|show drug details|
|Heumann brand of celecoxib|
|Mack brand of celecoxib|
|Parke Davis brand of celecoxib|
|Pfizer brand of celecoxib|
|Pharmacia brand of celecoxib|
|Pharmacia Spain brand of celecoxib|
|Searle brand of celecoxib|
|upper respiratory tract infection||0.0754|
|gastroesophageal reflux disease||0.047|
|toxic epidermal necrolysis||0.0010|
|stevens johnson syndrome||0.0010|
|acute renal failure||0.0010|
|congestive heart failure||0.0010|
|connective tissue disorders||0.0010|
|transient ischemic attacks||0.0010|
|deep venous thrombosis||0.0010|
|elevated blood pressure||0|
|liver function tests abnormal||0|
|abdominal pain upper||0|
|urinary tract infection||0|
|alkaline phosphatase increased||0|
|coronary artery disease||0|
|aortic valve incompetence||0|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV.. Nannan Chen; Andrew Restivo; Carol Shoshkes Reiss (2002) Prostaglandins & other lipid mediators display abstract
Cyclooxygenase (COX) is the key enzyme for prostaglandin (PG) synthesis. PGs are mediators of many critical physiological and inflammatory responses. There are two isoforms, COX-1 and COX-2, both of which are constitutively expressed in the central nervous system (CNS). Studies have shown that COX-1 and COX-2 are involved in physiological and pathological conditions of the brain. However, little is known about the role(s) of COX in the host defense system against a viral infection in the CNS. In this report, we used Vesicular Stomatitis Virus (VSV) induced acute encephalitis to distinguish between the contribution(s) of the two isoforms. COX-2 activity was inhibited with a COX-2 selective drug, celecoxib (Celebrex), and COX-1 was antagonized with SC560. We found that inhibition of COX-2 led to decreased viral titers, while COX-1 antagonism did not have the same effect at day 1 post infection. 5-lipooxygenase (5-LO) expression and neutrophil recruitment in the CNS were increased in celecoxib-inhibited mice. Furthermore, mice treated with celecoxib expressed more Nitric Oxide Synthase-1 (NOS-1), a crucial component of the innate immune system in the restriction of VSV propagation. The expression of type 1 cytokines, IFN-gamma and IL-12, were also increased in celecoxib-treated mice.
Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer.. Louise R Howe; Kotha Subbaramaiah; Jay Patel; Jaime L Masferrer; Aparna Deora; Clifford Hudis; Howard T Thaler; William J Muller; Baoheng Du; Anthony M C Brown; Andrew J Dannenberg (2002) Cancer research display abstract
Cyclooxygenase 2 (HER-2) (Cox-2), an inducible form of Cox, is overexpressed in HER-2/neu-positive human breast cancers. The aim of this study was to determine whether celecoxib, a selective Cox-2 inhibitor, protected against HER-2/neu-induced experimental breast cancer. Cox-2 protein was detected in breast carcinomas from mouse mammary tumor virus (MMTV)/neu mice. Treatment with celecoxib (500 ppm) significantly reduced the incidence of mammary tumors in MMTV/neu mice (P = 0.003) and caused about a 50% reduction in mammary prostaglandin E2 (PGE2) levels. Because mammary glands from MMTV/neu mice expressed all four PGE2 receptor subtypes, we speculate that signaling through PGE2 receptors is important for mammary tumorigenesis. These results strengthen the rationale for developing clinical trials to determine whether selective Cox-2 inhibitors possess anticancer properties in humans at risk for breast cancer.
Celecoxib and difluoromethylornithine in combination have strong therapeutic activity against UV-induced skin tumors in mice.. Susan M Fischer; Claudio J Conti; Jaye Viner; C Marcelo Aldaz; Ronald A Lubet (2003) Carcinogenesis display abstract
The cyclooxygenase-2 (COX-2) inhibitor celecoxib and the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) were each previously shown to prevent skin tumor development when administered throughout the course of UV irradiation. This raised the question of whether maintenance or continued growth of existing tumors required prostaglandins, the product of COX, or polyamines, the product of ODC. To address this question, SKH hairless mice were irradiated 3 times/week with 90 mJ/cm(2); this dose was increased 10% weekly to a maximum of 175 mJ/cm(2). UV was stopped at 27 weeks, at which time there were an average of 5 papillomas/mouse. The mice were then placed in one of four treatment groups: group 1, no treatment; group 2, 0.4% DFMO in the drinking water; group 3, 500 p.p.m. celecoxib in the diet (AIN76); group 4, both DFMO and celecoxib. The control group continued to produce new tumors in a nearly linear manner such that by week 31 the tumor number had nearly doubled, i.e. approximately 10 tumors/mouse. The group receiving DFMO showed significant tumor regression, losing an average of 1 tumor/mouse/week, such that 50% of the tumors remained at week 31. The celecoxib group showed a 25% reduction in tumor number. The group receiving the combination of celecoxib and DFMO showed the greatest regression, with an 89% reduction in tumor number compared with the control group. There was also a corresponding reduction in the size of the tumors. To determine whether tumor regression was permanent or required continued treatment, all treatments were stopped at 31 weeks. Over the next 4 weeks, tumors reappeared at the same rate in all treatment groups. It is concluded that the combination of celecoxib and DFMO are potent therapeutic agents for skin cancer, although the benefits are lost with the cessation of treatment.
Effect of combined cyclooxygenase-2 and matrix metalloproteinase inhibition on human sarcoma xenografts.. David S Dickens; Timothy P Cripe (2003) Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology display abstract
PURPOSE: Sarcomas express cyclooxygenase (COX)-2, an inducible enzyme with known tumor-promoting activity. COX-2 inhibition is efficacious against many cancer types but has not been tested for human sarcomas. Matrix metalloproteinase (MMP) inhibitors also possess antiproliferative activity. Because MMP inhibitor therapy induces COX-2 expression, the authors hypothesized that the combination of COX-2 and MMP inhibitors results in a synergistic antitumor effect. METHODS: Human osteosarcoma or rhabdomyosarcoma cells were injected into athymic mice. Tumor development and growth were measured following treatment with a COX-2 inhibitor (celecoxib), an MMP inhibitor (doxycycline), or both. The tumors were analyzed for necrosis, apoptosis, cyclooxygenase activity (PGE2 production), and MMP-2 levels. RESULTS: When treatment was started prior to tumor cell implantation, doxycycline inhibited osteosarcoma tumor growth alone and in combination with celecoxib (30% and 33% reduction, respectively). An effect on osteosarcoma tumor implantation rates was noted in mice receiving doxycycline alone and in combination with celecoxib (12.5% and 6.25% reduction, respectively). Established osteosarcoma and rhabdomyosarcoma tumors were inhibited only by combination therapy (36% and 55%, respectively). A higher proportion of osteosarcoma tumors in the combination therapy group had more than 50% necrosis (3/7) when compared with control tumors (0/8). Antitumor effects did not correlate with PGE2 levels, suggesting the observed interaction with doxycycline was due to previously described non-enzymatic effects of celecoxib. CONCLUSIONS: The authors' preclinical data suggest that the combination of inexpensive, nontoxic, oral COX-2 and MMP inhibitors may be useful for the treatment of some types of solid tumors.