Enzyme expression and morphological maturation of myeloid cells by cancer-derived polypeptide factors.
Item
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Title
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Enzyme expression and morphological maturation of myeloid cells by cancer-derived polypeptide factors.
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Identifier
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AAI9009715
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identifier
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9009715
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Creator
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Bailey, Steven Clark.
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Contributor
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Adviser: Olga Greengard
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Date
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1989
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, General
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Abstract
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Investigations were carried out on mammary carcinoma 5A (MC) with the objective of elucidating mechanisms underlying alterations in bone marrow function caused by non-hematopoietic malignancies. The progressive elevations in {dollar}\tau{dollar}-glutamyltanspeptidase (GGT) and alkaline phosphatase (AP) concentrations resulting from subcutaneous MC transplantation to rats were found to be reproducible in normal bone marrow cells by incubation with serum from MC hosts (MC-serum). A bioassay system in vitro could thus be established for the first time to examine the nature and provenance of blood-borne factors hypothesized to be responsible for enzymic abnormalities in "uninvolved" tissues of cancer hosts. The GGT and AP inducing factor(s), a heat-stable, {dollar}\alpha{dollar}-chymotrypsin sensitive, 60,000 molecular weight polypeptide, was found to be also elaborated by the carcinoma in vitro, and preparations with 200,000 times higher specific activity than in the MC-serum were obtained from the MC-conditioned medium (MC-CM).;Nuclear hypersegmentation, found in 30-50% of the mature blood granulocytes of MC-bearing rats, was also evoked in bone marrow from normal animals: after 48 hr incubation with MC serum or MC-CM preparations (but not with colony stimulation factors, CSFs now shown to induce both GGT and AP expression) half the mature neutrophils were hypersegmented. There were also decreases in the % of myeloblasts; promyelocytes, myelocytes, and metamyelocytes, with an increase in that of mature neutrophils. MC-CM exerted differentiational effects and growth inhibition in the WEHI-3 mouse myelomonocytic cell line and in primary culture of rat Shay leukemia cell, increased 40-fold the GGT content of the Shay cells, and stimulated AP expressions in leukemic cells from human subjects.;These investigations (1) demonstrate the elaboration by the mammary carcinoma of a polypeptide promoting the maturation of normal and leukemic myeloid cells, (2) describe the first enzymic response of bone marrow to CSFs, (3) introduce a new experimental system for the study of biochemical and morphological granulocyte maturation, and (4) provide evidence that neutrophil hypersegmentation can arise from the action of tumor-elaborated polypeptides on normal non-mitotic myeloid cells in the bone marrow.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
