Overall, 89% sequence coverage of the protein was achieved with these methods. In particular, an 88 amino acid tryptic peptide covering the presumed substrate binding domains HP1, TMD7, HP2, and TMD8 domains of EAAT2 was also identified after N-deglycosylation. Beyond the specific applicability to EAAT2, this study provides an efficient, simple and scalable approach to express, purify, digest and characterize integral membrane transporter proteins by mass spectrometry. (C) 2010 Published by Elsevier Inc.”
“Selective serotonin reuptake inhibitors (SSRIs) stimulate synaptic plasticity and neurogenesis, most likely via
the MAP-kinase signal transduction pathway (by phosphorilation of ERK) and by stimulating neurotrophic factors such as brain Selleck HM781-36B derived neurotrophic factor (BDNF) and the neuroprotective protein (Bcl-2). Using human neuroblastoma cells (SHSY5Y), we found that sertraline AICAR order and its derivative, desmethylsertraline, at low concentrations (1-10 mu M), induced potent neurotrophic activity. Subsequently, we have treated for 21 days young and aged mice with sertraline. Sertraline in certain doses improved significantly spatial memory learning,
in both young and old mice. Sertraline treatment resulted in up-regulation of brain BDNF, phospho-ERK and Bcl-2 that may be involved in the pro-cognitive effect of sertraline. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: A phase II study was performed to assess the efficacy and tolerability of intravesical oportuzumab monatox in patients with urothelial carcinoma in situ of the bladder. Bacillus Calmette-Guerin treatment had previously failed in all patients.
Materials and Methods: A total of 46 patients received 1 induction cycle of 6 (cohort 1) or 12 (cohort 2) weekly intravesical oportuzumab monatox (VB4-845) instillations of 30 mg, followed by up to 3
maintenance cycles of 3 weekly administrations every 3 months.
Results: A complete response to oportuzumab monatox was seen in 9 of 22 patients (41%) in cohort 1 and 9 of 23 (39%) in cohort 2 at the 3-month evaluation. A total of Depsipeptide in vivo 20 patients (44%) achieved a complete response. Two other patients without carcinoma in situ who achieved a complete response were not included in the study due to the development of noninvasive papillary (Ta) disease. Median time to recurrence in patients who achieved a complete response was 274 and 408 days in cohorts 1 and 2, respectively. Overall 7 patients (16%) remained disease-free. Post-study assessment demonstrated that these patients were still disease-free at last followup (18 to 25 months). The most common adverse events were mild to moderate reversible bladder symptoms.
Conclusions: Oportuzumab monatox was effective and well tolerated in patients with bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. These results demonstrate the clinical benefit of oportuzumab monatox and support its continued development for the second line treatment of nonmuscle invasive bladder cancer.