Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autocrine stimulation of cells by aberrant synthesis of growth factor may lead to malignant transformation, either as a direct consequence of endogenous factor production or as a first step of a series of successive events. Introduction of the granulocyte/macrophage colony-stimulating factor (GM-CSF) cDNA clone into a vector based on the myeloproliferative sarcoma virus allowed efficient transfer and expression of GM-CSF in factor-dependent myeloid cell lines (FDC-P1 and FDC-P2). Factor-independent growth was acquired when the vector was introduced into the GM-CSF-responsive FDC-P1 cell line but not the multi-CSF-dependent FDC-P2 line. Nonlinear clonability in the absence of exogenous growth factor and growth inhibition by GM-CSF antiserum support a model of autocrine stimulation that requires interaction of factor and receptor at the outer membrane. However, many, but not all, infected FDC-P1 cells acquired subsequently a second mutation that abrogated the requirement of GM-CSF secretion and external interaction. The nature of the second step, which presumably leads to tumorigenicity of these cells, is not well understood, but its frequency could be correlated with the level of GM-CSF released by an individual cell clone.
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PMID:Autocrine stimulation after transfer of the granulocyte/macrophage colony-stimulating factor gene and autonomous growth are distinct but interdependent steps in the oncogenic pathway. 331 8

Ten patients with acute myelomonocytic leukemia (AMML) and inversion of chromosome 16 who had CNS involvement were identified at M.D. Anderson Hospital between January 1972 and December 1984. The nervous system signs and symptoms were evaluated in detail. CT scans, CSF cytologies, and treatment modalities were reviewed. Two patients underwent biopsies of lesions that proved to be granulocytic sarcomas. AMML with inversion 16 carries a much higher (33%) incidence of CNS involvement in the form of leptomeningeal metastasis and/or granulocytic sarcoma than all other acute nonlymphocytic leukemias (5%). The reason for this appears to be related to the chromosomal aberration and not to prolonged survival.
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PMID:Central nervous system complications of a newly recognized subtype of leukemia: AMML with a pericentric inversion of chromosome 16. 347 Jun 29

A case is reported of a 46 year old woman who died after a five month illness characterized by focal neurological signs, evidence of meningeal irritation, and the finding of `blast' cells in the CSF. Immunoglobulin A was consistently absent from her serum and secretions. Necropsy showed extensive infiltration by a reticulum-cell sarcoma of the subarachnoid space, with tumour nodules on several cranial nerves and tumour infiltration of the tuber cinereum. The significance of the association between immunoglobulin A deficiency and neoplasia is discussed.
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PMID:Intracranial reticulum cell sarcoma associated with immunoglobulin A deficiency. 435 31

Granulocyte and macrophage precursors (GM-CFU-C-), which differentiate in vitro without added granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in the hematopoietic organs of mice infected with myeloproliferative sarcoma virus (MPSV). Retransplantation experiments have shown that the GM-CFU-C- are incapable of autonomous growth and depend on a factor present in medium conditioned by MPSV spleen cells (MPSV-CM). This factor is not MPSV and is not produced by spleen cells of noninfected mice. Two classical sources of GM-CSF, lung GM-CSF and GM-CSF contained in the plasma of endotoxin-treated mice, cannot replace the MPSV factor. Inversely, MPSV-CM does not stimulate the growth of retransplanted clusters induced in normal bone marrow with lung GM-CSF, whereas lung GM-CSF does. Two conditioned media containing activity promoting the in vitro proliferation and differentiation of hematopoietic stem cells in the mixed colony assay stimulate the growth of MPSV clusters: one medium was conditioned by pokeweed-mitogen-stimulated spleen cells, the other by the WEHI 3 cell line. The implication of the results in the comprehension of MPSV disease is discussed.
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PMID:Hematopoietic precursors in disease induced by the myeloproliferative sarcoma virus. 630 31

A granulocyte/macrophage colony-stimulating factor (Peak-1 CSF) was partially purified from the medium of a serum-free culture of Yoshida sarcoma cells (Line YSSF-212T). Its elution position in gel-filtration chromatography corresponded to a molecular weight of about 22,000. The factor had an isoelectric point at pH 4.5 and a sedimentation coefficient of 2.3 S. The major part of its activity was not bound by Concanavalin A-Sepharose. Although CSF activity behaved as a single component in the gel-filtration and isoelectrofocussing procedures, subsequently it was resolved into two species by preparative discontinuous polyacrylamide gel-electrophoresis. This resolution indicates microheterogeneity of the CSF molecule. Oxidation with periodate readily inactivated L . P3-cell CSF, but the YSSF-cell CSF was fairly resistant. Moreover, titration with anti-L cell CSF serum showed a definite difference between L . P3-cell CSF and YSSF-cell CSF.
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PMID:Molecular properties of a granulocyte/macrophage colony-stimulating factor obtained from the serum-free culture of Yoshida sarcoma cell Line YSSF-212T. 632 Oct 43

We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) induced sustained increases in cycling of myeloid progenitors in patients with sarcoma. However, decreased proliferation of these cells to a slow- or noncycling state, below pretreatment levels, occurred within 1 to 2 days and maintained for at least 1 week after discontinuation of GM-CSF. To assess possible biological differences in GM-CSF and granulocyte (G)-CSF in such kinetic effects, we evaluated cycling status of marrow progenitors before, during, and after administration of recombinant human G-CSF (5 micrograms/kg/d subcutaneously [s.c.]) to six patients with sarcoma for 8 days. On the last (8th) day of G-CSF treatment, cycling rates of colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and multipotent colony-forming units (CFU-GEMM) were enhanced 1.5- to 1.9-fold, to values of 40 +/- 10% to 58 +/- 5%. In sharp contrast to patients receiving GM-CSF, however, progenitor cells from patients off G-CSF treatment for 2 to 4 days were still rapidly proliferating. These differences in proliferative kinetics may be of use for design of clinical trials to efficaciously utilize these growth factors.
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PMID:Kinetic response of human marrow myeloid progenitor cells to in vivo treatment of patients with granulocyte colony-stimulating factor is different from the response to treatment with granulocyte-macrophage colony-stimulating factor. 750 71

We tested the ability of a constitutively activated erythropoietin receptor [EpoR(R129C)] to alter the growth requirements of primary hematopoietic precursors that terminally differentiate in culture. Two recombinant retroviruses expressing EpoR(R129C), spleen focus-forming virus (SFFVc-EpoR) and myeloproliferative sarcoma virus (MPSVcEpoR), were used to infect fetal liver cells that served as a source of hematopoietic progenitors. Methylcellulose cultures were incubated in the absence of any added growth factors or in combination with selected growth factors. EpoR(R129C) completely abrogated the Epo requirement of erythroid colony-forming units to form erythrocytes after 2-5 days in culture and did not interfere with the differentiation program of these cells. In the absence of added growth factors EpoR(R129C) did not enhance erythroid burst-forming unit development. In contrast to experiments in heterologous cell lines, EpoR(R129C) did not render progenitor cells independent of interleukin 3 or granulocyte/macrophage colony-stimulating factor (GM-CSF). However, when progenitors were cultured with added steel factor, but not with interleukin 3 or GM-CSF, EpoR(R129C) augmented the growth and differentiation of erythroid bursts, mixed erythroid/myeloid, and granulocyte/macrophage (GM) colonies. Furthermore, both viruses were capable of expressing EpoR(R129C) in erythroid, mixed erythroid/myeloid, and GM colonies. Thus an aberrantly expressed and constitutively activated EpoR can stimulate proliferation of some GM progenitors. The ability of EpoR(R129C) to abrogate the Epo requirement of primary hematopoietic cells, but not the requirement for other cytokines, is consistent with the induction of erythroblastosis in vivo.
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PMID:Expression of a constitutively active erythropoietin receptor in primary hematopoietic progenitors abrogates erythropoietin dependence and enhances erythroid colony-forming unit, erythroid burst-forming unit, and granulocyte/macrophage progenitor growth. 767 18

This review is a brief overview of recent advances in biology as well as in potential clinical application of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Biologically active rhGM-CSF is a recombinant human protein expressed in Escherichia coli. GM-CSF is produced by nontransformed (T-lymphocytes, trophoblasts, keratinocytes, osteoblasts, tracheal epithelial cells, renal mesangial cells, endothelial cells, macrophages, fibroblasts, smooth muscle cells) and transformed (murine plasmocytoma, bladder carcinoma HIBY cell line, anaplastic carcinoma of the gall bladder, Yoshida sarcoma cell line, HC3T3-osteoblast cell line) cells. RhGM-CSF increases the number of circulating neutrophils, monocytes and eosinophils and increases chemotactic, microcidal killing and cytotoxic activity of monocytes and granulocytes. The present clinically relevant uses of rhGM-CSF two general areas: restoration of haematopoietic dysfunction by raising cell counts from suppressed to normal levels, and augmentation of host defence against infection. Thus, rhGM-CSF reduces risk of infections. In addition, rhGM-CSF may increase tumour cell destruction in some malignant diseases. RhGM-CSF produces dose-dependent toxicity consisting of myalgic fever, fluid retention and serosal effusions.
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PMID:[Biologic effects and possible therapeutic use of the granulocyte-macrophage colony-stimulating factor. Modern treatment of leukopenia]. 772 60

PIXY321, a stimulator of multipotent colony-forming units (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming units granulocyte/macrophage (CFU-GM) progenitor cell proliferation in vitro, is currently being assessed in phase-I/-II clinical trials. We evaluated kinetics of CFU-GEMM, BFU-E, and CFU-GM proliferation in bone marrow (BM), blood, and granulocyte (CFU-G) and macrophage (CFU-M) progenitors in BM of chemotherapy-naive patients with sarcoma-administered PIXY321 (25 to 1000 micrograms/m2/day subcutaneously for 14 days). BM and/or blood cells from three to four patients at each dosage were assessed before, during, 1 to 2 days, and 7 days following treatment with PIXY321. Cells were pulse-treated in vitro with or without high-specific activity tritiated thymidine (3H-dThr) (to assess the percentage of progenitors in S-phase of cell cycle) and cultured for immature and more mature subsets of CFU-GEMM, BFU-E, CFU-GM, and for CFU-G and CFU-M. Despite heterogeneity in baseline cycling status of progenitors in BM, administration of 125 to 500 micrograms PIXY321 to patients at least doubled (p < 0.001) cycling rates of all BM progenitors. The cycling rates of blood progenitors increased from a slow or non-cycling state to > 38% cells in cycle. Within 1 to 2 days after cessation of PIXY321 infusion, all progenitors were in a slow or noncycling phase below that of many of the pre-BM samples (immature and mature CFU-GM and mature BFU-E) or were back to background levels (CFU-G, CFU-M, CFU-GEMM, and immature BFU-E). These cycling effects were similar to those previously noted for BM CFU-GM and BFU-E in patients on clinical trial with GM-CSF. In contrast, higher dosages of PIXY321, especially 1000 micrograms, increased cycling of BM and blood progenitor cells early during treatment, but cycling rates decreased while patients were still being administered PIXY321; decreased cycling was maintained after cessation of PIXY321. PIXY321 is thus highly active in vivo as a stimulator of multipotential and more lineage-restricted progenitors. The kinetics of progenitor cell proliferation noted in this study highlight differences seen with GM-CSF and G-CSF. The effects described here could be of relevance in design of future clinical trials using PIXY321 as an adjunct treatment in patients undergoing cytoreductive therapy.
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PMID:Effects of in vivo treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma. 789 81

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.
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PMID:The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group. 845 7


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