Genomes and Genes
Experts and Doctors on sirolimus in Switzerland
- Weber W, Fussenegger M. Artificial mammalian gene regulation networks-novel approaches for gene therapy and bioengineering. J Biotechnol. 2002;98:161-87 pubmed
- Haruki H, Nishikawa J, Laemmli U. The anchor-away technique: rapid, conditional establishment of yeast mutant phenotypes. Mol Cell. 2008;31:925-32 pubmed publisher..The AA technique is a powerful tool for nuclear biology to dissect the function of individual or gene pairs in synthetic, lethal situations. ..
- Steffel J, Latini R, Akhmedov A, Zimmermann D, Zimmerling P, Luscher T, et al. Rapamycin, but not FK-506, increases endothelial tissue factor expression: implications for drug-eluting stent design. Circulation. 2005;112:2002-11 pubmed..These findings may be clinically relevant for patients receiving drug-eluting stents, particularly when antithrombotic drugs are withdrawn or ineffective, and may open novel perspectives for the design of such stents. ..
- Zbinden R, Piccolo R, Heg D, Roffi M, Kurz D, Muller O, et al. Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial. J Am Heart Assoc. 2016;5:e003255 pubmed publisher..48, 95% CI 0.23-0.99, P=0.043, Pinteraction=0.026). Comparable safety and efficacy profiles of BP-SES and DP-EES were maintained throughout 2Â years of follow-up. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104. ..
- Benjamin D, Colombi M, Moroni C, Hall M. Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov. 2011;10:868-80 pubmed publisher..A new generation of ATP-competitive inhibitors that directly target the mTOR catalytic site display potent and comprehensive mTOR inhibition and are in early clinical trials. ..
- Schlatter S, Senn C, Fussenegger M. Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins. Biotechnol Bioeng. 2003;83:210-25 pubmed
- Crespo J, Hall M. Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 2002;66:579-91, table of contents pubmed..The current understanding of TOR and rapamycin is derived largely from studies with S. cerevisiae. In this review, we discuss the contributions made by S. cerevisiae to understanding rapamycin action and TOR function. ..
- Beckmann N, Cannet C, Fringeli Tanner M, Baumann D, Pally C, Bruns C, et al. Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation. Magn Reson Med. 2003;49:459-67 pubmed
- Marone R, Erhart D, Mertz A, Bohnacker T, Schnell C, Cmiljanovic V, et al. Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol Cancer Res. 2009;7:601-13 pubmed publisher..Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential in metastatic melanoma therapy. ..
- Schmelzle T, Beck T, Martin D, Hall M. Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Mol Cell Biol. 2004;24:338-51 pubmed..Our findings suggest that TOR signals through the RAS/cAMP pathway, independently of TAP42/SIT4. Therefore, the RAS/cAMP pathway may be a novel TOR effector branch. ..
- Cornu M, Albert V, Hall M. mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev. 2013;23:53-62 pubmed publisher..This review describes the most recent advances in TOR signaling with a particular focus on mammalian TOR (mTOR) in metabolic tissues vis-a-vis aging, obesity, type 2 diabetes, and cancer. ..
- Gander S, Bonenfant D, Altermatt P, Martin D, Hauri S, Moes S, et al. Identification of the rapamycin-sensitive phosphorylation sites within the Ser/Thr-rich domain of the yeast Npr1 protein kinase. Rapid Commun Mass Spectrom. 2008;22:3743-53 pubmed publisher..Site-directed mutagenesis confirmed the mass spectral assignments of the autophosphorylation sites and shows that Ser257 is specifically involved in forming an in vitro substrate-binding site. ..
- Gstaiger M, Luke B, Hess D, Oakeley E, Wirbelauer C, Blondel M, et al. Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI. Science. 2003;302:1208-12 pubmed..Thus, URI is a component of a signaling pathway that coordinates nutrient availability with gene expression. ..
- Wang L, Piguet A, Schmidt K, Tordjmann T, Dufour J. Activation of CREB by tauroursodeoxycholic acid protects cholangiocytes from apoptosis induced by mTOR inhibition. Hepatology. 2005;41:1241-51 pubmed..In conclusion, TUDCA activates CREB in cholangiocytes, reducing the apoptotic effect of CCI-779. These findings suggest a novel cytoprotective mechanism for this bile acid. ..
- Kaiser C, Brunner La Rocca H, Buser P, Bonetti P, Osswald S, Linka A, et al. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET). Lancet. 2005;366:921-9 pubmed..No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice...
- Barbet N, Schneider U, Helliwell S, Stansfield I, Tuite M, Hall M. TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell. 1996;7:25-42 pubmed..Such a pathway may constitute a checkpoint that prevents early G1 progression and growth in the absence of nutrients. ..
- Stefanini G, Kalesan B, Serruys P, Heg D, Buszman P, Linke A, et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. 2011;378:1940-8 pubmed publisher..Biosensors Europe SA, Switzerland. ..
- Park J, Leong M, Buse P, Maiyar A, Firestone G, Hemmings B. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999;18:3024-33 pubmed..Both hyperphosphorylation and nuclear translocation could be inhibited by wortmannin, but not by rapamycin. ..
- Baur B, Oroszlan M, Hess O, Carrel T, Mohacsi P. Efficacy and safety of sirolimus and everolimus in heart transplant patients: a retrospective analysis. Transplant Proc. 2011;43:1853-61 pubmed publisher..Both SRL and ERL allow an important reduction of calcineurin-therapy; however, both drugs have considerable side effects, which often require discontinuation of therapy. ..
- Castets P, RÃ¼egg M. MTORC1 determines autophagy through ULK1 regulation in skeletal muscle. Autophagy. 2013;9:1435-7 pubmed publisher..In conclusion, MTORC1 constitutes the master regulator of autophagy induction in skeletal muscle and its deregulation leads to pathologic alterations of muscle homeostasis. ..
- Kunz J, Loeschmann A, Deuter Reinhard M, Hall M. FAP1, a homologue of human transcription factor NF-X1, competes with rapamycin for binding to FKBP12 in yeast. Mol Microbiol. 2000;37:1480-93 pubmed..Our results suggest that FAP1 is a physiological ligand for FKBP12 that is highly conserved from yeast to man. Furthermore, prolyl isomerases may commonly bind and regulate transcription factors. ..
- Soulard A, Cremonesi A, Moes S, Schutz F, Jeno P, Hall M. The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates. Mol Biol Cell. 2010;21:3475-86 pubmed publisher..MPK1 phosphorylates BCY1 T129 directly. Thus, TORC1 activates PKA toward some substrates by preventing MPK1-mediated activation of BCY1. ..
- Saitoh M, Pullen N, Brennan P, Cantrell D, Dennis P, Thomas G. Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site. J Biol Chem. 2002;277:20104-12 pubmed..Moreover, in vitro mTOR directly phosphorylates Ser(371), and this event modulates Thr(389) phosphorylation by mTOR, compatible with earlier in vivo findings. ..
- Binda M, Péli Gulli M, Bonfils G, Panchaud N, Urban J, Sturgill T, et al. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell. 2009;35:563-73 pubmed publisher..Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO complex. ..
- Serra A, Kistler A, Poster D, Krauer F, Senn O, Raina S, et al. Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2009;24:3334-42 pubmed publisher..Here we report the preliminary safety results of the first 6 months of treatment...
- Martin D, Soulard A, Hall M. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell. 2004;119:969-79 pubmed..Thus, we describe a signaling mechanism linking an environmental sensor to ribosome biogenesis. ..
- Lempiäinen H, Uotila A, Urban J, Dohnal I, Ammerer G, Loewith R, et al. Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. Mol Cell. 2009;33:704-16 pubmed publisher..Finally, we show that the Sfp1-interacting protein Mrs6, a Rab escort protein involved in membrane trafficking, regulates both Sfp1 nuclear localization and TORC1 signaling. ..
- Biecker E, De Gottardi A, Neef M, Unternährer M, Schneider V, Ledermann M, et al. Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms. J Pharmacol Exp Ther. 2005;313:952-61 pubmed..This is paralleled by decreased levels of TGF-beta1, CTGF, and PDGF. Rapamycin influences the cell cycle by up-regulation of p27, down-regulation of p21, and inhibition of p70(s6k) phosphorylation. ..
- Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo J, Bonenfant D, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 2002;10:457-68 pubmed..Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man. ..
- Wanke V, Cameroni E, Uotila A, Piccolis M, Urban J, Loewith R, et al. Caffeine extends yeast lifespan by targeting TORC1. Mol Microbiol. 2008;69:277-85 pubmed publisher..This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man. ..
- Helliwell S, Wagner P, Kunz J, Deuter Reinhard M, Henriquez R, Hall M. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol Biol Cell. 1994;5:105-18 pubmed..Thus, TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation. TOR1 and TOR2 may be components of a novel signal transduction pathway controlling progression through G1. ..
- Kunz J, Schneider U, Howald I, Schmidt A, Hall M. HEAT repeats mediate plasma membrane localization of Tor2p in yeast. J Biol Chem. 2000;275:37011-20 pubmed..Our studies therefore place Tor proteins at the site of action of their known downstream effectors and suggest that they may be part of a multiprotein complex. ..
- Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg M, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004;6:1122-8 pubmed..mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth. ..