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pH regulating therapy for hepatocellular carcinoma

Research Project

Project/Area Number 10671199
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SADANAGA Noriaki (1999)  Medical Institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (20304826)

山縣 基維 (1998)  九州大学, 生体防御医学研究所, 講師 (90294975)

Co-Investigator(Kenkyū-buntansha) UTSUNOMIYA Tohru  Medical Institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (30304801)
INOUE Hiroshi  Medical Institute of Bioregulation Kyushu Univ. Assistant Professor, 生体防御医学研究所, 講師 (90203249)
MORI Masaki  Medical Institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (70190999)
定永 倫明  九州大学, 生体防御医学研究所, 助手 (20304826)
田中 真二  九州大学, 生体防御医学研究所, 助手 (30253420)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordshepatocellular carcinoma / intracellular pH (pHi) / tumor specific therapy / anti-tumor therapy / arterioembolization / 腫瘍細胞内PH / 腫瘍内pH / イオンポンプ / 低酸素
Research Abstract

Measurements of intracellular pH (pHi) have shown no significant difference in mean pHi (almost 7.2) between solid tumors and normal tissues. Two membranous ion pumps (N+/H+ antiport and Na+- dependentHCO3-/Cl- exchanger) contribute to the regulation of pHi. This study was planned to clarify the anti-tumor effect of inhibiting agents against the two ion exchangers. Human hepatocellular carcinoma (HCC) was selected as a target tumor since the extracellular pH (pHe) of the tumor has potential to be more acidic by transcatheter arterioembolization (TAE) that is one of the most effective therapy for HCC. Under in-vitro assay using human HCC cell lines, Exposure to EIPA : 5-(N-ethyl-N-isopropyl) amiloride (an inhibitor of N+/H+ antiport) and DIDS : 4,4-diisothiocyanstibene 2,2- disulfonic acid (an inhibitor of Na+-dependentHCO3-/Cl- exchanger) at pHe 6.6 caused 100-fold cell killing compared with pHe 7.2. The cytotoxicity was enhanced about 10-fold under the hypoxic condition. In vivo assay using nude mice bearing human HCC tumors at the left hind leg, the administration of these inhibiting agents at the maximal dose that no animal death occurred led to significant reduction of the tumor size with massive necrotic area. Cells from non-necrotic tissues of the tumor treated with the inhibiting agents were cultured in vitro and showed the tolerance to the pH regulating therapy compared with their wild type cells. The establishment of the HCC models on the liver of small animals was not achieved because of the technical problem, therefore the combination effects of those pH regulating therapy and TAE have not been estimated.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Mori M., et al: "Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse ranscription-polymerase chain reaction in patients with gastrointestiral or breast carcinomas."J Clin Oncol. 16. 128-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M., et al: "Motility relatedprotein 1 (MRP1/CD9) expression in colon cancer."Clin Cancer Res. 4. 681-684 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sadanaga N., et al.: "The heterogeneous expression of MAGE-2 protein; difference between primary lesions and metastatic lymph nodes in gastric carcinoma."Oncol Rep. 6. 975-977 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M., et al: "Lack of DMBT1 expression in oesophageal, gastric and colon cancer."Br. J Cancer. 79. 211-213 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M., et al: "Vascular endothelial growth factor/vascular permeability factor Mrna expression in patients with chronic hepatitis C and hepatocellular carcinoma"Int J Oncol. 14. 353-359 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Utsunomiya T., et al.: "Rare occurrence of colorectal cancer metastasis to the liver infected with hepatitis B or C virus."Am J Surg. 177. 279-281 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M. et al: "Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse ranscription-polymerase chain reaction in patients with gastrointestiral or breast carcinomas."J Clin Oncol. 16. 128-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M. et al: "Motility related protein 1 (MRP1/CD9) expression in colon cancer."Clin Cancer Res. 4. 681-684 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sadanaga N., et al: "The heterogeneous expression of MAGE-3 protein ; difference between primary lesions and metastatic lymph nodes in gastric carcinoma."Oncol Rep. 6. 975-977 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M. et al: "Lack of DMBT1 expression in oesophageal, gastric and colon cancer."Br J Cancer. 79. 211-213 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M. et al: "Vascular endothelial growth factor / vascular permeability factor mRNA expression in patients with chronic hepatitis C and hepatocellular carcinoma."Int J Oncol. 14. 353-359 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Utsunomiya T., et al: "Rare occurence of colorectal cancer metastasis to the liver infected with hepatitis B or C virus."Am J Surg. 177. 279-281 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori M.,et al.: "Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse ranscription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas"J Clin Oncol. 16. 128-132 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori M.,et al.: "Motility related protein 1(MRP1/CD9) expression in colon cancer."Clin Cancer Res. 4. 681-684 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sadanaga N.,et al.: "The heterogeneous expression of MAGE-3 protein; difference between primary lesions and metastatic lymph nodes in gastric carcinoma"Oncol Rep. 6. 975-977 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori M.,et al.: "Lack of DMBT1 expression in esophageal, gastric and colon cancer"Br J Cancer. 79. 211-213 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori M.,et al.: "Vascular endothelial growth factor/vascular permeability factor mRNA expression in patients with chronic hepatitis C and hepatocellular carcinoma"Int J Oncol. 14. 353-359 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Utsunomiya T.,et al.: "Rare occurrence of colorectal cancer metastasis to the liver infected with hepatitis B or C virus"Am J Surg. 177. 279-281 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamagata M, Hasuda K, Stamato T, Tannock: "The contribution oflactic acid to acidification of tumours: studies of varient cells lacking lactate dehydrogenase" British Journal of Cancer. 77巻. 1726-1731 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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