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Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study
2012
Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy da…
Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation,…
1996
There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01-10 mg ml-1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml-1) an anaesthetised, ventilated guinea-pigs. Ro…
First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction
2008
Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day). Protein and mRNA expression of Nox subunits were unaltered by chronic nitroglycerin treatment. Oxidative stress was determined in vascular rings and mitochondrial fractions of nitroglycerin-treated animals by L-012 enhanced chemiluminescence, revea…
Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells
2014
Hepatocellular carcinoma (HCC) is characterized by limited response to current drug therapies. Here, we report that SC66, a novel AKT inhibitor, reduced cell viability in a dose- and time-dependent manner, inhibited colony formation and induced apoptosis in HCC cells. SC66 treatment led to a reduction in total and phospho-AKT levels. This was associated with alterations in cytoskeleton organization, a reduction in expression levels of E-cadherin, β-catenin and phospho-FAK, together with up-regulation of Snail protein levels. All these alterations were coupled with anoikis cell death induction. In addition, SC66 induced the production of reactive oxygen species (ROS) and DNA damage. Pre-trea…
Ethnobotanical survey and cytotoxicity testing of plants of South-western Nigeria used to treat cancer, with isolation of cytotoxic constituents from…
2010
Abstract Ethnopharmacological relevance There is only scant literature on the anticancer components of medicinal plants from Nigeria, yet traditional healers in the area under study claim to have been managing the disease in their patients with some success using the species studied. Aim of study To document plants commonly used to treat cancer in South-western Nigeria and to test the scientific basis of the claims using in vitro cytotoxicity tests. Methods Structured questionnaires were used to explore the ethnobotanical practices amongst the traditional healers. Methanol extracts of the most common species cited were screened for cytotoxicity using the sulforhodamine B (SRB) assay in both…
Investigations of the dual contractile/relaxant properties showed by antioquine in rat aorta.
1993
1. In the present study we assessed the activity of antioquine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from Pseudoxandra sclerocarpa, by examining its effects on the contractile activity of rat isolated aorta, specific binding of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin to cerebral cortical membranes and the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta. 2. Contractions in rat aorta induced by high concentrations of KCl (80 mM) and noradrenaline (1 microM) were inhibited by antioquine in a concentration-dependent manner (0.1 microM- 300 microM). The alkaloid appeared more potent against KCl-induced contract…
Retinas of the Diurnal RodentArvicanthis ansorgeiAre Highly Resistant to Experimentally Induced Stress and Degeneration
2011
International audience; PURPOSE. Environmentally induced stress plays a significant role in retinal degeneration and blindness both in animals and in humans. Among such sources of stress, phototoxicity is well studied and has been shown to lead to photoreceptor-specific loss in a number of species. However, the vast majority of studies have been conducted in nocturnal, albino rod-dominant rat and mouse strains, and the pertinence of such findings to human pathology and cone loss is debatable. The authors examined retinal vulnerability to damage in the diurnal murid rodent Arvicanthis ansorgei, a pigmented species with a large number of cones. METHODS. The authors used established protocols …
Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction
2001
In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…
Antimutagenic effects of flavonoids, chalcones and structurally related compounds on the activity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and…
1993
Abstract Sixty-four flavonoids were tested for their antimutagenic potencies with respect to IQ in Salmonella typhimurium TA98 and in part also towards MeIQ, MeIQx, Trp-P-2, and Glu-P-1 and in S. typhimurium TA100. Antimutagenic potencies were quantified by the inhibitory dose for 50% reduction of mutagenic activity (ID 50 ). A carbonyl function at C-4 of the flavane nucleus seems to be essential for antimutagenicity: two flavanols and four anthocyanidines were inactive. Again, five isoflavons, except biochanin A, were inactive. Within the other groups of 21 flavones, 16 flavonols and 16 flavanones the parent compounds flavone, flavonol, and flavonone possessed the highest antimutagenic pot…
Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity
2011
Background & Aims: Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with beta-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate beta-cell dysfunction in patients, but little is known about its effects on pancreatic and hepatic fat accumulation. In this study, we validated in-vivo proton magnetic resonance spectroscopy ((1)H MRS) in pancreatic fat measurement with biochemical measurements in a pig model. Thereafter, the effects of increased physical activity on the amounts of pancreatic and liver fat…