Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Celecoxib (Celebrex) is the first of a new family of nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit cyclooxygenase 2 (COX 2) while sparing COX 1. Clinical trials indicate that it is approximately as effective in relieving the pain of osteoarthritis and the pain and inflammation of rheumatoid arthritis as nonselective NSAIDs, but causes less gastrointestinal ulceration and bleeding. This paper reviews the pharmacology and possible clinical role of celecoxib and other COX 2-selective NSAIDs.
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PMID:COX 2-selective NSAIDs: biology, promises, and concerns. 1064 79

Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins from arachidonic acid. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of prostaglandins. COX-1 is constitutively expressed in a wide range of tissues, whereas COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Two specific COX-2 inhibitors, namely rofecoxib (Vioxx) and celecoxib (Celebrex), both oral agents and U.S. Food and Drug Administration approved, have been shown preclinically and clinically to have efficacy comparable to that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal damage. Little is known about how angiogenesis is affected by the combination of rofecoxib and radiation. We have evaluated the combination of rofecoxib, at various concentrations, and radiation on cytokine-induced angiogenesis in vitro. We have found that rofecoxib inhibited endothelial cell proliferation, migration, and tube formation (differentiation) at clinically relevant doses. In combination with radiation, inhibition of endothelial cell function further increased twofold. The combination of rofecoxib and radiation suggests a complementary strategy with clinical ramifications to target angiogenesis-dependent malignancies.
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PMID:Targeting angiogenic processes by combination rofecoxib and ionizing radiation. 1158 92

Two cyclooxygenase (COX) isoforms have been identified: COX-1 and COX-2. COX-1 is the constitutively expressed form of the enzyme and is ubiquitous in its distribution. COX-2 is inducible and is present in inflammatory foci, tumors, and neovasculature. Expression of COX-2 appears to be important in tumor promotion, growth, and metastasis. It is up-regulated in a variety of premalignant disorders and malignancies. COX inhibitors have a major role in the treatment of inflammation and pain. Epidemiologic evidence in patients who take nonsteroidal anti-inflammatory drugs links COX inhibition with decreases in malignant esophageal, stomach, colon, lung, and breast tumors. Nonselective COX inhibitors have demonstrated efficacy in control of familial adenomatous polyposis, a disorder associated with the development of thousands of benign intestinal polyps. The selective COX-2 inhibitor celecoxib (Celebrex, Pharmacia) has been shown to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib has recently been approved for this indication and offers the potential for equivalent or greater efficacy than that seen with nonselective COX inhibitors but without the gastrointestinal mucosal toxicity and the inhibition of platelet function associated with those agents. Angiogenesis is a feature of both benign and malignant disease. Because COX-2 is up-regulated in the neovasculature of the rheumatoid pannus and in malignant tumors and their surrounding stroma, selective COX-2 inhibitors may be able to modify the progression of these disorders through the control of angiogenesis.
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PMID:Approach to angiogenesis inhibition based on cyclooxygenase-2. 1177 86

Many clinicians appear confused about the purported clinical advantages of the new generation COX-2 inhibitors compared to both over-the-counter and prescription nonsteroidal anti-inflammatory analgesic agents (NSAIDs). Infact, there is a paucity of published information comparing the safety and efficacy of these two classes of drugs when used to treat acute pain. This study was designed to compare the safety and analgesic efficacy of an over-the-counter (OTC) analgesic, ibuprofen (Advil Liqui-Gels), to the leading prescription COX-2 inhibitor celecoxib (Celebrex). Ibuprofen liquigel is an encapsulated, solubilized potassium salt of ibuprofen that has a higher Cmax and shorter tmax than traditional ibuprofen solid-dosage formulations. This trial evaluated the maximum approved OTC dosing regimen (400 mg x 3, q4-6h) of ibuprofen liquigels compared to a single dose of celecoxib (200 mg) and placebo in 174 patients with moderate orsevere pain following surgical extraction of impacted third molars. The study design was multiple dose, randomized (stratified by baseline pain and gender), placebo controlled, double blind, double dummy, and parallel group. The onset of pain relief was determined using a two-stopwatch procedure. Treatments were also compared using standard indices of pain intensity and pain relief. The study demonstrated assay sensitivity in that both active medications were significantly more effective than placebo for all efficacy measures. In comparing the two active medications, the time to meaningful relief was significantly shorter, and the mean 4-, 8-, and 12-hour summed pain relief combined with pain intensity difference scores were significantly higher for ibuprofen liquigels compared with celecoxib (p < 0.001). Analyses of other key efficacy variables, including the time to rescue medication and the patients' overall assessment of study medication, confirmed the superior efficacy of ibuprofen liquigels over celecoxib. Both active treatments were well tolerated, with no differences in incidence or severity of adverse events. Of particular interest, there were no differences in gastrointestinal-related side effects when comparing these doses of ibuprofen liquigels to celecoxib. In conclusion, ibuprofen liquigels were a significantly more effective analgesic and provided relief significantly faster compared with celecoxib in the treatment of postsurgical pain.
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PMID:Efficacy and tolerability of nonprescription ibuprofen versus celecoxib for dental pain. 1216 74

Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of PGs. Although COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Two specific COX-2 inhibitors, namely, rofecoxib (Vioxx) and celecoxib (Celebrex), both oral agents and FDA approved, have been shown preclinically and clinically to have efficacy comparable to that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal damage. Significant preclinical evidence strongly supports the potential role for these inhibitors for the treatment of cancer. On June 29, 2001, the Radiation Therapy Oncology Group (www.rtog.org), a National Cancer Institute-sponsored cooperative group, held a 1-day symposium focusing on the potential role of inhibitors of COX-2 in the treatment of cancer. This issue of the American Journal of Clinical Oncology contains the summary of those presentations.
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PMID:COX-2 inhibitors and cancer therapeutics: potential roles for inhibitors of COX-2 in combination with cytotoxic therapy: reports from a symposium held in conjunction with the Radiation Therapy Oncology Group June 2001 Meeting. 1290 55

Unresectable pancreatic cancer has few therapeutic options and a dismal prognosis. Cyclooxygenase-2 (COX-2) expression is increased at the RNA and protein levels in most human pancreatic cancers. The purpose of this trial was to determine whether the addition of a COX-2 inhibitor to chemotherapy was beneficial. To date, 11 patients with inoperable pancreatic cancer have been treated with the combination of gemcitabine (Gemzar), irinotecan (Camptosar), and celecoxib (Celebrex) at 400 mg orally twice daily. Encouraging pain relief, improvement in performance status, and decreases in CA 19-9 and carcinoembryonic antigen levels have been observed.
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PMID:Gemcitabine/Irinotecan/celecoxib in pancreatic cancer. 1568 34

The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation.
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PMID:COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. 1612 36

The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies for endometriosis-associated pain or recurrent disease are primarily aimed at downregulating ovarian function or antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is providing important results for the development of new, specific treatment modalities. Aromatase overexpression has recently been detected in endometriotic tissue. Aromatase (p450arom) is responsible for converting C19 androgens into estrogen in several types of human tissue. Aromatase activity causes local estrogen biosynthesis, which, in turn, stimulates prostaglandin E2 production by upregulating cyclooxygenase-2 (COX-2). Thus, a positive feedback cycle develops between the two systems. Another abnormality in endometriosis, the deficient 17beta-hydroxysteroiddehydrogenase type II (17beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations increase the amount of local estradiol and prostaglandin E2 in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance and even invasiveness. Consequently, aromatase and COX-2 are thought to be promising new therapeutic targets. Thus, specific aromatase inhibitors (e.g. Letrozol/Femara, Anastrozol/Arimidex or Exemestan/Aromasin) or selective COX-2 inhibitors (e.g. Celecoxib/Celebrex, Rofecoxib/Vioxx, Valdecoxib/Bextra) are of great interest and should be studied in clinical trials in premenopausal woman with endometriosis to expand the spectrum of currently available treatment options.
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PMID:Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: new questions--old answers? 1615 42

Dental pain is encountered daily by clinicians. Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used for pain management are traditionally cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors, and more recently selective COX-2 inhibitors. This study was designed to identify and quantify COX-1 and COX-2 gene expression level in inflamed rat molar pulps after administration of three NSAIDs: Celebrex, Vioxx, and Advil. Fifty male Wistar rats had their first and second molar pulps exposed and sealed with Cavit for 4 days. Rats were randomly divided into the three drug groups and two control groups. RNA was isolated from the rat pulps. Real Time Quantitative Reverse Transcriptase-Polymerase Chain Reaction assay, a relatively new PCR technique, was used to quantify COX-1 and COX-2 mRNA. Statistical analysis demonstrated no significant differences in COX-1 and COX-2 levels among the drug groups. However, Vioxx and Advil significantly reduced COX-2 expression levels compared to inflamed (positive control) pulps (p < 0.05).
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PMID:A real time quantitative PCR analysis and correlation of COX-1 and COX-2 enzymes in inflamed dental pulps following administration of three different NSAIDs. 1624 22

In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.
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PMID:COX-2 inhibitors: a story of greed, deception and death. 1635 94


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