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Alterations in intracellular metabolism and apoptosis in cancer cachexia Difference between tumor-bearing hosts and cancer cells

Research Project

Project/Area Number 08457309
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

NOGUCHI Yoshikazu  Yokohama City University University Hospital Assistant Professor, 医学部・附属病院, 講師 (50180724)

Co-Investigator(Kenkyū-buntansha) SATOH Shinobu  Yokohama City University University Hospital Assistant Professor, 医学部・附属病院, 講師 (80244424)
ITOH Takaaki  Yokohama City University School of Medicine Associate Professor, 医学部, 助教授 (70168392)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordscancer cachexia / apoptosis / insulin resistance / glucose transporters / MKN28 / STSA
Research Abstract

In this research over the past two years, following results were obtained.
(1) Insulin resistance observed in cancer patients was associated significantly increased tissue TNF alpha mRNA levels. Both were negatively correlated. Although insulin resistance in diabetic patients were documented to be induced by tissue TNF alpha, insulin resistance in the tumor-bearing state may be induced in the similar fashion by TNF alpha. This would be the first documentation of the mechanisms of insulin resistance in the human tumor-bearing. Methodological accuracy is under further examination by using competitive RT-PCR.
(2) Gastric cancer cell lines (MKN28,45, STKM-1, STSA) were documented to have Glut1 mRNA as well as Glut4 mRNA.Glucose transport assay documented basic transport observed in all cell lines and significant stimulation by insulin in the cells showing high concentration of Glut4 protein. Whether basic transport is induced by glucose transporters or not is under further examination.
(3) Im … More munohistochemistry of the gastric cancer specimens obtained from 70 gastric cancer patients demonstrated significant correlation of Glutl expression and tumor invasiveness in the gastric wall and vessel invasions. Expression of Glut1 was correlated with other Glut expressions except Glut4. Expression of Glut protein and Ki67 or apoptosis was not correlated.
Glut1 mRNA was rarely observed in normal gastric mucosa, while all RNA samples obtained from 25 gastric cancer specimens demonstrated Glut1 mRNA.
In parallel examination of colon cancer specimens, we found that expression of Glut was not observed in either normal colon mucosa or hyperplastic polyp, however, adenoma or cancer tissue expressed Glut more frequently.
(4) Glut 4mRNA in the gastric cancer specimens were not demonstrated by single pair of primers as in the skeletal muscle. Considering presence of some significant abnormalities in sequence, several attempts were made so far. However, definite results are not obtained yet.
Thus in this research project, several significant findings were obtained. A part of mechanisms of insulin resistance in the tumor-bearing state in humans is dissected and a possible mediator was clarified. Gastric cancer as well as colon cancer obtains the ability to transport glucose into cancer cells by newly obtaining Glut1 mRNA,whose protein expression is positively correlated with tumor invasiveness, but not with apoptosis or Ki67. Glut4 mRNA in the tumor tissue may be not of normal sequence as seen in the skeletal muscle.
Further dissection toward the mechanisms of insulin resistance and to clarify the difference between tumor and tumor-bearing hosts especially in regards to glucose metabolism will be continued. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yoshikawa T: "Insulin resisnance and the alterations of GLUT4 in adipose cells from cachectic tumor-bearing rats" Journal of Parenteral and Enternal Nutrition. 21. 1-3 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T: "Cellular and molecular mechanisms of insulin resistance in adipose cells from tumor-bearing rats" Surgical Forum. 7-8 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nomura K: "Plasma Interleukin-6 is not a mediator of changes in lipoprotein lipase activity in cancer patients" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y: "Tumor-associated metabolic alterations in patients with gastric and esophageal cancer (changes in lipoprotein lipase activity in cancer patients)" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T: "Relationships between insulin resistance and glucose oxidation,glucose storage,and fat oxidation in patients with cancer" Journal of Parenteral and Enternal Nutrition. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi C.: "Alteration in immunoexpressionof glucose transporter 2 in liver of tumor-bearing rats" Int.J Exp Pathol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y: "Surgical Oncology : Role of videolaparoscopy in interventional videoendosurgery in cancer" Younes RN and Cohen V ed. (RG Landes Biomedical Publishers)(in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y: "Nutrition in cancer in pathophysiological basis of modern surgery" Birolini D and Younes R ed.(inpress),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T.: "Insulin resistance and the alterations of GLUT4 in adipose cells from cachectic rats" Journal of Parenteral and Enternal Nutrition. 21. 1-3 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T.: "Cellular and molecular mechanisms of insulin resistance in adipose cells from tumor-bearing rats" Surgical Forum. 7-8 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nomura K.: "Plasma Interleukin-6 is not a mediator of changes in lipoprotein lipase activity in cancer patients" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y.: "Tumor-associated metabolic alterations in patients with gastric and esophageal cancer (changes in lipoprotein lipase activity in cancer patients)" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T.: "Relationships between insulin resistance and glucose oxidation, glucose storage, and fat oxidation in patients with cancer" Journal of Parenteral and Enternal Nutrition. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi C.: "Alteration in immunoexpression of glucose transporter 2 in liver of tumor-bearing rats" Int J Exp Pathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y.: "Surgical Oncology : Role of videolaparoscopy in interventional videoendosurgery in cancer Younes RN,Cohen V.ed." RG Landes Biomedical Publishers. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi Y.: "Nutrition in cancer in pathophysiological basis of modern surgery Birolini D,Younes R.ed." (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa T: "Insulin resistance and the alterations of GLUT4 in adipose cells from cachectic tumor-bearing rats" Journal of Parenteral and Enternal Nutrition. 21. 1-3 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshikawa T: "Celluiar and molecular mechanisms of insulin resistance in adipose cells from tumor-bearing rats" Surgical Forum. 7-8 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nomura K: "Plasma Interleukin-6 is not a mediator of changes in lipoprotein lipase activity in cancer patients" Hepato-Gastroenterology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Noguchi Y: "Tumor-associated metabolic alterations in patients with gastric and esophageal cancer(changes in lipoprotein lipase activity in cancer patients)" Hepato-Gastroenterology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshikawa T: "Relationships between insulin resistance and glucose oxidation,glucose storage,and fat oxidation in patients with cancer" Journal of Parenteral and Enternal Nutrition. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Doi C: "Alteration in immunoexpression of glucose transporter2 in liver of tumor-bearing rats" Int.J.Exp pathol. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Noguchi Y.: "Surgical Oncology:Role of videolaparoscopy in interventional videoendosurgery in cancer" Younes RN and Cohen V ed(RG Landes Biomedical publishers),

    • Related Report
      1997 Annual Research Report
  • [Publications] Noguchi Y: "Nutrition in cancer in pathophysiological basis of modern surgery" Birolini D and Younes R ed.(in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Noguchi Y: "Role of insulin resistance in decreasing lipoprotein lipase activity in tumor-bearing rats" Surgery Today. 26. 271-275 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Noguchi Y: "Are cytokines possible mediators of cancer cachexia?" Surgery Today. 26. 467-475 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Noguchi Y: "The possible role of TNF-α and Interleukin-2 in inducing tumor-associated metabolic alterations." Surgery Today. 26. 36-41 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sato Y: "Immunohistochemical localozation of facilitated-diffusion glucose transporters in rat pancreatic islet." Tissue & Cell. 28. 637-643 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nomura K: "The stimulation of decreased lipoprotein lipase activity in the tumor-bearing state by the anti-hyperlipidemic drug Bezafibrate" Surgery Today. 26. 89-94 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshikawa T: "Alimentary hyperglucemia in patients with subtotal gastrectomy is associated with decreased insulin secretion but not with insulin resistance" International Surgery. 81. 32-35 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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