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Biotech / Medical : Biotech Short Candidates -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (616)	12/1/2003 11:20:59 PM
From: tuck	Read Replies (2) \| Respond to of 897

>>I would like to know what were pts status (and genetic make up) at baseline<< Well, this is an interesting question. The degree of involvement of Raf-1 in kidney cancer appears to be hit or miss depending on your genetic makeup and degree of disease progression. >>Cancer Res. 1995 Sep 15;55(18):4182-7. Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. Oka H, Chatani Y, Hoshino R, Ogawa O, Kakehi Y, Terachi T, Okada Y, Kawaichi M, Kohno M, Yoshida O. Department of Urology, Faculty of Medicine, Kyoto University, Japan. Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.<< 69% of grade 2 patients showing MAPK activation. Are you wondering if there is a preponderance of grade 2 patients in the PII trial? From the PR: >>In October 2003, interim Phase II clinical data for BAY 43-9006 were presented at NDDO's Second International Symposium on Signal Transduction Modulators in Cancer Therapy in Amsterdam, The Netherlands (www.nddo.org), showing that the agent demonstrated encouraging signs of tumor shrinkage and disease stabilization. The initial data analysis included 41 participants with advanced and progressive renal cell carcinoma (kidney cancer) who were evaluable after 12 weeks of treatment. Of the evaluable patients, 44 percent (18 patients) had tumor shrinkage of at least 25 percent. Twenty-nine percent (12 patients) had their tumors stabilized within 25 percent of pretreatment size. Overall, 73 percent (30 patients) of this cohort of study participants did not demonstrate tumor progression by the 12-week evaluation point, as assessed by investigators. The remaining 27 percent (11 patients) discontinued study treatment either because of progressive disease or adverse effects.<< Stages of Kidney Cancer: cancerhelp.org.uk >>"Avastin on market", is main driver for this "rush" toward RCC PIII trial.<< There's no doubt, Bayer could really use a blockbuster soon. >>No activity at all(or minimal one), so far, in other indications.<< And if this is the case, then Onyx probably is a good short. What do you think? Cheers, Tuck