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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (548)	3/17/2000 2:10:00 PM
From: juneau_boy	Respond to of 1834

Thought not. Just a reality check. Thanks. <EOM>

To: scaram(o)uche who wrote (548)	3/24/2000 7:08:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 1834

The "why" here is not obvious to me, but a FWIW post..... Publishing ID: 4294 Activity of a recombinant Interleukin-4-Pseudomonas Exotoxin is reduced in tumor cell lines overexpressing the Multidrug Resistance Protein MRP1, but not cell lines overexpressing P-glycoprotein, Breast Cancer Resistance Protein, MRP2 or MRP3 Mariska C de Jong, George L Scheffer, J. W Slootstra, H. J Broxterman, R. H Meloen, S. R Husain, B. H Joshi, R. K Puri, Rik J Scheper, Acad Hosp Vrije Univ, Amsterdam, Netherlands; Institute for Animal Sci and health, Lelystad, Netherlands; Institute for Animal Sci and Health, Amsterdam, Netherlands; Ctr for Biologics Evaluation & Res, Bethesda, MD. Previous studies have shown that a variety of human cancer cells overexpress the interleukin-4 (IL-4) receptor (IL-4R). A recombinant fusion protein comprised of circularly permuted IL-4 and Pseudomonas exotoxin (IL-4 toxin) was developed and shown to effectively target these cells in vitro. In vivo experiments with nude mice showed significant antitumor activity against human IL-4R overexpressing glioblastoma cells and based on these results, phase I clinical trials have started for the treatment of brain tumors. In this study, we investigated whether tumor cells that are resistant to established anti-cancer drugs like doxorubicin and mitoxantrone are still sensitive to this IL-4 toxin. Cytotoxicity experiments with lung carcinoma, breast carcinoma and multiple myeloma cells and their respective doxorubicin and mitoxantrone selected sublines showed that cell lines that overexpress P-glycoprotein or Breast Cancer Resistance Protein are sensitive while cells overexpressing MRP1 are resistant to IL-4 toxin. Also, ovarian carcinoma cells transfected with MRP2 and MRP3 cDNA showed sensitivity while cells transfected with MRP1 were resistant to IL-4 toxin. This resistance could be reversed by adding the known MRP1 antagonists probenecid and MK-571 to the cultures. We conclude that most ABC transporter proteins involved in multidrug resistance are not associated with resistance to IL-4 toxin except for MRP1. Studies are ongoing to unravel the role of MRP1 in resistance to IL-4 toxin.