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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1 beta was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.
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PMID:IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2. 131 27

We established a method of in vitro immunization of human lymphocytes against human cancer cells and efficiently obtained human-human hybridomas producing cancer-specific antibodies using the in vitro immunized lymphocytes. Human lymphocytes were cocultured with human lung cancer cell line A549 for four days in medium containing various immunoactive reagents. In vitro immunization was effectively caused by the addition of OK-432 or muramyl peptides, IL-2, and IL-6, to the coculture of A549 cells and lymphocytes. Although specific antibodies of both IgM and IgG classes were produced by this method, the ratio of IgG to IgM was greater than or equal to 2. The efficiencies of in vitro immunization fluctuated about threefold in lymphocytes derived from several donors. The in vitro immunized lymphocytes were fused with human fusion partner A4H12 cells. Hybridomas producing specific antibodies reactive to A549 cells were efficiently obtained by sequential cell fusion. The efficiency of acquisition of hybridomas producing specific antibodies with the in vitro immunized lymphocytes was about 10-fold higher than that with lymphocytes spontaneously immunized in bodies of lung cancer patients.
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PMID:In vitro immunization of human lymphocytes with human lung cancer cell line A549. 157 23

We investigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432 injection. The neutrophil count was significantly correlated with NCA level. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCA and neutrophil count. OK-432 treatment also induced a marked increase of IL-1 beta and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1 beta and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment.
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PMID:OK-432 induces production of neutrophil chemotactic factors in malignant pleural effusion. 764 1

Tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha) and IL-6, when released in excess, have been suggested to be important host mediators of the immunoinflammatory response to injury and infections. Corticosteroids suppress this response in vitro. This study was undertaken to investigate if a single dose of methylprednisolone (MP) could modify the cytokine response in patients undergoing lung surgery. Twenty-one patients with lung cancer were allocated randomly to treatment with MP 30 mg/kg i.v. (MP group) or isotonic saline (control group). Patients were anaesthetized with a balanced anaesthesia combined with thoracic epidural anaesthesia. MP or saline was administered immediately before induction of anaesthesia. The cytokines in plasma were measured by ELISA, and blood samples were collected preoperatively, at the end of surgery, 4 h later, and 1 and 5 days postoperatively. All patients had detectable IL-6 in plasma. Compared to preoperative values, plasma IL-6 levels in the MP group increased from 114 pg/ml (12-350 pg/ml) (mean, range) to peak value 146 pg/ml (15-580 pg/ml) on the first postoperative day. In the control group, IL-6 levels increased from 99 pg/ml (17-350 pg/ml) preoperatively to 125 pg/ml (10-300 pg/ml) on the first postoperative day. The increases were not significant. TNF alpha was detectable in only two patients, one from each group. Low levels of IL-1 alpha were demonstrated in three patients in the MP group and in four patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of methylprednisolone on the cytokine response in patients undergoing lung surgery. 768 9

A cell line derived from human lung cancer (AOI) was employed in the present study. A panel of cytokines were quantified by ELISA technique following cellular exposure to X-irradiation. Tremendous increase in the levels of both IL-1 alpha and IL-6 were observed, GM-CSF was also detected. A comparison of time kinetics of IL-1 alpha and IL-6 production was made with that of cell cycle progression which was determined by FCM BrdU/DNA bivariate analysis. No cell cycle specific changes were found. The biological implication of radiation-induced cytokine production was discussed.
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PMID:Ionizing radiation-induced IL-1 alpha, IL-6 and GM-CSF production by human lung cancer cells. 780 55

Cytokines play an important role in activating the immune system against malignant cells. One of these cytokines, interleukin-4 (IL-4) has entered clinical phase I trials because of its immunoregulatory potency. In the present study we report that recombinant human (rh) IL-4 has major direct antiproliferative effects on one human lung cancer cell line (CCL 185) in vitro as measured by a human tumor cloning assay (HTCA), tritiated thymidine uptake, and counting cell numbers and marginal activity in a second cell line (HTB 56) in the HTCA. This activity could be abolished by neutralizing antibody against rhIL-4. The biological response of the tumor cells to the cytokine is correlated with expression of receptors for human IL-4 on both the mRNA level and the protein level. The responsive cell line, CCL 185, secretes IL-6 after being incubated with rhIL-4. On the other hand, neutralizing antibodies against IL-6 showed no influence on the growth modulatory efficacy of rhIL-4 in this cell line. Furthermore, CCL 185 does not show detectable production of IL-1, tumor necrosis factor alpha or interferon gamma after incubation with rhIL-4. Thus, the response to rhIL-4 is not mediated through autocrine production of these cytokines triggered by rhIL-4. In a next series of experiments some of the cell lines were xenotransplanted to BALB/c nu/nu mice. Subsequently, the mice were treated for 12 days with two doses of 0.5 mg/m2 rhIL-4 or control vehicle subcutaneously per day. Treatment with rhIL-4 yielded a significant inhibition of tumor growth versus control in two of the non-small cell lung cancer cell lines being responsive in vitro (CCL 185, HTB 56). Histology of the tumors in both groups showed no marked infiltration of the tumors with murine hematopoietic and lymphocytic cells consistent with the species specificity of IL-4. In contrast, no tumor growth inhibition was found in the small cell lung cancer cell lines (HTB 119, HTB 120) being nonresponsive in vitro. We conclude that rhIL-4 has direct antiproliferative effects on the growth of some human non-small cell lung cancer cell lines in vitro and in vivo, which together with its regulatory effects on various effector cell populations makes this cytokine an interesting candidate for further investigation in experimental cancer treatment.
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PMID:Recombinant human interleukin-4 inhibits growth of some human lung tumor cell lines in vitro and in vivo. 821 32

The hematopoietic stimulating activity of a human lung cancer cell line, MC-1, was investigated. The protein fraction (MC-1 protein) was prepared from the serum-free culture supernatant of MC-1 cells using hydroxyapatite and concanavalin A-agarose columns. In serum-containing cultures, MC-1 protein stimulated colony formation by megakaryocyte colony-forming units (CFU), erythroid burst-forming units and granulocyte/macrophage (GM) CFU. The stimulating effect was strongest for megakaryocyte CFU. The factor having megakaryocyte colony-stimulating activity was shown to be a protein whose molecular weight was determined to be 23,000 daltons by gel filtration. By various analyses, this protein was shown to be molecularly different from the heretofore-identified cytokines that may affect megakaryocytopoiesis, i.e., interleukin-1 (IL-1), IL-2, IL-3, IL-6, IL-7, IL-11, granulocyte colony-stimulating factor (CSF), macrophage CSF, GM-CSF, leukemia inhibitory factor, stem cell factor and tumor necrosis factor. Under serum-free conditions, MC-1 protein augmented murine megakaryocyte colony formation in the presence of murine IL-3 and increased the acetylcholinesterase activity of purified murine megakaryocytes. It was also shown that MC-1 protein stimulated human megakaryocyte colony formation. It was concluded that MC-1 cells produce a megakaryocyte potentiator which is molecularly different from any heretofore-identified cytokines.
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PMID:A novel megakaryocyte potentiator produced by MC-1 human lung cancer cell line. 829 93

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

Lung cancer is a leading cause of cancer death and standard chemotherapies are resulting in only marginal improvements in outcome. Experimental approaches involving gene therapy are attractive in this clinical setting. There are two basic types of genes utilized, either those intended to induce immunity or those that are directly tumoricidal. Immunity-inducing genes that have been used in model (and some human) systems include MHC molecules, costimulatory molecules, and cytokines such as IL-2, IL-4, IL-6, GM-CSF. These are intended to induce effective systemic immune responses against tumor antigens which would not otherwise develop. Direct toxic approaches include the reintroduction of tumor suppressor genes or enzymes which convert non-toxic drugs to toxic ones, such as herpes thymidine kinase. As a means for gene delivery, retroviruses are the most common vehicle, although Adenovirus vectors and direct DNA delivery have specific advantages.
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PMID:Gene therapy for lung cancer. 861 19

Interleukin-3 (IL-3) is a glycoprotein produced primarily by activated T-lymphocytes. As a hematopoietic growth factor it affects the proliferation, maturation, and survival of progenitor cells of the myeloid, erythroid, and megakaryocyte lineages. Initial studies in cancer patients with normal bone marrow using IL-3 doses of > 5 micrograms/kg daily produced a doubling of the neutrophil count within 2-3 days and that of platelet counts by days 10-12. Phase I-II clinical trials have examined the response to IL-3 in various clinical states, and ongoing phase III studies are currently assessing the clinical relevance. In the treatment of relapsed lymphoma, small-cell lung cancer, and breast and ovarian cancer, IL-3 at doses of 5-10 micrograms/kg daily given mainly subcutaneously for 5-10 days has been shown to maintain chemotherapy schedules while preserving adequate granulocyte and platelet numbers in the peripheral blood. At these doses, side effects were uncommon. The translation of these observations into clinical phase III studies has been disappointing, with no clear-cut clinical advantage being observed in the treated group. This reflects the relative lack of myelosuppression seen with most current regimens for solid tumors. The role of combined treatment with IL-3 in association with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor after cytotoxic treatment has yet to be established. However, it has been shown that they may act synergistically, resulting in significantly higher numbers of progenitor cells in the peripheral blood than when either is used alone. Combinations with IL-6 are also under study, as is the use of "cocktails" for ex vivo expansion of progenitors. This latter approach would allow single, small collections to be used for multiple infusions of progenitors and could support significant dose-intensification regimens by relieving myelosuppression. It is clear that the place of these newer cytokines in current treatment remains to be clarified.
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PMID:Is interleukin 3 active in anticancer drug-induced thrombocytopenia? 876 24


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