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)

Macrophages from mice bearing Lewis lung carcinoma release higher amounts of C3 molecules than macrophages from healthy mice. The C3 pro-releasing activity operating in vivo was suspected to be due to an immunological network. Indeed, the supernatants of splenocytes from tumor bearing mice, but not from normal mice, induced in vitro an increased release of C3 molecules by macrophages. Recombinant IFN gamma and TNF alpha were strong inducers of C3 release, while IL-2 acted poorly. The C3 pro-releasing activity of splenocyte supernatants was largely prevented by their pretreatment with specific mAb anti IFN gamma or anti TNF alpha, but not completely prevented by the simultaneous neutralization of the two cytokines. Taken together, these results show that murine macrophages increase the release of C3 molecules upon treatment with IFN gamma or TNF alpha and that these cytokines released in vivo by splenocytes from tumor bearing mice may account, together with a yet unknown factor, for a humoral network causing the increased release of C3 by peritoneal macrophages.
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PMID:IFN gamma and TNF alpha cause an increased release of C3 by murine macrophages. 789 Mar 16

Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 activated natural killer (NK) cells with potent anti-tumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic cancers. However, it has been shown that intravenously transferred LAK cells have a poor homing capacity to tumor sites. For the present study, the effects of tumor-derived factors on the in vitro migratory capacity of A-LAK cells was investigated. In a micropore migration assay the conditioned medium from 3LL Lewis lung carcinoma cell cultures was found to exert a strong chemotactic, but not chemokinetic effect on A-LAK cells. This effect was partially inhibited by neutralizing antibodies against the cytokines TGF-beta 1 and IL-6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor-cell-conditioned medium. Purified TGF-beta 1 and recombinant IL-6 were chemotactic for A-LAK cells. Biological activities of both cytokines were detectable in the tumor-cell-conditioned medium. The in vivo relevance of these findings, with respect to tissue infiltration of NK cells and LAK cells in inflammation or cancer, remains to be elucidated.
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PMID:Tumor-derived transforming growth factor-beta 1 and interleukin-6 are chemotactic for lymphokine-activated killer cells. 819 78

This study investigated the generation of primary tumor-specific CTL activity in vitro to several mouse tumors. We report that the development of optimal primary tumor-specific CTL to the P815 mastocytoma, the EL4 thymoma, and the Lewis lung carcinoma is dependent on tumor Ags, on enhancement of T cell costimulation by B7.1, and on exogenous T helper activity in the form of IL-2 and IL-4. A relatively low concentration of IL-2 and IL-4 was required to limit the induction of lymphokine-activated killer cells. In the case of P815, the CTL were directed toward molecularly defined tumor rejection Ags. These primary cultures yielded long term T cell lines that were heterogeneous in fine tumor Ag specificity and in cytokine production.
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PMID:Generation of primary tumor-specific CTL in vitro to immunogenic and poorly immunogenic mouse tumors. 855 87

Interleukin-4 (IL-4) is currently being used for therapeutic intervention in a wide range of malignant diseases as an antitumour agent. Although bioassays have been developed that measure the proliferative capacity of IL-4, none measure the antiproliferative activity of this molecule. We have developed a simple, sensitive bioassay for human IL-4 based on the ability of this cytokine to inhibit the proliferation of the human lung carcinoma line, CCL-185, an easy to maintain, cytokine independent, cell line. It is rapid, reproducible and sensitive, able to detect 2 pg/ml IL-4. The assay is completely unresponsive to all other interleukins from IL-2 to IL-12, to the colony stimulating factors and transforming growth factor beta and is 100-fold less sensitive to interferon-alpha, tumour necrosis factor-alpha, IL-1 beta and IL-13. The assay can be made completely specific for IL-4 by including specific neutralizing antibodies for IL-4 and is suitable for the estimation of IL-4 in both plasma and serum samples.
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PMID:An antiproliferative bioassay for interleukin-4. 857 74

Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and increase the presence of granulocyte/macrophage (GM) progenitor cells having natural suppressor activity. Treatment of these tumor-bearing mice with interleukin-12 (IL-12) resulted in minimal immune modulation. The objective of this study was to determine whether eliminating natural suppressor activity would allow for immune stimulation by IL-12. Treatment of LLC-LN7 tumor-bearing mice with vitamin D3 eliminated natural suppressor activity. In mice that were first treated with vitamin D3 and then also with IL-12, there was stimulation of splenic T cell proliferation in response to immobilized anti-CD3 plus IL-2. In addition, spleen and lymph node cells from vitamin-D3/IL-12-treated tumor-bearing mice became stimulated in response to autologous tumor to produce interferon gamma (IFN gamma), although IL-2 production was not stimulated. A prominent effect of the combined vitamin-D3/IL-12 treatment regimen was the synergistic augmentation of autologous tumor-specific cytolytic activity within the regional lymph nodes. The generation of these tumor-specific effector cells required the presence of the tumor mass since such activity was not elicited in the lymph nodes of mice from which the tumors had been surgically excised. The results of this study show that, after treatment of tumor bearers with vitamin D3 to eliminate GM-suppressor cells, IL-12 can induce select regional antitumor immune responses, particularly IFN gamma production and cytolysis by regional lymph node cells of autologous tumor.
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PMID:Immune modulation by interleukin-12 in tumor-bearing mice receiving vitamin D3 treatments to block induction of immunosuppressive granulocyte/macrophage progenitor cells. 866 68

Growth of Lewis lung carcinoma (LLC-LN7) tumors results in an increase in CD34+ granulocyte-macrophage progenitor cells having natural suppressor (NS) activity. These CD34+ NS cells were capable of inhibiting the cytotoxic activity of tumor-reactive lymph node cells. In vivo studies showed that adoptive treatment of LLC-LN7 tumor-bearing mice with tumor-reactive lymph node cells plus IL-2 failed to reduce the development of metastases. Studies were conducted to determine if diminishing the levels of CD34+ NS cells would allow for improved anti-tumor effectiveness of the adoptively transferred cells. The suppressive activity of CD34+ cells toward the cytolytic activity of tumor-reactive lymph node cells could be blocked by in vitro culture of CD34+ cells with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3. Similarly, treatment of LLC-LN7-bearing mice with vitamin D3 alone diminished the levels of CD34+ NS cells within regional lymph nodes, spleens and tumors. This treatment resulted in an increased immune reactivity to autologous tumor, as shown by the production of IFN-gamma by lymph node cells in response to the presence of LLC-LN7 cells. The extent of tumor metastasis in mice receiving vitamin D3 treatment was also reduced. When tumor-reactive lymph node cells were adoptively transferred into these LLC-LN7-bearing mice that were receiving vitamin D3 treatment, there resulted a pronounced synergistic reduction in tumor metastasis. The results of this study show that treatment of tumor bearers with vitamin D3 to eliminate CD34+ NS cells improves the anti-tumor effectiveness of adoptively transferred tumor-reactive lymph node cells.
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PMID:Failure of tumor-reactive lymph node cells to kill tumor in the presence of immune-suppressive CD34+ cells can be overcome with vitamin D3 treatment to diminish CD34+ cell levels. 956 45

Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 micrograms/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction.
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PMID:Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice. 959 10

Interleukin-15 is a recently discovered cytokine which is functionally similar to IL-2. In order to learn more about possible targets for modulation of the expression of IL-15 we investigated the expression of IL-15 mRNA and protein in the A549 (human lung carcinoma) cell line. Constitutive expression of IL-15 mRNA was detected in A549 cells. Treatment with TNF-alpha or IL-1 beta (10 ng/ml each) induced an about 2-fold increase of IL-15 mRNA; IFN-gamma induced significant effects only at 100 ng/ml. Stimulation with a combination of TNF-alpha and IFN-gamma was not superior to stimulation with TNF-alpha alone. EGF, KGF and the combination thereof were without effects. IL-15 protein was detected in cellular lysates of unstimulated cells and was increased by stimulation with TNF-alpha or IL-1 beta. No significant amounts of IL-15 protein were detected in cellular supernatants.
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PMID:Induction of IL-15 mRNA and protein in A549 cells by pro-inflammatory cytokines. 971 64

MyD118 and Gadd45 are two related genes which encode for proteins that play important roles in negative growth control, including both growth suppression and apoptosis. A strategy was employed to clone new members of the MyD118 and Gadd45 family of genes. Based on alignment of the deduced amino acid sequences, one cDNA clone was found to encode for the murine homologue of human CR6, originally cloned as an IL-2 immediate-early response gene. The murine and human CR6 proteins were observed to be 97% identical, indicating that CR6 is an evolutionarily conserved protein. Analysis of CR6 expression during hematopoietic cell development associated with growth arrest and apoptotic cell death, upon exposure of hematopoietic cells to a variety of growth arrest and apoptotic stimuli, and in a variety of murine tissues, has revealed that CR6 expression differs significantly from the expression of the related MyD118 and Gadd45 genes. Nevertheless, CR6, like MyD118 and Gadd45, suppressed colony formation of human lung carcinoma H1299 cells. These data suggest that CR6 plays similar, but not identical, roles to MyD118 and Gadd45 in negative control of cell growth.
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PMID:CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control. 1049 Aug 24

We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced T cell-derived IL-10 on antitumor immunity in vivo, we utilized transgenic mice expressing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic mice compared with control littermates. In this study, we show that transfer of T cells from IL-10 transgenic mice to control littermates transferred the IL-10 immunosuppressive effect and led to enhanced 3LL tumor growth. In addition to changes in T cell-mediated immunity, professional APC from IL-10 transgenic mice were found to have significantly suppressed capacity to induce MHC alloreactivity, CTL responses, and IL-12 production. Tumor Ag-pulsed dendritic cells from IL-10 transgenic mice also failed to generate antitumor reactivity. These results suggest that increased levels of T cell-derived IL-10 severely impair antitumor immunity in vivo, due to defects in both T cell and APC function.
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PMID:T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function. 1052 7


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