1993 Fiscal Year Final Research Report Summary
Metabolic Alterations associated with Cancer Cachexia An analysis of mechanisms from microstructure and molecular biology-
| Project/Area Number |
03670593
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Yokohama City University |
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Principal Investigator |
NOGUCHI Yoshikazu Yokohama City University : School of Medicine : Assistant Professor, 医学部, 講師 (50180724)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Akihiko Yokohama City University : School of Medicine : Professor, 医学部, 教授 (20045975)
ITO Takaaki Yokohama City University : School of Medicine : Assistant Professor, 医学部, 講師 (70168392)
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| Project Period (FY) |
1991 – 1993
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| Keywords | insulin resistance / lipoprotein lipase / phosphoenolpyruvate carboxykinase / TNF alpha / Interleukin-2 / Bezafibrate |
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| Research Abstract |
(1) Effects of insulin and glucose concentrations on phosphoenolpyruvate carboxykinase(PEPck), a key regulatory enzyme for gluconeogenesis, and lipoprotein lipase(LPL), a pacemaker enzyme for triglycerideclearance from the circulation, were investigated.
Decreased LPL activity in the tumor-bearing state was not stimulated either by high physiologic or hyperphysiologic insulin concentrations, which may suggest insulin sensitivity as well as insulin responsiveness are both decreased in the tumor-bearing state. Part of these findings were published in the J Jpn Surg Soc as a rapid communication 94 : 131,1994.
(2) Study on the mediators of cancer cachexia
In vitro injection of TNF alpha or Interleukin-2 induced a variety of alterations in pace maker enzymes. However their changes were different from those induced by the tumor effects or the changes observed ion the tumor-bearing state, these findings would suggest that TNFalpha or IL-2 are not direct mediators of cancer cachexia, although more complex reaction through cytokine cascade can not be ruled out. Further investigation in this field in still going on.
(Part of the findings were published in Surgery Today 23 : 621-625,1993)
(3) An attempt to reverse tumor-induced metabolic alterations by Bezafibrate
Daily injection of Bezafibrate into MCA sarcoma-bearing Fisher344 rats resulted in marked increase of LPL activity in the cachectic state. There is some possibility that this kind of therapy can be applied to the treatment of cancer cachexia.(Published as a rapid communication in J Jpn Surg Soc 93 : 759,1993.
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