Search results for "Benzamide"
showing 10 items of 199 documents
Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK …
2013
Background: Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer. Methods: Two dose levels (I/II) were defined: capecitabine 850/1000 mg m−2 twice daily on days 1–14; oxaliplatin 100/130 mg m−2 on day 1; bevacizumab 7.5 mg kg−1 on day 1; imatinib 300 mg day−1 on days 1–21 every 21 days. The primary study endpo…
New heteronuclear gold(I)-platinum(II) complexes with cytotoxic properties: are two metals better than one?
2014
A series of mono- and heterodinuclear gold(I) and platinum(II) complexes with a new bipyridylamine-phosphine ligand have been synthesized and characterized. The X-ray structures of the ligand precursor 4-iodo-N,N-di(pyridin-2-yl)benzamide, and of one gold derivative are reported. All the complexes display antiproliferative properties in vitro in human cancer cells in the range of cisplatin or higher, which appear to correlate with compounds' uptake. Interestingly, studies of the interactions of the compounds with models of DNA indicate different mechanisms of actions with respect to cisplatin. The biological activity study of these complexes provides useful information about the interest of…
Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management
2013
Dermatofibrosarcoma protuberans (DFSP) is a rare superficial tumor characterized by high rates of local recurrence and low risk of metastasis. DFSP occurs most commonly on the trunk and proximal extremities, affects all races, and often develops between the second and fifth decade of life. The tumor grows slowly, typically over years. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. These include pigmented (Bednar tumor), myxoid, myoid, granular cell, sclerotic, atrophic DFSP, giant cell fibroblastoma, and DFSP with fibrosarcomatous areas. Of all these variants, only the DFSP with fibrosarcomatous areas is…
Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors
2014
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach involving the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET im…
Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.
2008
Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr-abl-driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr-abl dependent- and independent-signaling pathways in imatinib-resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STAT5 and CrkL a…
Synthesis and antifungal activity of new N-isoxazolyl-2-iodobenzamides
1999
N-Isoxazolyl-2-iodobenzamides 3 and 9, with a benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 2 and 8 with potassium iodide for 1 h with the aim to ascertain if they were active as fungicides against Phytophthora citricola Saw., Botrytis cinerea Pers., Rhizoctonia sp. and Alternaria sp. Among the tested iodo derivatives, compounds 3b and 9a possess interesting activities against the aforesaid fungal strains in several cases similar to that of benodanil I taken as reference drug.
Antitumor effects of dehydroxymethylepoxyquinomicin, a novel nuclear factor-kappaB inhibitor, in human liver cancer cells are mediated through a reac…
2009
Activation of the nuclear transcription factor-kappa B (NF-kappa B) has been implicated in liver tumorigenesis. We evaluated the effects of a novel NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in two human liver cancer cell lines HA22T/VGH and HuH-6. DHMEQ treatment dose dependently decreased the DNA-binding capacity of the NF-kappa B p65 subunit, inhibited cell growth and proliferation, and increased apoptosis as shown by caspase activation, release of cytochrome c, poly(ADP-ribose) polymerase cleavage, and down-regulation of survivin. DHMEQ also induced a dose-dependent activation of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling, …
Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.
2012
Reactive oxygen species (ROS) are involved in the pathogenesis of many inflammatory diseases such as chronic obstructive pulmonary disease (COPD). They can alter the expression of genes involved in cellular damage by activating transcription factors, including the NF-κB and the activator protein 1 (AP-1). Phosphodiesterase type 4 (PDE4) inhibitors have anti-inflammatory and antioxidant effects, as described in in vivo and in vitro COPD models. This study analysed the effects of piclamilast, a selective PDE4 inhibitor, on modulating the global gene expression profile in A549 cells exposed to H(2)O(2).Changes in gene expression were analysed using high-density Affymetrix microarrays and valid…
Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD.
2014
Abstract Background Epithelial to mesenchymal transition (EMT) is under discussion as a potential mechanism of small airway remodelling in COPD. In bronchial epithelium of COPD and smokers markers of EMT were described. In vitro, EMT may be reproduced by exposing well-differentiated human bronchial epithelial cells (WD-HBEC) to cigarette smoke extract (CSE). EMT may be mitigated by an increase in cellular cAMP. Objective This study explored the effects of roflumilast N-oxide, a PDE4 inhibitor on CSE-induced EMT in WD-HBEC and in primary bronchial epithelial cells from smokers and COPD in vitro. Methods WD-HBEC from normal donors were stimulated with CSE (2.5%) for 72 h in presence of roflum…
Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiat…
2014
Cigarette smoking contributes to epithelial-mesenchymal transition (EMT) in COPD small bronchi as part of the lung remodeling process. We recently observed that roflumilast N-oxide (RNO), the active metabolite of the PDE4 inhibitor roflumilast, prevents cigarette smoke-induced EMT in differentiated human bronchial epithelial cells. Further, statins were shown to protect renal and alveolar epithelial cells from EMT. To analyze how RNO and simvastatin (SIM) interact on CSE-induced EMT in well-differentiated human bronchial epithelial cells (WD-HBEC) from small bronchi in vitro. Methods: WD-HBEC were stimulated with CSE (2.5%). The mesenchymal markers vimentin, collagen type I and α-SMA, the e…