Neoplastic transformation

However, the preliminary data presented in this paper suggests that microsomal enzymes may, in fact, alter the course of metal carcinogenesis in tissue culture. 

The effects of metals on tissue culture systems will be divided into 3 sections. The first section involves toxic effects of the same metals on cell cultures the second section will discuss the effects of metals on transcriptional, translational. 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

Arsenic competes with phosphate for incorporation into precursors of DNA or RNA such as dATP, rATP, dGTP, rGTP, etc. (28,37.38.39). If arsenic is incorporated into molecules such as ATP, then it may also be added to serine and threonine residues of cellular proteins, since protein kinase uses the terminal phosphate of ATP in the phosphorylation of a variety of cellular proteins. 

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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. 

Androgens act via the AR and play an important role in the development and differentiation of the male sexual organ. Furthermore, they are involved in several diseases, the most important being partial and complete androgen insensitivity syndrome (AIS formerly known as the testicular feminization syndrome), spinal and bulbar muscle atrophy (SBMA Kennedy s disease), and the neoplastic transformation of the prostate. The two natural occurring androgens are testosterone (T) and the... 

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 ... 

B and T cells can undergo neoplastic transformation that is governed by specific mutations in their chromosomes that result in populations of malignant lymphoma cells. 

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. 

Hix LM, Frey DA, McLaws MD, 0sterlie M, Lockwood SF, and Bertram JS. 2005. Inhibition of chemically-induced neoplastic transformation by a novel tetrasodium diphosphate astaxanthin derivative. Carcinogenesis 26(9) 1634-1641. 

Bertram, J. S., A. Pung, M. Churley et al. 1991. Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis 12(4) 671-678. 

Hossain, M. Z., L. R. Wilkens, P. P. Mehta, W. Loewenstein, and J. S. Bertram. 1989. Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10(9) 1743-1748. 

Hotz-Wagenblatt, A. and Shalloway, D. 1993. Gap junctional communication and neoplastic transformation. CritRev Oncog 4 541-558. 

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... 

In vitro models could be used to study the molecular mechanisms involved in the process of neoplastic transformation and as screening tools for the classification of the carcinogenic potential of a substance. Among the in vitro tests available to the scientific community, the CTA may represent an important tool for the identification of carcinogens, particularly those that are not identifiable by classic mutagenicity tests such as the Ames test. 

Cells do not stop their proliferation upon reaching confluence, pile up in stacks (foci) of morphologically transformed cells that can be considered as an endpoint of neoplastic transformation (Fig. 5). 

Rosenwald, I. B. (2004). The role of translation in neoplastic transformation from a pathologist s point of view. Oncogene 23, 3230—3247. 

Protonated N-hydroxy arylamines have also been proposed to be ultimate carcinogens for the urinary bladder (16,17,140,141) since urine pH is slightly acidic in a number of species (14,142). Furthermore, pharmacokinetic studies have shown that increased urine acidity and decreased frequency of urination are predictive of relative species susceptibility to urinary bladder carcinogenesis (142) and neoplastic transformation of cultured human fibroblasts by N-hydroxy arylamines is greatly enhanced by incubation at pH 5 as compared to pH 7 (143). 

Nitro PAHs have been shown to exhibit a large variety of biological activities. Included in these are the induction of mutations in bacterial (Table I) and eukaryotic cells (9,17,54-57), the neoplastic transformation of cultured mammalian cells (58-59), and the induction of DNA strand breaks (60), DNA repair (61-62), sister chromatid exchanges (63-64), and chromosomal aberrations (65-66). Nitro PAHs have also been demonstrated to bind cellular DNA in bacteria (67-73) and mammalian cells (74-77), to inhibit preferentially the growth of repair-deficient bacteria (78), to have recombinogenic activity in yeast (66,79-80) and to induce tumors in experimental animals (Table II). 

Percival SS, Talcott ST, Chin ST, Mallak AC, Lound-Singleton A and Pettit-Moore J. 2006. Neoplastic transformation of BALB/3T3 cells and cell cycle of HL-60 cells are inhibited by mango (Mangifera indicaL.) juice and mango juice extract. J Nutr 136 1300-1304. 

The incidence of ovarian tumors in mice, guinea pigs, and rabbits increased after 3 years of chronic irradiation at doses as low as 1.1 mGy daily (Lorenz et al. 1954). Unlike other tumors, the induction of ovarian tumors depended on a minimum total dose and seemed to be independent of a daily dose (Lorenz et al. 1954). Radiation-induced neoplastic transformation of hamster cells may be associated initially with changes in expression of the genes modifying cytoskeletal elements (Woloschak et al. 1990b). 

Mammary epithelium is very sensitive to hormonal stimulation. It is where proliferative events take place and where neoplastic transformation begins. 

Rhim, J. S. 1993. Neoplastic transformation of human cells in vitro. Crit Rev Oncog 4(3) 313-35. 

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... 

The traditional principle of tumour histogenesis is that neoplasms characterized by a certain phenotype arise from normal cells of similar phenotype. Considerable evidence has accumulated in recent years which indicates that this histogenetic assumption is incorrect. Most, if not all, neoplasms arise from immature cells, which in the course of neoplastic transformation acquire phenotypic features equivalent to those of one or more normal ceU types. Often this differentiation develops along lines analogous to those expected under normal conditions for that particular cell. 

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

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