Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Olga Kondrashova … M.K. Oehler … [et al.] (Australian Ovarian Cancer Study (AOCS)

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Agency for Science, Technology and Research (A*STAR). EC is supported by the A*STAR Graduate Scholarship program

First sagittarius A* Event Horizon Telescope results. IV. Variability, morphology, and black hole mass

Galaxie

A universal power-law prescription for variability from synthetic images of black hole accretion flows

Instrumentatio

Characterizing and mitigating intraday variability: reconstructing source structure in accreting black holes with mm-VLBI

Instrumentatio

Isolation and Characterization of Streptomyces spp. from Soils

The isolation of forty-eight strains of actinomycetes from eight soil samples was done with the conventional dilution plate method on Humic acid-vitamin agar (HVA), Starch Casein agar and Sorenson's agar. HVA was found to be the best isolation medium as more strains of actinomycete could be isolated. Based on the aerial mycelium colour scheme, three colour groups were recognised. Representative isolates from each colour group were subjected to macrorestriction analysis with the pulsed-field gel electrophoresis (PFGE). The different coloured strains exhibited low levels of similarity (Dice coefficient, F<0.50). Acetone extracts of the isolates were screened on mutant yeasts for Mitogen-Activated Protein Kinase (MAPK) Kinase and MAPK Phosphatase inhibitor to find an indirect inhibitor of ras. However, no inhibitor was found but seven isolates exhibited toxic effect towards the yeasts. PFGE analysis of these isolates showed that two of isolates were identical. From the phenotypic and genotypic characteristics, the two isolates were shown to be of the same strai

Isolation and characterization of Streptomyces spp. from soils

The isolation of forty-eightstrains of actinomycetesfrom eightsoil sampleswas donewith the conventional dilution plate method on Humic acid-vitamin agar (lfVA), Starch Casein agar and Sorenson's agar. FIVAwas found to be the best isolation medium as more strains of actinomycete could be isolated. Based on the aerial mycelium colour scheme, three colour groups were recognised. Representative isolates from each colour group were subjected to macrorestriction analysis with the pulsed-field gel electrophoresis (PFGE). The different coloured strainsexhibitedlowlevelsofsimilariry(Dice coefficient,F<0.50).A cetoneextractsoftheisolateswerescreened on mutant yeastsf or Mitogen-Activated Protein Kinase (MAPK) Kinase and MAPK Phosphatasei nhibitor to find an indirect inhibitor of ras. However, no inhibitor was found but seven isolates exhibited toxic effect towards the yeasts. PFGE analysis of these isolates showed that two of isolateswere identical. From the phenotlpic and genotypic characteristics, the two isolates were shown to be of the same strain

Retracted: Significance of personalized learning style in promoting E-technology

This article was withdrawn and retracted by the Journal of Fundamental and Applied Sciences and has been removed from AJOL at the request of the journal Editor in Chief and the organisers of the conference at which the articles were presented (www.iccmit.net). Please address any queries to [email protected]