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Biotech / Medical : NexStar Pharm(NXTR) -- Ignore unavailable to you. Want to Upgrade?

To: Steven Yang who wrote (310)	11/18/1998 11:20:00 PM
From: Miljenko Zuanic	Respond to of 328

Hi Steven: Agree, AR didn't increase significantly for last Q. I will fill better when AR start to decline, but we may not witness this. Stock come to life probably on rumor that NXTR general is for sale. NXTR is consolidating its finance and borrowing, so rumor may be correct. For now I am not betting on this (I will love that it is true). I will like to see grow in AmBisome sale (France) and progress in MiKasome trials. Will see what will develop in next few weeks. Miljenko

To: Steven Yang who wrote (310)	11/28/1998 12:34:00 AM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 328

Ambisome versus Abelce, and CTLA-4 blocade by mAb for GVHD/GVL (ASH conference): ex2.excerptamedica.com Abstract #4438 (publish only) COMPARATIVE ANALYSIS OF LIPOSOMAL (AMBISOME-AMB) AND LIPID COMPLEX (ABELCET-ABLC) AMPHOTERICIN B PREPARATIONS AFTER INTENSIVE AND MYELOABLATIVE CHEMOTHERAPY REGIMENS J.M.F. Lacerda, B. Gomez, C. Martins, M.E. Pereira, G. Esteves, M.J. Costa, L. Guerra, J. Raposo, J.A. Carmo, P. Neves, J.F. Lacerda University of Lisbon, Santa Maria Hospital, Lisbon, Portugal -------------------------------------------------------------------------------- Patients (pts) with prolonged severe neutropenia induced by remission induction chemotherapy or myeloablative transplant regimens were randomized to receive i.v. AMB 3 mg/kg/day (n = 36) or ABLC 5 mg/kg/day (n = 27) due to persistent fever after empiric treatment with amikacin, piperacillin/tazobactam and vancomycin. As depicted, both drugs were equally effective (p = NS). At the onset of treatment, Clcr was conserved in both groups (AMB 93.9 ± 39 Vs ABLC 87.3 ± 29; p = NS). However, at the end of treatment the ABLC arm had a significantly lower Clcr (AMB 95.1 ± 39 Vs ABLC 72 ± 19; p = 0.007) Pts receiving ABLC also had a higher incidence of serum creatinine duplication (p = 0.031) and required higher i.v. potassium supplementation (p = 0.03). AMB ABLC Mean age (SD) 43.8 ± 14.5 46.9 ± 17.8 Sex 16 M/12 F 10 M/13 F Diagnosis: - AML/ALL/CML/MF 18/0/2/1 16/1/3/0 - AA/HD/NHL/CLL/MM 1/0/2/1/3 0/2/0/0/1 Anti-fungal treatment courses 36 27 Anti-neoplastic regimens: - Induction 12 12 - Re-induction 16 9 - Autologous SCT 2 3 - Allogeneic BMT 6 3 Fungal infection prophylaxis: - Fluconazole 23 22 - Itraconazole 10 4 Positive fungal cultures 2 (1 blood) 4 (2 blood) Median days Ampho B (range) 14 (731) 14 (530) Afebrile 96 hours after Ampho B 19 (52.8%) 13 (48.1%) Toxicity: - Serum K+ < 3.5 mMol/L 24 (66.7%) 23 (85.2%) - Serum K+ < 2.5 mMol/L 1 (2.8%) 2 (7.4%) - Clcr < 50 ml/min 6 (16.7%) 8 (29.6%) - Allergic reactions 3 (8.3%) 1 (3.7%) K+ supplementation: - > 100 mEq/day 12 (33.3%) 17 (62.9%) - > 150 mEq/day 4 (11.1%) 12 (44.4%) Abstract #1798 - Monday, December 7, 1998 - Hall C, 11:30 am-1:00 Posterboard 470-III, EXPERIMENTAL TRANSPLANTATION - GVL/GVT and Adoptive Immunotherapy Post-BMT REGULATION OF GVHD AND GRAFT-VERSUS-LEUKEMIA (GVL) BY CD28/B7 AND CTLA-4/B7 INTERACTIONS P.A. Taylor, D.A. Vallera, A. Panoskaltsis-Mortari, A.H. Sharpe*, B.R. Blazar U. Minn. Canc. Ctr., Mpls., MN; Brigham and Women's Hosp., Boston, MA, USA -------------------------------------------------------------------------------- Sustained T cell activation requires signals from the T cell receptor and costimulatory pathways. We and others have shown that the in vivo blockade of the CD28/CTLA-4:B7 costimulatory pathway can markedly reduce GVHD-induced mortality. Although CD28 and CTLA-4 are homologous T cell receptor determinants, CD28/B7 and CTLA-4/B7 interactions have been implicated in the delivery of positive and negative regulatory signals, respectively. Since blockade with B7 antagonists interferes with both B7:CD28 and B7:CTLA-4 interactions, which may have opposing effects on T-cell expansion, we separately examined the roles of these pathways on in vivo alloresponses. A critical role of B7:CD28 interaction was demonstrated by the markedly compromised expansion of CD28-deficient T-cells. When CD28-deficient CD4+ or CD8+ T-cells were infused into sublethally irradiated MHC class II or I disparate recipients, GVH lethality was diminished by >10-fold and >3-fold, respectively. In a system in which both CD4+ and CD8+ T cells were infused into MHC disparate recipients, CD28-deficient donor T cells expanded less in vivo than wild-type cells as measured by cannulation of the thoracic duct lymphatics. Selective blockade of CTLA-4:B7 in vivo by aCTLA-4 mAb infusion significantly augmented GVHD lethality induced by wild-type but not CD28-deficient cells in this system. The enhanced expansion of wild-type T-cells in mAb treated recipients was strikingly advantageous in the GVL effects of delayed donor splenocyte infusion in recipients given acute myelogenous leukemia (0% AML occurrence in mAb treated vs. 100% in DLI controls). Conversely, CD28-deficient donor splenocytes had a markedly reduced GVL effect. aCTLA-4 administration given early post-transplantation, however, reduced bone marrow graft acceptance in two different engraftment systems. In conclusion, our data indicate that selective blockade of the CD28-B7 interactions early post-transplantation, which preserve CTLA-4:B7 interactions, would be preferable to approaches that block both pathways in order to optimally inhibit GVHD without inhibiting graft acceptance. Selective blockade of CTLA-4:B7 interactions later post-BMT provides a potent and previously unidentified means for augmenting the GVL effect of delayed donor splenocytes infusion. Selective blockade of CD28:B7 or CTLA-4:B7 binding can have important therapeutic benefits.