Progressive tumor growth results in increased wasting of body protein and fat stores. Whether this is due to relative starvation or abnormalities of host metabolism induced by the presence of a neoplasm or some combination of both is poorly understood. The liver occupies a central position among the tissues that regulate host metabolism. In this proposal attention is focused upon glucose and amino acid metabolism in the tumor influenced liver, in an effort to describe the etiology of dissolution of the cancer bearing host. The model chosen for this investigation is isolated, fresh, intact hepatocyte cells from adult male Fischer (F344) rats. Using the isolated hepatocytes from tumor bearing and control animals we propose a systematic examination of the regulation of glucose and amino acid metabolism in the cancer bearing host. Studies will be conducted with hepatocytes from control rats and rats bearing a transplantable methylcholanthrene-induced sarcoma, to investigate (a) the hormonal sensitivity and substrate control of glucose production, oxidation and storage, of protein (cellular and export) synthesis and breakdown (b) oxygen consumption in the presence or absence of exogenous substrate(s) with or without hormones (c) alanine transport and (d) the effect of specific mediators, if any, present in the serum of tumor-bearing rats, or supernatant of tumor cells grown in tissue culture. On the basis of this investigation, a mechanism will be proposed at the cellular level for the observed alterations in glucose and protein metabolism and their interrelationships in the host tissue due to the influence of a distant tumor. Better understanding of the basic mechanisms that alter the host-tumor interrelationships will permit the design of more efficient nutritional support modalities in cancer patients and would help to determine the optimal substrate mixture that may be utilized by the cancer-bearing host.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038858-03
Application #
3177235
Study Section
Pathology B Study Section (PTHB)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Memorial Hospital for Cancer & Allied Di
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021
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Posner, M C; Burt, M E; Stone, M D et al. (1990) A model of reversible obstructive jaundice in the rat. J Surg Res 48:204-10

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