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)

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
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PMID:[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. 163 23

We have tried to demonstrate and identify colony-stimulating factor (CSF) activity in the plasma, pleural fluid, ascites or culture supernatant of tumor cells in 11 patients with malignant tumors associated with unexplained persistent leukocytosis. The specimens were treated with anti-granulocyte (G)-CSF or anti-granulocyte/macrophage (GM)-CSF monoclonal antibodies, then added to GM-progenitor (CFU-GM) cultures without exogenous CSFs. In all patients, untreated specimens generated CFU-GM-derived colonies, and colony formation was clearly inhibited by only one of the two antibodies, indicating the presence of either G-CSF or GM-CSF in the specimens. Furthermore, we measured the concentrations of G-CSF or GM-CSF in the specimens using an enzyme-linked immunosorbent assay, and confirmed the results by CFU-GM assay. Two patients were shown to have GM-CSF-producing tumors, while the other patients were G-CSF-producing. These assays are useful in identifying CSF activity in patients with CSF-producing tumors.
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PMID:Identification of colony-stimulating factor activity in patients with malignant tumors associated with excessive leukocytosis. 166 58

In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.
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PMID:Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor. 168 38

Granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF enhance phagocyte survival and function and are produced by fibroblasts and endothelial cells after induction by inflammatory mediators such as IL-1. Our ability to detect G-CSF and GM-CSF activity in the conditioned medium of the human astroglial tumor cell line, U87MG, and molecularly clone the cDNA for G-CSF from a U87MG cDNA library raised the possibility that astroglial cells are capable of G-CSF and GM-CSF production within the central nervous system; if so, the production of these CSF by astroglial cells may be inducible by IL-1. We examined the effects of IL-1 alpha and IL-1 beta on the production of G-CSF and GM-CSF by U87MG and U373MG, another astroglial tumor cell line that does not constitutively produce CSF. We demonstrate that both U87MG and U373MG can be induced to produce G-CSF and GM-CSF by exposure to IL-1 alpha and IL-1 beta. This response, measured by accumulation of increased CSF mRNA, is rapid, sensitive and due to the enhanced stability of CSF message following IL-1 exposure. The implications of these findings to the immunopathogenesis of central nervous system infections are discussed.
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PMID:Monokine modulation of human astroglial cell production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. I. Effects of IL-1 alpha and IL-beta. 169 Feb 40

There has been increasing interest in autologous peripheral stem cell transplantation (APSCT) in the treatment of malignant disease because it is a convenient method and may have a lower risk of tumor cell contamination than autologous bone marrow transplantation (ABMT). Recently, it is reported that the number of peripheral blood stem cells increase during recovery phase of hemopoiesis after chemotherapy, and further increase is reported on the case of treatment with G-CSF. But influences of G-CSF to the residual malignant cells is still unknown. In this report, we have used clonal cell culture and kappa-lambda imaging (KLI) analysis to trace the level of CFU-GM, BFU-E, and malignant B-cell population (mBp) in peripheral blood before and after treatment with rhG-CSF. The peak level of CFU-GM in peripheral blood was a 2-fold increased when rhG-CSF was administered, and this peak appeared 5-7 days earlier than that in the case without rhG-CSF. MBp was detected in bone marrow, however, no mBp was detected before and after treatment with rhG-CSF in peripheral blood. These findings suggest that APSCT is acceptable for this patient in case of minimal bone marrow involvement. And KLI analysis might be an effective method for detecting residual malignant cells in bone marrow and peripheral blood.
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PMID:[The basic study of autologous peripheral stem cell transplantation--useful application of KLI and G-CSF]. 169 4

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells results in significant tumor regression in patients with advanced cancer. We have investigated the kinetics of circulating erythroid (BFU-E) and granulocytic-macrophage (CFU-GM) progenitors after IL-2 therapy in 11 cancer patients, mainly affected by metastatic melanoma and renal cell carcinoma. Administration of IL-2 from day 1 through day 5 constantly induced a dramatic decrease of the number of circulating BFU-E and CFU-GM, which then showed a striking rebound (up to values fourfold and sevenfold higher, respectively, than the pretherapy levels) on discontinuation of IL-2, ie, from day 5 through day 10. A similar kinetic pattern was observed during and after the second cycle of IL-2 administration. 3[H]-thymidine killing experiments showed that the cycling activity of the progenitors was virtually unmodified in the rebound phases. To explore the mechanism(s) underlying this kinetic pattern, we have analyzed the plasma concentration of several hematopoietic growth factors, including IL-1 beta, IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and erythropoietin (Ep). No modifications in the levels of IL-3, GM-CSF, or IL-1 beta were observed, whereas a pronounced increase of IL-6 and G-CSF concentration was monitored, starting at day 3 and peaking at day 5 of treatment (a parallel, but modest, increase of Ep level was also observed). The elevation of IL-6 and G-CSF concentration is directly correlated with and may, at least in part, underlie the subsequent rebound of circulating hematopoietic progenitors. Furthermore, the increase in IL-4 level observed at day 10 of therapy may mediate the eosinophilia gradually starting at this stage of treatment.
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PMID:Adoptive immunotherapy with high-dose interleukin-2: kinetics of circulating progenitors correlate with interleukin-6, granulocyte colony-stimulating factor level. 170 62

Fc receptors are important effector molecules of neutrophilic granulocytes (polymorphonuclear neutrophils [PMN]), connecting phagocytic cells and the specific immune response. Neutrophils from healthy donors express the low-affinity receptors for IgG Fc gamma RII (CD32) and Fc gamma RIII (CD16), but not the high-affinity receptor Fc gamma RI (CD64). The latter has been found on neutrophils from patients with certain bacterial infections and can be induced in vitro after incubation with interferon-gamma. We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF). PMN from patients receiving rhG-CSF displayed higher cytotoxicity against Daudi lymphoma cells in vitro compared with control patients and with healthy donors. Fab fragments against Fc gamma RII (monoclonal antibody [MoAb] IV.3) inhibited neutrophil-mediated cytotoxicity of healthy donors but not of patients during rhG-CSF therapy. Therefore, expression of Fc receptors by PMN was investigated by flow cytometry and the mean fluorescence intensity (MFI) was compared. After staining with MoAb 32.2 against Fc gamma RL, the median MFI of neutrophils from G-CSF patients (median, 4.78; range, 2.40 to 8.50; n = 5) was significantly higher (P = .002 and P = .001, respectively) than the median MFI of patients not receiving G-CSF (median, 1.23; range, 1.01 to 1.58; n = 6) and the median MFI of healthy donors (median, 1.04; range, 0.67 to 1.12; n = 6). Fc gamma RI disappeared after the discontinuing of the G-CSF injections, but was reinduced during the next treatment cycle with rhG-CSF. The high expression of Fc gamma RI during rhG-CSF therapy correlated with enhanced cytotoxicity. In vitro incubation with rhG-CSF also enhances cytotoxicity, but only minor increments in Fc gamma RI expression were observed. Thus, during in vivo application of rhG-CSF neutrophils acquire an additional potent receptor for mediating tumor cell killing in vitro by induction of the high-affinity receptor for IgG (Fc gamma RI, CD64).
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PMID:Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor. 171 27

Expression of the Cytokine genes in human astroglial cell lineage was studied. Primers for 5 different human cytokine, TNF-alpha, -beta, IFN-gamma, G-CSF and GM-CSF, were used to analyze messenger RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell lines and fresh brain specimens by polymerase chain reaction (PCR). Three out of 5 unstimulated astrocytomas, U138, U251, U373 MG and IMR32 neuroblastoma cells expressed TNF-alpha genes. After stimulation with IL-1 beta (1000 U/ml) all these cell lines expressed TNF-alpha genes. TNF-beta genes could not be detected in these cell lines even in the presence of any cytokine stimuli. We were able to detect expression of IFN-gamma genes within 2 astrocytoma cell lines (U87MG and A172), which interestingly did not show TNF-alpha activity. Constitutive expression of mRNA transcripts of GM -CSF could be detected in all astrocytoma and two out of 5 unstimulated astrocytomas, U87MG and U138MG, expressed G-CSF genes. After stimulation with IL-1 beta, all cell lines expressed G-CSF. In addition, we also examined gene expression of these cytokines within 4 human malignant astrocytoma specimens, 2 peritumoral brain and 2 autopsied normal brains. The results show that tumor and surrounding lesions express TNF-alpha (4 of 6), TNF-beta (1/6), IFN-gamma (4/6), G-CSF (3/6) and GM-CSF (5/6) but not normal brains. One tumor specimen also expresses TNF-beta as well as TNF-alpha genes (case 2). From these results, it is suspected that astroglial cell-derived cytokines may participate in local immune reactions accompanying glioma in the brain.
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PMID:[Expression of cytokine genes within astrocytoma cell lines and brain specimens]. 179 21

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
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PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17

The paraneoplastic syndrome (PNS) is an association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia, neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous thromboembolism and disseminated intravascular coagulation (DIC). These abnormalities are, by and large, due to the production of biologically active growth factors, hormones or as yet unidentified "humors" by the tumor. As our understanding of growth factors controlling hematopoiesis has increased in recent years, the biologic basis of hematologic PNS are better understood. For instance, tumor-associated neutrophilia is now known to be caused by the production of G-CSF by the tumor. The mechanism by which tumor causes thromboembolism have also been extensively investigated. Cancer cells induce platelet aggregation both in vitro and in vivo. Platelet aggregating material has been isolated and partially characterized from tumor cells. The involvement of platelet glycoprotein II b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells contain a unique procoagulant, cancer procoagulant A, that directly activates factor X. Together with tissue factor, this procoagulant appears to have been contribute to a high incidence of thromboembolism in cancer patients. Better understanding of hematologic PNS is important for clinical care of the patients with cancer.
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PMID:[Paraneoplastic syndrome hematologic abnormalities]. 200 36


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