Progress in Tumor Research最新文献

There is evidence that aspirin--and apparently other NSAIDs--may be protective agents against cancer in the gastrointestinal tract. These effects are particularly well documented in the colon and rectum. Even considered in isolation, the observational data regarding colorectal neoplasia are quite strong, and the reality of a protective effect is buttressed by clinical trial data showing that aspirin prevents sporadic adenomas. Furthermore, the NSAIDs sulindac celecoxib have actually led to the regression of existing colorectal polyps in patients with FAP. Clearly, NSAIDs have the potential to suppress carcinogenesis in the large bowel. Observational data suggesting inverse associations of NSAIDs with cancers of the stomach and esophagus have emerged from several case-control studies and a few cohort analyses. In some studies the findings display features often associated with causal relationships, for example decreasing risks with increasing doses or duration of use. Nonetheless, the data currently do not support a secure conclusion that NSAIDs protect against these malignancies. The relevant data are not nearly as extensive as those for the colorectum, and case-control investigation of these upper gastrointestinal sites may be particularly delicate. It is conceivable that early symptoms of cancer (or of pre-invasive lesions) may have discouraged NSAID use in the cancer patients, creating the appearance of a protective association of the drugs with the risk of these malignancies. More extensive observational data particularly from cohort studies would be desirable to confirm the existing findings and clarify the doses and durations of use required for an effect. Clinical trial investigation might also be practical for pre-neoplastic endpoints, or--in carefully selected populations--perhaps with cancer as the focus. There are only relatively limited data available regarding the effect of NSAIDs on cancer of the pancreas. However, the studies that have investigated this malignancy have reported indications that NSAIDs may have a protective effect. The effects of NSAIDs on cancers outside the gastrointestinal tract are not clear. Some investigations suggest that NSAID use, particularly aspirin, is inversely associated with risk of cancers of the breast or ovary, but several well-done studies have not seen these associations, and the observations could have been due to bias or confounding. Findings regarding prostate cancer are similarly conflicting. The urinary tract is one organ system in which several studies have reported an increased cancer risk in association with NSAID use. Nonetheless, the effects remain unclear. There is only limited available information regarding carcinoma of the bladder, and no firm conclusions can be drawn at this point. More extensive data have been generated regarding the effect of NSAIDs--largely salicylates--on renal cell carcinoma or cancer or the renal pelvis and ureter. Although some studies have reported in

Cancer development is a multistep process that involves both the activation of protooncogenes and the inactivation of tumor suppressor genes. Furthermore, both epidemiological and experimental data indicate that a third class of genes, tumor susceptibility genes, control the propensity to develop carcinogen-induced tumors. Recent studies suggest that tumor susceptibility is determined by the combined effect of both sensitivity and resistance genes. The mouse skin model of multistage carcinogenesis is an excellent paradigm in which to study the genetics of cancer susceptibility. This is particularly true with regard to tumor promotion, a process that occurs in other organs and species including humans. We have studied the genetics of tumor promotion susceptibility in the mouse two-stage skin tumor model using crosses between sensitive DBA/2 or C3H and resistant C57BL/6 mice. Our results suggest that TPA promotion susceptibility is a multigenic trait. We have tentatively mapped one tumor susceptibility locus, Psl1, to mouse chromosome 9 and are currently identifying and characterizing candidate tumor susceptibility genes that map to this chromosomal region. The multistage model of carcinogenesis in mouse skin has, for more than 50 years, provided a conceptual framework from which to study the carcinogenesis process. Many concepts now currently applied to other tissues and model systems were originally derived from the mouse skin model. Because tumor promotion is an important component of carcinogenesis in humans, the identification of genes that modify response to tumor-promoting stimuli would be a significant advancement in our understanding of the genetic basis of susceptibility to cancer.