The general purpose of this investigation is to elucidate mechanisms whereby neoplasms alter the biochemical and functional attributes of anatomically distant, apparently uninvolved tissues of the host organism. In response to the subcutaneously transplanted mammary and hepatocellular carcinomas studied, the enzymic composition of the liver becomes partially undifferentiated, and there are striking increases in the gamma-glutamyltranspeptidase and alkaline phosphatase activity of the bone marrow in lung as well as liver. The active principle(s) is of polypeptide nature; its purification and characterization are specific aims of the present project. Additional objectives are: (1) to determine, using normal hepatocytes cultures, whether the diminution of hepatotypic enzymes is attributable to the same tumor-factors as is the rise of gamma-glutamyl-transpeptidase in the bone marrow and liver; (2) to elucidate the underlying mechanisms and consequences of the increased gamma-glutamyltranspeptidase activity of granulocytes; and (3) to examine the role of this enzyme in stimulated growth. (B)

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National Cancer Institute (NCI)
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Biochemistry Study Section (BIO)
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Mount Sinai School of Medicine
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Head, J F; Chahinian, A P; Greengard, O (1991) Enzymic composition and growth rate of human pleural mesothelioma transplants in nude mice. Cancer Biochem Biophys 12:127-36
Bailey, S C; Head, J F; Greengard, O (1989) Neutrophil maturation and hypersegmentation promoted in normal bone marrow by a carcinoma-elaborated protein factor. Am J Hematol 31:159-65
Russo, S A; Greengard, O (1989) gamma-Glutamyltranspeptidase activity in intact leukocytes: flow cytometric analysis and sorting. J Histochem Cytochem 37:323-30
Russo, S A; Tugal, O L; Harris, M B et al. (1989) Mitogen activation of human lymphocytes from normal and acute lymphocytic leukemia (ALL) subjects. Enzyme 41:217-26
Head, J F; Bailey, S C; Bhargava, G et al. (1988) Enhancement of gamma-glutamyl transpeptidase expression in bone marrow cells by colony stimulating factors. Enzyme 40:204-11
Russo, S A; Harris, M B; Greengard, O (1987) Lymphocyte thymidine kinase and treatment response in acute lymphocytic leukemia. Leuk Res 11:149-54
Greengard, O; Head, J F; Chahinian, A P et al. (1987) Enzyme pathology of human mesotheliomas. J Natl Cancer Inst 78:617-22
Russo, S A; Harris, M B; Greengard, O (1987) Diminished lymphocyte and granulocyte gamma-glutamyltranspeptidase activity in acute lymphocytic leukemia and response to chemotherapy. Am J Hematol 26:67-75
Bhargava, G; Head, J F; Bailey, S C et al. (1987) Characterization of a mammary carcinoma elaborated factor stimulating gamma-glutamyltranspeptidase expression in bone marrow cells. Cancer Res 47:6262-6
Greengard, O; Head, J F; Goldberg, S L et al. (1986) Pulmonary carcinoid tumors: enzymic discriminants, growth rate, and early age of inception. Cancer Res 46:2600-5

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