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Biotech / Medical : Cell Therapeutics (CTIC) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (189)	2/24/2004 3:31:48 PM
From: tuck	Respond to of 946

>>Clinical Cancer Research Vol. 10, 1508-1520, February 2004 Experimental Therapeutics, Preclinical Pharmacology RWJ-241947 (MCC-555), A Unique Peroxisome Proliferator-Activated Receptor- Ligand with Antitumor Activity against Human Prostate Cancer in Vitro and in Beige/Nude/ X-Linked Immunodeficient Mice and Enhancement of Apoptosis in Myeloma Cells Induced by Arsenic Trioxide Takashi Kumagai1, Takayuki Ikezoe1, Dorina Gui2, James O’Kelly1, Xiang-Jun Tong1, Fredric J. Cohen3, Jonathan W. Said2 and H. Phillip Koeffler1 Division of Hematology/Oncology, Departments of1 Medicine and 2 Pathology, Center of Health of Science, University of California at Los Angeles School of Medicine, Los Angeles, California, and 3 Global Clinical Research, Johnson and Johnson Pharmaceutical Research and Development, La Jolla, California Purpose: RWJ-241947 (MCC-555) is a novel peroxisome proliferator-activated receptor- ligand of the thiazolidinedione class that was recently developed as an antidiabetic drug with unique properties. Some thiazolidinediones have anticancer activity against solid and hematological malignancies; the anticancer potency of RWJ-241947 has not been examined. We, therefore, investigated these effects in vitro and in vivo either alone or in combination with other compounds. Experimental Design: Tumor growth was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, soft agar colony assay in vitro, and xenografts in nude mice. Its effects on cell cycle, differentiation, and apoptosis were examined. Results: In vitro studies using various solid and hematological tumor cell lines showed that RWJ-241947 had antiproliferative activity against prostate cancer cells, with the strongest effect against the androgen-independent PC-3 prostate cancer cells. It increased expression of cyclin-dependent kinase inhibitor p21WAF1, deceased cyclin E, and induced apoptosis in PC-3 cells. It increased E-cadherin and lowered protein expression of prostate-specific antigen without down-regulating the androgen receptor in androgen-dependent LNCaP prostate cancer cells. Reporter gene assays showed that this peroxisome proliferator-activated receptor- ligand inhibited androgen activation of the androgen receptor response elements of the prostate-specific antigen gene. Remarkably, in vivo treatment of male beige/nude/X-linked immunodeficient (BNX) mice with RWJ-241947 profoundly suppressed growth of PC-3 prostate cancer xenografts with prominent apoptosis, as well as fibrosis, including inflammatory and giant cell reaction in the remaining tumor tissue. Notably, the experimented mice had a significantly decreased cholesterol. In addition, we studied the combination of arsenic trioxide (As2O3), which is used in the treatment of multiple myeloma, and RWJ-241947; these two reagents together prominently inhibited proliferation and caused apoptosis of multiple myeloma cells. Conclusions: RWJ-241947 has surprisingly potent antiproliferative effects against prostate cancer cells in vivo, and it enhances the antitumor activity of As2O3 against myeloma cells. Small, well-defined clinical studies using RWJ-241947 are in order for these cancers. << Cheers, Tuck

To: Icebrg who wrote (189)	2/28/2004 3:35:53 AM
From: Icebrg	Read Replies (1) \| Respond to of 946

Cephalon to work on R&D with Italian company John George May 7, 2002 [Some background info on the Cephalon - NovusPharma agreement on an oral proteasome inhibitor]. Cephalon Inc. of West Chester formed a research and development collaboration with Novuspharma of Bresso, Italy, to discover and develop new drugs for the treatment of cancer. Under the terms of the initial three-year agreement, Novuspharma will use its expertise in pre-clinical research to optimize the performance of Cephalon's proteasome inhibitors that have exhibited anti-cancer activity. (The proteasome regulates the activity of proteins involved in cell progression, cell survival and tumor growth.) The discovery of any new compounds will be jointly owned by the two companies. Cephalon will have the marketing rights in the Americas and Japan for any new drug the collaboration in the Americas and Japan: Novuspharma will have the rights in Europe. Financial terms of the deal were not disclosed. Cephalon also released its first-quarter results that showed the biotechnology company earned $14.3 million, excluding special items and charges. The company took first-quarter charges of $13.6 million tied to the termination of a sales and marketing joint venture with two of the company's institutional investors. Those charges resulted in an overall loss of $2.9 million. In the first quarter of 2001 Cephalon lost $11.8 million. Product sales, led by the company's narcolepsy drug Provigil, soared to $96 million in the first quarter, as compared to sales of $41 million during the first quarter of last year. bizjournals.com