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David G Hicks Brian J Yoder Sarah Short Shannon Tarr Nichole Prescott Joseph P Crowe Andrea E Dawson G Thomas Budd Steven Sizemore Muzaffer Cicek Toni K Choueiri Raymond R Tubbs Daniel Gaile Norma Nowak Mary Ann Accavitti-Loper Andra R Frost Danny R Welch Graham Casey 《Clinical cancer research》2006,12(22):6702-6708
PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors. 相似文献
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Ana Vanson Arthur P. Arnold Barney A. Schlinger 《General and comparative endocrinology》1996,102(3):342-350
3β-hydroxysteroid dehydrogenase/Δ5−Δ4isomerase (3β-HSD) activity was measured in primary dissociated cell cultures prepared from telencephalons of developing zebra finches. 3β-HSD activity was confirmed after cultures were incubated with [7-3H]pregneno- lone (Preg) or (1,2,6,7-3H-) dehydroepiandrosterone (DHEA) and3H-progesterone (Prog) and3H-androstenedione (AE) were detected in the medium. Product identity was confirmed by recrystallizations and by HPLC analysis. When DHEA was used as substrate,3H-estradiol and3H-estrone were also detected in the culture medium, presumably derived from the aromatization of3H-AE or3H-T produced from3H-DHEA. To test this idea, cultures were incubated with3H-DHEA together with radioinert AE or with fadrozole HCl, a potent and specific aromatase inhibitor. In the presence of radioinert AE,3H-AE increased but metabolites of3H-AE decreased in the media; in the presence of fadrozole,3H-estrogens decreased but3H-AE and its androgenic metabolite3H-5β-androstanedione increased. These data demonstrate 3β-HSD activity in the songbird brain. The presence of Prog and estradiol in these cultures suggest that Preg and DHEA can potentially serve as substrates for the ultimate formation of active sex steroids in the songbird telencephalon. 相似文献
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We tested the effects of pre-treatment with dexamethasone on topically induced ocular anaphylaxis in the rat. Rats were immunized with dinitrophenylated Ascaris suum extract and challenged with di-DNP-lysine. Dexamethasone was administered topically once (24, 6, or 1 h before challenge) or three times (6, 4, and 2 h before challenge). A single pre-treatment given at 24 or 6 h had no significant effect. A single pre-treatment 1 h before challenge reduced the extent of edema assessed histologically but not clinically, and had no significant effect on the eosinophil count in conjunctival tissue examined 6 h after challenge. Eyes pre-treated with dexamethasone 6, 4, and 2 h before challenge showed a significant reduction in conjunctival edema assessed histologically and clinically 1 h after challenge. In addition, 6 h after challenge the number of eosinophils was significantly reduced. We conclude that repeated pre-treatment with dexamethasone can suppress both the immediate phase and the cellular late phase of topically induced ocular anaphylaxis. 相似文献
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Dr. Monica Cyr Pharm.D. Dr. S. Casey Laizure Pharm.D. Dr. Carl M. daCunha M.D. 《Pharmacotherapy》1997,17(2):387-389
A 74-year-old man became delirious 2 days after beginning oral therapy with methazolamide. The delirium was manifested by intermittent psychosis, incontinence of bowel and bladder, lethargy, and disorientation. These symptoms continued for 25 days despite many changes in his drug regimen, and complete laboratory, urologic, and neurologic work-ups. The symptoms resolved completely within 1 week of discontinuing methazolamide. This is the first case reported of delirium associated with methazolamide not accompanied by a metabolic imbalance. 相似文献