Search results for "celecoxib"
showing 10 items of 32 documents
Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity
2016
SummaryThe extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a h…
Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
2017
Abstract Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone‐mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose‐dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase‐2 (COX‐2) and prostac…
Rosuvastatin Prevents Conduit Artery Endothelial Dysfunction Induced by Ischemia and Reperfusion by a Cyclooxygenase-2–Dependent Mechanism
2010
ObjectivesThe purpose of this study was to determine whether single-dose rosuvastatin (40 mg) protects against ischemia and reperfusion (IR)–induced endothelial dysfunction in humans and whether this effect is cyclooxygenase (COX)-2 dependent.BackgroundAnimal studies have demonstrated that rosuvastatin can limit damage and improve recovery after IR.MethodsIn a double-blind, parallel design, 20 volunteers were randomized to a single dose of oral rosuvastatin (40 mg) or placebo. Twenty-four hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protoc…
Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study
2011
Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) w…
FOLFIRI regimen in advanced colorectal cancer: the experience of the Gruppo Oncologico dell'Italia Meridionale (GOIM)
2005
Purpose: To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy. Patients and methods: Patients entered in three consecutive trials of the GOIM (protocols no. 9706, 9901, and 2301) were reported in this analysis. A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen: Irinotecan 180mg/m 2 on day 1 with LV5FU2 regimen (LV at 100mg/m 2 administered as a 2-hour infusion before FU at 400mg/m 2 as an intravenous bolus injection, and FU at 600mg/m 2 as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2); the treatment was repeated every 2 weeks. Results: 287 patients entered in th…
FOLFIRI with or without celecoxib in advanced colorectal cancer: a randomized phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)
2006
Background The aim of the study was to verify the efficacy and safety of the addition of celecoxib to FOLFIRI combination therapy in patients affected by advanced colorectal cancer. Patients and methods Eighty-one chemotherapy-naive patients entered in this randomized phase II trial of the GOIM (protocol no. 2301). Patients were randomized to receive FOLFIRI regimen (arm A): irinotecan 180 mg/m2 on day 1 with LV5FU2 regimen (LV at 100 mg/m2 administered as a 2-h infusion before FU at 400 mg/m2 as an intravenous bolus injection, and FU at 600 mg/m2 as a 22-h infusion immediately after 5-FU bolus injection on day 1 and 2); or FOLFIRI plus celecoxib 400 mg twice daily for 14 days (arm B). Both…
Novel Insights and Therapeutical Applications in the Field of Inhibitors of COX-2
2004
The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyretic properties of COX-2 selective inhibitors. The coxibs rofecoxib and celecoxib have been introduced into therapy and seem to offer some advantages over the classical non-selective NSAIDs. The search for new COX-2 inhibitors is going on, the development of etoricoxib and lumiracox…
Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review
2015
Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.Methods: The literature was systematically reviewed …
The novel NF-κB inhibitor DHMEQ synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ROS-dependent mechanism
2012
In a previous work of ours dehydroxymethyl-epoxyquinomicin (DHMEQ), an inhibitor of NF-κB, was shown to induce apoptosis through Reactive Oxygen Species (ROS) production in hepatoma cells. The present study demonstrated that DHMEQ cooperates with Celecoxib (CLX) to decrease NF-κB DNA binding and to inhibit cell growth and proliferation more effectively than treatment with these single agents alone in the hepatoma cell lines HA22T/VGH and Huh-6. ROS production induced by the DHMEQ-CLX combination in turn generated the expression of genes involved in endoplasmic reticulum (ER) stress and silencing TRB3 mRNA significantly decreased DHMEQ-CLX-induced cell growth inhibition. Moreover, the DHMEQ-…
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…