Disease relevance of Celebra

• The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis [1].
• RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups) [1].
• Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial [2].
• Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity [3].
• There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS [4].
• A combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer [5].
• IDEA-033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis [6].
• Celecoxib potentiates the antitumor effect of chemotherapeutic drugs currently used in neuroblastoma treatment, which argues for clinical trials combining these drugs [7].

Psychiatry related information on Celebra

• Acute onset of auditory hallucinations after initiation of celecoxib therapy [8].
• We hypothesized that celecoxib augmentation therapy would improve psychopathology ratings compared with placebo [9].
• RESULTS: Our base-case analysis assumed a 50% risk reduction in the incidence of adenomas among patients using celecoxib [10].
• Long-term efficacy and safety of celecoxib in Alzheimer's disease [11].
• RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls [12].

High impact information on Celebra

• Rofecoxib vs celecoxib vs acetaminophen for treatment of osteoarthritis [13].
• Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study [3].
• The overall incidences of GI tract adverse effects were 19% for placebo; 28%, 25%, and 26% for celecoxib 100 mg, 200 mg, and 400 mg twice per day, respectively; and 31 % for naproxen [14].
• The incidence of endoscopically determined gastroduodenal ulcers in placebo-treated patients was 4 (4%) of 99, and the incidences across all dosages of celecoxib were not significantly different (P>.40): 9 (6%) of 148 with 100 mg twice per day, 6 (4%) of 145 with 200 mg twice per day, and 8 (6%) of 130 with 400 mg twice per day [14].
• OBJECTIVE: To test whether celecoxib has efficacy as an anti-inflammatory and analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis [14].

Chemical compound and disease context of Celebra

• Rofecoxib vs celecoxib vs acetaminophen for treatment of osteoarthritis [15].
• Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis (FAP) [16].
• The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001) [17].
• Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites [18].
• These data indicate that a major antitumor mechanism of action of celecoxib is inhibition of COX-2-derived prostaglandins, particularly PGE2, and suggest celecoxib as a novel therapeutic agent for human head and neck cancer [19].

Biological context of Celebra

• Some celecoxib derivatives that lacked COX-2 inhibitory activity facilitated apoptosis and vice versa [20].
• Moreover, celecoxib and apoptosis-active celecoxib derivatives mediated cell death by inhibiting the same pathway [20].
• The molecular structures of celecoxib and rofecoxib were used as starting points to examine the structural features that contribute to this discrepancy [21].
• Celecoxib or Herceptin inhibits HCA-7 cell growth in vitro and in vivo [22].
• METHODS: Gene expression array analysis ([RG-U34] GeneChip) was performed in normal and transformed rat intestinal epithelial cells before and after exposures to celecoxib [23].

Anatomical context of Celebra

• Celecoxib, but not SC-560, significantly increased leukocyte adherence, whereas SC-560, but not celecoxib, reduced gastric blood flow [24].
• Celecoxib treatment caused exfoliation of the mucosal surface epithelium, but neither caused deep erosions or altered survivin expression [25].
• These findings suggests that (i) aspirin and NCX-4016 trigger ATL formation in humans, (ii) celecoxib inhibits ATL formation and exacerbates the mucosal injury caused by low doses of aspirin, and (iii) the NO-donating moiety of NCX-4016 protects the gastric mucosa even in the presence of suppression of COX-1 and COX-2 [26].
• Increased levels of PGs were found in the cerebrospinal fluid after carrageenan injection and were markedly reduced by celecoxib, but were not affected by SC-560 [27].
• Here we show that DMC (and celecoxib) inhibits the proliferation of various multiple myeloma cell lines, including several (multi) drug-resistant variants [28].

Associations of Celebra with other chemical compounds

• Western blotting was used to monitor the effects of the compounds on phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated kinase 2 (ERK2), two components of celecoxib-induced apoptosis signaling [21].
• We compared small intestinal function and morphology in untreated wild-type, COX-1- and COX-2-deficient mice and the effect of indomethacin, selective COX-1 (SC-560), and COX-2 (celecoxib) inhibition [29].
• METHODS: The effects of SC-560, celecoxib (selective COX-2 inhibitor), or a combination of both inhibitors on gastric damage and prostaglandin synthesis were determined [24].
• METHODS: We conducted a randomized, controlled trial of selenomethionine 200 microg daily and/or celecoxib 200 mg twice daily (2 x 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline [30].
• By contrast, both ibuprofen and celecoxib suppressed a biochemical index of COX-2 activity (endotoxin induced PGE2 in whole blood ex vivo) to a comparable degree (-93.3 +/- 2% vs. -83 +/- 6.1%) [31].
• An alternative mechanism is proposed for the cancer-preventive role of celecoxib other than the classic mechanism of inhibiting prostaglandin synthesis, stressing mainly the role of cyclin D1 [32].
• The pharmacokinetics of celecoxib is not significantly affected by the concomitant administration of phenytoin [33].
• In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E(2), after 1 week of celecoxib administration [34].

Gene context of Celebra

• We examined the variability in degree and selectivity of COX-2 inhibition in humans in response to celecoxib and rofecoxib [35].
• Furthermore, long-term celecoxib administration in wild-type animals was associated with similar damage as in the COX-2(-/-) mice [29].
• However, celecoxib, having caused no damage in COX-1(+/+) animals, caused small bowel ulcers in COX-1(-/-) animals [29].
• Treatment of various pancreatic cancer cells with celecoxib suppressed VEGF expression at both the mRNA and protein level in a dose-dependent manner [36].
• Cyclooxygenase-2 expression and effect of celecoxib in gastric adenomas of trefoil factor 1-deficient mice [37].
• A genetically null mutant of Drosophila Shab (Kv2) channels reproduced the cardiac effect of celecoxib, and the drug was unable to further enhance the effect of the mutation [38].

Analytical, diagnostic and therapeutic context of Celebra

• The increase of VEGF was abolished after treatment with celecoxib, a selective COX-2 inhibitor [39].
• Celecoxib treatment initiating before polyposis (3.5-10 months) led to a dramatic reduction in tumor burden (86%) and was associated with decreased vascularity of the polyps [40].
• These studies support the use of low doses of celecoxib in omega-3 PUFA-rich diet as a promising approach for clinical trials [41].
• Treatment with celecoxib was examined and compared to treatment with the general NSAID, ibuprofen, and to a control group receiving only dimethylbenz(a)anthracene [42].
• Our findings suggest that celecoxib may be useful in chemoprevention of prostate cancer [43].

References