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Biotech / Medical : VD's Model Portfolio & Discussion Thread -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (7737)	3/17/2000 1:48:00 PM
From: scaram(o)uche	Respond to of 9719

Publishing ID: 4169 IDENTIFICATION OF PROTEINS BINDING TO MGI 114. Michael J Kelner, Anissa Elayadi, Trevor C McMorris, UCSD, San Diego, CA. MGI 114 (HMAF) is a novel semisynthetic anticancer agent currently in phase I and II trials to evaluate activity against various solid tumors. The agent demonstrates significant activity against multidrug resistant tumors regardless of the mechanism of resistance. The mechanism of action of MGI 114 remains unknown. In order to gain insight into the mechanism of action of MGI 114, the proteins capable of directly binding to the drug were identified. A derivative of MGI 114 was covalently linked to biotin via a hydrazide linker. This biotinylated drug complex was combined with an avidin-resin to make a target affinity column. A control column was prepared by attaching the hydrazide linker to biotin (no drug attached). A cell lysate was prepared from MV522 lung carcinoma cells and added to the column. Nonbinding proteins were washed off using a neutral phosphate saline buffer. Bound proteins were eluted by increasing salt concentration, altering pH, or by adding a competing drug ligand. The bound proteins from the drug affinity column were separated by PAGE, and recovered for direct amino acid analysis. No proteins were recovered from the control column (linker, biotin, avidin, resin). Sequence analysis revealed that the bound proteins were all members of the 60S Ribosomal complex. This suggests that MGI 114 is capable of directly binding to ribosomes.

To: Biomaven who wrote (7737)	3/17/2000 1:50:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 9719

Publishing ID: 1524 Sequencing Evaluation of MGI-114 Combinations with Standard Chemotherapy Agents Against Human Tumor Cell Lines. H. Barrera, Rodney Moore, S. J Waters, J. R MacDonald, S. Weitman, Institute for Drug Development, CTRC, San Antonio, TX; MGI Pharma, Inc, Bloomington, MN. 6-Hydroxymethylacylfulvene (MGI-114), a semisynthetic antitumor agent derived from the mushroom toxin illudin S., was evaluated in combination with SN-38, mitoxantrone, or gemcitabine against human colon, prostate, and pancreatic tumor cell lines. These studies were undertaken to determine the drug-drug interaction (e.g., additive, synergistic, or antagonistic) that exists between MGI-114 and standard agents and the importance of sequence of exposure to these agents. Multiple combinations of MGI-114 with the standard cytotoxic agent were used with a model free design (Laska, et al. Biometrics 50:834, 1994) to describe the type of drug-drug interaction. These studies suggest that regardless of sequence of exposure between MGI-114 and standard chemotherapy agents, an additive pattern of drug-drug interaction is most typically observed. However, as previously observed, an occasional synergistic (concurrent exposure with mitoxantrone or SN-38; pre-exposure to MGI-114 followed by SN-38) or additive/synergistic (pre-exposure to gemcitabine or SN-38) pattern of drug-drug interaction was observed. Evidence of antagonism was observed only when the DU-145 prostate tumor cell line was pre-exposed to MGI-114 or mitoxantrone. These studies suggest that MGI-114 which is in multiple Phase II clinical trials, could be combined with several cytotoxic agents against a broad-range of tumor types.

To: Biomaven who wrote (7737)	3/18/2000 12:47:00 AM
From: RWReeves	Read Replies (1) \| Respond to of 9719

>MOGN's MGI 114 vs. OvaRex Remember that these patients have already been through the wringer and then some - multiple treatment taxol/platinol failures. Thus the drop outs are possibly not all MGI-114's fault. This is a very tough patient population indeed.< This release from AXO: OvaRex(TM) Clinical Data Presented at the Society of Gynecologic Oncologists Annual Meeting -Additional Data Reinforces Emerging Potential of Monoclonal Antibody- SAN DIEGO, Feb. 8 /CNW/ -- AltaRex Corp. (Toronto: AXO) today announced the presentation of additional retrospective data of OvaRex(TM) MAb, for the treatment of advanced stage ovarian cancer, at the 31st Annual Meeting of the Society of Gynecologic Oncologists in San Diego. The findings are a result of work conducted by Richard Baum, MD, PhD, Professor of Nuclear Medicine, University of Frankfurt/Main, Chairman of the Clinic of Nuclear Medicine / P.E.T. Center Bad Berka, involving Positron Emission Tomograpy (PET Imaging) on a group of 11 relapsed ovarian cancer patients with advanced disease who received multiple doses of OvaRex(TM) MAb. Professor Baum documented disease stabilization or regression of selected lesions using PET imaging in five of the 11 patients treated with OvaRex(TM) MAb. "The package of clinical data that is emerging from our studies supports the potential utility of OvaRex(TM) MAb in the treatment of advanced ovarian cancer," remarked Christopher Nicodemus, MD, Senior Vice President of Clinical Research and Development for AltaRex. "We believe the data from this analysis, while from a small group of patients, demonstrates that immunotherapy with OvaRex(TM) MAb may be capable of stabilizing and, in some cases, shrinking tumors. Coupled with updated results from a similar group of relapsed ovarian cancer patients being treated with OvaRex(TM) MAb in an open- label phase II study in Vancouver, we believe that the clinical development of OvaRex(TM) MAb is progressing extremely well." "The compilation of this data has given the Company the support it needs to continue its aggressive pursuit of the appropriate corporate partner," remarked Richard Bagley, President and CEO of AltaRex. "We believe we have a very compelling opportunity for a corporate partner with OvaRex(TM) MAb, which is in late-stage development. This clinical data allows us to move forward with partnering approaches that differ considerably from our previous efforts and we believe assists us in structuring a deal that will see OvaRex(TM) reach its full potential while rewarding shareholders accordingly." AltaRex Corp. is an antibody-based company focused on the development and commercialization of unique products for the treatment of late stage cancers. The Company's proprietary platform technology, Antibody-based ImmunoTherapy, or AIT(R), is designed to enhance the ability of the human immune system to produce its own anti-tumor response and allows for a cost-effective and timely evaluation of preclinical candidates. The Company has identified five product candidates for clinical evaluation. Aggressive disease, glad to see promising results. RWR