Search results for "sirolimus"

Relapsed and/or Refractory Mantle Cell Lymphoma: What Role for Temsirolimus?

2012

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved. We here focus on the rationale, current clinical knowledge and future concepts of Temsirolimus, an inhibitor of mTOR, in the treatment of MCL. At this time this drug has been shown to be effective as single agent for relapsed disease and early combination data show promising results. In addition, with a brief outline of other treatment options, we aim to g…

Chronically elevated branched chain amino acid levels are pro-arrhythmic.

2022

Aim. Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach. Methods and Results. We employed a phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6-9 weeks) in the absence of prior symptoms. Affected mice were found to be homozyg…

L’uso di stent con sirolimus e’ significativamente associate alla riduzione della mortalita’ totale e della morbidita’ cardiovascolare sia a 6 mesi c…

2006

Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.

2009

Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits …

mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA

2013

Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…

IBRUTINIB VS TEMSIROLIMUS: THREE-YEAR FOLLOW-UP OF PATIENTS WITH PREVIOUSLY TREATED MANTLE CELL LYMPHOMA FROM THE PHASE 3, INTERNATIONAL, RANDOMIZED,…

2017

Long-term clinical outcomes after drug-eluting stent implantation in unprotected left main coronary artery disease.

2009

Objective: To investigate long-term outcomes of unprotected left main coronary artery (ULMCA) disease treatment using drug-eluting stents (DES). Background: In several studies, DES implantation in ULMCA appeared safe and effective at mid-term; however, to date, there is limited long-term data. Methods: All consecutive patients undergoing sirolimus- or paclitaxel-eluting stent implantation in ULMCA disease at a single institution were evaluated. The primary endpoint was long-term major adverse cardiac events (MACE) defined as cardiac death, nonfatal myocardial infarction, or target lesion revascularization (TLR). Stent thrombosis (ST), according to Academic Research Consortium definitions, w…

Initial experience with the novel BioMime 60 mm-long sirolimus-eluting tapered stent system in long coronary lesions

2017

Checkpoint adaptation in recombination-deficient cells drives aneuploidy and resistance to genotoxic agents.

2020

Abstract Human cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ recombination-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge. We demonstrate that adaptation inhibit…

Longevity-related molecular pathways are subject to midlife “switch” in humans

2019

Emerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that oppos…