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An introduction to aspirin, NSAids, and COX-2 inhibitors for the primary prevention of cardiovascular events and cancer and their potential preventive role in bladder carcinogenesis: part II.

Aspirin and the nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) have been commercially available for decades, and their ability to reduce pain and inflammation are well known. The ability of some of these agents to also reduce a primary or secondary cardiovascular event or to potentially reduce the risk of colorectal cancer has also been documented. These observations collectively have initiated a wide variety of investigations to determine whether or not these agents may have an ability to reduce the risk or progression of numerous cancers. Some urologic cancers have been included in these recent studies. For example, prostate cancer may be sensitive to these compounds based on a small number of preliminary studies. Bladder cancer may also be sensitive to the effects of these agents. Older patients and those with more aggressive tumors may benefit most from these initial studies. Many cancers also demonstrate a greater upregulation of cyclooxygenase-2 (COX-2), and this has lead to recent interest, especially in colorectal cancer, to test the ability of these selective agents against the development of precancerous colon polyps. High-risk patients for colorectal cancer may have benefited by taking a selective COX-2 inhibitor in a recent randomized trial, but whether or not this benefit continues to occur after the COX-2 inhibitor is removed remains controversial and needs further study. Prostate and bladder cancer also seem to demonstrate an upregulation of COX-2, and laboratory studies suggest that these selective NSAIDs may have a greater effect on reducing the development of these tumors. Randomized clinical trials are needed, but because numerous individuals are currently using COX-2 inhibitors, a large volume of data should make at least retrospective studies more plausible in the near future. The challenge for researchers and clinicians is to further understand which NSAIDs and what dosage and duration may provide the optimal benefit (if any), and to accurately construe the available current data on these agents for patients inquiring about these compounds.

Anti-Inflammatory Agents, Non-Steroidal↗

[DUCLOS LHERMITE DISEASE: REPORT OF ONE CASE AND LITERATURE REVIEW]

Lhermitte-Duclos disease (also known as dysplastic gangliocytoma of the cerebellum) is an unusual disorder, is now known to occur in young patients as a manifestation of Cowden disease. We report the case of a young male, 31 years old, with this unusual disease who was sugically treated for the neurologic neoplasia. And submitted to colonoscopic polypectomy for the hamartomatous colonic polyps.

Journal Article↗

Hypermethylation of HPP1 is associated with hMLH1 hypermethylation in gastric adenocarcinomas.

The HPP1 gene was initially discovered because of its frequent hypermethylation in hyperplastic colon polyps, but it is also hypermethylated in colorectal adenomas and carcinomas. Expression of the DNA mismatch repair gene hMLH1 is diminished or absent in some hyperplastic polyps, and it has been suggested that HPP1 inactivation is associated with the progression of microsatellite-unstable colorectal tumors. We sought then to determine the prevalence of HPP1 silencing by DNA methylation in gastric adenocarcinomas and to define any association of this event with microsatellite instability (MSI) or hMLH1 hypermethylation. Thirty-two matched normal-gastric adenocarcinoma DNA pairs were studied for MSI status and hypermethylation of HPP1 and hMLH1. Five (100%) of 5 MSI-H tumors, 2 (50%) of 4 MSI-L tumors, and 8 (35%) of 23 MSS tumors demonstrated HPP1 hypermethylation. Eight (25%) of 32 tumors (5 of 5 MSI-H, 2 of 4 MSI-L, and 1 of 23 MSS) showed evidence of hMLH1 hypermethylation. All (8 of 8) of these hMLHI-methylated tumors demonstrated concomitant methylation at the HPP1 locus: there were no cases of hMLH1 methylation occurring in the absence of HPP1 methylation. In gastric adenocarcinoma, hypermethylation frequently targets HPP1. Moreover, hMLH1 hypermethylation occurs predominantly in the setting of HPP1 hypermethylation. HPP1 hypermethylation may represent an early event in mismatch repair-deficient gastric tumorigenesis.

Adaptor Proteins, Signal Transducing↗

Osteoporosis. Part III--Not just for bone loss: potential benefits of calcium and vitamin D for overall general health.

The potential benefits of dietary or supplemental calcium and vitamin D for osteoporosis prevention have been well reviewed. However, less well known is the potential of these two compounds to reduce the risk of recurrence of a number of overall general health conditions. For example, calcium may play a role in increasing levels of high-density lipoprotein, preventing colon polyp formation, reducing blood pressure in some hypertensive individuals, reducing kidney stone recurrence, promoting weight loss, and reducing the symptoms of premenstrual syndrome. Vitamin D may play a role in cancer prevention, provide synergism or enhancement to some chemotherapy protocols, prevent Type I diabetes, and along with calcium reduce the risk of tooth loss.

Calcium↗

Selenium in the blood of patients with colorectal cancer and neoplastic polyp.

Samples of whole blood were obtained from 51 patients with newly diagnosed colorectal cancer as well as from 76 patients with neoplastic colorectal polyp, and from 30 healthy blood bank donors. Selenium was determined by the fluorimetric method. Significantly decreased selenium concentrations of blood samples from patients with colorectal cancer and villous adenoma were found. There was not any correlation between the blood selenium levels of patients with adenomatous polyp and the severity of dysplasia in removed polyps. The lowest mean selenium level in patients with villous adenoma indicates that selenium deficiency may be an important factor in the development of colorectal cancer arising from villous adenomas.

Adenoma↗