Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

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

To: tuck who wrote (10057)	1/19/2004 2:24:37 PM
From: nigel bates	Respond to of 52153

...deriving targets from gene sequences just got way more unlikely. It's a little early to say that. As everyone's favourite blogger has it: ...Who knows! It might turn out to be a rare curiosity, or it might turn out to be something really important that we've completely missed seeing all these years. To be sure, no one's reporting coming across a lot of important proteins whose sequences couldn't be matched in the genome somewhere. But there are an awful lot of proteins whose sequence we don't know, so the upper and lower bounds of this new phenomenon are fuzzy... Certainly a 'watch this space', though. It also implies a longer road for companies with a proteomics approach to drug discovery I'm not sure that necessarily follows, even if this turns out to be a widespread phenomenon - though of course it does imply a larger 'proteome'.

To: tuck who wrote (10057)	1/19/2004 3:07:07 PM
From: zeta1961	Respond to of 52153

<<C2 CTLs, cloned from human CTLs infiltrating a renal cell carcinoma, kill cancer cells overexpressing fibroblast growth factor-5 (FGF-5).>>> Tuck, thanks for posting this...they don't quantify the level of "cancer cell killing"... interesting to note future followup in live species...something I find important in assessing the implications...Perhaps you've seen the below? At first I was excited about it's results and also concerned re: how it would affect INGN's p53 therapy...but the devil in the details of this report despite it's positive title is < Treatment of mice with subcutaneous osteosarcoma tumor xenografts with Nutlin-3 inhibited tumor growth 90% relative to control treatment after 20 days.>>>>> sounds exciting upon first glance but this does not indicate tumor stabilization or regression at all... Unfortunately, even gvt. agency scientists have to "spruce up" their headlines to justify their research grants...$$$$$ and jobs... That said...it is my belief that many illnesses(cancers, infections, autoimmune and even cardiology)...will see dramatic improvement in treatment with the increased focus of looking at T cell and and other immune system components' role in dis-ease...it seems more prudent to find ways to help "fix" the systems which have allowed the human species to prevail per Darwin...all my opinion of course... Regards, Zeta NEW YORK (Reuters Health) Jan 02 - "Nutlins," a series of synthetic cis-imidazoline analogs, inhibit the oncogene MDM2, thus stabilizing the p53 tumor suppressor protein and inhibiting the growth of malignant tumors, researchers report. Treatment of mice with subcutaneous osteosarcoma tumor xenografts with Nutlin-3 inhibited tumor growth 90% relative to control treatment after 20 days. The use of MDM2 antagonists "may be applicable not only to tumors with aberrant MDM2 expression but possibly to many of the 50% of all human malignancies that have retained wild-type p53," write lead investigator Dr. Lyubomir T. Vassilev and colleagues at Hoffman-La Roche Inc., in Nutley, New Jersey report in the journal Science, published online on January 2. The authors explain that the MDM2 gene is amplified or overexpressed in many human malignancies, which presumably leads to p53 inactivation. Nutlins displace p53 protein from its complex with MDM2, and their findings suggest that MDM2 blockage causes cell cycle arrest or apoptosis or both. To examine their effect in vitro, they incubated colon cancer cells with wild-type p53 with Nutlin-1, and observed a dose-dependent increase in MDM1, p53 and p21 after 8 hours. Co-culture of Nutlin-1 with cancer cells exhibited an antiproliferative/cytotoxic effect that was more pronounced in cell lines with normal p53 genes or an amplified MDM2 gene. When normal diploid fibroblasts with a functional p53 pathway were treated with Nutlin-3, the investigators observed reduced proliferation but no change in viability even after 1 week. The authors note that Nutlin-3 was well tolerated, with no weight loss and no apparent abnormalities revealed by necropsy. "Our data strengthen the notion that unleashing the powerful growth suppressive and pro-apoptotic activity of p53 by MDM2 antagonists is a potentially valuable strategy for treating cancer," Dr. Vassilev and colleagues write.

To: tuck who wrote (10057)	1/19/2004 10:44:26 PM
From: Biomaven	Respond to of 52153

tuck, I think once the estimated number of genes dropped (if not before) it was pretty clear that the "one gene one protein" mantra was a serious over-simplification. But from my limited knowledge I would doubt that this discovery will have much short or medium-term impact on drug development. Not only is it quite unclear how widespread this protein-splicing is, but I think there are more fundamental issues in genomics as a source of targets. I think the more significant factor is that cells are so complex and there is so much redundancy that most single genes are just not good targets in the first place. Peter