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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer is an excellent model for studying cancer prevention by means of secondary (e.g., polypectomy to remove a precursor adenoma) and primary (chemoprevention) strategies. Evidence has shown that regular users of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have a reduction in risk of colorectal cancer. A possible mechanism of this benefit is decreased prostaglandin production, which is achieved through inhibition of cyclooxygenase (COX) activity, and possibly other pathways. Two isoforms of COX--COX-1 and COX-2--have been identified. COX-2 is expressed in colorectal adenomas and carcinomas, both in humans and rodents. Inhibition of COX-2 has been shown to decrease the incidence of carcinogen-induced neoplasia in rats and to lower the incidence of adenomas in murine models. Several COX-2 inhibitors, with the potential for less toxicity than that associated with traditional NSAIDs, are under development. This paper reviews potential chemoprevention of colorectal cancer using COX-2 inhibitors in patients at increased risk, e.g., patients with familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and sporadic adenomas. Included are the rationale for use of such agents, results of a study showing a significant reduction in adenoma burden in familial adenomatous polyposis patients who received the selective COX-2 inhibitor celecoxib (Celebrex), and the design of other ongoing or planned clinical trials.
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PMID:COX-2 inhibition in clinical cancer prevention. 1130 36

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.
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PMID:Chemoprevention of colorectal cancer. 1180 36

We hypothesized that hand-foot syndrome is an inflammatory phenomenon mediated by the overexpression of cyclooxygenase 2 (COX-2). Therefore, a specific COX-2 inhibitor such as celecoxib (Celebrex) could attenuate both the incidence and severity of hand-foot syndrome. We undertook a retrospective study comparing the incidences of hand-foot syndrome in 67 patients with metastatic colorectal cancer who took capecitabine (Xeloda) with or without celecoxib. Surprisingly, celecoxib seemed to attenuate capecitabine-induced diarrhea as well. Capecitabine/celecoxib was also associated with increased tumor response, proportion of stable disease (62.5% vs 22.8%, P = .001), and increase in median time to tumor progression (6 vs 3 months, P = .002) compared with capecitabine alone, despite the fact that patients on capecitabine/celecoxib had less favorable disease characteristics (age, performance status, and prior chemotherapies). Overexpression of COX-2, implicated in promoting angiogenesis, enhanced tumor invasiveness, evasion of apoptosis, and immune suppression, is a bona fide molecular target for many solid tumors, including colorectal cancer. Combining capecitabine with celecoxib in the treatment of colorectal cancer has strong preclinical rationales. A prospective study is being designed to evaluate capecitabine and celecoxib with or without epidermal growth factor receptor antagonist ZD1839 in the frontline treatment of metastatic colorectal cancer. These regimens under study are orally based and may significantly impact quality of life in the frontline treatment of metastatic colorectal cancer.
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PMID:Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity. 1252 Jun 38

Celecoxib (Celebrex, Pfizer, NY, USA) is a worldwide top branded COX-2-specific inhibitor. It was shown to provide relief of arthritic pain and inflammation and has recently been under investigation for the prevention and treatment of cancer. However, recent studies showed that long term use of high doses of celecoxib is associated with an increased cardiovascular toxicity. We discovered that the addition of curcumin, a natural COX-2 inhibitor, to celecoxib synergistically (up to 1000%) augments the growth inhibitory effects of celecoxib in in-vitro and in-vivo models of arthritis and cancer, thus rendering effective action of the drug at up to tenfold lower dose. This may pave the way for a novel strategy to treat arthritis and cancer because its effect [1] can be achieved in the serum of patients receiving standard anti inflammatory or anti-neoplastic dosages of celecoxib, and [2] involves a regimen with a very low profile of side effects. Preliminary data suggest that the combination is not limited only to celecoxib and that addition of curcumin to other NSAIDs such as sulindac, synergistically augments neoplastic cell growth inhibition. Based on these finding we received an IRB approval to evaluate celecoxib+curcumin in patients with osteoarthritis, pancreatic cancer and metastatic CRC. We hope to complete these novel human clinical trials, in 12-18 months.
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PMID:Compositions for treatment of cancer and inflammation. 1828 24