celecoxib, Celebrex
[Effectiveness and tolerability of celecoxib in outpatient department practice]

[Article in Italian]

Cancilleri F, Caione G, Di Martino A, Marinozzi A, Stellato GM, Denaro V.

Universita Campus Bio-Medico, Area di Ortopedia e Traumatologia, Roma, Italia. F.Cancilleri unicampus.it

OBJECTIVES: Object of this work is to evaluate activity and tolerance of Celecoxib in out-patient's department practice. PATIENTS AND METHODS: In this study we enlisted 46 patients, affected by pain of inflammatory or degenerative origin; any of them ever did continued therapy with NSAIDs before. We administered 200 mg daily dose of Celecoxib for at least three months. Each patient has been evaluated by the Visual Analogic Score (VAS) Scale before and after the therapy. RESULTS: The data We obtained agree with those of multicenter studies like CLASS. Celecoxib had similar efficacy respect with traditional NSAIDs, with good control of pain in both osteoarthrosic and arthritic pain (p < 0.000). Not good results were obtained for control of acute-onset pain. In our population We didn't find side-effects different from those included in the technical-form of the drug. The only patient who complained of epigastric pain did not stop the treatment, because the symptom resolved with assumption of the drug during meals. CONCLUSIONS: By the analysis of the results We consider Celecoxib useful for the control of pain in the treatment of osteoarthrosis and autoimmune diseases like Rheumatoid Arthritis. Anyway, treatment with Celecoxib (as with all Coxib-family drugs) should be reserved for long-lasting treatments in patients at risk for gastrointestinal bleeding.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12854279&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Comparison of the incidence rates of thromboembolic events reported for patients prescribed celecoxib and meloxicam in general practice in England using Prescription-Event Monitoring (PEM) data.

Layton D, Hughes K, Harris S, Shakir SA.

Drug Safety Research Unit, University of Southampton, Southampton, UK. deborah.layton dsru.org

BACKGROUND: Celecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the post marketing safety of these drugs in England using the non-interventional observational cohort technique of Prescription-Event Monitoring (PEM). OBJECTIVES: To compare the incidence rates of selected thromboembolic (TE) (cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed celecoxib and meloxicam in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996-March 1997) and celecoxib (May and December 2000). Simple questionnaires requesting details of events occurring during/after treatment, indication and potential risk factors (including age, sex and whether NSAIDs had been prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RRs) were obtained using Poisson regression modelling. RESULTS: During the 9 months after starting treatment, 28 (0.16%) and 19 (0.10%) of patients were reported to have experienced cardiovascular TE events, 68 (0.39%) and 52 (0.27%) cerebrovascular TE events, and 17 (0.10%) and 20 (0.10%) experienced peripheral venous thrombotic events for celecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from 30 days after the start of treatment for both the cardiovascular TE event group (log rank test P = 0.0153) and cerebrovascular TE event group (log rank test P = 0.0055). Indication and use of an NSAID within 3 months prior to starting treatment had no effect on the relative risk estimates of the event groups and was excluded in subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, the cerebrovascular TE event group rate was higher for celecoxib than for meloxicam, RR 1.66 (95% CI 1.10-2.51), over the study period and no different for the cardiovascular TE event group, RR 1.72 (95% CI 0.87-3.40) or peripheral venous thrombotic group, RR 1.06 (95% CI 0.51-2.19). CONCLUSIONS: This study reports a relative increase in the rate of cerebrovascular TE events in users of celecoxib compared to meloxicam. There was no difference in the rate of cardiovascular TE events or peripheral venous thrombotic events between users of these two drugs. The incidence of these three groups of events reported in each of these two drug cohorts was low (<0.5%), therefore the relevance of our findings need to be taken into consideration with other clinical and pharmacoepidemiological studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12867585&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis.

Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, Zhang W, Wei H, Sung M, Wang W, Li X.

Department of Pathology, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA. David.Zhang mssm.edu

Scutellaria baicalensis is a widely used Chinese herbal medicine that has been used historically in anti-inflammatory and anticancer therapy. The purpose of this study is to verify its anticancer activity on head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E(2) (PGE(2)) and is highly expressed in HNSCC. Two human HNSCC cell lines (SCC-25 and KB) and a nontumorigenic cell line (HaCaT) were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with Scutellaria baicalensis extract. Its effects were compared with those of baicalein (a flavonoid isolated from Scutellaria baicalensis), indomethacin (a nonselective COX inhibitor), and celecoxib (a selective COX-2 inhibitor). Four nude mice with s.c. inoculation of KB cells were tested for its anticancer activity in vivo by oral administration of Scutellaria baicalensis at a dose of 1.5 mg/mouse (75 mg/kg), five times/week for 7 weeks. Scutellaria baicalensis and other agents demonstrated a strong growth inhibition in both tested human HNSCC cell lines. No growth inhibition of HaCaT cells was observed with Scutellaria baicalensis. The IC(50)s were 150 micro g/ml for Scutellaria baicalensis, 25 micro M for celecoxib, and 75 micro M for baicalein and indomethacin. Scutellaria baicalensis, as well as celecoxib and indomethacin, but not baicalein, suppressed proliferation cell nuclear antigen expression and PGE(2) synthesis in both cell types. Scutellaria baicalensis inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. A 66% reduction in tumor mass was observed in the nude mice. Scutellaria baicalensis selectively and effectively inhibits cancer cell growth in vitro and in vivo and can be an effective chemotherapeutic agent for HNSCC. Inhibition of PGE(2) synthesis via suppression of COX-2 expression may be responsible for its anticancer activity. Differences in biological effects of Scutellaria baicalensis compared with baicalein suggest the synergistic effects among components in Scutellaria baicalensis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12874003&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Apoptosis induction and enhancement of cytotoxicity of anticancer drugs by celecoxib, a selective cyclooxygenase-2 inhibitor, in human head and neck carcinoma cell lines.

Hashitani S, Urade M, Nishimura N, Maeda T, Takaoka K, Noguchi K, Sakurai K.

Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

Colorectal carcinomas are well known to highly express COX-2 and their growth is markedly inhibited by COX-2 inhibitors, but little is known about head and neck carcinomas. In this study, we investigated the effect of a selective COX-2 inhibitor, celecoxib, on growth and apoptosis induction of four human head and neck carcinoma cell lines, SCC25, KB, HSG and HSY, in comparison with frequently used COX inhibitor sulindac. Also, we examined whether celecoxib augments the sensitivity of these cell lines to anticancer drugs such as doxorubicin (DOX), vincristine (VCR), cisplatin (CDDP), bleomycin (BLM) and 5-fluorouracil (5-FU). The growth of all cultured cell lines particularly SCC25 and HSG was inhibited by celecoxib and sulindac in a dose-dependent manner. The IC50 of celecoxib was ten times lower than that of sulindac. SCC25 produced ample PGE2 whereas KB, HSG and HSY produced a small amount of PGE2. The PGE2 production and COX-2 expression were inhibited more efficiently by celecoxib than by sulindac. Exogenous addition of PGE2 resulted in an increased cell growth of SCC25 even under the celecoxib-treated condition, but not of HSG. These results suggested that PGE2 is involved in the growth of SCC25 but not of HSG. The ability of celecoxib to induce apoptosis is greater than that of sulindac. Treatment of SCC25 and HSG with non-cytotoxic 1 micro M or less cytotoxic 5 micro M of celecoxib enhanced the sensitivity of both cell lines to anticancer drugs, particularly in DOX, VCR and BLM two to ten times as demonstrated by lowering of IC50s. The enhanced rate was almost parallel to the degree of apoptosis induction. These findings indicated that a selective COX-2 inhibitor celecoxib inhibits cell proliferation, induces apoptosis and augments sensitivity to anticancer drugs in human head and neck carcinoma cells. Therefore, celecoxib would be useful as biological modulator in treatment of head and neck cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12888902&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin.

Fiorucci S, Distrutti E, Mencarelli A, Morelli A, Laufor SA, Cirino G, Wallace JL.

Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale, Universita degli Studi di Perugia, Perugia, Italy. fiorucci unipg.it

(1) Unlike other nonsteroidal anti-inflammatory drugs that inhibit formation of cyclooxygenase (COX)-dependent eicosanoids, acetylation of COX-2 by aspirin switches eicosanoid biosynthesis from prostaglandin E(2) (PGE(2)) to 15-epi-lipoxin A(4) (15-epi-LXA(4) or aspirin-triggered lipoxin, ATL). ATL formation by activated leukocytes (PMN) requires the intervention of 5-lipoxygenase (5-LOX), an enzyme that is involved in leukotriene B(4) (LTB(4)) formation. (2) In the present study, we have examined the role of acetylated COX-2 and 5-LOX in modulating antiadhesive effects of aspirin on adhesion of PMN to endotoxin (LPS)-primed human umbilical endothelial cells (HUVEC). (3) Treating PMN/HUVEC cocultures with aspirin resulted in a concentration-dependent inhibition of cell-to-cell adhesion induced by LPS. Treating HUVEC with selective COX-2 inhibitors, celecoxib and rofecoxib, caused an approximately 70% reversion of antiadhesive effect of aspirin. In contrast, inhibition of neutrophil's 5-LOX pathway with 1 micro M ZD2138, a selective 5-LOX inhibitor, 1 micro M BAY-X-1005, a FLAP inhibitor, or 100 micro M licofelone, a dual COX/5-LOX inhibitor, did not affect antiadhesive properties of aspirin. (4) Exposure to celecoxib (100 micro M) or rofecoxib (10 micro M) completely suppressed ATL formation caused by aspirin without affecting LTB(4) levels. ZD2138, licofelone and BAY-X-1005 inhibited ATL formation as well as LTB(4) generation. (5) Treatment with LXA(4) reduced PMN adhesion to HUVEC and counteracted the proadhesive effect of celecoxib. In contrast, exposure to Boc-1, an LXA(4) antagonist, counteracts the antiadhesive activities of aspirin. Exposure to U75302, an LTB(4) receptor antagonist, enhances the antiadesive effect of aspirin. (6) Reversal of antiadhesive activities of aspirin by celecoxib was associated with increased expression of LFA-1 on PMN and E-selectin on HUVEC. Addition of LXA(4), ZD2138 and U75302 inhibited these changes. (7) The present results support the notion that inhibition of ATL formation is mechanistically linked to the reversal of the antiadhesive activity of aspirin caused by selective COX-1 inhibitors and suggests that the LTB(4)/ATL balance modulates pro- and antiadhesive activity of nonsteroidal anti-inflammatory drugs at the leukocyte-endothelial cell interface.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12890715&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence.

Rahme E, Barkun AN, Toubouti Y, Bardou M.

Division of Clinical Epidemiology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. elham.rahme mcgill.ca

BACKGROUND & AIMS: Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are believed to develop from colorectal adenomas. We examined the effect of the selective cyclooxygenase-2 inhibitors rofecoxib and celecoxib, nonselective nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen on colorectal neoplasia (colorectal cancer, colorectal adenoma, or both). METHODS: This was a nested case-control study, which used data from a government insurance database on patients 65 years and older who underwent a diagnostic test or procedure for colorectal neoplasia between January and June 2001. Logistic regression models were used to determine the effect of exposure to the drugs of interest for at least 3 months on the occurrence or recurrence of colorectal neoplasia. RESULTS: The control group included 2568 patients found to be free of colorectal neoplasia; 730 patients were diagnosed with colorectal adenoma, and 179 were diagnosed with colorectal cancer. Patients more likely to have colorectal adenoma (odds ratio, 95% confidence interval) were those diagnosed with colorectal adenoma (4.12, 3.27-5.18) or colorectal cancer (3.74, 2.32-6.03) in the previous 1-3 years and those with hemorrhage of the rectum or unspecified anemia in the prior month (3.19, 2.46-4.12). Exposures to rofecoxib (0.67, 0.46-0.98) and nonselective nonsteroidal anti-inflammatory drugs (0.41, 0.21-0.83) reduced the risk of colorectal adenoma. Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs were all protective against both neoplasias (0.64, 0.45-0.91; 0.73, 0.54-0.99; and 0.47, 0.26-0.86, respectively). CONCLUSIONS: Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs seem to protect against the development of colorectal neoplasia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12891542&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Topical inhibition of oral carcinoma cell with polymer delivered celecoxib.

Wang Z, Polavaram R, Shapshay SM.

Department of Otolaryngology, Head and Neck Surgery, Boston Medical Center, Boston University School of Medicine, D616, 88 East Newton Street, Boston, MA 02118, USA. zwang bu.edu

Celecoxib has a potential role for oral cancer chemoprevention but its systemic side effects are a concern. Topical chemoprevention is a promising way to reduce the toxicity. This study was designed to determine whether topical application of polymer delivered celecoxib would have an inhibitory effect on human oral carcinoma cells. Seventeen nude mice were intradermally inoculated with the carcinoma cells, and then were divided into control and treatment groups. Tumor growth was measured for 15 days, at which significant difference was found between two groups (P<0.001). This study indicates a potential role of polymer film delivered celecoxib for topical inhibition of oral cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12893430&dopt=Abstract celecoxib, Celebrex