66 research outputs found
Gastrointestinal adverse effects of short-term aspirin use: A meta-analysis of published randomized controlled trials
Background and Objectives: Aspirin is widely used for short-term treatment of pain, fever or colds, but there are only limited data regarding the safety of this use. To summarize the available data on this topic, we conducted a meta-analysis of the published clinical trial literature regarding the gastrointestinal adverse effects of short-term use of aspirin in comparison with placebo and other medications commonly used for the same purpose.
Data Sources and Methods: An extensive literature search identified 119,310 articles regarding possible adverse effects of aspirin, among which 23,131 appeared to possibly include relevant data. An automated text-mining procedure was used to score the references for potential relevance for the meta-analysis. The 3,983 highest-scoring articles were reviewed individually to identify those with data that could be included in this analysis. Ultimately, 78 relevant articles were identified that contained gastrointestinal adverse event data from clinical trials of aspirin versus placebo or an active comparator. Odds ratios (ORs) computed using a Mantel–Haenszel estimator were used to summarize the comparative effects on dyspepsia, nausea/vomiting, and abdominal pain, considered separately and also aggregated as ‘minor gastrointestinal events’. Gastrointestinal bleeds, ulcers, and perforations were also investigated.
Results: Data were obtained regarding 19,829 subjects (34 % treated with aspirin, 17 % placebo, and 49 % an active comparator). About half of the aspirin subjects took a single dose. Aspirin was associated with a higher risk of minor gastrointestinal events than placebo or active comparators: the summary ORs were 1.46 (95 % confidence interval [CI] 1.15–1.86) and 1.81 (95 % CI 1.61–2.04), respectively. Ulcers, perforation, and serious bleeding were not seen after use of aspirin or any of the other interventions.
Conclusions: During short-term use, aspirin is associated with a higher frequency of gastrointestinal complaints than other medications commonly used for treatment of pain, colds, and fever. Serious adverse events were not observed with aspirin or any of the comparators.
Electronic supplementary material: The online version of this article (doi:10.1007/s40268-013-0011-y) contains supplementary material, which is available to authorized users
Prevention of venous thromboembolism in patients with cancer: guidelines of the Italian Society for Haemostasis and Thrombosis
Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles
Background: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. Methods: Lehman’s TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. Results: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug–target interactions were found among the upregulated genes in the M, IM and MSL subsets. Conclusions: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amount of information from several data sets has allowed us to identify a well-determined minimal number of genes that may help in the recognition of TNBC subtypes. These genes, most of which have been previously found to be associated with breast cancer, have the potential to become novel diagnostic markers and/or therapeutic targets for specific TNBC subsets
Cyclooxygenase-2 overexpression abrogates the antiproliferative effects of TGF-β
The influence of cyclooxygenase-2 (COX-2) overexpression on the development of tumours has been well documented. The underlying mechanism however has still not been completely elucidated. An escape of proliferating cells from the regulatory influence of TGF-β for example in the intestine has been discussed as well as a preponderance or prolongation of growth factor stimulation. The experiments presented here demonstrated that COX-2 transfection of a TGF-β-sensitive cell line abrogates the growth inhibitory effects of TGF-β. However, analysis of the TGF-β/Smad-signalling pathway clearly revealed that COX-2 overexpression did not interfere with that. Neither TGF-receptor expression nor Smad phosphorylation and signal transfer into the nucleus were influenced by COX-2 overexpression. In addition, a TGF-β reporter assay revealed no difference between controls and COX-2-transfected cells. Thus, the proliferation inhibiting effects must have been well compensated by growth-inducing stimuli. Indications for this came from experiments showing an induction of TGF-α expression and secretion with a higher and prolonged stimulation of the ERK 1/2 (p42/44) pathway in COX-2 transfectants. This effect could have been triggered by direct prostaglandin receptor stimulation or changes in intracellular lipid mediators. An increase in PPAR signalling as proven by a reporter assay is indication for the latter. Therefore, inhibiting both COX-2 as well as the PPAR and TGF/EGF pathway could be effective in the inhibition of adenoma or even carcinoma development in the intestine
DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity
Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity
Low temperature alteration of trioctahedral micas to beidellite in a karstic environment
WEATHERING OF PHLOGOPITE TO BEIDELLITE IN A KARSTIC ENVIRONMENT
The extent of natural weathering of phlogopite crystals in a karstic environment and the composition of its weathering products have been examined through a multi-method investigation carried out on a volcanoclastic deposit discovered in the Grotta del Cervo cave, Pietrasecca, central Italy. Phlogopite crystals are a mixture of 1M and 2M1 polytypes and show mixed-layering with a low amount (1-4%) of smectite in the glass groundmass. Phlogopite crystals vary in composition from phlogopite to ferroan phlogopite. Their average structural formula is (K0.92Na0.03Ba0.03Ca0.02)(Mg2.05Al0.01Fe2+0.19Fe3+0.40Mn0.01Ti0.150.19(Si2.63Al1.37)O10.16(OH1.57F0.27). Micromorphological, X-ray diffraction (XRD), Fourier Transform Infrared (FTIR), scanning electron microscopy (SEM), and microprobe analyses (EMPA) showed that the mineralogical evolution of phlogopite crystals is consistent with in-situ pseudomorphic weathering of mica to Al-rich dioctahedral (rather than Mg-rich) clay minerals (beidellite-like) via phlogopite-smectite mixed-layer phases. The main mechanism of transformation is a layer-by-layer modification in which water composition, enriched in Si and Al from glass dissolution, is a major control. Mg loss, Ca and Na exchange for K, enrichment in Si and Al are the main processes required for beidellitization of phlogopite. Glass alteration produced sequentially smectite, chabazite, phillipsite and analcime, as leaching progressed and the interstitial fluids became increasingly alkaline. The type of zeolite found in the several samples (in the chabazite, phillipsite, analcime series) indicates that the alteration extent increases from wall to the ceiling and to the floor of the cave
Structure and mineralogy of layer silicates: recent perspectives and new trends
Because of their many novel and advanced applications, there is increasing interest in layer silicates from the scientific and technical communities. Appropriate application of these minerals requires deep understanding of their properties and of the processes where they are involved. This chapter, by providing fundamental definitions and crystal structural and chemical data pertaining to layer silicates, aims to introduce this field to new researchers and technicians, by describing the fundamental features leading to different behaviours of layer silicates in different natural or technical processes. The subject addressed is vast and so the reader is referred in some cases to work already published. The focus here is on layer silicates for which detailed crystal structures are given in the literature and which are likely to be used in an applied way in the future. Layer-silicate minerals fulfilling these requirements are: (1) kaolin-serpentine group (e. g. kaolinite, dickite, nacrite, halloysite, hisingerite, odinite, lizardite, berthierine, amesite, cronstedtite, nepouite, kellyite, fraipontite, brindleyite, guidottiite, bementite, greenalite, caryopilite; minerals of the pyrosmalite series); (2) talc and pyrophyllite groups (e. g. pyrophyllite, ferripyrophyllite, willemseite); (3) mica group (i.e. some recent advances in crystal chemistry and structure of dioctahedral and trioctahedral micas); (4) smectite group (e. g. montmorillonite, saponite, hectorite, sauconite, stevensite, swinefordite); (5) vermiculite group; (6) chlorite group (e. g. trioctahedral chlorite such as clinochlore, di,trioctahedral and dioctahedral chlorites such as cookeite and sudoite); (7) some 2: 1 layer silicates involving a discontinuous octahedral sheet and a modulated tetrahedral sheet such as kalifersite, palygorskite and sepiolite; and (8) imogolite and allophane
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