Human tumorigenesis

Two well known and isoform unselective PI3K inhibitors are the fungal metabolite wortmannin (compound 7, Fig. 3) and LY294002 (compound 8, Fig. 3). These two compounds have served as powerful research tools for more than a decade to elucidate the role of PI3Ks in human tumorigenesis and evaluate the potential utility of PI3K inhibitors as cancer therapeutics. 

Initiation-Promotion Studies. Carcinogenesis has been demonstrated to be a multistage process in the cells of certain animal tissues, including skin. lung, liver, and bladder. This process is believed to occur in human tumorigenesis as well. The PAHs have been studied extensively for their ability to act as tumor initiators and/or promoters. Following is a brief discussion, by chemical, ofthe results of the initiation-promotion studies performed with 13 of the 17 PAHs discussed in this profile. Only those studies considered adequate and reliable are presented in Table 2- 3. 

TTi. Mabjeesh NJ, Amir S. Hypoxia-inducible factor (HIE) in human tumorigenesis. Histol... 

CXCLS is markedly elevated and contributes to the overall angiogenic activity of nonsmall cell lung cancer (NSCLC) (Smith et al, 1994). Extending these studies to an in vivo model system of human tumorigenesis (i.e., human NSCLC/SCID mouse chimera) (Arenberg et al, 1995),... 

Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Stricter RM. Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. J Clin Invest 1996 97(12) 2792-2802. 

Anderson E (2002) The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Breast Cancer Res 4 197... 

Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ (1990) Comparative study of human and rat mammary tumorigenesis. Lab Invest 62(3) 244-278... 

Cancer. Only one report was located regarding an association between hexachloroethane and cancer in humans (Selden et al. 1989). In this study a liver tumor was found in an adult male who had used a product containing hexachloroethane at work for 6 years. However, under the conditions of use, the hexachloroethane reacted to form hexachlorobenzene and other chlorinated compounds which were as likely, or more likely, to have contributed to the tumorigenesis as the hexachloroethane. 

Cook, J.C., G.R.Klinefelter, LF.Hardisty, R.M.Sharpe, and P.M.D Foster. 1999. Rodent Leydig cell tumorigenesis a review of the physiology, pathology, mechanisms, and relevance to humans. Crit. Rev. Toxicol. 29 169—261. 

Grinstein E, Wernet P, Snijders PJ, Rosl F, Weinert I, Jia W, Kraft R, Schewe C, Schwabe M, Hauptmann S, Dietel M, Meijer CJ, Royer HD (2002) Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer. J Exp Med 196 1067-1078 Grisendi S, Bernard R, Rossi M, Cheng K, Khandker L, Manova K, Pandolfi PP (2005) Role of nucleophosmin in embryonic development and tumorigenesis. Nature 437 147-153 Hanakahi LA, Bu Z, Maizels N (2000) The C-terminal domain of nucleolin accelerates nucleic acid annealing. Biochemistry 39 15493-15499... 

Epidemiological studies in humans do not suggest an association between excess exposure to selenium and cancer." Low levels of intake, however, have been associated with an increased risk of developing many kinds of cancers. With the exception of selenium sulfide, most animal studies have shown that selenium compounds inhibit tumorigenesis." High doses of selenium sulfide administered by gavage caused liver tumors in rats and lung... 

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