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The role that aspirin might have in reducing the rates of certain cancers has been the subject of many studies. However, given the side-effects of NSAIDs on increased gastrointestinal bleeding and rates of heart disease, there is no current medical recommendation to use these drugs for cancer reduction.
* Prostate - While there is some epidemiological information suggesting a correlation between the reduction of prostate cancer and aspirin use, two recent studies (a multicentric case-control study and epidemiological study) were inconclusive.
* Colon - A 2005 JAMA article states that aspirin may prevent carcinoma of the colon, when taken in at least twice-daily adult (325 mg) doses. It follows an earlier study, also using the Nurses' Health Study (NHS) women, which had similar conclusions but with a smaller testing population. The conclusion of the JAMA study was that both aspirin and other non-aspirin NSAIDs used over a long time (best results seen after at least a decade of regular use) reduce risk of colorectal cancer. The risk was reduced the most at doses higher than 14 tablets per week (full-strength aspirin twice a day). However, these doses can have a higher incidence of serious gastrointestinal bleeding, and reduced doses (even the low doses recommended for cardiovascular health (81 mg/day)) also seem to have an anti-cancer effect, albeit not as much as the higher doses. The results of these studies have been correlated with experimental studies in human volunteers and in rodents. At least four clinical trials show that small doses of aspirin reduce, modestly, intestinal polyps recurrence in patients with some history of adenomas. Some twenty carcinogenesis studies in rats or mice also support that aspirin can prevent cancer, also reported in the Chemoprevention of Colorectal Cancer Database.
* Gall bladder - There is some evidence that aspirin may increase gall bladder motility and thus be effective in treating gall bladder disease.
* Pancreatic - A study in 2004 showed that increases in dose and duration of aspirin may significantly increase the risk of pancreatic cancer in women (only women were in the study); however this did not seem to affect current, regular users.
* Upper GI tract - A study published in 2003 reported that people who had been taking aspirin regularly for 5 or more years seemed to have a two-thirds less risk of mouth, throat and esophageal cancer than non-users. This study was done on both cancer patients and other people in hospital for various reasons, and was done by comprehensive epidemiological questionnaires of life habits rather than empirical testing.
* Lung - A 20-year study published in 2002 showed that in a group of 14,000 women in New York City, regular aspirin use (defined as at least once a week, various doses) reduced their risk of lung cancer, especially small-cell carcinoma. This may be because many lung tumors have high amounts of COX-2 enzymes expressed in them, especially in adenocarcinomas and tumors caused by asbestosis.[30] Aspirin is a known blocker of both COX-1 and COX-2 enzymes, although this study suggests that if the COX-2 link is direct, other COX-2 inhibitors may also play a similar role.
Another study in 2002 of both men and women found that risk reduction was more significant in males than females; overall, the effects of smoking were far more influential than aspirin use in determining cancer risks. Of those who smoked, those who smoked the least got the most benefit from aspirin use. Some of the heaviest smokers saw no benefit from aspirin at all.
Aspirin
In 1971, the British pharmacologist, John Robert Vane, who was then employed by the Royal College of Surgeons in London, showed that aspirin had suppressed the production of prostaglandins and thromboxanes. For this piece of research he was awarded both a Nobel Prize in Physiology or Medicine in 1982 and a knighthood.
Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its non-competitive and irreversible inhibition of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.
Prostaglandins are local hormones (paracrine) produced in the body and have diverse effects in the body, including but not limited to transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and their reduction with the introduction of small amounts of aspirin has been seen to be an effective medical intervention. The side-effect of this is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin.
There are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. Normally COX-2 produces prostanoids, most of which are pro-inflammatory. Aspirin-modified COX-2 produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs called COX-2 selective inhibitors have been developed that inhibit only COX-2, with the hope for reduction of gastrointestinal side-effects.
However, several of the new COX-2 selective inhibitors have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the microvasculature in the body express COX-2, and, by selectively inhibiting COX-2, prostaglandins (specifically PGI2; prostacyclin) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGI2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, an important difference with reversible inhibitors.
Furthermore, aspirin has 2 additional modes of actions, contributing to its strong analgesic, antipyretic and anti-inflammatory properties:
* It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the inner membrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons. In short, aspirin buffers and transports the protons. (Note: This effect in high doses of aspirin actually causes fever due to the heat released from the electron transport chain, instead of its normal antipyretic action.)
* It induces the formation of NO-radicals in the body that enable the white blood cells (leukocytes) to fight infections more effectively. This has been found recently by Dr. Derek W. Gilroy, winning Bayer's International Aspirin Award 2005.
More recent data suggest that salicylic acid and its derivatives will modulate NF?B signaling. NF?B is a transcription factor complex that plays a central role in many biological processes, including inflammation.
• Circulation Problems - Aspirin...
• Circulation Problems - Aspirin as Genericized Trademark...
• Circulation Problems - Discovery...
• Circulation Problems - Synthesis of Aspirin...
• Circulation Problems - Mechanism of Action...
• Circulation Problems - Indications...
• Circulation Problems - Toxicity of Low-dose Aspirin...
• Circulation Problems - Contraindications and Warnings...
• Circulation Problems - Common side-effects...
• Circulation Problems - Interactions...
• Circulation Problems - Overdose...
• Circulation Problems - Research Into Cancer Prevention...
• Circulation Problems - Aspirin in Pets...
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