Search results for " Screening"
showing 10 items of 898 documents
The Translesion Polymerase Rev3L in the Tolerance of Alkylating Anticancer Drugs
2009
Temozolomide and fotemustine, representing methylating and chloroethylating agents, respectively, are used in the treatment of glioma and malignant melanoma. Because chemoresistance of these tumors is a common phenomenon, identification of the underlying mechanisms is needed. Here we show that Rev3L, the catalytic subunit of the translesion DNA polymerase zeta, mediates resistance to both temozolomide and fotemustine. Rev3L knockout cells are hypersensitive to both agents. It is remarkable that cells heterozygous for Rev3L showed an intermediate sensitivity. Rev3L is not involved in the tolerance of the toxic O6-methylguanine lesion. However, a possible role of Rev3L in the tolerance of O6-…
Photogenotoxicity of folic acid.
2013
Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). FA is photoreactive and has been shown to generate DNA modifications when irradiated with UVA (360 nm) in the presence of DNA under cell-free conditions. To investigate the relevance of this reaction for cells and tissues, we irradiated three different cell lines (KB nasopharyngeal carcinoma cells, HaCaT keratinocytes, and a melanoma cell line) in the presence of FA and quantified cytotoxicity and DNA damage generation. The results indicate that FA is phototoxic and photogenotoxic by two different mechanisms. First, ext…
Ligand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental support
2010
Abstract Two-dimensional bond-based linear indices and linear discriminant analysis are used in this report to perform a quantitative structure–activity relationship study to identify new trypanosomicidal compounds. A database with 143 anti-trypanosomal and 297 compounds having other clinical uses, are utilized to develop the theoretical models. The best discriminant models computed using bond-based linear indices provides accuracies greater than 90 for both training and test sets. Our models identify as anti-trypanosomals five out of nine compounds of a set of already-synthesized substances. The in vitro anti-trypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi…
An open-source computational and data resource to analyze digital maps of immunopeptidomes
2015
We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the de…
The cost-effectiveness of neonatal versus prenatal screening for congenital toxoplasmosis
2019
BackgroundCongenital Toxoplasmosis (CT) can have severe consequences. France, Austria, and Slovenia have prenatal screening programs whereas some other countries are considering universal screening to reduce congenital transmission and severity of infection in children. The efficiency of such programs is debated increasingly as seroprevalence among pregnant women and incidence of congenital toxoplasmosis show a steady decrease. In addition, uncertainty remains regarding the effectiveness of pre- and postnatal treatments.MethodTo identify cost-effective strategies, prenatal and neonatal screenings were compared using a decision-analytic model based on French guidelines and current knowledge …
Digital holographic microscopy for diabetes screening
2016
A digital holographic microscope operating in telecentric mode could be used to diagnose diabetes and evaluate long-term glycemic control in patients with diabetes.
Atom- and Bond-Based 2D TOMOCOMD-CARDD Approach and Ligand-Based Virtual Screening for the Drug Discovery of New Tyrosinase Inhibitors
2008
Two-dimensional atom- and bond-based TOMOCOMD-CARDD descriptors and linear discriminant analysis (LDA) are used in this report to perform a quantitative structure-activity relationship (QSAR) study of tyrosinase-inhibitory activity. A database of inhibitors of the enzyme is collected for this study, within 246 highly dissimilar molecules presenting antityrosinase activity. In total, 7 discriminant functions are obtained by using the whole set of atom- and bond-based 2D indices. All the LDA-based QSAR models show accuracies above 90% in the training set and values of the Matthews correlation coefficient (C) varying from 0.85 to 0.90. The external validation set shows globally good classifica…
Dottore, mio figlio non impara a leggere”. I Disturbi Specifici dell’Apprendimento (DSA) e il pediatra di famiglia
2015
Si parla di Disturbo Specifico di Apprendimento (DSA) quando sono presenti delle difficoltà isolate e circoscritte nella lettura (Dislessia) e/o nella scrittura (Disortografia) e/o nel calcolo (Discalculia) nonostante la presenza di adeguate capacità cognitive e opportunità scolastiche. Tali difficoltà hanno carattere evolutivo e persistente, presentandosi con diversa espressività clinica nelle varie fasi dello sviluppo. La prevalenza mondiale del disturbo si attesta tra il 5 e il 15% (DSM 5, 2013). L’incidenza è maggiore nei maschi, con un rapporto M/F stimato intorno a 2:1, 3:1 (DSM 5, 2013). In Italia la stima di prevalenza dei DSA fra i bambini in età scolare oscilla fra il 3 e il 5% (C…
Synthesis of N-acyl Derivatives of Aminocombretastatin A-4 and Study of their Interaction with Tubulin and Downregulation of c-Myc.
2021
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