Search results for "musculo"
showing 10 items of 1726 documents
Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study
2020
AbstractBackgroundHER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to d…
Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized t…
2019
Highlights • Hormonal receptors positive breast tumor and prostate cancer are managed with endocrine therapies. • Endocrine therapies designed for breast and prostate cancer are often associated to serious adverse skeletal related events, such fractures. • Denosumab is a monoclonal anti-body binding RANKL which acts as inhibitor of osteoclasts activity, thus increasing bone mass. • Denosumab was showed to strongly prevent hormonal therapies-related skeletal issues. • Denosumab administration results safe in bone mass increase and reduction of fractures risk.
Autoimmune polyglandular diseases.
2019
Autoimmune polyglandular diseases (APD) are defined as the presence of two autoimmune -induced endocrine failures. With respect to the significant morbidity and potential mortality of APD, the diagnostic objective is to detect APD at an early stage, with the advantage of less frequent complications, effective therapy and better prognosis. This requires that patients at risk be regularly screened for subclinical endocrinopathies prior to clinical manifestation. Regarding the time interval between manifestation of first and further endocrinopathies, regular and long-term follow-up is warranted. Quality of life and psychosocial status are poor in APD patients and involved relatives. Familial c…
Differential glutamatergic and GABAergic contributions to the tetrad effects of Δ9-tetrahydrocannabinol revealed by cell-type-specific reconstitution…
2020
Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa, exerts its actions through the endocannabinoid system by stimulation of the cannabinoid type 1 (CB1) receptor. The widespread distribution of this receptor in different neuronal cell types and the plethora of functions that is modulated by the endocannabinoid system explain the versatility of the effects of THC. However, the cell types involved in the different THC effects are still not fully known. Conditional CB1 receptor knock-out mice were previously used to identify CB1 receptor subpopulations that are "necessary" for the tetrad effects of a high dose of THC: hypothermia, hypolocomotion, catalepsy and …
Modulation of information processing by AMPA receptor auxiliary subunits
2020
AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate…
Interactions between odorants and glutathione transferases in the human olfactory cleft
2020
AbstractXenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites). Enzymes, such as cytochrome P450 and glutathione transferases (GSTs), have been proposed to participate in odorant clea…
Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake
2017
The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derived N-substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor. The highly potent (IC50 = 10 nM) inhibitor N-(3,4-dimethoxyphenyl)ethyl amide (WOBE437) exerted pronounced canna…
Diversity in AMPA receptor complexes in the brain.
2017
AMPA receptor (AMPAR) complexes comprise four of the AMPAR subunits GluA1-4 and several additional interacting proteins. Subunit composition determines AMPAR function. However, AMPAR function depends to a large extent also on interacting proteins, which influence trafficking to the cell surface, activity-dependent subcellular localization and gating of AMPARs. In this review we report about recent findings on the diversity of AMPAR complexes that allow us to better understand functional properties of native receptors in the brain.
Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions
2016
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and …
Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula.
2017
The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a me…