Search results for " THERAPY"
showing 10 items of 9467 documents
Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy
2021
Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis …
The Sea Urchin sns5 Chromatin Insulator Shapes the Chromatin Architecture of a Lentivirus Vector Integrated in the Mammalian Genome.
2016
Lentivirus vectors are presently the favorite vehicles for therapeutic gene transfer in hematopoietic cells. Nonetheless, these vectors integrate randomly throughout the genome, exhibiting variegation of transgene expression due to the spreading of heterochromatin into the vector sequences. Moreover, the cis-regulatory elements harbored by the vector could disturb the proper transcription of resident genes neighboring the integration site. The incorporation of chromatin insulators in flanking position to the transferred unit can alleviate both the above-mentioned dangerous effects, due to the insulator-specific barrier and enhancer-blocking activities. In this study, we report the valuable …
Modulating endothelial adhesion and migration impacts stem cell therapies efficacy
2020
Abstract Background Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors a…
Magnetic Nanoparticle-Based Hyperthermia Mediates Drug Delivery and Impairs the Tumorigenic Capacity of Quiescent Colorectal Cancer Stem Cells
2021
Cancer stem cells (CSCs) are the tumor cell subpopulation responsible for resistance to chemotherapy, tumor recurrence, and metastasis. An efficient therapy must act on low proliferating quiescent-CSCs (q-CSCs). We here investigate the effect of magnetic hyperthermia (MHT) in combination with local chemotherapy as a dual therapy to inhibit patient-derived colorectal qCR-CSCs. We apply iron oxide nanocubes as MHT heat mediators, coated with a thermoresponsive polymer (TR-Cubes) and loaded with DOXO (TR-DOXO) as a chemotherapeutic agent. The thermoresponsive polymer releases DOXO only at a temperature above 44 °C. In colony-forming assays, the cells exposed to TR-Cubes with MHT reveal that qC…
Enhanced Antibacterial Activity of Repurposed Mitomycin C and Imipenem in Combination with the Lytic Phage vB_KpnM-VAC13 against Clinical Isolates of…
2021
Study Group on Mechanisms of Action and Resistance to Antimicrobials (GEMARA) on behalf of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).
MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses.
2021
Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients (n = 22) compared with healthy subjects (n = 21) and located in pulmonary arteries, bronchial epithelial cells, fibroblasts, and hyperplastic alveolar type II cells. Decreased expression of MUC4 using siRNA–MUC4 inhibited the mesenchymal/myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as cell senescence and fibroblast proliferation induced by TGF-β1. The induction of the overexpression of MUC4 increased the effects of TGF-β1 on mesen…
Danger signals: Chemotherapy enhancers?
2017
IF 9.614; International audience; Endogenous danger signals are molecules normally present in a given cell compartment that are rapidly released following cell stress and induce immune responses. We and others have shown that dying tumor cells treated with some chemotherapies are able to induce anticancer immune responses, which rely on their release of danger signals such as the nuclear protein HMGB1. DNA can also be released from chemotherapy-treated tumor cells, act as a danger signal, and boost anticancer immunity. While the immunostimulatory properties of DNA have been identified for decades, the recent discovery of a novel family of receptors, cytosolic DNA sensors, has provided a nov…
Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.
2021
Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expressi…
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
2018
Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5′ splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformati…
Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study.
2018
Abstract Introduction Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. Aim To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. Patients and methods Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th–75th IQR). Results Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3…