Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human monocytic colony-stimulating factor (hM-CSF) is a glycoprotein which stimulates monocyte production in the bone marrow. It enhances CSF (such as G- and GM-CSF) production of monocytes and megakaryocyte-potentiating activity (Meg-POT). It also enhances tumor-killing activity of monocytes against several leukemic cell lines such as K562, U937, HL60 and Daudi. In the clinical studies, it was shown that hM-CSF infusions accelerated the recovery from neutropenia as well as thrombopenia after anticancer chemotherapy against hematological, gynecologic and urogenital malignancies. Human M-CSF infusions were tolerable without any serious side effects. It is reported that infusions of G-CSF and GM-CSF cause the increment of leukemic cell counts in some cases, but hM-CSF infusions did not increase leukemic cell counts. These results indicate that hM-CSF may be potentially useful for the treatment of myelosuppression induced by cancer chemotherapy in cancer patients.
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PMID:[Human monocytic colony-stimulating factor]. 268 18

Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G-CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.
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PMID:Response patterns of purified myeloma cells to hematopoietic growth factors. 271 8

Malignant prostatic carcinoma, a major cause of cancer mortality in males, most often metastasizes to secondary sites in bone. Frequently, the growth rate of the secondary tumor in bone marrow is considerably greater than that of the slowly growing primary prostatic tumor. We now report that two lines of human prostatic carcinoma cells proliferate in response to conditioned media from unstimulated human, rat, or bovine bone marrow. Nonprostatic tumor cell lines showed little or no growth response to the same medium. The proliferative activity found in bone marrow was not duplicated by any of a variety of purified growth factors including epidermal growth factor (EGF), acidic or basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF) alpha or beta, interleukins 1, 2, 3, 4 or 6, granulocyte (G), macrophage (M) or granulocyte-macrophage (GM) colony stimulating factor (CSF). Whereas a mixture of G-CSF, M-CSF, and IL 3 produced a mitogenic response in the prostatic carcinoma cells, these three factors were not present in our bone marrow samples in sufficient quantities to promote the observed proliferative response. To further identify the cellular source of the proliferative activity present in bone marrow-conditioned medium, we tested conditioned media made from human bone marrow stromal cells. The stromal cell conditioned medium stimulated increased growth of the prostatic carcinoma cells to levels equivalent to those observed with the bone marrow conditioned medium. These results suggest that novel mitogenic factors that are produced by bone marrow stromal cells and remain in the bone marrow cavity may account, in part, for the preferential growth of prostatic metastases in bone.
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PMID:Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. 278 90

The conditioned media of 34 human tumor cell lines were screened for the ability to induce granulocyte-macrophage colonies in vitro in bone marrow cultures, to stimulate proliferation of a murine IL-3 dependent hemopoietic cell line (32D clone 3) and to stimulate thymidine incorporation in suspension cultures of acute myelogenous leukemia cells. Twelve tumor cell lines produced factors that were active in these assays. The conditioned medium of the glioblastoma cell line U87 MG was characterized in detail and found to contain G-CSF and GM-CSF. Cloning and sequencing of the U87 MG G-CSF indicated that it was derived from G-CSF b mRNA, which encodes a protein with a deletion of 3 amino acids at residues 36-38. The gene for G-CSF was mapped to human chromosome 17 band q21, a region involved in translocations frequently found in acute promyelocytic leukemia. G-CSF (U87MG) was able to induce granulocytic differentiation of the total population of a murine IL-3 dependent cell line, 32D clone 3; this effect was antagonized by IL-3. GM-CSF (U87-MG) supported the proliferation without inducing differentiation of two growth factor-dependent leukemic cell lines, TALL 101 and AML-193.
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PMID:Tumor-derived growth factors that support proliferation and differentiation of normal and leukemic hemopoietic cells. 283 Aug 26

In contrast to mature spleen cells and macrophages, which produce colony-stimulating factor (CSF) in response to lipopolysaccharide (LPS), murine bone marrow (BM) cells do not respond to LPS alone. However, when BM cells are treated with LPS and the tumor-promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) simultaneously, they generate significant levels of CSF. The non-tumor-promoter 4-O-methyl-TPA will not replace TPA, and if BM cells from C3H/HeJ mice are employed, no CSF is produced after stimulation with LPS and TPA. Lipid A is as effective as LPS in stimulating BM cells in the presence of TPA, but other mitogens, such as phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM), are ineffective. B-lymphocytes may be the main source of the CSF from BM cells, since BM cells adherent to surfaces coated with goat antimouse immunoglobulin produced CSF in amounts similar to those produced by unseparated BM cells after stimulation with LPS and TPA. Finally, the CSFs produced by BM cells under these experimental conditions were identified as belonging to the GM-CSF and G-CSF subclasses. We interpret these results as suggesting that B cells present in the BM, as opposed to mature spleen cells and macrophages, require at least two signals for CSF production.
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PMID:Synergistic action of lipopolysaccharide and tumor-promoting phorbol esters: two-signal requirement for colony-stimulating factor production by murine bone marrow cells. 294 98

The presence of macrophages both within and around human bladder transitional cell carcinomas xenografted into nude mice has been examined using immunocytochemical staining. Nine different xenograft lines derived from bladder tumors of eight patients were stained for F4/80, MHC II and PGP-1 labelled cells. The results revealed considerable heterogeneity both within and between tumors. All of the tumors generated some macrophage response at the tumor periphery, and this was marked in two instances, UCRU-BL-13, passage 9 and UCRU-BL-17, passage 2. In only two tumors was there substantial penetration of the tumor epithelium by macrophages, though infiltrating Ia+, F4/80+, PGP-1+ cells were sometimes seen spreading along the base of the epithelial sheets. Three of the tumors were characterized by the presence of L3T4+ T lymphocytes at the invasion front. The presence of macrophages or lymphocytes either at the invasion front or within the tumors did not correlate with the pathological grade of the tumors. PGP-1 monoclonal antibodies also stained granulocytes, which were present within the tumor mass in UCRU-BL-15, passage 2, possibly reflecting the production by the tumor of G-CSF. In addition, the PGP-1 antibodies stained some of the bladder tumors cells themselves, and, in some cases, the interstitial structures within the tumors. The significance of this staining is not yet understood. The xenografted tumors will provide a useful model to examine the constraints on tumor therapy using macrophage activating stimuli.
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PMID:Antigenic variation and macrophage infiltration of human bladder tumors xenografted into nude mice. 316 11

We have identified a leukemia-differentiating activity (LDA) in medium conditioned by the LD-1 melanoma, a G-CSF secreting human tumor line. Partially-purified LDA induces HL-60 cells to produce superoxide, become phagocytic, and to develop macrophage-like morphology and surface markers. The LDA markedly suppresses clonal growth in agar of HL-60 cells, and cells of the human myeloid leukemia lines PBL 985 and K562, but does not suppress clonal growth of the B-lymphoblast lines Raji and Daudi. The molecular weight of this material is approx. 40,000 daltons. It can be separated from the bulk of the colony stimulating activity on phenyl sepharose chromatography. The LDA is not neutralized by antibodies to G-CSF, GM-CSF, IFN alpha, IFN gamma, TNF, urokinase, and tissue plasminogen activator, and is not inhibited by preincubation with aprotinin. The LDA in conditioned medium may be different from previously described differentiating factors, and may represent an additional class of human growth regulators.
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PMID:Leukemia-differentiating activity expressed by the human melanoma cell line LD-1. 316 98

A colony-stimulating factor (CSF) has been purified to homogeneity from the serum-free medium conditioned by one of the human CSF-producing tumor cell lines, CHU-2. The molecule was a hydrophobic glycoprotein (mol. wt 19,000, pI = 6.1 as asialo form) with possible O-linked glycosides. Amino acid sequence determination of the molecule gave a single NH2-terminal sequence which had no homology to the corresponding sequence of the other CSFs previously reported. The biological activity was apparently specific for a neutrophilic granulocyte-lineage of both human and mouse bone marrow cells with a specific activity of 2.7 X 10(8) colonies/10(5) non-adherent human bone marrow cells/mg protein. The purified CSF can be regarded as a G-CSF of human origin and will become a useful material for investigation of regulatory mechanisms of human granulopoiesis.
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PMID:Purification and characterization of human granulocyte colony-stimulating factor (G-CSF). 348 49

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was purified from 3 liters of serum-free conditioned medium of the Hodgkin's tumor cell line L428 KSA. The conditioned medium contained a high specific activity of 2.5 X 10(5) units of total colony-stimulating factor per mg protein. Colony-stimulating factor activity was determined by colony formation by human fetal liver cells or mouse bone marrow cells. The latter bioassay discriminated colony-stimulating factor 1, a subclass specific for monocyte/macrophage production, and G-CSF, specific for granulopoiesis, from GM-CSF. The starting material contained predominantly GM-CSF with CSF-1 and G-CSF constituting 10% and 12%, respectively, of the total activity. A seven-stage purification scheme was employed. The first stage involved concentration by batch chromatography on calcium phosphate gel. Subsequent stages involved gel filtration on Ultrogel AcA44, affinity chromatography on concanavalin A-Sepharose, batch chromatography on calcium phosphate gel and high-performance liquid chromatography on C1 reversed-phase (TSK TMS-250), gel permeation and C8 reversed-phase columns. The purified material showed a single disperse band, having an Mr of 30,000, by silver staining on sodium dodecyl sulfate polyacrylamide gel electrophoresis. An amino-terminal sequence of 20 amino acids was determined in a gas-phase sequencer with 500 ng of purified material. The sequence was identical to that predicted from the cDNA sequence. It was active on human fetal liver cells with half-maximum colony formation at 1 X 10(-12) M, but was not active on mouse bone narrow cells.
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PMID:Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. 353 1

The effects of an autologous transplanted mammary tumor (RIII-T3) on hemopoiesis in RIII mice are described. Tumor-bearing animals died 30 to 40 days after inoculation and displayed splenomegaly, extreme neutrophilia, and moderately increased monocyte levels in the spleen, peripheral blood, and bone marrow. The precursors of neutrophils and monocytes, granulocyte/macrophage colony-forming cells (GM-CFC) were elevated in the spleen, bone marrow, and peripheral blood. RIII-T3-conditioned medium stimulated bone marrow GM-CFC and caused the myelomonocytic cell line, WEHI-3B, to differentiate in vitro. The conditioned medium did not stimulate erythroid, megakaryocyte, or eosinophil colony formation. When conditioned medium was fractionated, two peaks of activity corresponding to GM-CSF and G-CSF were observed, suggesting that the extreme neutrophilia observed in tumor-bearing animals may result from chronic exposure of the hemopoietic system to these hemopoietic hormones.
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PMID:Effects of a murine mammary tumor on in vivo and in vitro hemopoiesis. 387 4


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