Search results for "Pyrazole"
showing 10 items of 315 documents
ChemInform Abstract: Researches on Antiinflammatory Agents. Studies on Some New 3-(Pyrazol-5-yl)-1,2,3-benzotriazin-4(3H)-ones and -quinazolin-4(3H)-…
2010
Following our research on analgesic and antiinflammatory active compounds containing the pyrazole nucleus, a number of 3-(pyrazol-5-yl)-1,2,3-benzotriazin-4(3H)-ones and quinazolin-4(3H)-ones was synthetized and tested. The results of tests for analgesic, antiexudative and antioedema activities, as well as for induction of lesion in the gastric mucosa, are reported and discussed.
6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.
2003
The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE2 generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition. © 2003 Elsevier Science Ltd. All rights reserved.
Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices
2019
Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and trig…
Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia
2012
Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure.We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance of a platelet transfusion before, during, and up to 7…
12 weeks of interferon-based therapy is feasible in patients with hepatitis C-related cirrhosis and thrombocytopenia: A post hoc analysis of eltrombo…
2015
Background: A 24-48-week course of interferon-based therapy poorly tolerated in hepatitis C virus (HCV) cirrhosis patients with thrombocytopenia. Aim of the study was to identify patients at low-risk of liver-related complications over a 12-week course of interferon-based therapy. Methods: We assessed the rate of complications and death during the first 12 weeks of interferon-based therapy in HCV cirrhotics with thrombocytopenia (platelets ≤75×109/L) enrolled in the ENABLE-1 and -2 phase 3 randomised controlled trials. Results: Overall, among 1441 patients, 89 complications (6.9%) and 10 deaths (0.7%) were observed within the first 12 weeks of therapy. At univariate analysis baseline albumi…
Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition …
2007
The molecular mechanisms behind the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are not completely understood and cannot be explained by the inhibition of the cyclooxygenase (COX) enzymes COX-1 and COX-2 alone. We previously reported that both the selective COX-1 inhibitor SC-560 and the selective COX-2 inhibitor CAY10404 exhibit anti-tumor effects in human hepatoma cells. NSAID inhibitors have many COX-independent actions and, among others, the mitogen-activated protein kinase (MAPK) pathways are targets for NSAIDs. Here, we examined the role of MEK/ERK1/2 signaling in the anti-neoplastic effects of both selective COX-1 and COX-2 inhibitors in two human hepato…
Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
2014
The RAF family of kinases mediates RAS signaling, and RAF inhibitors can be effective for treating tumors with BRAF V600E mutant protein. However, RAF inhibitors paradoxically accelerate metastasis in RAS -mutant tumors and become ineffective in BRAF V600E tumors because of reactivation of downstream mitogen-activated protein kinase (MAPK) signaling. We found that the RAF isoform ARAF has an obligatory role in promoting MAPK activity and cell migration in a cell type–dependent manner. Knocking down ARAF prevented the activation of MAPK kinase 1 (MEK1) and extracellular signal–regulated kinase 1 and 2 (ERK1/2) and decreased the number of protrusions from tumor cell spheroids in three-dimensi…
Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor ce…
2010
Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex®) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependen…
Zn(II)-coordination and fluorescence studies of a new polyazamacrocycle incorporating 1H-pyrazole and naphthalene units.
2010
The synthesis and Zn(2+) coordination properties of a new macrocycle (L1) obtained by dipodal (2 + 2) condensation of the polyamine 3-(naphthalen-2-ylmethyl)pentane-1,5-diamine with 1H-pyrazole-3,5-dicarbaldehyde are reported. pH-metric studies show that L1 bears five measurable protonation steps in the 2.0-11.0 pH range. Fluorescence emission studies indicate that the removal of the first proton from the H(5)L1(5+) species leads to a significant decrease in the emission due to a photoinduced electron transfer process. Addition of Zn(2+) promotes a boat-like conformation that approaches both fluorophores and facilitates the formation of an excimer which reaches its highest emission for a 1 …
Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma : an international, randomised, open-label, phase 3 study
2016
Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index…