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

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

It has been considered that growth of human lung cancer cells, like other malignant cells, is positively and negatively regulated by a variety of growth factors via autocrine as well as paracrine mechanisms. The autocrine mechanism is considered to be important in the autonomy of proliferation of cancer cells. Recently, the role of autocrine growth-inhibiting factors such as transforming growth factor beta attracts special attention for better understanding of growth regulation of malignant cells. Here, we have demonstrated that a multifunctional cytokine interleukin 6 (IL-6) had an inhibitory effect on the proliferation of human non-small cell lung cancer cell lines, as shown by the growth accelerating effect of the specific anti-IL-6 antibody as well as the effect of exogenously added IL-6. Moreover, IL-6 can be expressed and released by human lung cancer cells, and these cells had specific IL-6 receptors on their cell surfaces, suggesting an autocrine mechanism. The growth-inhibitory effect of IL-6 was additive to that of transforming growth factor beta, and could not be neutralized by the addition of anti-transforming growth factor beta antibody. These results suggested that IL-6 may function as another class of autocrine growth-inhibiting factor in the growth regulation of human lung cancer. Relatively lower IL-6 sensitivity of these cells than noncarcinogenic human bronchial epithelial cells also suggested that escape from growth regulation by inhibitory factors such as IL-6 could be involved in lung cancer oncogenesis.
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PMID:Growth inhibition of human lung cancer cell lines by interleukin 6 in vitro: a possible role in tumor growth via an autocrine mechanism. 836 12

Lung cancer remains the leading cause of cancer deaths in the United States. We have developed a new immunotherapeutic approach to the treatment of small cell carcinoma of the lung (SCCL) by targeting the gastrin-releasing peptide receptor (GRP-R) expressed on the surface of these cells. Bispecific immunoconjugates were constructed by chemical fusion of a GRP analog or a GRP antagonist with monoclonal antibodies directed to the cytotoxic trigger molecules Fc gamma RI and Fc gamma RIII on various immune effector cells. We demonstrated that these bispecific immunoconjugates bound to target SCCL cells in a dose-dependent manner. In the presence of these immunoconjugates, more than 80% of SCCL cells were lysed by cytokine-activated monocytes and natural killer (NK) cells measured by a 51Cr-release assay. These data indicate that bifunctional antibodies targeting GRP may have clinical use.
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PMID:Lysis of small cell carcinoma of the lung (SCCL) cells by cytokine-activated monocytes and natural killer cells in the presence of bispecific immunoconjugates containing a gastrin-releasing peptide (GRP) analog or a GRP antagonist. 858 71

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

The effect of hyperthermia and cytokine (IFN-gamma) in the expression of carcinoembryonic antigen (CEA) on the surface of cells was studied in vitro. The human lung cancer cell line, GLL-1, was used. The results demonstrate increase in CEA expression after hyperthermia. The magnitude of elevated CEA expression increased with increasing temperature (41-43 degrees C). Time-course study demonstrated that the peak CEA expression was 3 days after heating at 43 degrees C. The relative CEA expression was 1.3 at 1 day, 1.6 at 2 days, 1.9 at 3 days, 1.8 at 4 days, and 1.5 at 5 days, respectively. Hyperthermia plus IFN-gamma showed a synergistic effect in the expression of CEA. The four fold marked increase of CEA expression was detected. Furthermore, the pattern of time-course of CEA expression in hyperthermia combined with IFN-gamma was different from that in hyperthermia alone.
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PMID:Modifications of tumor-associated antigen expression on human lung cancer cells by hyperthermia and cytokine. 866 32

Fibrosis is a pathological process characterized by the replacement of normal tissue by mesenchymal cells and the extracellular matrix produced by these cells. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in the area of derangement. The same sequence of events occurs in wound healing with normal granulation tissue and scar formation, but, while normal scar formation is very localized and transient, in contrast, in fibrosis, the repair process is exaggerated and usually widespread and can be chronic. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of three human fibrotic lung diseases, two diffuse [idiopathic pulmonary fibrosis (IPF), and the adult respiratory distress syndrome (ARDS)], and one focal (tumor stroma in lung cancer), has shown that several cytokines participate to the local injury and inflammatory reaction [interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha)], while other cytokines are involved in tissue repair and fibrosis [platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)]. A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.
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PMID:Cytokines in human lung fibrosis. 867 88

Fibrosis is a disorder characterized by a qualitative and quantitative alteration of the deposition of extracellular matrix with accumulation of mesenchymal cells in replacement of normal tissue. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in this area. A similar sequence of events occurs in wound healing with formation of normal, limited and transient granulation tissue, while in fibrosis, a maladaptive repair leads to an extensive, exaggerated process with functional impairment. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of several human fibrotic lung diseases, five diffuse (idiopathic pulmonary fibrosis (IPF); adult respiratory distress syndrome (ARDS); coal workers' pneumoconiosis (CWP); Hermansky-Pudlak syndrome (HPS); systemic sclerosis (SS)) and two focal (tumour stroma in lung cancer; and obliterative bronchiolitis (OB) after lung transplantation), has shown that several cytokines participate in the local injury and inflammatory reaction (interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha)), while other cytokines are involved in tissue repair and fibrosis (platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)). A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.
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PMID:The role of cytokines in human lung fibrosis. 868 Mar 82

We have analysed the expression of interleukin-2 receptor (IL-2R) on a panel of small-cell lung cancer (SCLC) cell lines. None of the 11 SCLC cell lines studied expressed detectable surface IL-2R alpha or beta chains by indirect immunofluorescence. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses indicated that only one out of 11 cell lines expressed detectable IL-2R beta mRNA while two expressed a weak positivity for IL-2R gamma. Five SCLC cell lines were transfected with the plasmid vector RSV.5 neo containing IL-2 cDNA coding sequence. Stable transfectants secreted biologically active IL-2 (ranging from 25 to 100 U ml-1 in the culture supernatant). IL-2 transfection did not produce significant modifications in the expression of surface molecules such as IL-2R alpha and beta chains, intercellular adhesion molecule-1 (ICAM-1), CD44, HLA class I and II or in IL-2R beta or gamma mRNA. More importantly, IL-2-transfected N592 and NCI H69 cell lines completely lost their tumorigenic potential in nude mice after subcutaneous injection, whereas experimental controls transfected with RSV.5 neo vector only, displayed an in vivo growth pattern identical to that of untransfected cells. In addition, in the N592 model, IL-2-producing N592 inhibited the growth of wild-type N592 injected at the same site, while injection of parental cells on the opposite side did not significantly affect the growth of wild-type tumour cells. Histopathological analysis of the rejection process of IL-2-transfected cells demonstrated the presence of MAC-1+, MAC-3+ macrophages and of RB68C5+ granulocytes, whereas T cells were undetectable and NK cells were scarcely represented. In addition, a reduction of the tumour blood vessels was observed. The possible relevance of these data for the development of vaccination strategies using cytokine-engineered tumour cells in SCLC is discussed.
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PMID:Analysis of IL-2 receptor expression and of the biological effects of IL-2 gene transfection in small-cell lung cancer. 879 83

Interleukin (IL)-1 is a key cytokine in inflammatory reactions. To clarify the mechanism of inflammation in the pleural cavity, we investigated the contribution of IL-1 and its antagonism to inflammatory processes in the pleural cavity. Interleukin-1 receptor antagonist (IL-1Ra) levels as well as IL-1 beta and interferon-gamma (IFN-gamma) levels were measured by enzyme immunoassay in pleural effusions from 70 patients. Pleural macrophages were also examined as possible sources of these cytokines in 10 patients. IL-1Ra was detectable in 28 patients (40%) out of 70 patients with pleural effusions. Patients with tuberculosis had significantly higher IL-1Ra as well as IFN-gamma levels in pleural effusion than patients with lung cancer. Transudative pleural effusions had low or undetectable IL-IRa levels. On the other hand, IL-1 beta levels were low, except in cases of parapneumonic pleural effusion. Spontaneous production of IL-1Ra pleural macrophages was observed in six patients, and IL-4 significantly augmented its production. Although spontaneous production of IL-1 beta was observed in only two patients, pleural macrophages produced significant amounts of IL-1 beta in response to lipopolysaccharide in all 10 patients examined. These results suggest that interleukin-1 receptor antagonist regulates various reactions by interleukin-1 in pleural effusion, and that pleural macrophages may act in situ as a source of interleukin-1 receptor antagonist.
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PMID:Interleukin-1 receptor antagonist in pleural effusion due to inflammatory and malignant lung disease. 880 40

Cytokine-supported ex vivo expansion of peripheral blood progenitor cells (PBPCs) offers new perspectives for autografting after high-dose chemotherapy. One of the potential advantages is the possibility to reduce the volume of blood processed from the patient, thus allowing reduction of the overall tumor cell number in the final autograft. However, ex vivo expansion will only be advantageous if contaminating tumor cells are not expanded concomitantly. This question has not previously been addressed. Therefore, we analyzed unseparated PBPC preparations, CD34(+)-selected cell fractions, and ex vivo-expanded cell preparations from stage IV (n = 16) and high-risk stage II/III (n = 8) breast cancer patients for the presence of human epithelial antigen- (HEA) or cytokeratin (CK)-positive tumor cells. We found that three of 16 (18.8%) of the unseparated PBPC products from stage IV patients were HEA- and/or CK-positive, whereas none of the stage II/III patients were found to be positive after two cycles of induction chemotherapy with etoposide (VP16), ifosfamide, cisplatin, and epirubicin (VIP-E). After CD34+ cell selection (Ceprate SC; CellPro, Bothell, WA) and stem-cell factor (SCF), interleukin (IL)-1, IL-3, IL-6, and erythropoietin (EPO)-mediated ex vivo expansion of the CD34+ cells for 14 to 21 days, no tumor cells could be detected in these primary breast cancer patients at a sensitivity of 1 tumor cell per 4 x 10(5) nucleated cells. Thus, to answer the question of whether tumor cells are expanded concomitantly on ex vivo expansion of normal CD34+ cells, we cocultured defined numbers of primary renal carcinoma cells (RS-85), xenograft-derived breast cancer cells, and small-cell lung cancer cells with CD34+ cells selected from normal donors or cancer patients, either in serum or serum-free culture media. We found that none of the three epithelial tumor cell types increased significantly in number during a 14-day coculture period when compared with normal CD34+ cells alone or tumor cells alone, which increased 110- +/- 77-fold and 45- +/- 26-fold, respectively. However, during coculture, the tumor cells did not undergo cell death and were able to regrow when maintained in serum for longer time periods. We conclude that cytokine-supported expansion cultures of positively selected CD34+ PBPCs from primary high-risk stage II/III or stage IV breast cancer patients do not contain detectable tumor cells, which suggests that there is no increased risk of concomitantly expanding tumor cells. Moreover, cocultures of exogenously mixed tumor cell lines with normal CD34+ cells showed a relative disadvantage of tumor cell growth compared with the growth of hematopoietic cells, again without an apparent risk of concomitantly expanding tumor cells. However, considering the pronounced heterogeneity of tumor cell kinetics, ex vivo-expanded PBPC from cancer patients should be monitored for minimal residual disease.
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PMID:Ex vivo expansion of CD34+ peripheral blood progenitor cells: implications for the expansion of contaminating epithelial tumor cells. 883 66


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