Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL-8)) of this acute phase protein were examined in healthy subjects (n=11) and patients with non-small-cell lung cancer (n=50). Leukaemia inhibitory factor and CNTF were below detection limits in all controls and patients. C-reactive protein, interleukin-6, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and IL-8 concentrations were significantly elevated in cancer patients (P< or =0.001). Cancer patients with elevated C-reactive protein concentrations had greater concentrations of interleukin-6 (P<0.01) and interleukin-1 receptor antagonist (P<0.05). On regression analysis only interleukin-6 was independently associated with C-reactive protein (r=0.616, P<0.001). Interleukin-6 is an important independent mediator of elevated C-reactive protein concentrations in patients with non-small-cell lung cancer.
 ...
PMID:The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. 1557 Mar 10

Respiratory epithelial cells are known to contribute to immune responses through the release of mediators. The aim of this study was to characterize the immunomodulatory effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco carcinogen, on respiratory epithelial cells and to compare two metabolic pathways, alpha-methylhydroxylation and alpha-methylenehydroxylation, involved in these effects using selective precursors, 4-(acetoxy-methylnitrosamino)-1-(3-pyridil)-1-butanone (NNKOAc) and N-nitroso (acetoxymethyl) methylamine (NDMAOAc), respectively. Human bronchial and alveolar epithelial cell lines, BEAS-2B and A549, respectively, were treated with NNK, NNKOAc and NDMAOAc for 24 h with and without tumour necrosis factor (TNF) and mediators released in cell-free supernatants were measured by enzyme-linked immunosorbent assay (ELISA). NNK significantly inhibited interleukin (IL)-8, IL-6 and monocyte chemoattractant protein-1 (MCP-1) production in both cell types. Similar results were observed with primary bronchial and alveolar epithelial cells. Although NNK increased prostaglandin E(2) (PGE(2)) production by A549 cells, its immunomodulatory effects were not mediated by PGE(2) according to the results with cyclo-oxygenase inhibitors. NNKOAc mimicked NNK effects, whereas NDMAOAc significantly inhibited IL-8 production in BEAS-2B cells and MCP-1 in both cell types. These results demonstrate that NNK and its reactive metabolites have immunosuppressive effects on respiratory epithelial cells, which could contribute to the increased respiratory infections observed in smokers and the development and/or the progression of lung cancer.
 ...
PMID:4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a component of tobacco smoke, modulates mediator release from human bronchial and alveolar epithelial cells. 1576 74

While cases of silicosis are often complicated by various autoimmune disorders, patients with asbestosis develop malignant tumors such as lung cancer and malignant mesothelioma. These differences may derive from different biological effects, particularly on immunological cells, of silica and asbestos. To find differences between silica and asbestos, the early activation antigen, CD69, on T cells was examined because dysregulated and continuous activation of T cells may promote the survival of self-recognizing T cells. After cultivation of peripheral blood mononuclear cells with or without silica or chrysotile-A, an asbestos, only silica induced CD69 expression on the lymphocytes. This induction of CD69 expression was mediated by protein kinase C activation. In addition, cell-cell contact mediated by HLA-DR was more important than soluble factors secreted from silica-phagocytosed cells such as IL-1beta, IL-6, and IL-8, even though IL-6 and IL-8 were produced during the culture of PBMCs with silica and chrysotile-A. It should be examined how these activated, CD69-expressing lymphocytes affect other immune systems as well as alter themselves in terms of cytokine production and cell-cell interaction, leading to autoimmune disorders in silicosis patients.
 ...
PMID:Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A. 1579 May 20

Nude rats bearing the LC-6-JCK human lung cancer xenograft displayed cancer-associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL-6, leukemia-inducing factor, IL-8, IL-5 and IL-11, were secreted to the bloodstream. Proinflammatory cytokines induce acute-phase reactions, as evidenced by a decrease of serum albumin and an increase in alpha1-acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute-phase reactions, whereas anti-PTHrP antibody affected neither proinflammatory cytokine production nor acute-phase reactions. Nevertheless, tumor resection and administration of anti-PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti-PTHrP antibody was associated with increased food consumption; increased body weight from anti-PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC-6-JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti-PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP-induced wasting syndrome.
 ...
PMID:Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. 1580 Sep 41

Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy in lung cancer patients.
 ...
PMID:Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer. 1611 7

Type 2 cytokines are usually predominant in tumor patients and associated with tumor progression. To explore whether reversing of type 2 predominance could be a promising strategy in tumor immunotherapy, PBMC of 35 lung cancer patients and 19 healthy subjects were prepared and subjected to be examined for cytokine secretion and gene expression. Tetra-Methylpyrazine (TTMP), extracted from a traditional Chinese medicinal herb which has been used in clinic to reverse the Th2 status of cancer patients in China, was added to PBMC culture. Determined by RT-PCR, the positive percentages of mRNA expression of type 1 cytokines (8.6% for IFN-gamma and 11.4% for IL-2) were lower than those of type 2 cytokines (71.4% for IL-4, 60% for IL-6 and 80% for IL-10) in patients' PBMCs. The potential of gene expressing (measured as relative intensity to the ratio of beta-actin) in the patients for type 1 cytokines was also in a low level (0.111 for IFN-gamma, 0.119 for IL-2) in comparison with a relative high level for type 2 cytokines (0.319 for IL-4, 0.303 for IL-6 and 0.377 for IL-10). Meanwhile, both positive percentage and relative intensity of gene expression were lower for a type 1 cytokine-related transcription factor T-bet (31.4% and 0.142, respectively) than those for type 2 cytokine-related GATA3 (85.7% and 0.378, respectively). The blood serum levels of IFN-gamma and IL-2 in the patients were slightly lower but not significantly when compared with healthy control. In contrast, the levels IL-4 and IL-6 in patients were significantly higher than those in healthy subjects by ELISA analysis. TTMP could enhance supernatant concentration and gene expression levels of IFN-gamma, IL-2 and T-bet, but reduce those of type 2 cytokines. These results demonstrate that the lung cancer patients had a predominant expression of type 2 cytokines and TTMP could reverse the type 2 dominant status, which might offer an alternative therapeutic regime for lung cancer patients.
 ...
PMID:Type two cytokines predominance of human lung cancer and its reverse by traditional Chinese medicine TTMP. 1621 23

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-alpha, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-alpha immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-alpha (p < 0.001) and CRP (p < 0.001), and lower leptin (p = 0.021) levels in patients than in controls. Serum IL-6 cytokine (p = 0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-alpha, and CRP were all similar in lung cancer patients independently from severity of weight loss (p > 0.05). A direct relationship was found between serum IL-6 and TNF-alpha levels (r = 0.530, p = 0.004). We found that both serum leptin (p = 0.046) and IL-6 (p = 0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-alpha and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p = 0.06) related to a worse prognosis.
 ...
PMID:Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer. 1626 Aug 52

Apart from cigarette smoking, genetic factors seem to be of importance in the development of lung cancer. The present case-control study investigated frequencies of five inflammatory response gene polymorphisms (TNF-alpha-308, TNF-beta-Intron1-252, IL-6-174, IL-10-819 and IL-10-1082) in patients with lung cancer and controls. The study population consisted of 117 patients with lung cancer (77 patients with NSCLC, including 40 Squamous Cell Carcinoma and 26 Adenocarcinoma, and 40 patients with SCLC), 117 matched controls without pulmonary disease and 243 healthy individuals (population control). Genotype analyses revealed no difference in genotype frequencies using matched-pair analysis. However, in comparison to the population control, the IL-10-1082 genotypes carrying the G allele appeared with higher frequency in the SCLC group (p=0.006) [SCLC: 84.6%, population controls: 64.6%]. This yields an odds ratio of 3.01 for SCLC (95% CI = [1.21, 7.48]). No associations were seen for all other polymorphisms analysed. The study raises the possibility of a correlation between the IL-10-1082_G allele and the presence of SCLC in a German population. The functional IL-10-1082 polymorphism correlates with altered IL-10 levels and might influence lung cancer susceptibility by altered inflammatory responses in the airways.
 ...
PMID:TNF-alpha, TNF-beta, IL-6, and IL-10 polymorphisms in patients with lung cancer. 1627 11

The alveolar macrophage (AM) is believed to be of central importance in the immune response against infection and tumour. We examined patients with lung cancer in order to evaluate the immuno-stimulatory potential of AM in lung cancer. Bronchoalveolar lavage fluid samples were obtained from patients with adenocarcinoma, squamous cell carcinoma, large cell undifferentiated lung carcinoma, small cell carcinoma and control subjects. AM were isolated and phagocytic function, flow cytometry and cytokine analysis were assessed. AM from patients with small and squamous cell carcinoma had impaired uptake in vitro of 40 nm fluorescent polystyrene beads. AM from patients with small, squamous and large cell undifferentiated carcinoma showed impaired uptake of 1000 nm fluorescent polystyrene beads. Secreted levels of TNF-alpha and IL-1 from AM of patients with small, squamous, and large cell undifferentiated carcinoma were decreased compared to controls. Secreted AM IL-6 levels were decreased in small and large cell undifferentiated carcinoma. AM from adenocarcinoma patients showed similar levels of IL-10, IL-6, IL-1 and TNF-alpha compared to controls. Phenotypic analysis demonstrated that patients with small cell carcinoma were the only group that showed a decrease in MHC class II surface expression. Surface expression of ICAM-1 and CD83 was decreased on AM from patients with large, squamous and small cell carcinoma compared to controls but not adenocarcinoma. Mannose receptor levels were only decreased on AM from patients with squamous and small cell carcinoma but not adenocarcinoma and large cell undifferentiated carcinoma. We conclude that there are type-specific alterations in uptake ability, cytokine secretion and phenotype of AM from lung cancer patients, which may result in an inability to stimulate anti-tumour immunity. The observed differences between lung cancer subgroups may explain previously reported inconsistencies in descriptions of AM characteristics in lung cancer.
 ...
PMID:Alveolar macrophage function is altered in patients with lung cancer. 1641 62

Malignant pleural effusion (MPE) is a poor prognostic sign for patients with non-small-cell lung cancer (NSCLC). The generation of MPE is largely regulated by vascular endothelial growth factor (VEGF), and upregulation of VEGF by Stat3 has been observed in several types of tumor cells. In this study, we demonstrate constitutively activated Stat3 in several human lung cancer cell lines and in tumor cells infiltrated in the pleurae of patients with adenocarcinoma cell lung cancer (ADCLC) and MPE. The observations suggest that activated Stat3 plays a role in the pathogenesis of ADCLC. In PC14PE6/AS2 cells, a Stat3-positive human ADCLC cell line, autocrine IL-6 activated Stat3 via JAKs, not via Src kinase. PC14PE6/AS2 cells express higher VEGF mRNA and protein than do Stat3-negative PC14PE6/AS2/dnStat3 cells. In an animal model, PC14P6/AS2/dnStat3 cells produced no MPE and less lung metastasis than did PC14P6/AS2 cells. PC14PE6/AS2 cells also expressed higher VEGF protein, microvessel density, and vascular permeability in tumors than did PC14P6/AS2/dnStat3 cells. Therefore, we hypothesize that autocrine IL-6 activation of Stat3 in ADCLC may be involved in the formation of malignant pleural effusion by upregulating VEGF. Higher levels of IL-6 and VEGF were also found in the pleural fluids of patients with ADCLC than in patients with congestive heart failure. The autocrine IL-6/Stat3/VEGF signaling pathway may also be activated in patients with ADCLC and MPE. These findings provide novel targets for the management of MPE.
 ...
PMID:Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. 1651 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>