Search results for "MAI"
showing 10 items of 6279 documents
Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines
2008
Adaptation to hypoxia, a universal hallmark of carcinomas, is a critical step for tumor cell survival and growth. One of the principal regulators of hypoxia-responsive pathways is the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha). Currently, it is known that tumoral production of members of the vascular endothelial growth factor (VEGF)-family (VEGFs) may promote tumor growth and progression by acting on carcinoma cells that express the cognate receptors (VEGFRs). However, the influence of hypoxia in the formation of such a tumoral VEGF/VEGFR loop is not completely understood. In the present study we examined the potential existence of a HIF-1 alpha/VEGF/VEGFR autocrine…
Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma.
2006
AbstractInhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors. Addition of the respective specific ligands further increased apoptosis, indicating that COX-2 inhibition induced the expression of functional death receptors. Overexpression of a dominant-negative Fas-associated death domain mutant reduced COX…
Recent Advances in the Treatment of Patients with Multiple Myeloma
2020
Simple Summary The evolving data from trials assessing novel combinations as a part of the frontline and relapse treatment in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients’ prognosis. Current treatment objectives are focused to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their…
Abstract 753: Genomic alterations of autophagy genes disrupts autophagic flux in human lung adenocarcinomas
2015
Abstract Targeted therapy using EGFR tyrosine kinase inhibitor (TKI) is a standard therapy for a subset of non-small cell lung cancer (NSCLC) patients with lung adenocarcinomas (LADs) harboring EGFR kinase domain mutations; however, EGFR TKI therapy shows limited efficacy due to de novo and acquired resistance. Consequently, formulating strategies to potentiate the efficacy of EGFR TKI is of great interest. In EGFR TKI sensitive cells harboring EGFR mutation, it has been shown that EGFR inhibition induces autophagy to protect the cells from metabolic stress. Hydroxychloroquine (HQ), an inhibitor of autophagy, has been shown to potentiate EGFR TKIs in preclinical models, however, preliminary…
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia
2013
Author version made available in accordance with the publisher's policy.
Apoptosis induced in HepG2 cells by the synthetic cannabinoid WIN: involvement of the transcription factor PPARgamma.
2008
It has recently been shown that cannabinoids induce growth inhibition and apoptosis in different tumour cell lines. In the current study, the effects of WIN 55,212-2 (WIN), a synthetic and potent cannabinoid receptor agonist, are investigated in hepatoma HepG2 cells and a possible signal transduction pathway is proposed. In these cells, WIN induces a clear apoptotic effect which was accompanied by up-regulation of the death-signalling factors Bax, Bcl-X(S), t-Bid and down-regulation of the survival factors survivin, phospho-AKT, Hsp72 and Bcl-2. Moreover, WIN-induced apoptosis is associated with JNK/p38 MAPK pathway activation and mitochondrial depolarisation demonstrated by a cytofluorimet…
Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse H…
2021
Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties.…
Global sensitivity analysis of the SCOPE model : what drives simulated canopy - leaving sun - induced fluorescence?
2015
This study provides insight into the key variables that drive sun-induced chlorophyll fluorescence (SIF) emanating from vegetation canopies, based on a global sensitivity analysis (GSA) of the Soil-Canopy Observation of Photosynthesis and Energy (SCOPE) balance model. An updated version of the SCOPE model was used here (v1.53) which contains novel leaf physiological modules for determination of the steady state fluorescence yield: a photosynthesis model coupled with (a) submodels having empirically derived relationships, identified as TB12 for unstressed and TB12-D for drought conditions and (b) a mechanistic (MD12) submodel based on theoretical relationships. By inspecting Sobol's total or…
Boundary elements analysis of adhesively bonded piezoelectric active repair
2009
Abstract This paper presents the analysis of active piezoelectric patches for cracked structures by the boundary element method. A two-dimensional boundary integral formulation based on the multidomain technique is used to model cracks and to assemble the multi-layered piezoelectric patches to the host damaged structures. The fracture mechanics behavior of the repaired structures is analyzed for both perfect and imperfect interface between patches and host beams. The imperfect interface, representing the adhesive between two different layers, is modeled by using a “spring model” that involves linear relationships between the interface tractions, in normal and tangential directions, and the …
The mixed capacitated general routing problem with turn penalties
2011
In this paper we deal with the mixed capacitated general routing problem with turn penalties. This problem generalizes many important arc and node routing problems, and it takes into account turn penalties and forbidden turns, which are crucial in many real-life applications, such as mail delivery, waste collection and street maintenance operations. Through a polynomial transformation of the considered problem into a Generalized Vehicle routing problem, we suggest a new approach for solving this new problem by transforming it into an Asymmetric Capacitated Vehicle routing problem. In this way, we can solve the new problem both optimally and heuristically using existing algorithms. A powerfu…