Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of a murine mammary carcinoma (CE maca) into mice induces marked granulocytosis and hypercalcemia secondary to excessive bone resorption. Such responses are not induced by another murine mammary carcinoma Bc66. In order to understand the mechanisms of these unique phenomena, we analyzed mRNA of tumor cells for expression of murine granulopoietic growth factors and studied interactions of tumor-derived factors using antiserum to a growth factor in vitro and in vivo. The Northern blot analysis of CE tumor clones revealed the expression of granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), but no other CSF genes, while the Bc66 clone expressed only M-CSF. The G-CSF and M-CSF gene expression in CE tumor clones was accompanied by secretion of these proteins in culture. The granulocyte stimulating activity of CE tumor-derived G-CSF or recombinant human G-CSF was markedly enhanced by purified M-CSF in vitro. Significant but variable neutrophilia was observed in mice inoculated with CE tumor clones. Anti-M-CSF treatment of CE tumor-bearing mice significantly reduced neutrophilia, but did not affect hypercalcemia. These studies document that G-CSF and M-CSF are produced constitutively from the CE maca, and G-CSF is likely responsible for granulocytosis induced by this tumor. G-CSF and M-CSF function synergistically in granulocyte stimulation in vitro and this synergism may also play a role in marked granulocytosis of tumor-bearing animals, providing further evidence of the effect of CSFs in vivo.
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PMID:Mechanisms of tumor-induced neutrophilia: constitutive production of colony-stimulating factors and their synergistic actions. 247 93

Patients with refractory carcinoma were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by intravenous (IV) infusion. During the period of treatment, studies of polymorphonuclear leukocyte superoxide (O2-) release in response to formylmethionylleucylphenylalanine (fMLP) and phorbol myristate acetate (PMA) and studies of chemotaxis in response to fMLP and C5a were performed. We observed that patients receiving rhGM-CSF in vivo exhibited primed O2- release after stimulation both with fMLP and PMA. Chemotaxis, however, was not enhanced by the treatment. These data suggest that host defenses may be enhanced by this treatment and that rhGM-CSF may be a useful therapeutic adjunct in compromised patients.
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PMID:The effect of recombinant human granulocyte macrophage colony-stimulating factor on neutrophil activation in patients with refractory carcinoma. 253 16

Marrow progenitor cells from 14 myelodysplastic (MDS) patients and 17 normal donors were assayed in semisolid cultures supplemented with increasing doses of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or medium conditioned by 5637 bladder carcinoma cells (5637CM). At doses of supplements shown to be optimal for colony formation in cultures of normal marrow, myeloid (day 14) colony numbers were subnormal in 10 of 14 MDS marrows cultured in 5637CM and in 8 of 14 cultures containing rhGM-CSF (2.5 ng/ml). However, a high dose of rhGM-CSF (20 ng/ml) raised myeloid colony numbers in cultures of many MDS marrows, so that 9 of 14 now yielded colonies within the normal range; increased levels of 5637CM failed to do this. Erythroid colony growth was poor in 13 of 14 MDS marrow cultures supplemented with erythropoietin in addition to 5637CM or rhGM-CSF. High concentrations of rhGM-CSF did not increase erythroid growth. These data suggest that myeloid progenitors from the MDS clone may have a decreased responsiveness to hemopoietins which can be overcome at high concentrations of growth factors.
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PMID:In vitro growth of myeloid and erythroid progenitor cells from myelodysplastic patients in response to recombinant human granulocyte-macrophage colony-stimulating factor. 264 75

A synergistic factor that is produced by the human bladder carcinoma cell line 5637 (SF-1) stimulates primitive bone marrow progenitor cells, termed high proliferative-potential colony-forming cells (HPP-CFC), in the presence of an optimal dose of macrophage colony stimulating factor (CSF-1). Recent reports have demonstrated that interleukin-1 alpha (IL-1) is identical to hemopoietin 1 and have suggested that IL-1 is the synergistic factor present in 5637 conditioned medium (cm). We have compared the ability of recombinant human IL-1 alpha and partially purified preparations of SF-1 to synergize with optimal doses of CSF-1 to stimulate HPP-CFC. In all experiments performed the numbers of HPP-CFC colonies formed with IL-1 were significantly less than with SF-1. Replating experiments demonstrated that SF-1 plus CSF-1 generated HPP-CFC (responsive to IL-3 plus CSF-1); however, IL-1 plus CSF-1 resulted in no generation of HPP-CFC. Multiple factor combinations of IL-1 and SF-1 with G-CSF, GM-CSF, and CSF-1 also resulted in less HPP-CFC colony formation in cultures containing IL-1 compared with SF-1. Incubation of SF-1 with an antibody to IL-6 had no effect on HPP-CFC colony formation and IL-6 did not synergize with IL-1 plus CSF-1 or SF-1 plus CSF-1. These data suggest the presence of a factor in 5637 cm, which is distinct from G-CSF, GM-CSF, and IL-6, which synergizes with IL-1 to produce the SF-1 effect.
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PMID:Studies on the myeloid synergistic factor from 5637: comparison with interleukin-1 alpha. 264 51

The effect of human recombinant GM-colony-stimulating factor (CSF) was evaluated in ten patients with refractory metastatic carcinoma. Initially they received an intravenous (IV) bolus injection of 5 or 25 micrograms/m2 for assessment of acute responses. Six days later, continuous IV infusions of 100 or 500 micrograms/m2 were initiated for a 14-day treatment course. All patients developed profound leukopenia within five to 30 minutes of the bolus injection. This appeared to result from increased expression of an adhesion-promoting glycoprotein (GP) on neutrophils and monocytes as judged by increased reactivity to the Mo1 monoclonal antibody (MoAb). Leukocyte counts returned to normal levels within two hours as cells were released from marrow stores. With the continuous infusion, leukocyte counts increased by 24 hours; peak values of 22,960 and 75.900/microL were achieved after ten to 14 days of treatment with the two dose levels of GM-CSF. This leukocytosis was due to an increase in virtually all cell types. At the high dose level, there was a striking increase in neutrophils (49,400/microL) and eosinophils (20,905/microL) with a sixfold increase in monocytes and two- to threefold increase in lymphocytes. Leukocyte counts declined promptly after cessation of the infusion but remained above baseline for as long as 2 weeks in some patients. These results suggest that GM-CSF may be useful as an adjuvant therapy by stimulating myelopoiesis in cancer patients.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in patients with refractory metastatic carcinoma. 266 36

Human peripheral blood mononuclear cells (lymphocytes and monocytes) were preincubated for 0-24 h with human recombinant granulocyte-monocyte-colony-stimulating factor (GM-CSF) and used as effector cells in an 18 h antibody-dependent cellular cytotoxicity (ADCC) assay with SW948 (a human colorectal carcinoma cell line) as target cells and mAb 17-1A. A significant increase in the lytic capability was noted after 0.5-2 h of preactivation while longer preincubation times did not significantly increase the lytic potential. GM-CSF at 0.01 microgram/ml induced the best tumor cell lysis while higher concentrations were inhibitory. GM-CSF pretreatment induced a statistically significant increase in the lytic capacity of both monocytes and lymphocytes in ADCC as well as in the spontaneous cytotoxicity.
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PMID:Granulocyte-monocyte-colony-stimulating factor augments the cytotoxic capacity of lymphocytes and monocytes in antibody-dependent cellular cytotoxicity. 266 35

We investigated the interaction between GM-CSF and its receptor on human granulocytes and on several human tumor cell lines. Specific high-affinity binding for GM-CSF was characterized by Scatchard plot analysis. The specific radioactivity of the 125I-labeled derivative of rH. GM-CSF was determined by self-displacement analysis and calculated to be 30 microCi/micrograms. The maximum concentration of binding sites (B max) in granulocytes was 40 fmol/mg protein (2,200 molecules GM-CSF bound/cell) and the dissociation constant (KD) was 0.42 nM. No binding sites for GM-CSF were found in two lung cancer cell lines, SCLC-16HV and NCI-N417 or in the urinary bladder carcinoma cell line 5637, whereas the promyelocytic leukemia cell line HL60 was positive for GM-CSF binding. Time course experiments showed maximum binding of GM-CSF in granulocytes after an incubation period of 60 min and a decrease in binding after an incubation period of 2 h. In parallel, we found a maximum biological signal when granulocytes were preincubated for 90 min with GM-CSF, and a decrease after an incubation time of 120 min. Preincubation of the cells with rH. GM-CSF induced an enhancement of the production of activated oxygen species by the cells in response to PMA.
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PMID:Granulocyte-macrophage colony-stimulating factor binding sites and oxidative metabolism in human granulocytes. 268 55

An autopsy case of HTLV-I associated myelopathy (HAM) was reported. The patient was a 55-year-old man from Kagoshima, who had no history of blood transfusion. He was admitted to our hospital because of muscle weakness of legs and dysuria, which having since one month ago. On admission, he was able to walk with assistance, but his legs were severely spastic, and Babinski's sign was positive bilaterally. Superficial sensation was normal, but vibration sense was mildly decreased in his legs. CSF showed mild mononuclear pleocytosis with elevated protein. Myelogram and CT were normal. Serum and CSF antibodies to HTLV-I were positive at titers of X4,096 and X128, respectively by immunofluorescent assay, and specific IgG bands (p19, p24, p28 and p53 in serum and p19, p24, p53 in CSF) were detected by western blot analysis. His paraparesis continued to worsen. He became bed-ridden within 2 months. He was received corticosteroid medication. He regained the ability to walk with assistance, and continued taking corticosteroid. In July 4, 1986, macrohematuria appeared and inoperable transitional cell carcinoma of rt. kidney was found by further examination. Chemotherapy were not effective against the carcinoma and he died on July 21, 1987. Neuropathological findings were summarized as follows: cerebral hemisphere was normal except for mild cellular infiltration in the leptomeninges; lesions consisted in unilateral pyramidal tract of pons & medulla and in partial anterior, posterior and lateral columns of the spinal cord; demyelination with axonal degeneration, marked gliosis, numerous lipid-laden macrophages and mild perivascular infiltration of mononuclear cells in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of HTLV-I associated myelopathy (HAM)]. 275 64

Regulatory mechanisms affecting the growth of leukemic cells are attractive targets for new treatments. The blast cells of acute myeloblastic leukemia (AML) may be considered as a lineage; a minority are stem cells capable of both self-renewal and determination followed by terminal divisions ending in proliferatively inert cells retaining blast morphology. Two cell culture methods are available for the study of blasts. The first is a clonogenic assay. Blast stem cells form colonies in methylcellulose, containing proliferatively inert blast cells, together with a small number of new progenitors. Growth factor(s) are usually required. These may be supplied by media conditioned by the continuous bladder carcinoma cell line HTB9 (HTB9-CM). The recombinant growth factors GM-CSF and G-CSF are also active, and in many instances are synergistic. Blast progenitors will also grow in suspension, provided the cell density is high and growth factors are provided. In these cultures, blast progenitors increase in number, reflecting their self-renewal capacity. Evidence is also available that specific genes may be involved in the self-renewal process. Thus, three forms of growth regulation, similar to those encoded by proto-oncogenes, can be shown to be operative in AML blast cell cultures.
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PMID:Genetically determined regulators acting on the blast cells of acute myeloblastic leukemia. 282 86

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.
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PMID:The release of bombesin-like peptides from small cell lung cancer cells. 285 97


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