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Biotech / Medical : Biotech Lock-Up Expiration Hell Portfolio -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (14)	5/22/2001 6:45:30 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 1005

>> Or do you think we won't get one for a while? Do you have ideas for an entry target/range? << I don't wait for pullbacks. I admire those who can, but I don't. You're asking the wrong person. >> An analysis of research premium relative to cash or book, however terse? << Very, very difficult to call. The company has the guts or foolishness -- not determined which yet -- to say that they're taking 286 forward alone. That will spell dilution. If it's a good drug, it'll spell dilution with gilt. 199..... everything would need to be PERFECT. If there's any question at all re. toxicity, the project is dead IMO. The potenital market is enormous, and they're posed to begin clinicals. Therefore, IMO, deserves some research premium. I assign $10 million. Insulin sensitizers...... I like what they're saying, but I lack the knowledge to evaluate the program. I assign $30 million, but only because Wick has referred to it as potential first in class. Research premium is modest in relation to leverage and markets addressed. IPO was launched into terrible conditions, and cash:risk is low. Phase II for 286/colon is accruing patients. Phase II for 286/ovarian should start any day now, 1 gm/m(2) once every three weeks, patient accrual (M.D. Anderson) should be no problem. Brain mets are rare for ovarian, 286 not known to pass BBB. Free Radic Res 1999 Dec;31(6):549-58 Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells. Goto S, Iida T, Cho S, Oka M, Kohno S, Kondo T. Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan. In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.