Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An anti-Purkinje cell antibody was found in the serum and CSF of a man with adenocarcinoma of the lung and paraneoplastic cerebellar degeneration (PCD). This antibody differed from the autoantibodies found in patients with gynecologic cancer and PCD in that it produced a different pattern of Purkinje cell cytoplasmic staining, did not react with PCD antigens in Purkinje cell Western blots, and the antigen had a different species distribution. Unlike the antinuclear antibody found in patients with PCD and small-cell lung carcinoma, the antigen was restricted to the cytoplasm of Purkinje cells. If autoantibodies are important in the pathogenesis of PCD, this case illustrates that they can recognize different antigenic epitopes in the nervous system, but cause similar clinicopathologic syndromes.
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PMID:A variant of the anti-Purkinje cell antibody in a patient with paraneoplastic cerebellar degeneration. 329 Jul

The possibility that production of some cytokines in the carcinoma microenvironment is associated with the presence and differentiation of cells belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was investigated. Immunohistochemical examination showed the presence of intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located close to lymphoid aggregates. In situ hybridization performed in four cases (three LC positive and one LC negative) of squamous cell carcinoma and in five cases (four LC positive and one LC negative) of adenocarcinoma showed that some mononuclear cells in the interstitium displayed hybridization with granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive carcinomas did epithelial cells close to lymphoid aggregates display small amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis performed in the 20 cases of lung carcinoma showed that epithelial cells in tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF monoclonal antibody. Specimens negative for GM-CSF contained very few LCs. Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive expression of TNF alpha mRNA was found in all of them, whereas only three showed a low constitutive expression of GM-CSF mRNA. In the latter three cell lines treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular factors produced by reactive lymphocytes and/or macrophages may influence the production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this production could favor the arrival and differentiation of DCs and activate LC functions.
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PMID:Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. 763 48

Metastatic Lewis lung carcinoma (LLC-LN7) tumors that secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF) stimulate myelopoiesis and induce bone marrow-derived immunosuppressor cells that are homologous to granulocyte/macrophage progenitor cells. In vitro treatment of the LLC-LN7 cells with 1 alpha,25-dihydroxyvitamin D3 reduced tumor cell production of suppressor-inducing activity, although suppressor-inducing activity could be restored by reconstituting the tumor supernatants with recombinant GM-CSF. Treatment of mice having LLC-LN7 tumors with vitamin D3 reduced tumor production of GM-CSF and the frequency of myeloid progenitor cells. This was associated with a reduction in immunosuppressor activity and an increase in T cell function. Vitamin D3 treatment of mice having palpable tumors transiently retarded tumor growth, but caused a prominent reduction in tumor metastasis. Treating mice with vitamin D3 after tumor excision resulted in a reduction in the tumor-induced myelopoietic stimulation and associated immunosuppressive activity, and enhanced T cell function. These mice had a markedly reduced incidence of tumor recurrence. The results of this study suggest that vitamin D3 treatment of mice with GM-CSF-secreting tumors can interrupt the myelopoiesis-associated immunosuppressor cascade and, in turn, reduce tumor metastasis and recurrence.
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PMID:Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence. 764 Dec 18

In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.
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PMID:An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines. 766 28

This study was aimed at preventing of chemotherapy-induced neutropenia and improving the therapeutic result by reducing the cycle length of cisplatin (25 mg/m2/day, 5-day continuous infusion) and vindesine (3 mg/m2, bolus, days 1 and 8) (PiV) through the use of recombinant human granulocyte colony-stimulating factor (rG-CSF) (2-5 micrograms/kg/day, subcutaneous, days 6-21) for non-small cell lung carcinoma (NSCLC). PiV regimen with rG-CSF was repeated every 21 days. 28 out of 33 previously untreated patients, who completed two or more cycles of PiV regimen on schedule, were evaluable for analysis. The absolute neutrophil count in the third week after chemotherapy was 8187 +/- 5376/ml. It became possible to administer PiV therapy at 3-week intervals. The response rate was 74% (23/31). In conclusion, the combined administration of rG-CSF enabled shortening of administration schedule of PiV therapy and increasing the dose intensity.
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PMID:Recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for non-small cell lung cancer. 838 69

We reacted dispersed cultures of newborn rat cerebellar granule cells with serum, purified IgG, and CSF from patients with type IIa ("anti-Hu") antibody response accompanying paraneoplastic neurologic syndromes. All type IIa sera, IgGs, and CSFs, but not those of normal or cancer controls, produced bright nuclear immunofluorescence of cultured granule neurons. Type IIa serum and CSF labeled proteins of 35-42 kd in rat granule cell blots, identical in molecular weight to proteins labeled by type IIa antibodies in blots of human granule cells. IgGs eluted from the 35-42 kd band in blots of rat granule cells labeled proteins of similar molecular weights in blots of human granule cells and produced typical type IIa immunostaining of human cerebellar sections. Human IgG could be identified in nuclei and cytoplasm of neurons incubated for 72 hours with 2/4 type IIa sera tested, but not with normal sera. Type IIa sera or IgGs from 4/7 patients produced specific lysis of rat granule cells in the presence of complement, as compared with controls using normal serum or heat-inactivated complement. Prolonged (7-day) incubation of cultures with type IIa antibody without complement also resulted in specific lysis, whereas incubation with normal serum or serum from neurologically normal patients with small-cell carcinoma of the lung did not. Rat granule cell cultures provide a valuable in vitro system with which to study the interaction of type IIa antibody with neurons. The present study provides the first reported evidence that type IIa antibodies may cause cell injury directly, in the absence of lymphocyte-mediated immune response.
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PMID:Type IIa ('anti-Hu') antineuronal antibodies produce destruction of rat cerebellar granule neurons in vitro. 841 65

Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma cells (LLC-LN7) was previously shown to contribute to the maintenance of phenotypic characteristics associated with an increased capacity to metastasize. In the present study, pre-incubation of LLC-LN7 cells with neutralizing anti-GM-CSF antibodies diminished the capacity of the tumor cells to form experimental metastases after i.v. inoculation, while pre-incubation with recombinant GM-CSF (rGM-CSF) increased formation of metastases. In the presence of rGM-CSF, the LLC-LN7 cells exhibited an increased capacity to migrate, invade through a reconstituted basement membrane, and adhere to lung tissue. Studies to identify the signal transduction pathway through which GM-CSF enhanced the in vitro metastatic properties of the LLC-LN7 tumor cells implicated protein kinase A (PKA). Signaling through PKA was suggested by the demonstration that the stimulation of tumor-cell motility by GM-CSF was blocked in the presence of the adenylate cyclase inhibitor nicotinic acid, or the PKA inhibitors A3 or KT5720. In addition, the role of PKA as a signaling mechanism for GM-CSF was assessed by using REV-LN7 cells, which are LLC-LN7 cells that have been stably transfected with an expression vector encoding a mutant PKA RI alpha subunit and which, in turn, express a cAMP-resistant PKA. Adherence and invasion by the PKA-defective REV-LN7 cells were not stimulated by rGM-CSF, contrasting with the stimulation observed for wild-type LLC-LN7 cells. These data suggest that rGM-CSF can further enhance the in vitro metastatic characteristics of LLC-LN7 tumor cells and that this is dependent on signal transduction through PKA.
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PMID:Granulocyte-macrophage colony-stimulating factor stimulates the metastatic properties of Lewis lung carcinoma cells through a protein kinase A signal-transduction pathway. 843 41

Interleukin-12 (IL-12) was found to be an active anti-tumor agent in 3 established murine solid tumors: B16 melanoma, Lewis lung carcinoma and renal cell carcinoma (RenCa). IL-12 was well tolerated over a 100-fold dose range. Only the high-dose treatment of IL-12 resulted in a clear reduction in the number of lung metastases from B16 melanoma and Lewis lung carcinoma. Treatment of animals bearing Lewis lung carcinoma with IL-12 in combination with fractionated radiation therapy was markedly dose-modifying, indicating that IL-12 was acting synergistically with radiation. Treatment of animals bearing the same tumor with monocyte colony-stimulating factor (M-CSF) along with fractionated radiation therapy resulted in a parallel increase in tumor growth delay with increasing dose of M-CSF, indicating that M-CSF was affecting a subpopulation of tumor cells in addition to those killed by radiation therapy. The combination of IL-12 with M-CSF was most effective with radiation therapy, especially in the clinically relevant dosages of 2 and 3 Gy per fraction. By isobologram analysis, IL-12 and M-CSF, along with fractionated radiation therapy, resulted in a greater-than-additive (synergistic) tumor response.
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PMID:In vivo studies with interleukin-12 alone and in combination with monocyte colony-stimulating factor and/or fractionated radiation treatment. 854 1

This study was designed to analyze the possible immunomodulation induced in vivo by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-1, IL-6, TNF alpha and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-1 alpha decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.
Lung Cancer 1995 Oct
PMID:Interleukin-1 alpha and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF. 858 94

Cloned high-metastatic Lewis lung carcinoma. A11 cells were retrovirally transduced with either granulocyte macrophage-colony stimulating factor (GM-CSF) or beta-galactosidase gene and examined for their tumorigenicity. GM-CSF-engineered A11 cells produced a much higher amount of GM-CSF than the parental and control cells. Unexpectedly, GM-CSF-engineered A11 cells grew more rapidly than the control cells, while in vitro growth rates of these cells were almost the same. The enhanced tumor growth seemed to be unique to GM-CSF among various cytokines, because interleukin 2 (IL-2), interleukin 4 (IL-4) and interleukin 6 (IL-6) producer cells exhibited suppressed tumor growth.
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PMID:Augmentation of in vivo growth of Lewis lung carcinoma cells transduced with granulocyte macrophage-colony stimulating factor gene. 868 29


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