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

TNF-related apoptosis-inducing ligand (TRAIL/Apo- 2L), a newly identified member of the TNF family promotes apoptosis by binding to the transmembrane receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). TRAIL known to activate NF-kappaB in number of tumor cells including A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells exerts relatively selective cytotoxic affects to the human tumor cell lines without much effect on the normal cells. We set out to identify an agent that would sensitize lung cancer cells to TRAIL-induced apoptosis through inhibition of NF-kappaB activation. We found that triptolide, an oxygenated diterpene extracted and purified from the Chinese herb Tripterygium wilfordii sensitized A549 and NCI-H1299 cells to TRAIL-induced apoptosis through inhibition of NF-kappaB activation. Pretreatment with MG132 which is a well-known NF-kappaB inhibitor by blocking degradation of IkappaBalpha also greatly sensitized lung cancer cells to TRAIL-induced apoptosis. Triptolide did not block DNA binding of NF-kappaB activated by TRAIL as in the case of TNF-alpha. It has been already proven that triptolide blocks transactivation of p65 which plays a key role in NF-kappaB activation. These observations suggest that triptolide may be a potentially useful drug to enhance TRAIL-induced tumor killing in lung cancer.
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PMID:Triptolide sensitizes lung cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by inhibition of NF-kappaB activation. 1252 88

Clinical scientists from eight European countries and China gathered in the ancient Chinese capital of Xi'an on April 26-28, 2001 to discuss collaboration on a modern approach to gastric cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer presented their most up-to-date research results on topics ranging from epidemiology and immune mechanisms to Helicobacter pylori and vaccine development. Researchers then formed groups with their Chinese or European counterparts to plan future research endeavors which will benefit Chinese and European populations alike. After 3 years of organization between the Institute of Digestive Diseases of the Fourth Medical University in Xi'an, China and the Laboratory of Immunogenetics, VU University Medical Center in Amsterdam, the first workshop came into being under the joint sponsorship of the Commission of the European Union, National Natural Science Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As gastric cancer is the most prevalent malignant tumor in China, the workshop was of special significance to the Chinese researchers and to the Chinese population in general. During the workshop, presentations on the epidemiology of gastric cancer showed that this disease is in fact common the world over: it is the second most common cancer next to lung cancer and about 1 million new cases were diagnosed in 2000. Three-quarters of the cases of gastric cancer occur in Asia, and approximately 80% of these cases are in China and Japan. Genetic factors and environmental factors such as diet and H. pylori infection play a role in gastric carcinogenesis. As a recognized cause of gastric cancer, H. pylori was the subject of various presentations ranging from immunological studies, molecular analysis of strains and pathogenesis to vaccine development. Specific areas of discussion included bacterial-epithelial interactions in H. pylori infection, epidemiology in China, global distribution of vacA and cagA genotypes, new evidence for host factors, nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor for gastric cancer, new diagnostic techniques for H. pylori using serum levels of pepsinogen I, and autoimmune processes in corpus atrophy. Vaccine development using a variety of strategies against H. pylori was the subject of an entire session of talks. Oral immunization with urease with Escherichia coli heat labile enterotoxin was shown to be safe and immunogenic in humans as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium as a vehicle for DNA-mediated immunization in mice were also presented. A final presentation discussed an ongoing trial comparing strain variability in the vacA and cagA gene sequences and disease expression between H. pylori infection in Europe and China. Researchers also discussed the role of IL1 gene family and TNF gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer, such as down-regulation of NF kappa B, IL-1 and IL-1RA, cyclooxygenase signalling, and identification of MGAg antibodies. An interactive discussion followed each presentation and ideas and suggestions were provided. According to specialty, the presenters were then assigned to groups of four or five to make plans for joint research projects. A number of international and Chinese observers were present, including representatives from the European Commission, the World Health Organization and the Chinese National Center for Biotechnology Development, and offered input on the financial feasibility of such projects.
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PMID:The immunogenetics and pathogenesis of gastric cancer. Highlights of the First Sino-European Workshop on the Immunogenetics and Pathogenesis of Gastric Cancer. 1253 77

A loss of TNF receptors expression has been found in advanced lung cancers, and human A549 lung adenocarcinoma cells are resistant to the cytotoxic effects of TNF-alpha and cisplatin. Here, the mechanisms of the drug resistance of A549 were extensively studied by gene modulation of the cells by solamargine (SM) which was isolated from Solanum incanum herb. SM induced morphological changes of chromatin condensation, DNA fragmentation, and sub-G(1) peak in a DNA histogram of A549 cells, indicating cell death by apoptosis. SM elevated the expressions of TNF-R1 and -R2 and overcame the resistance of A549 cells to TNF-alpha and -beta. The recruitment of TRADD, FADD, and activation of caspase-8 and -3 in SM-treated A549 cells evidenced the activation of TNFRs signal transduction. In addition, release of cytochrome c from mitochondria, down-expression of Bcl-2 and Bcl-x(L), up-regulation of Bax, and caspase-9 activities were observed in SM-treated A549 cells. Combinational treatment of SM and cisplatin synergistically enhanced caspase-8, -9, and -3 activities in A549 cells. Thus, SM sensitizes A549 cells through TNFRs and mitochondria-mediated pathways and may have anticancer potential against TNFs- and cisplatin-resistance lung cancer cells.
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PMID:Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. 1533 28

Lung cancer continues to be a leading cause of death in the US, and in its most advanced stages remains incurable. Cytotoxic chemotherapies have been the standard of care for the treatment of unresectable disease. However, recent advances in the development of epidermal growth factor receptor (EGFR) inhibitors have led the way to a new generation of targeted biological agents. During the second annual symposium entitled 'the future of lung cancer: a translational focus', which was sponsored by the Physician s Education Resource, new strategies for the treatment of lung cancer were discussed. Besides the role of EGFR inhibitors, potential targets include the angiogenesis pathway; other growth factor pathways, such as phosphoinositol-3 kinase/Akt and Raf-MEK; the 26S proteasome, the histone deacetylase mechanism; and the TNF-related apoptosis-inducing factor receptors. Agents that are directed against these targets are all in varying stages of clinical development. As more is learned about their mechanisms of action and clinical spectrum of activity, the author anticipates their incorporation into novel regimens with enhanced activity against lung cancer.
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PMID:The second annual symposium on the future of lung cancer: a translational focus. 11-12 November 2005, Washington D.C., USA. 1670 87

Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.
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PMID:[VEGF in the cancer anorexia-cachexia syndrome in patients with lung cancer]. 1726 67

Blockage of either nuclear factor-kappaB (NF-kappaB) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-kappaB activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-kappaB. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-kappaB activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-kappaB activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-kappaB and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-kappaB and Akt, which may be applied in lung cancer therapy.
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PMID:Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-kappaB and Akt pathways. 1731 70

Cancers of the lung and pleura remain a major cause of cancer deaths, both in men and women, with strong causal relationships between cigarette smoking and asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The poor survival rates for small cell lung cancer and mesotheliomas argue powerfully for greater understanding of mechanisms of carcinogenesis, genetic abnormalities and the role of tumour suppressor genes and proteins in carcinomas of the lung and pleura. Despite progress in the development of newer cytotoxic drugs, lung cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a modest improvement in survival of patients with advanced disease. Increased knowledge of molecular mechanisms of lung cancer and apoptosis are providing opportunities for treating lung cancer with new classes of molecularly targeted drugs. These novel therapies should target the abnormalities in lung cancer by maximizing the effects of anti-tumour molecules, with minimal side effects on normal tissues. Of the several molecular targets, those receiving attention are p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several studies have shown benefits, there is a need for well planned clinical trials of drugs that target the apoptotic cascade. Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies.
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PMID:Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets. 1803 30

Interleukins IL-1beta, IL-6 and TNF are increased in plasma of patients with severe infections and septic shock. Our objective was the evaluation of IL-1beta, IL-6 and TNF in plasma and exudates of pleural fluid and their contribution to the diagnosis. We studied 44 patients, 27 men and 17 women with mean age 66.81 +/- 11.75 years; 16 with pneumonia and parapneumonic effusion, 14 with primary lung cancer and pleural effusion and 14 with tuberculous pleuritis. We measured IL-1beta, IL-6 and TNF in serum and pleural fluid with ELISA. In patients with pneumonia and parapneumonic effusion the mean value of IL-1beta IL-6 and TNF in plasma was 9.05, 19.24 and 21.34 pg/ml and in pleural fluid 10.34, 32.19 and 25.30 pg/ml. In patients with lung cancer the mean values of IL-1beta, IL-6 and TNF were 5.33, 11.74 and 11.51 pg/ml and 6.70, 13.13, 20.89 pg/ml, respectively. In those with tuberculous pleuritis the respective mean values were 10.33, 49.94, 21.27 pg/ml and 14, 56.59, 23.58 pg/ml. In conclusion, IL-1beta and IL-6 were found increased in plasma and tuberculous pleural fluid, indicating an inflammatory status.
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PMID:Interleukin -1beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor (TNF) in plasma and pleural fluid of pneumonia, lung cancer and tuberculous pleuritis. 1808 54

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.
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PMID:Curcumin and cancer: an "old-age" disease with an "age-old" solution. 1846 66

Studies on the relationships between inflammatory pathway genes and lung cancer risk have not included African-Americans and have only included a handful of genes. In a population-based case-control study on 198 African-American and 744 Caucasian women, we examined the association between 70 cytokine and cytokine receptor single-nucleotide polymorphisms (SNPs) and risk of non-small cell lung cancer (NSCLC). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals in a dominant model adjusting for major risk factors for lung cancer. Separate analyses were conducted by race and by smoking history and history of chronic obstructive pulmonary disease among Caucasians. Random forest analysis was conducted by race. On logistic regression analysis, IL6 (interleukin 6), IL7R, IL15, TNF (tumor necrosis factor), and IL10 SNP were associated with risk of non-small cell lung cancer among African-Americans; IL7R and IL10 SNPs were also associated with risk of lung cancer among Caucasians. Although random forest analysis showed IL7R and IL10 SNPs as being associated with risk for lung cancer among African-Americans, it also identified TNFRSF10A SNP as an important predictor. On random forest analysis, an IL1A SNP was identified as an important predictor of lung cancer among Caucasian women. Inflammatory SNPs differentially predicted risk for NSCLC according to race, as well as based on smoking history and history of chronic obstructive pulmonary disease among Caucasian women. Pathway analysis results are presented. Inflammatory pathway genotypes may serve to define a high risk group; further exploration of these genes in minority populations is warranted.
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PMID:Cytokine and cytokine receptor single-nucleotide polymorphisms predict risk for non-small cell lung cancer among women. 1950 16


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