Disease relevance of ns-398

• The effects of long-term administration of NS-398 on gastric ulcers were examined [1].
• Treatment with NS-398 (a COX-2 inhibitor) significantly decreased the severity of pancreatitis [2].
• The same doses of NS-398 and celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective effects of late PC against both myocardial stunning and myocardial infarction, indicating that COX-2 activity is necessary for this phenomenon to occur [3].
• Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells [4].
• Additionally, we demonstrated that NS-398 enhanced PDT responsiveness in RIF tumors without increasing toxicity to normal tissue [5].

Psychiatry related information on ns-398

• Rapid eye movement sleep and brain temperature were not altered by any dose of NS-398 [6].
• In contrast, NS-398 in doses up to 50 mug failed to increase exploratory behavior [7].
• Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide (vehicle) or COX-1 (SC-560) or COX-2 (NS-398) inhibitors [7].

High impact information on ns-398

• The effect is inhibited by antibodies to combinations of angiogenic factors, by NS-398 (a selective COX-2 inhibitor), and by aspirin [8].
• The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours [9].
• PGE(2) levels were determined in supernatants from epithelial cells treated with the selective COX-2 inhibitor NS-398, proinflammatory cytokines (interleukin 1beta and tumor necrosis factor-alpha), and conditioned medium from fibroblast cultures (both unstimulated and stimulated with proinflammatory cytokines) [10].
• The addition of exogenous PGE(2) reversed the antiproliferative effect of NS-398 on Barrett's esophageal epithelial cells [10].
• Par-4 levels were increased in cells treated with COX inhibitors such as NS-398, nimesulide, SC-58125, and sulindac sulfide [11].

Chemical compound and disease context of ns-398

• The effect of four NSAIDs (diclofenac, indomethacin, piroxicam, and NS-398) on pO2 was studied in murine TLT liver tumors and FSaII fibrosarcomas [12].
• Treatment with NS-398 (50 microM), a specific inhibitor of COX-2, suppressed PGE2 production of all melanoma cell lines by 50-96% [13].
• The cPLA(2) inhibitor arachidonyl fluorophosphonate (MAFP) and the COX-2 inhibitor NS-398 significantly inhibited HGF- and IL-6-induced release of AA, PG synthesis, and proliferation in SG231 cells as well as two other human cholangiocarcinoma cell lines, HuCCT1 and CC-LP-1 cells [14].
• Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats [15].
• Carrageenan-induced paw edema was inhibited by pretreatment with FR167653, anti-tumor necrosis factor (TNF)-alpha antibody, and NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide), a selective cyclooxygenase-2 inhibitor [16].

Biological context of ns-398

• Also, a selective Cox-2 inhibitor, NS-398, significantly enhanced genotoxic stress-induced apoptosis in several types of p53+/+ normal human cells, through a caspase-dependent pathway [17].
• Treatment of bystander cells with NS-398, which suppresses COX-2 activity, significantly reduced the bystander effect [18].
• The COX-2-selective inhibitors NS-398 and nimesulide and the TXA(2) receptor antagonist BMS 180,291 inhibited TNF-alpha- and Ang II-mediated increases in DNA content and cell number by approximately 95% [19].
• The cyclooxygenase inhibitors, NS-398 and indomethacin, were found to be less potent blockers of cell proliferation and poor inducers of cellular AA accumulation than CoA-IT inhibitors in these breast cancer cell lines [20].
• The aim of our study was to determine whether selective inhibition of COX-2 by NS-398 would alter the rates of cell growth and apoptosis in human Barrett's-associated esophageal adenocarcinoma cell lines [21].

Anatomical context of ns-398

• Administration of 15d-PGJ(2) into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment [22].
• Additionally, VEGF- and bFGF-induced angiogenesis in vivo was also inhibited by about 50% by NS-398 or piroxicam, and this inhibitory effect was accompanied by decreased expression of CXCR4 on murine endothelial cells [23].
• Administration of the cyclooxygenase 2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ(2) accumulation and PrxI expression [22].
• We could show that proliferation of melanoma cell lines was not influenced by treatment with NS-398 in concentrations up to 100 microM [13].
• Cell growth was compared in flurbiprofen-treated and untreated tumor cell lines; cell growth and apoptosis were compared in NS-398-treated and untreated tumor cell lines [21].

Associations of ns-398 with other chemical compounds

• We investigated the relationship between suppression of inflammation by COX-2 inhibitors (NS-398, nimesulide, DuP697, and etodolac) and their effects on gastric prostaglandin synthesis [24].
• Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE(2) and 6-keto-PGF(1alpha) [3].
• However, addition of PGE(2) to cultures containing both GDF-9 and NS-398 overrides the NS-398 block in progesterone synthesis [25].
• LPS-induced PGE2 and thromboxane B2 (TXB2) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398 [26].
• We also observed that systemic administration of NS-398 decreased PDT induction of both PGE2 and vascular endothelial growth factor in treated RIF tumors [5].

Gene context of ns-398

• To further define the PGE(2)-dependent pathway, we show that butaprost, a specific EP2 agonist, stimulates progesterone synthesis and overrides the NS-398 block [25].
• Treatment of HeLa cells overexpressing COX-1 with the dual COX enzyme inhibitor indomethacin or selective COX-2 inhibitor NS-398 significantly reduced PGE(2) synthesis [27].
• Aspirin and NS-398, in contrast to PD98059, did not suppress ERK1/2 phosphorylation induced by HGF [4].
• In conclusion, our results suggest that aspirin and NS-398 inhibit HGF-induced invasiveness of HepG2 human hepatoma cells through ERK1/2 [4].
• Selective COX-2 inhibition by NS-398 restored TNFalpha-mediated apoptosis [28].

Analytical, diagnostic and therapeutic context of ns-398

• COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist [1].
• We evaluated the effect of cyclooxygenase (COX) inhibitors (NSAIDs) on human colon carcinoma cells (HCA-7) and identified several genes that are regulated after treatment with NS-398, a selective COX-2 inhibitor [11].
• In response to pulses of acid or bile salts in an ex vivo organ culture system, COX-2 expression increased significantly in BE tissues, and this effect was attenuated by the selective COX-2 inhibitor NS-398 [29].
• NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner [30].
• NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system [30].

References