Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1), trigger the activation of transcription factor NF-kappaB that induces the expression of a variety of genes, including intercellular adhesion molecule (ICAM)-1. Odoroside A [3beta-O-(beta-D-diginosyl)-14-hydroxy-5beta,14beta-card-20(22)-enolide] was found to inhibit the cell-surface expression of ICAM-1 induced by TNF-alpha and IL-1 at comparable concentrations in human lung carcinoma A549 cells. In this study, the molecular mechanism underlying the inhibition of TNF-alpha-induced cell-surface ICAM-1 expression by odoroside A together with the specific Na(+)/K(+)-ATPase inhibitor ouabain was further investigated. Odoroside A and ouabain neither prevented IkappaBalpha degradation nor NF-kappaB translocation to the nucleus upon TNF-alpha stimulation. While odoroside A and ouabain had no inhibitory effect on the induction of ICAM-1 mRNA, they inhibited the TNF-alpha-induced ICAM-1 expression at the protein level. Consistent with these results, odoroside A and ouabain potently reduced de novo protein synthesis, largely due to its ability to block Na(+)-dependent transport of amino acids across the plasma membrane, but not to interfering with the translation machinery. As a direct molecular target, odoroside A was found to inhibit the ATP-hydrolyzing activity of Na(+)/K(+)-ATPase as potently as ouabain. These results clearly demonstrate that odoroside A and ouabain prevent NF-kappaB-inducible protein expression by blocking the Na(+)-dependent amino acid transport.
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PMID:Odoroside A and ouabain inhibit Na+/K+-ATPase and prevent NF-kappaB-inducible protein expression by blocking Na+-dependent amino acid transport. 1955 78

Early recognition of lung cancer is a prerequisite for any strategy to improve lung cancer treatment outcome. Here we report a cross-sectional study intended as a proof of principle investigation using breath based detection (exhaled breath condensate, EBC) of angiogenic markers (VEGF, bFGF, angiogenin), TNF-alpha and IL-8 to discriminate 74 individuals, with confirmed presence or absence (X-ray, CT) of non-small lung cancer (NSCLC). Levels of angiogenic markers bFGF, angiogenin and VEGF in EBC significantly discriminated between 17 individuals with newly detected NSCLC versus stable and exacerbated chronic obstructive pulmonary disease (COPD) patients as well as healthy volunteers. Levels of IL-8 and TNF-alpha in EBC indicated acute inflammation, e.g. in acute exacerbated COPD (AECOPD) and were not indicative of lung cancer. In a different group of patients that were already treated with two cycles of chemotherapy and who responded with at least a 25% reduction in primary tumor diameter, levels of angiogenic markers were lower compared to patients with newly diagnosed NSCLC. We suggest that breath based detection of angiogenic markers may help in the early detection of lung cancer.
Lung Cancer 2010 May
PMID:Angiogenic markers in breath condensate identify non-small cell lung cancer. 1964 34

Activation of initiator caspases is dependent on interacting proteins, and Ipaf [ICE (interleukin-1beta-converting enzyme)-protease activating factor] {NLRC4 [NLR (Nod-like receptor) family CARD (caspase activation and recruitment domain)-containing 4]} an inflammasome component, is involved in caspase 1 activation and apoptosis. Investigating the mechanisms of Ipaf activation, we found that the C-terminal LRR (leucine-rich repeat) domain of Ipaf, through intramolecular interaction, negatively regulates its apoptosis-inducing function. In A549 lung carcinoma cells, expression of Ac-Ipaf (LRR-domain-deleted Ipaf) induced cell death that was dependent on caspase 8, but not on caspase 1. A yeast two-hybrid screen using Ac-Ipaf as bait identified human Sug1 (suppressor of gal 1), a component of the 26S proteasome, as an interacting protein. In mammalian cells Sug1 interacts and co-localizes with Ipaf. Sug1 binds to amino acids 91-253 of Ipaf, which is also the region that the LRR domain binds to. It potentiates cell death induced by Ipaf and Ac-Ipaf, and co-expression of Sug1 and Ipaf induces caspase-8-dependent cell death. Cellular complexes formed by Ipaf and Sug1 contain caspase 8. Expression of Ac-Ipaf or co-expression of Sug1 with Ipaf results in the formation of cytoplasmic aggregates and caspase 8 activation. Sug1 co-expression enabled modification of Ipaf by ubiquitination. Tagging ubiquitin molecules to Ipaf led to aggregate formation, enhanced caspase 8 interaction and activation, resulting in induction of cell death. Using RNAi (RNA interference) and dominant-negative approaches, we have shown that cell death induced by Ac-Ipaf expression or by treatment with TNF-alpha (tumour necrosis factor alpha) or doxorubicin is dependent on Sug1. Our results suggest a role for ubiquitination of Ipaf that is enabled by its interaction with Sug1, leading to caspase 8 activation and cell death.
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PMID:Interaction with Sug1 enables Ipaf ubiquitination leading to caspase 8 activation and cell death. 2008 38

The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1% or 5% (w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-alpha production in lungs, only 5% dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation.
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PMID:Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. 2042 58

We hypothesized that plasma level of tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 may be a potential tool for diagnosis, prognosis and prediction of treatment outcome in non-small cell lung carcinoma (NSCLC). Plasma levels of TNF-alpha and TGF-beta1 were quantified in 100 NSCLC patients and 100 controls. Association of TNF-alpha and TGF-beta1 with response to therapy and survival was determined in 42 patients. An increased presence of TNF-alpha and TGF-beta1 was observed in NSCLC compared with controls. TNF-alpha and TGF-beta1 levels did not correlate with survival and response to chemotherapy. TNF-alpha and TGF-beta1 do not appear to be reliable markers for predicting survival and response to therapy in advanced NSCLC.
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PMID:Utility of plasma tumour necrosis factor-alpha and transforming growth factor-beta1 as predictors of survival and treatment outcome in advanced non-small cell lung carcinoma. 2048 67

We found that Aged Garlic Extract (AGE) could be a significant immuno-potentiator, and could exhibit anti-tumor activities through immune modulation. Consequently, AGE stimulated the proliferation of mouse spleen cells and the release of cytokines, such as IL-2, TNF-alpha and IFN-gamma, increased NK activities, and enhanced phagocytosis of peritoneal macrophages. AGE treatment also stimulated the reactivity of lymphocytes in response to cytokines or mitogens. AGE was far superior to PSK in IL-2 induction, but slightly inferior to PSK in nitric oxide induction. AGE, as effectively as PSK (Krestin), significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in NK and killer activities of spleen cells were observed in Sarcoma-180 bearing mice treated with AGE. These results strongly suggest that AGE is as effective as PSK, and could serve as a potent biological response modifier on NK cells and T lymphocytes, and subsequently inhibit the growth of transplanted tumors.
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PMID:Immunomodulation and antitumor activities of Aged Garlic Extract. 2319 97


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