![]() In one study, Kelloff and his group of researchers measured the effects of six months of celebrex at lowor high-dose versus placebo, or dummy pill, on the duodenum in FAP patients. More importantly, cancer specialists are optimistic that COX-2 inhibitors that work well on FAP (Familial adenomatous polyposis, an inherited disorder) could help individuals who suffer from common forms of colon cancer. Hence, the timing of cancer treatment to block the enzyme is vital. This also suggested that COX-2 inhibitor drugs may prevent DNA damage caused by COX-2 enzymes.ĬOX-2 expression achieves its zenith at a particular stage of the cancer pathogenesis (disease progression). The finding offered a new insight into how aspirin, along with diets rich in fruits, grains and vegetables, seemed to decrease the risk of some forms of cancer. When Taketo and his group deciphered the route to this corridor, they "knocked them out".Īs a matter of fact, the first evidence that COX-2 enzymes were involved in causing DNA damage associated with cancer was provided in a University of Pennsylvania study. This activity sets off a process for the tumour to spread. It causes inflammation and promotes tumour formation in response to growth factors, cytokines protein molecules, or communication links, between immune systemcells or oncogene, a gene that can cause a cell to develop into a tumour, or cancer.ĬOX-2 stimulates the production of a particular type of prostaglandins, which activates a specific epithelium receptor. In contrast, COX-2, which can be, more or less, 'influenced' by means fair and square, is not made in normal epithelium or layers of cells that line hollow organs and glands. In otherwords, COX-1, the 'housekeeping' variant', is expressed in several cells it provides the basic functions of life. They also inhibit COX-2 enzymes, which are synthesised from arachidonic acid in cell membranes. NSAIDs weaken two forms of the coxib enzymes and, of the two it is only one, COX-1, which causes adverse effects. Coxibsalso cause 'minimal' side-effects, unlike aspirin, which causes gastro-intestinal ulceration and bleeding. According to Makoto Taketo, MD, DMedSc, a professor of pharmacology at Japan's Kyoto University Graduate School of Medicine, these "aspirin-like NSAIDs" act pharmacologically as anti-inflammatory agents and analgesics and, in so doing, they reduce fever. Blocking it, he adds, isn't harmful, because it doesn't disrupt normal function. Gary J Kelloff, MD, a researcher at the National Cancer Institute, US, who lists the requirements for a molecular tar-get, such as the COX-2 enzyme, says it must be highly expressed in pre-cancer, or cancer cells, and not in others. This is, indeed, the fun-damental reason why researchers have designed coxibs with a definitive purpose: to crush inflammation.ĬOX-2 inhibitors have emerged as lead players for preventing cancer, an inflammatory disorder also, its recurrence. In another study, a randomised comparison of coxib drugs, such as celebrex and indomethacin, suggested that they caused clinically inconsequential and transitory retention of sodium, but no real slump in kidney filtration rate. A meta-analysis (research synthesis) on the effect of NSAIDs on post-operative kidney function reports a clinically unimportant and short-lived reduction in renal function with NSAIDs. Research suggests that this could be accountable for certain cases of peripheral oedema (swelling) seen in clinical trials. ![]() It may also be emphasised that conventional NSAIDs and COX-2 inhibitors subdue renal, or kidney, activity. In an editorial published in "The Journal of the American Medical Association", it was estimated that for low-risk patients for whom the hazard of developing a NSAID-related ulcer complication is 0.4 per cent, the cost of preventing a single complication was US$350,000. In addition to this, as evidence for damage continues to ascend with traditional, or conventional, NSAIDs in causing deaths,reports suggest that on an average 1 in 1,200 patients taking them for at least four weeks could die from gastro-duodenal complications.
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