By J. Martin Brown PhD, Bradly G. Wouters PhD (auth.), John A. Hickman, Caroline Dive (eds.)

The prior few years have witnessed an stunning foreign attempt that verified the position of a few 20 new molecules in apoptosis and further activation or suppression of apoptosis to the authorised organic capabilities of a good many others already commonplace in melanoma biology. a few of these molecules are receptors, transducing cytokine-mediated indications; others seem to accentuate or decrease the chance compro­ mised phone will hearth its apoptosis effector mechanism. All are of curiosity as strength objectives for tumor remedy, and a few may perhaps end up to be keep an eye on issues motivated within the pathogenesis of melanoma and different illnesses as different as viral an infection, neurodegenerative issues, and stroke. occasionally, in the middle of those advancements, a type of euphoria ap­ pears to have gripped the study neighborhood, with the expectancy that apoptosis will come up with the money for reasons to many unsolved questions in cellu­ lar law. This publication, in a chain of considerate and provocative ar­ ticles--some from confirmed leaders within the box, and others from more youthful scientists--seeks to redress the balance.

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Anticancer Res 1995; 15: 639--644. "36. Buttitta F, Marchetti A, Gadducci A, Pellegrini S, Morganti M, Carnicelli V, et al. p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study. Br J Cancer 1997; 75: 230-235. Correlates p53 mutations with resistance to cisplatin-based therapy in aggressive ovarian carcinoma. In this setting, loss of p53 function does not appear to Chapter 2 I p53, Apoptosis, and Chemosensitivity 33 enhance cisplatin-based toxicity, although in some other settings it does (see refs.

55. Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB. DNA damage induces phosphorylation of the amino terminus ofp53. Genes Dev 1997; 11: 3471-3481. "56. Garkavtsev I, Grigorian lA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AY. Candidate tumour suppressor p331NGI cooperates with p53 in cell growth control. Nature 1998; 391: 295-298. "57. Kamijo T, Weber JS, Zambetti G, Zindy F, Roussel MF, Sherr CJ. Interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci USA 1998; 95: 8292-8297.

DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325-334. 55. Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB. DNA damage induces phosphorylation of the amino terminus ofp53. Genes Dev 1997; 11: 3471-3481. "56. Garkavtsev I, Grigorian lA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AY. Candidate tumour suppressor p331NGI cooperates with p53 in cell growth control. Nature 1998; 391: 295-298. "57. Kamijo T, Weber JS, Zambetti G, Zindy F, Roussel MF, Sherr CJ.

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