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Biotech / Medical : Millennium Pharmaceuticals, Inc. (MLNM) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (2042)	3/9/2004 7:17:18 PM
From: tuck	Respond to of 3044

>>Apoptosis. 2004 Mar;9(2):149-55. 2-Methoxyestardiol and bortezomib/proteasome-inhibitor overcome dexamethasone-resistance in multiple myeloma cells by modulating Heat Shock Protein-27. Chauhan D, Li G, Auclair D, Hideshima T, Podar K, Mitsiades N, Mitsiades C, Chen LB, Munshi N, Saxena S, Anderson KC. The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115. Multiple myeloma (MM) remains fatal despite all available therapies. Initial treatment with conventional drugs such as, Dexamethasone (Dex) effectively induces MM cell death; however, prolonged drug exposures results in the development of chemoresistance. Our prior study demonstrated that 2-Methoxyestradiol (2ME2) induces apoptosis in multiple myeloma (MM) cells resistant to Dexamethasone (Dex). Here, we show the mechanism whereby 2ME2 overcomes Dex-resistance. The oligonucleotide array analysis demonstrates that Heat Shock Protein-27 (Hsp27) is upregulated in Dex-resistant, but not in Dex-sensitive MM cells. Proteomics analysis of Hsp27-immunocomplexes revealed the presence of actin in Dex-resistant, but not in Dex-sensitive cells. Biochemical interaction between Hsp27 and actin was examined by co-immunoprecipitation with anti-Hsp27 or actin Abs. Far western blot analysis using GST-Hsp27 fusion protein showed a direct association with actin both in vitro and in vivo. Importantly, 2ME2- or Bortezomib/Proteasome inhibitor (PS-341)-induced apoptosis in Dex-resistant MM cell lines and MM patient cells is associated with disruption of the Hsp27-actin complexes. Finally, blockade of Hsp27 by anti-sense strategy enhanced anti-MM activity of both 2ME2 and PS-341. These findings provide the clinical application of novel therapeutics targeting Hsp27 to improve patient outcome in MM.<< Cheers, Tuck

To: Icebrg who wrote (2042)	3/10/2004 3:45:05 AM
From: Icebrg	Read Replies (2) \| Respond to of 3044

Women Get Less Aggressive Heart Treatment-Study Tue Mar 9, 5:52 PM ET [This is one of the conclusions drawn from the material in the Millennium-funded CRUSADE registry]. WASHINGTON (Reuters) - Women with serious heart conditions are getting less aggressive treatment in U.S. hospitals than men, researchers reported on Tuesday. That is even though women are at higher risk than men, and the aggressive therapies are shown to save lives, the researchers told a meeting of the American College of Cardiology in New Orleans. "We found that, despite being at higher risk, women who arrive at the hospital with symptoms of a heart attack were less likely to receive recommended medications and procedures than men," said Dr. Andra Blomkalns of the University of Cincinnati Medical Center, who presented the findings. "Through (this study), we are working to understand the reasons for this disparity so that we can ensure that all patients at risk for a heart attack, female or male, receive care that has been proven to save lives." Blomkalns' team analyzed the records of more than 35,000 patients for their study. They found that women admitted to hospitals with acute coronary syndrome were less likely than men to be given recommended therapies such as the blood thinner heparin, glycoprotein IIb-IIIa inhibitors, or procedures such as angioplasty to open clogged arteries. Yet the women were more likely to die -- 5.6 percent of the women in the study died in the hospital versus 4.3 percent of the men. The women were usually admitted at an older age and a more advanced stage of heart disease, and thus should get more aggressive treatment, not less, the researchers said. "This is one of the paradoxes that we see in medicine, that the patients who are in greatest need of effective therapies are not receiving them," said Dr. Judith Hochman of New York University School of Medicine, who worked on the study. Heart disease is the No. 1 killer of both men and women in the United States. According to the American Heart Association (news - web sites), 267,000 American women die of heart disease each year.