Cancer neoplastic transformations

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

In breast cancer patients, total PR status is measured for hormonal treatment. The presence of PR is associated with increased survival rates and hormonal responsiveness of mammary tumors. PR agonists are widely used in contraception, HRT, breast cancer, and endometrial hyperplasia. Antiprogestins such as RU486 are used for blocking ovulation and preventing implantation, and in addition they are in clinical testing for the induction of labor and to control various neoplastic transformations. 

Targeted cancer therapy refers to anticancer treatments that selectively interfere with molecules ( oncogenes and antioncogenes) considered to be important in neoplastic transformation, cell proliferation, invasion... 

Epidemiologic studies of the macroenvironment focused on the diet and the long incubation period have led us to postulate that long-lasting disturbances in the normal gastric mucosa may determine the final outcome of the neoplastic transformation W. This explains the present interest in precursor lesions rather than in cancer itself. We, therefore, need to scrutinize the gastric microenvironment and attempt to point out the components that may be relevant to neoplasia. The microenvironment could be considered to be determined by three basic elements ... 

TM-GPCRs, like CXCR2, may be involved in pre-neoplastic to neoplastic transformation and the development of cancer. 

Dunkel VC, Pienta RJ, Sivak A, et al. 1981. Comparative neoplastic transformation responses of Balb/3T-3 cells, Syrian hamster embryo cells, and Rauscher murine leukemia virus-infected Fischer 344 rat embryo cells to chemical carcinogens. J Nat Cancer Inst 67 1303-1315. 

In recent decades, the development of chemical, biochemical, and biological techniques has allowed the creation of analytical tools which can be used to facilitate the identification of the mechanisms involved in neoplastic transformation. Animal models remain, however, the most widely used approach of investigation. Cancer bioassays are usually conducted in rodents (rats and mice) and the experimental protocol takes 18-24 months and it is followed by extensive histopathological and statistical analysis. The procedure is time and... 

Milo, G. E., I. Noyes, J. Donahoe, and S. Weisbrode. 1981. Neoplastic transformation of human epithelial cells in vitro after exposure to chemical carcinogens. Cancer Res 41(12 Pt 1 ) 5096—102. 

Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100 11606-11611... 

B. Development of cancer or neoplastic transformation requires an accumulation of mutations in the same cell. 

DiPaolo, J.A., Takano, K. and Popescu, N.C. (1972). Quantitation of chemically induced neoplastic transformation of Balb/c 3T3 cloned cell Unes, Cancer Res. 32,2686. 

Proteases are involved also in the expression of mutations in bacteria, in tumor promotion in mice, and in the X-ray-induced neoplastic transformation in hamster and mouse cells (21,22). Protease inhibitors will block tumor promotion in mice (23) and plant protease inhibitors in the diet have been proposed to account for the low incidence of breast and bladder cancer in countries where diet is high in plant proteins. 

Mil. Markwalder, R., and Reubi, I. C., Gastrin-releasing peptide receptors in the human prostate Relation to neoplastic transformation. Cancer Res. 59, 1152—1159 (1999). 

Induction of Morphological and Neoplastic Transformation in Mammalian Cells Cell Culture Models for Chemically Induced Cancer Proceeding through Mutagenesis... 

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