Search results for "block"
showing 10 items of 1177 documents
The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials.
2021
The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresect…
Cemiplimab for locally advanced and metastatic cutaneous squamous-cell carcinomas: Real-life experience from the French CAREPI study group
2021
Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%
Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex
2013
Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy-related genes rema…
Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats
2013
Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize…
WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture
2015
Alzheimer's disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death. Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD. However, studies on the effects of cannabinoids on astrocytes functions are scarce. In primary cultured astrocytes we studied cellular viability using MTT assay. Inflammatory and oxidative stress mediators were determined by ELISA and Western-blot techniques both in…
Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardioto…
2015
Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal model…
Ability of short-time Fourier transform method to detect transient changes in vagal effects on hearts: a pharmacological blocking study.
2006
Conventional spectral analyses of heart rate variability (HRV) have been limited to stationary signals and have not allowed the obtainment of information during transient autonomic cardiac responses. In the present study, we evaluated the ability of the short-time Fourier transform (STFT) method to detect transient changes in vagal effects on the heart. We derived high-frequency power (HFP, 0.20–0.40 Hz) as a function of time during active orthostatic task (AOT) from the sitting to standing posture before and after selective vagal (atropine sulfate 0.04 mg/kg) and sympathetic (metoprolol 0.20 mg/kg) blockades. The HFP minimum point during the first 30 s after standing up was calculated and…
Prediction of CRT Activation Sequence by Personalization of Biventricular Models from Electroanatomical Maps
2020
[EN] Optimization of lead placement and interventricular delay settings in patients under cardiac resynchronization therapy is a complex task that might benefit from prior information based on models. Biophysical models can be used to predict the sequence of electrical heart activation in a patient given a set of parameters which should be personalized to the patient. In this paper, we use electroanatomical maps to personalize the endocardial activation of the right ventricle, and the different tissue conductivities in a pig model with left bundle branch block, to reproduce personalized biventricular activations. Following, we tested the personalized heart model by virtually simulating card…
Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?
2015
Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their …
High anti-JCPyV serum titers coincide with high CSF cell counts in RRMS patients
2020
Background: Progressive multifocal leukoencephalopathy (PML) can in rare cases occur in natalizumab-treated patients with high serum anti-JCPyV antibodies, hypothetically due to excessive blockade of immune cell migration. Objective: Immune cell recruitment to the central nervous system (CNS) was assessed in relapsing-remitting multiple sclerosis (RRMS) patients stratified by low versus high anti-JCPyV antibody titers as indicator for PML risk. Methods: Cerebrospinal fluid (CSF) cell counts of 145 RRMS patients were quantified by flow cytometry. Generalized linear models were employed to assess influence of age, sex, disease duration, Expanded Disability Status Scale (EDSS), clinical/radiol…