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Institution

Novartis

CompanyBasel, 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.


Papers
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Journal ArticleDOI
TL;DR: YP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure ofImatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors.
Abstract: Purpose: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib. Experimental Design: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response. Results: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by ∼68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages. Conclusions: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials.

411 citations

Journal ArticleDOI
Pierre Martin1
TL;DR: The incorporation of 2′-O-‘ethyleneglycol’- and 2′,3-dihydroxypropyl-substituted ribonucleosides into oligon nucleotides affords a new generation of oligonucleotides with high affinity for RNA, high specificity, and increased nuclease resistance.
Abstract: A New Access to 2′-O-Alkylated Ribonucleosides and Properties of 2′-O-Alkylated Oligoribonucleotides A general access to 2′-O-alkylated ribonucleosides using the key intermediate 5 is presented. The incorporation of 2′-O-‘ethyleneglycol’- and 2′-O-‘glycerol’-substituted (i.e., 2′-O-(2-hydroxyethyl)- and 2′-O-(2,3-dihydroxypropyl)-substituted) ribonucleosides into oligonucleotides affords a new generation of oligonucleotides with high affinity for RNA, high specificity, and increased nuclease resistance.

411 citations

Journal ArticleDOI
TL;DR: A pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression is identified, indirectly affecting telomere-length homeostasis.
Abstract: Dicer initiates RNA interference by generating small RNAs involved in various silencing pathways. Dicer participates in centromeric silencing, but its role in the epigenetic regulation of other chromatin domains has not been explored. Here we show that Dicer1 deficiency in Mus musculus leads to decreased DNA methylation, concomitant with increased telomere recombination and telomere elongation. These DNA-methylation defects correlate with decreased expression of Dnmt1, Dnmt3a and Dnmt3b DNA methyltransferases (Dnmts), and methylation levels can be recovered by their overexpression. We identify the retinoblastoma-like 2 protein (Rbl2) as responsible for decreased Dnmt expression in Dicer1-null cells, suggesting the existence of Dicer-dependent small RNAs that target Rbl2. We identify the miR-290 cluster as being downregulated in Dicer1-deficient cells and show that it silences Rbl2, thereby controlling Dnmt expression. These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis.

411 citations

Journal ArticleDOI
03 Apr 2009-Cell
TL;DR: It is reported here that posttranslational modification of the mutant Huntingtin (Htt) by acetylation at lysine residue 444 facilitates trafficking of mutant Htt into autophagosomes, significantly improves clearance of the mutants protein by macroautophagy, and reverses the toxic effects of mutant huntingtin in primary striatal and cortical neurons and in a transgenic C. elegans model of HD.

410 citations

Patent
01 Jun 2005
TL;DR: In this paper, a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound was described, which relates to a methods of treating cancers using N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methaneulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazaolinamine and salts and solvates thereof in combination with at
Abstract: The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.

410 citations


Authors

Showing all 41972 results

NameH-indexPapersCitations
Irving L. Weissman2011141172504
Peter J. Barnes1941530166618
Paul G. Richardson1831533155912
Kenneth C. Anderson1781138126072
Jie Zhang1784857221720
Lei Jiang1702244135205
Marc A. Pfeffer166765133043
Jorge E. Cortes1632784124154
Ian A. Wilson15897198221
Peter G. Schultz15689389716
Bruce D. Walker15577986020
Timothy P. Hughes14583191357
Kurt Wüthrich143739103253
Leonard Guarente14335280169
Christopher D.M. Fletcher13867482484
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202318
202285
20211,321
20201,377
20191,376
20181,456