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

A prerequisite to the developement of an efficient cell and/or gene therapy for lung cancer is a precise characterization of the inflammatory cell populations spontaneously present in the tumor stroma associated with this cancer. This study was designed to define the cytotoxic potential and the relationship with stroma development of tumor infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM). Tumor samples from 48 patients undergoing surgery for non-small cell lung cancer (NSCLC) were analyzed, by immunohistochemistry and in situ hybridization, with a panel of antibodies and probes specific for cell proteins linked to cytotoxicity, cytokines, and growth factors, and the replication status of TIL and TAM was evaluated by in vivo 5-bromodeoxyuridine incorporation. It was shown that, in NSCLC: (1) tumor stroma inflammatory cells are mainly TIL (approximately 2/3) (among them, 80 % are T-cells) and TAM (approximately 1/3), with almost no natural killer (NK) cells, and a few dentritic cells; (2) TAM and TIL are poorly replicating, but mainly recruited to the tumor stroma; (3) more than half TAM show an antibody-dependent cytotoxic potential, and one third of T-cells are TIA-1 positive CD8 activated cytotoxic lymphocytes; (4) cancer cells from only a few tumor express HLA class I and II antigens; (5) TAM production of cytotoxic cytokines [interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha)] and of transforming growth factor-beta1 (TGF-beta1) is low, in contrast to their strong release of platelet-derived growth factor (PDGF). We concluded that, in NSCLC, TIL cytotoxicity is likely to be low because of a poor class I MHC expression by tumor cells, and TAM low production of cytotoxic cytokines is a major limit to their possible cytotoxic activity. In contrast, TAM may favor tumor progression by contributing to tumor stroma formation and angiogenesis through their release of PDGF, in conjunction with TGF-beta1 production by tumor cells.
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PMID:Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression. 1243 33

Lung cancer is one of the most common malignant diseases and is amongst the leading causes of death. Cell-mediated immune response and cytokines could play an important role in antitumour immunity. The aim of the study was to evaluate the cytokines', tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6, releasing capacity in patients with lung carcinoma and benign lung disease. A group of 41 patients were tested for the production of TNF-alpha, IL-1beta and IL-6 in bronchoalveolar lavage (BAL) and blood. The levels of cytokines in the lung cancer patients were: (1) in BAL - IL-6, 173 +/- 85 pg/ml; TNF-alpha, 170 +/- 116 pg/ml; and IL-1beta, 473 +/- 440 pg/ml; (2) in the blood - IL-6, 197 +/- 53 pg/ml; TNF-alpha, 311 +/- 202 pg/ml; and IL-1beta, 915 +/- 239 pg/ml. Alveolar macrophages of the patients with a lung cancer secreted significantly more cytokines, IL-6 (P = 0.0004) and IL-1beta (P = 0.0047), than alveolar macrophages of the patients with a nonmalignant lung cancer. However, significantly lower levels of cytokine production by the BAL cells were found in patients with small cell lung cancer. This production decreased further in phase IV of nonsmall cell lung cancer.
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PMID:Cytokines in patients with lung cancer. 1258 64

We examined whether interleukin-1 (IL-1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL-1beta enhanced expression of various cytokines (IL-6, IL-8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule-1 (ICAM-1) by A549, PC14, RERF-LC-AI, and SBC-3 cells expressing IL-1 receptors. A549 cells transduced with human IL-1beta-gene with the growth-hormone signaling-peptide sequence (A549/IL-1beta) secreted a large amount of IL-1beta protein. Overexpression of IL-1beta resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2). A549/IL-1beta cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti-IL-1beta antibody inhibited formation of lung metastasis by A549/IL-1beta cells. Moreover, A549/IL-1beta cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL-1beta cells. Histological analyses showed that more host-cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL-1beta cells, compared with tumors derived from control A549 cells. These findings suggest that IL-1beta facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis.
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PMID:Multifunctional interleukin-1beta promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules. 1282 17

We examined the effects of bronchoalveolar lavage (BAL) and BAL fluid characteristics on the systemic proinflammatory cytokine expression and their relation to clinical and laboratory findings. Thirty patients suspected to have lung cancer were subjected to fiber-optic bronchoscopy (FOB) and BAL. Clinical and laboratory findings were determined at baseline, 4 h, and 24 h, including lung auscultation, temperature, chest X-ray, WBC, neutrophils, and serum IL-1beta, IL-6, and TNF-alpha. BAL fluid characteristics were determined including cytokine levels. Fifteen volunteers served as controls to determine serum variation of the same cytokines. Significant temperature elevation was defined as 1 degrees C increase compared to baseline. BAL was associated with temperature and serum TNF-alpha and IL-6 but not IL-1beta increase at 4 h. Four patients (13.3%) developed temperature over 38 degrees C. In controls there were no significant changes between baseline and 24 h measurements for the same cytokines. Eleven patients (36.6%) developed a significant temperature elevation 4 h after BAL. These patients had a statistically significant ( p < 0.05) increase in serum IL-6 at 4 h and in TNF-alpha at both 4 and 24 h after BAL compared with the nonsignificant temperature increase group. BAL characteristics were not different between the two groups. On the other hand, BAL fluid IL-6 and TNF-alpha levels were significantly higher ( p < 0.05) in the nonfever group. Significant temperature increase was observed in 36.6% of the patients undergoing BAL and associated with significant serum TNF-alpha and IL-6 increase at 4 h. Lung cytokines levels, alveolar macrophages, and BAL fluid characteristics are not related to temperature and serum proinflammatory cytokine increase. The hypothesis of alveolar macrophages derive from cytokine production and shift to the systemic circulation cannot be supported by our data.
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PMID:Temperature and serum proinflammatory cytokine changes in patients with NSCLC after BAL. 1287 38

Th2 cytokine is predominant in tumor patients and was found to be associated with tumor progression. Reversing of Th2 dominant status is thought to be a promising strategy. In the present study, peripheral blood mononuclear cells (PBMNC) of 37 lung cancer patients and 19 healthy subjects were prepared and used for examination of cytokine secretion and gene expression. The positive percentage of mRNA transcripts of Th1 cytokines (8.1% for IFNgamma and 13.5% for IL-2) in patients' PBMNC were lower than those of Th2 cytokines (70.3% for IL-4, 64.9% for IL-6 and 83.8% for IL-10). The gene expression capacity (measured as relative intensity to ratio of beta-actin) of patients for Th1 cytokines was low, but constitutively relatively high for Th2 cytokines. Both positive percentage and relative intensity were lower in transcript factor for Th1 cytokine, T-bet (40.5% and 0.139, respectively) than those for Th2 cytokine, GATA3 (89.2% and 0.364, respectively). Traditional Chinese medicine, Astragalus (AG) was observed to reverse Th2 status of lung cancer. AG enhanced culture supernatant and gene expression levels of Th1 cytokine (IFNgamma and IL-2) and its transcript factor (T-bet), and reduced those of Th2 cytokines in cultured PBMNC of lung cancer patients. These results demonstrated that traditional Chinese medicine AG might reverse the Th2 predominant status in lung cancer patients, which is a probable alternative therapeutic regime in future.
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PMID:Traditional Chinese medicine Astragalus reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients. 1288 32

Recent research advances in cancer and molecular biology have furthered our understanding of the etiology and natural history of lung cancer. Through translational research, a growing understanding of the molecular changes that underlie cancer progression has contributed to the development of novel molecular approaches for early detection, further defining prognosis, refining treatment schedules, identifying new therapeutic targets, and identifying patients at risk for treatment-related toxicity from aggressive therapy, such as pneumonitis and esophagitis. In this article, we review progress in molecular/gene screening and prognosis, and we present a clinical study, based on preclinical research, in which we apply low-dose radiosensitizing paclitaxel for locally advanced non-small-cell lung cancer (NSCLC); this resulted in superior local tumor control while keeping treatment toxicity low. We also review progress made in identifying cytokines: interleukin [IL]-1alpha, IL-6, and transforming growth factor [TGF] beta as markers for lung cancer treatment-related radiation pneumonitis. Finally, we summarize different targeted therapy approaches and discuss their application to clinical trials. Irrespective of the slow progress toward clinical improvements, we have gained much knowledge through translational research using new molecular and biologic technology. We believe that knowledge of lung cancer biology will continue to provide the foundation for future improvements in lung cancer treatment.
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PMID:Translational research in lung cancer. 1450 54

We carried out an open, non-randomized phase II study including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective response (complete response, CR, or partial response, PR) or stable disease (SD). The treatment consisted of administration of recombinant interleukin-2 (rIL-2) at a dose of 1.8 MIU subcutaneously three times/week (every other day) for the first 2 weeks of every month plus medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant agents alpha-lipoic acid 300 mg/day and N-acetyl cysteine 1800 mg/day or carbocysteine lysine salt oral solution 2.7 g/day. The treatment was administered for 1 year except when progression of disease occurred. The primary study endpoints were to define clinical outcome, i.e. duration of response, survival (overall survival, OS and progression-free survival, PFS), the toxicity profile, and the evaluation of quality of life (QL). As secondary endpoints, we measured the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin, blood levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were elderly (> 65 years). The majority of patients had either head and neck cancer or lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76% had ECOG 0. Forty patients were previously treated with chemotherapy (27 also with radiotherapy), two with IL-2 and interfiron (IFN), one with endocrine therapy and one with only surgery. We obtained an objective response to maintenance treatment of 50%. Median duration of response was 19 months and median PFS was 33 months. Median duration of maintenance treatment was 12 months, median follow-up duration from diagnosis to June 2003 was 40 months, and median follow-up duration from study entry to June 2003 was 17 months. The median overall survival has not been reached. Toxicity was negligible. As for QL, a significant improvement of cognitive functions was observed, whereas all other functioning and symptom scales did not change significantly. As for laboratory parameters, absolute lymphocyte count increased significantly, IL-6, IL-1 beta, tumor necrosis factor-alpha, CRP, and fibrinogen decreased significantly whereas IL-2 and leptin increased significantly after treatment. ROS decreased significantly, whereas GPx increased significantly after treatment. Patients alive at study end showed a significant increase in absolute lymphocyte count, IL-2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP, fibrinogen, and ROS, whereas patients who died before study end exhibited only a significant increase in absolute lymphocyte count, IL-2, and GPx and a significant decrease of ROS. Long-term combined maintenance therapy with rIL-2 + MPA + antioxidant agents is feasible, has a very low toxicity, and results in the improvement of clinical outcome, QL, and laboratory parameters.
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PMID:Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and antioxidants in advanced cancer responders to previous chemotherapy: phase II study evaluating clinical, quality of life, and laboratory parameters. 1456 91

Breast cancer cells frequently metastasize to the skeleton, where they induce OCL formation and activity, resulting in extensive bone destruction. However, the mechanisms by which breast cancer cells mediate increased osteolysis remain unclear. To elucidate this point, we investigated how 3 human breast cancer cell lines, MDA-MB-231, MDA-MB-435 and MCF-7, induce OCL formation using a murine osteoblast-spleen cell coculture system and compared their effects with a human colorectal cancer cell line, HCT-15; a human lung cancer cell line, HT-1080; and a normal human breast cell line, HME. The breast cancer cell lines supported OCL formation only when osteoblasts were present in spleen cell cocultures, whilst the non-breast cancer cell lines and the normal breast cell line, HME, had no effect. Fractionation of BCCM by ultrafiltration established that osteoclastogenic activity was associated with factors having m.w. >3 kDa. Breast cancer cell lines produced primarily PTHrP, with lesser amounts of IL-6, IL-11 and TNF-alpha. The effect of BCCM on OCL formation in osteoblast-spleen cell cocultures was partially prevented by a neutralising antibody to human PTHrP and completely prevented by a neutralising antibody to either murine IL-11 or the murine IL-11 receptor; neutralising antibodies to human IL-6, IL-11 or TNF-alpha were without effect. BCCM or human PTHrP induced an increase in murine osteoblast IL-11 mRNA and protein production, effects that were prevented in the presence of a neutralising antibody to human PTHrP. The osteoclastogenic activity of IL-11 was mediated by enhancing osteoblast production of PGE(2) effects, which were abrogated by an inhibitor of cyclooxygenase. PGE(2) apparently enhanced OCL formation by downregulating GM-CSF production by spleen cells since recombinant murine GM-CSF inhibited OCL formation and a neutralising antibody to murine GM-CSF blocked these inhibitory effects. We conclude that breast cancer cells induce OCL formation by stimulating osteoblastic production of IL-11. The subsequent release of PGE(2) followed by inhibition of GM-CSF production by cells within the bone microenvironment plays an important part in mediating the effects of breast cancer cells on OCL formation and their resorptive activity.
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PMID:Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor. 1499 70

We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed.
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PMID:Sera of lung cancer patients affect the release of Th1, Th2 and monocyte-derived cytokines, and the expression of IL-2Ralpha by normal, stimulated mononuclear cells. 1504 52

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.
Lung Cancer 2004 Jun
PMID:Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients. 1514 May 43


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