carcinoma.2003

    • Author(s)
      Yoshino S, et al.
    • Journal Title

      Liver Cancer. 9

      Pages: 152-159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Primary biliary cirrhosis complicated with sigmoid clonic varices : the usefulness of computed tomographic angiography2003

    • Author(s)
      Kakizaki S, et al.
    • Journal Title

      Abdominal Imaging 28・6

      Pages: 831-834

    • Related Report
      2004 Annual Research Report
  • [Book] Trends in Bone Cancer Research2005

    • Author(s)
      Takagi, et al.
    • Publisher
      Nova Publisher
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Trends in Bone Cancer Research(EV Birch ed.)2005

    • Author(s)
      Takagi H, et al.
    • Total Pages
      350
    • Publisher
      NOVA Publishers
    • Related Report
      2004 Annual Research Report
  • [Publications] Takagi H, et al.: "Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis"Int J Vitam Nutr Res. 73. 411-415 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimoda R, et al.: "CC1(4)-induced acute liver injury in mice is inhibited by hepatocyte growth factor overexpression but stimulated by NK2 overexpression"Toxicol Sci. 3. 294-300 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kakizaki S, et al.: "Alcoholic chronic pancreatitis with simultaneous multiple severe complications-extrahepatic portal obliteration, obstructive jaundice and duodenal stricture"Abdom Imaging. 28. 831-834 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arai R, et al.: "Metastasis of hepatocellular carcinoma to the maxilla and right ventricle"HepatoGastroenterology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kakizaki S, et al.: "Primary biliary cirrhosis complicated with sigmoid colonic varices ; the usefulness of computed tomographic angiography"HepatoGastroenterology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山崎勇一, 他: "アメーバ性肝膿瘍との鑑別が困難であった肝内胆管癌の1剖検例"肝臓. 44. 145-149 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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