Institution
Novartis
Company•Basel, Switzerland•
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.
Topics: Alkyl, Population, Alkoxy group, Tolerability, Receptor
Papers published on a yearly basis
Papers
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TL;DR: These analyses reveal somatic mutations in chromatin-regulating genes MLL, M LL2, MLL3 and ARID1A in 20% of patients that are associated with improved survival and have implications for new avenues of therapeutic intervention.
Abstract: Somatic mutations have been reported in pancreatic adenocarcinomas. Here, Sausen et al. identify further mutations and find that mutations in the chromatin modifying gene, MLL, are associated with increased survival, and that the presence of circulating tumour DNA in the serum of patients is associated with poor survival.
366 citations
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TL;DR: Using the yeast two-hybrid system, two structurally related proteins are identified that interact with the amino-terminal region of Raf-1 and are members of the 14-3-3 family of proteins.
Abstract: THE protein Raf-1, a key mediator of mitogenesis and differentia-tion, associates with p21*"a5 (refs 1-3). However, the regulation of the serine/threonine kinase activity of Raf-1 is still not understood4 13. Using the yeast two-hybrid system8'14"16, we identi-fied two structurally related proteins that interact with the amino-terminal region of Raf-1. These proteins, 14-3-3 £ (PLA2) and 14-3-3 p (HS1), are members of the 14-3-3 family of proteins17'23. Expression of 14-3-3 proteins in Xenopm oocytes enhanced Raf-1 activity and promoted Raf-1-dependent oocyte maturation. A dominant negative mutant of Raf-1 blocked the effects of 14-3-3 protein.
365 citations
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TL;DR: Currently available drugs as well as novel therapeutic strategies, in particular those targeting amyloid and tau pathologies, are discussed.
Abstract: Alzheimer's disease is an age-related progressive neurodegenerative disorder with an enormous unmet medical need. It is the most common form of dementia affecting ∼5% of adults over 65 years. In view of our ageing society the number of patients, as well as the economical and social impact, is expected to grow dramatically in the future. Currently available medications appear to be able to produce moderate symptomatic benefits but not to stop disease progression. The search for novel therapeutic approaches targeting the presumed underlying pathogenic mechanisms has been a major focus of research and it is expected that novel medications with disease-modifying properties will emerge from these efforts in the future. In this review, currently available drugs as well as novel therapeutic strategies, in particular those targeting amyloid and tau pathologies, are discussed.
365 citations
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TL;DR: It was shown that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits and there was no unexpected increased incidence of adverse events with longer exposure.
Abstract: Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35-0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44-1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18-1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.
365 citations
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TL;DR: This work discovered that HDAC6, a cytoplasmic deacetylase that acts on tubulin and HSP90 and also binds ubiquitinated proteins with high affinity, is a novel critical SG component and found that SGs are strongly positive for ubiquitin.
Abstract: An essential part of the cellular response to environmental stress is a reversible translational suppression, taking place in dynamic cytoplasmic structures called stress granules (SGs). We discovered that HDAC6, a cytoplasmic deacetylase that acts on tubulin and HSP90 and also binds ubiquitinated proteins with high affinity, is a novel critical SG component. We found that HDAC6 interacts with another SG protein, G3BP (Ras-GTPase-activating protein SH3 domain-binding protein 1), and localizes to SGs under all stress conditions tested. We show that pharmacological inhibition or genetic ablation of HDAC6 abolishes SG formation. Intriguingly, we found that the ubiquitin-binding domain of HDAC6 is essential and that SGs are strongly positive for ubiquitin. Moreover, disruption of microtubule arrays or impairment of motor proteins also prevents formation of SGs. These findings identify HDAC6 as a central component of the stress response, and suggest that it coordinates the formation of SGs by mediating the motor-protein-driven movement of individual SG components along microtubules.
364 citations
Authors
Showing all 41972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Irving L. Weissman | 201 | 1141 | 172504 |
Peter J. Barnes | 194 | 1530 | 166618 |
Paul G. Richardson | 183 | 1533 | 155912 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Jie Zhang | 178 | 4857 | 221720 |
Lei Jiang | 170 | 2244 | 135205 |
Marc A. Pfeffer | 166 | 765 | 133043 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Bruce D. Walker | 155 | 779 | 86020 |
Timothy P. Hughes | 145 | 831 | 91357 |
Kurt Wüthrich | 143 | 739 | 103253 |
Leonard Guarente | 143 | 352 | 80169 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |