Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is the leading cause of cancer-related deaths in the United States. Despite improvements in radiation, surgery and chemotherapy the 5 year survival statistics of non-small cell lung cancer (NSCLC) have improved little over the past two decades. It has been proposed that NF-kappaB is a participant in the cytoprotection against several redox-mediated therapeutic agents including ionizing radiation. Cyclooxygenase-2 (COX-2) inhibition has become an attractive target for enhancing the efficacy of radiation and chemotherapy. Numerous mechanistic pathways have been proposed as the means through which COX-2 inhibition enhances the efficacy of radiation. We hypothesize that the COX-2 inhibitor, nimesulide, will improve the efficacy of radiation therapy (RT), at least in part, via the suppression of NF-kappaB mediated cytoprotective pathways. In this study we used the COX-2 inhibitor nimesulide to improve the efficacy of RT when measured by tumor regrowth assays in vivo and clonegenic survival in vitro. For the in vivo assay, A549 tumor cells representing NSCLC were subcutaneously injected into the right flanks of female athymic nude mice (n=10/group). Mice were given nimesulide via drinking water at a concentration of 5 microg/g body weight (b.w.) and the water was replenished daily. Tumors were treated with 30 Gy fractionated radiation and measured bi-weekly. For our in vitro study, clonogenic survival assays were evaluated to determine the effect of nimesulide, radiation, and the combination. The NF-kappaB mediated mechanism of nimesulide was measured by Western blot analysis of NF-kappaB target genes, MnSOD and survivin. In vivo, mice that received combined treatments of 5 microg/g b.w. nimesulide and 30 Gy radiation (3 Gy/fraction, 10 daily fractions) had significant reduction in tumor size in comparison to the 30 Gy radiation control group (p<0.05). In vitro, nimesulide alone produced a significant decrease in clonogenic survival at doses from 0-300 microM. Nimesulide demonstrated an additive effect in combination with radiation. Nimesulide alone reduced MnSOD and survivin protein levels in a dose-dependent manner. 6 Gy radiation caused an initial elevation of MnSOD protein levels which was inhibited by prior treatment of nimesulide suggesting an inhibition of radiation induced NF-kappaB target genes. These results support the hypothesis that COX-2 inhibitors such as nimesulide can increase the efficacy of radiation therapy. In vitro, our results suggest that the radiosensitization of A549 tumor cells by nimesulide is mediated by the suppression of NF-kappaB-mediated, radiation-induced cytoprotective genes.
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PMID:Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo. 1696 92

Lung tissue is directly exposed to high oxygen pressure, as well as increased endogenous and exogenous oxidative stress. Reactive oxygen species (ROS) generated in these conditions play an important role in the initiation and promotion of neoplastic growth. In response to oxidative stress, the antioxidant activity increases and minimizes ROS-induced injury in experimental systems. The aim of the present study was to evaluate the activity of antioxidant enzymes, such as superoxide dismutase (SOD; isoforms: Cu/ZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), along with the concentration of malondialdehyde (MDA) in tumor and adjacent noncancerous tissues of two histological types of NSCLC, i.e., adenocarcinoma and squamous cell carcinoma, collected from 53 individuals with surgically resectable NSCLC. MDA concentration was similar in tumors compared with adjacent noncancerous tissues. Tumor cells had low MnSOD activity, usually low Cu/ZnSOD activity, and almost always low catalase activity compared with those of the corresponding tumor-free lung tissues. Activities of GSH-related enzymes were significantly higher in tumor tissues, irrespective of the histological type of cancer. This pattern of antioxidant enzymes activity could possibly be the way by which tumor cells protect themselves against increased oxidative stress.
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PMID:Activity of Antioxidant Enzymes in the Tumor and Adjacent Noncancerous Tissues of Non-Small-Cell Lung Cancer. 3178 31