celecoxib, Celebrex
Suppression of accelerated tumor growth in surgical wounds by celecoxib and indomethacin.

Roh JL, Sung MW, Kim KH.

Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Chungnam National University College of Medicine, Daejeon, Korea.

BACKGROUND.: Tumor growth is accelerated in surgical wounds. However, few experiments seeking to prevent such accelerated tumor growth have been performed. METHODS.: We created surgical wounds in three syngeneic mice for the implantation of three murine cancer cell lines, SCC VII, CT-26, and B16F10. The tumor growth in the wound group was compared with that in non-wound-control mice. Celecoxib or indomethacin was administered to the mice that had tumor implanted into the surgical wound to observe the tumor-suppressive effect. RESULTS.: The surgical wounds promoted tumor growth with different degrees, depending on the type of tumor. Such an accelerated tumor growth did not seem to be affected by cyclooxygenase-2 expression of tumors per se, but its mechanism needs to be explained by further studies. Celecoxib and indomethacin had a significant inhibitory effect on the tumor growth in the surgical wound. This suppressive effect is most obvious when celecoxib is administered daily from 1 day before surgical wounding and tumor implantation. CONCLUSION.: Our results can justify that the preventive use of celecoxib in patients in whom local recurrence by tumor contamination is predicted. (c) 2005 Wiley Periodicals, Inc. Head Neck 27: XXX-XXX, 2005.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15719392&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites.

Claria J, Kent JD, Lopez-Parra M, Escolar G, Ruiz-Del-Arbol L, Gines P, Jimenez W, Vucelic B, Arroyo V.

DNA Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis. (HEPATOLOGY 2005;41:579-587.).

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celecoxib, Celebrex
A pharmacological study of celecoxib and gemcitabine in patients with advanced pancreatic cancer.

Xiong HQ, Plunkett W, Wolff R, Du M, Lenzi R, Abbruzzese JL.

Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA, qxiong mailmdanderson.org.

PURPOSE: To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs).METHODS: Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were eligible for the study. The initial dose of gemcitabine was 750 mg/m(2) administered intravenously at a rate of 10 mg/m(2)/min on days 1, 8, and 15 every 4 weeks. Celecoxib was administered orally at 400 mg twice a day starting 2 days after the first dose of gemcitabine. Serial blood samples were taken during the first and second gemcitabine infusions and the cellular dFdCTP levels from PBMCs were analyzed.RESULTS: Five patients received gemcitabine at 750 mg/m(2) and six patients received it at 650 mg/m(2). Severe adverse events included neutropenia, thrombocytopenia, enteritis, and gastric perforation. Two patient died early during treatment. Cellular pharmacology studies showed that the conversion of gemcitabine into dFdCTP was not affected by celecoxib.CONCLUSION: Despite the increased clinical toxicities encountered with the combination, celecoxib did not alter the conversion of gemcitabine into its active metabolites in PBMCs. Gemcitabine 650 mg/m(2) infusion over 65 min on days 1, 8, and 15 every 4 weeks in combination with celecoxib at 400 mg twice a day was the dose recommended for further study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15726370&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Celecoxib improves the efficiency of the locomotor mechanism in patients with knee osteoarthritis. A randomised, placebo, double-blind and cross-over trial.

Detrembleur C, De Nayer J, van den Hecke A.

Rehabilitation and Physical Medicine Unit, Universite catholique de Louvain, Brussels, Belgium.

OBJECTIVE: To compare the effect of celecoxib vs placebo treatment on clinical and gait variables in knee osteoarthritis (OA) patients; focusing on the efficiency of the locomotor mechanism. METHODS: Study design: A prospective, randomised, double-blind placebo-controlled trial. Patients: Eight adult patients with painful OA of the knee. Outcome measures: Clinical assessment included knee pain assessed by the visual analogue scale, range of knee motion assessed by goniometer, and locomotor function status assessed by a Knee Score Scale. Gait was assessed by means of instrumented analysis including synchronous kinematic, dynamic, electromyographic, and energetic recordings. Statistical analysis: The effect of treatment on the primary variable, the efficiency of the locomotor mechanism, and on secondary clinical and gait variables was assessed by the Hills and Armitage non-parametric approach. RESULTS: Celecoxib treatment improved the efficiency of the locomotor mechanism significantly. Among the secondary outcome measures assessed, celecoxib treatment improved walking cadence and reduced the knee pain significantly. CONCLUSION: This study shows that celecoxib is effective in improving locomotor function and pain in patients with knee OA.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15727886&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
A placebo-controlled screening trial of celecoxib for the treatment of cocaine dependence.

Reid MS, Angrist B, Baker S, Woo C, Schwartz M, Montgomery A, Majewska D, Robinson J, Rotrosen J.

New York University School of Medicine and VA New York Harbor Healthcare System, Department of Psychiatry, New York, NY, USA.

ABSTRACT Aims To conduct a medication screening trial study on the efficacy of celecoxib versus placebo for the treatment of cocaine dependence. Design A modified blinded, parallel group study in an outpatient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design. Setting The study was performed at the New York Medications Development Research Unit (MDRU). Participants All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Twenty-three participants were enrolled in the treatment phase of the study. Intervention After a 2-week screening period, subjects were assigned randomly to receive either celebrex (200 mg/day) or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment. Measurements Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs and extrapyramidal side-effects tests. Results Study retention was similar across both treatment groups and safety measures indicated that celecoxib was moderately tolerated. Cocaine use, as measured by self-report and urine BE levels at end of treatment, indicated weaker improvement in the celecoxib group. Reductions in the intensity of cocaine craving were also weaker in the celecoxib group. Cocaine abstinence rates, global impression scores and all other related psychometric measures did not differ significantly between treatment groups. Conclusion This study does not support the effectiveness of celecoxib for the treatment of cocaine dependence.

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celecoxib, Celebrex
The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion.

Reuben SS, Ekman EF.

Baystate Medical Center and Tufts University School of Medicine, 759 Chestnut Street, Springfield, MA 01199. scott.reuben bhs.org.

BACKGROUND: Cyclooxygenase (COX)-2-specific inhibitors demonstrate analgesic efficacy comparable with that of conventional nonsteroidal anti-inflammatory drugs but are associated with reduced gastrointestinal side effects and an absence of antiplatelet activity. Thus, they can be administered to patients undergoing spinal fusion surgery without an added risk of bleeding. However, concerns regarding a possible deleterious effect on bone-healing have limited their routine use. Celecoxib, a COX-2 inhibitor, recently was approved for the treatment of acute pain. The goals of the present study were to examine the analgesic efficacy of celecoxib and to determine the incidence of nonunion at one year following spinal fusion surgery. METHODS: Eighty patients who were scheduled to undergo spinal fusion received either celecoxib or placebo one hour before the induction of anesthesia and every twelve hours after surgery for the first five postoperative days. Pain scores and morphine use were recorded one hour after arrival in the post-anesthesia care unit and at four, eight, twelve, sixteen, twenty, and twenty-four hours later. Intraoperative blood loss was recorded. The status of the fusion was determined radiographically at the time of the one-year follow-up. RESULTS: There were no differences in demographic data or blood loss between the two groups. Pain scores were lower in the celecoxib group at one, four, eight, sixteen, and twenty hours postoperatively. There were no differences between the two groups with regard to the pain scores at twelve and twenty-four hours postoperatively. Morphine use was lower in the celecoxib group at all postoperative time-intervals. There was no difference between the celecoxib group and the placebo group with regard to the incidence of nonunion at the time of the one-year follow-up (7.5% [three of forty] compared with 10% [four of forty]). CONCLUSIONS: The perioperative administration of celecoxib resulted in a significant reduction in postoperative pain and opioid use following spinal fusion surgery. In addition, the short-term administration of this COX-2-specific non-steroidal anti-inflammatory drug had no apparent effect on the rate of nonunion at the time of the one-year follow-up. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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celecoxib, Celebrex
Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation.

Wallace JL, Zamuner SR, McKnight W, Dicay M, Mencarelli A, del Soldato P, Fiorucci S.

Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1. wallacej ucalgary.ca

Aceylation of cyclooxygenase (COX)-2 by aspirin can trigger the formation of 15(R)-epilipoxin A4, or aspirin-triggered lipoxin (ATL). ATL exerts protective effects in the stomach. Selective COX-2 inhibitors block ATL synthesis and exacerbate aspirin-induced gastric damage. Nitric oxide-releasing aspirins, including NCX-4016, have antiplatelet effects similar to aspirin but do not cause gastric damage. In the present study, we examined whether or not NCX-4016 triggers ATL synthesis and/or upregulates gastric COX-2 expression and the effects of coadministration of NCX-4016 with a selective COX-2 inhibitor on gastric mucosal injury and inflammation. Rats were given aspirin or NCX-4016 orally and either vehicle or a selective COX-2 inhibitor (celecoxib) intraperitoneally. Gastric damage was blindly scored, and granulocyte infiltration into gastric tissue was monitored through measurement of myeloperoxidase activity. Gastric PG and ATL synthesis was measured as was COX-2 expression. Whereas celecoxib inhibited gastric ATL synthesis and increased the severity of aspirin-induced gastric damage and inflammation, coadministration of celecoxib and NCX-4016 did not result in damage or inflammation. NCX-4016 did not upregulate gastric COX-2 expression nor did it trigger ATL synthesis (in contrast to aspirin). Daily administration of aspirin for 5 days resulted in significantly less gastric damage than that seen with a single dose, as well as augmented ATL synthesis. Celecoxib reversed this effect. In contrast, repeated administration of NCX-4016 failed to cause gastric damage, whether given alone or with celecoxib. These studies support the notion that NCX-4016 may be an attractive alternative to aspirin for indications such as cardioprotection, including in individuals also taking selective COX-2 inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14665439&dopt=Abstract celecoxib, Celebrex