Search results for "mTOR"
showing 10 items of 275 documents
Temsirolimus for the treatment of mantle cell lymphoma.
2010
Although recent progress has been made in the treatment of mantle cell lymphoma (MCL) the majority of patients experience relapse and ultimately die of their disease. The translocation t(11;14) is a prerequisite for the diagnosis of MCL and results in overexpression of cyclin D1. Its protein translation is controlled by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an attractive therapeutic target. Temsirolimus, a specific inhibitor of mTOR, has been evaluated in two Phase II trials in patients with relapsed MCL, and promising response rates up to 40% were found. Subsequently, a randomized Phase III trial was initiated, in which superiority in remission induction and pro…
Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis
2021
Objective Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hep…
Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review
2018
The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. To review characteristics of ONJ in cancer patients receiving non-antiresorptives. A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 wa…
Mediterranean diet and healthy ageing: a Sicilian perspective.
2014
Traditional Mediterranean diet (MedDiet) is a common dietary pattern characterizing a lifestyle and culture proven to contribute to better health and quality of life in Mediterranean countries. By analyzing the diet of centenarians from the Sicani Mountains and eating habits of inhabitants of Palermo, it is reported that a close adherence to MedDiet is observed in the countryside, whereas in big towns this adherence is not so close. This has an effect on the rates of mortality at old age (and reciprocally longevity) that are lower in the countryside than in big towns. Concerning the health effects of the diet, the low content of animal protein and the low glycaemic index of the Sicilian Med…
PTEN Mediates the Antioxidant Effect of Resveratrol at Nutritionally Relevant Concentrations
2014
Introduction.Antioxidant properties of resveratrol have been intensively studied for the last years, bothin vivoandin vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant.Aims.In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect.Methods.We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibit…
Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
2019
Este es el artículo que se ha publicado de forma definitiva en: https://molecularautism.biomedcentral.com/articles/10.1186/s13229-019-0262-8 En este artículo también participa Joan Climent, Vera Pancaldi, Lourdes Fañanás, Celso Arango, Mara Parellada, Anaïs Baudot, Daniel Vogt, John L. Rubenstein, Alfonso Valencia y Rafael Tabarés-Seisdedos. Background: Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Methods: Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer t…
p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles
2020
p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional pr…
Sprint and Strength Training Modulates Autophagy and Proteostasis in Aging Sprinters
2020
Purpose Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly-trained middle-aged or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle autophagy and unfolded protein response (UPR) and on sprint running performance in masters sprinters. Methods Thirty-two male competitive sprinters (aged 40–76 years) were randomly divided into experimental (EX) and control (CTRL) groups. The EX training program was a combination of heavy and explosive strength and sprint exercises aimed at improving sprint performance. Fifteen and thirteen participants completed the 20-week intervention period in …
Biphasic Erk1/2 activation sequentially involving Gs and Gi signaling is required in beta3-adrenergic receptor-induced primary smooth muscle cell pro…
2013
Abstract The beta3 adrenergic receptor (B3-AR) reportedly induces cell proliferation, but the signaling pathways that were proposed, involving either Gs or Gi coupling, remain controversial. To further investigate the role of G protein coupling in B3-AR induced proliferation, we stimulated primary human myometrial smooth muscle cells with SAR150640 (B3-AR agonist) in the absence or presence of variable G-protein inhibitors. Specific B3-AR stimulation led to an Erk1/2 induced proliferation. We observed that the proliferative effects of B3-AR require two Erk1/2 activation peaks (the first after 3 min, the second at 8 h). Erk1/2 activation at 3 min was mimicked by forskolin (adenylyl-cyclase a…