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https://www.readbyqxmd.com/read/27891692/smarce1-mutation-screening-in-classification-of-clear-cell-meningiomas
#1
Miriam J Smith, Soomin Ahn, Jung-Il Lee, Michael Bulman, Daniel du Plessis, Yeon-Lim Suh
AIMS: Clear cell meningioma is a rare subtype of meningioma and shows not only unusual histology, but also unique clinical features. Recently, SMARCE1 mutations have been shown to cause spinal and cranial clear cell meningiomas. We present 12 cases which were diagnosed with a clear cell meningioma in a single institution between 1997 and 2014, and investigate their SMARCE1 mutation status. METHODS AND RESULTS: To investigate the SMARCE1 mutation status of these tumours, we used a combination of Sanger sequencing and multiplex ligation dependent probe amplification analysis and also performed SMARCE1 immunohistochemical staining...
November 28, 2016: Histopathology
https://www.readbyqxmd.com/read/27881076/clustering-of-disulfide-rich-peptides-provides-scaffolds-for-hit-discovery-by-phage-display-application-to-interleukin-23
#2
David T Barkan, Xiao-Li Cheng, Herodion Celino, Tran T Tran, Ashok Bhandari, Charles S Craik, Andrej Sali, Mark L Smythe
BACKGROUND: Disulfide-rich peptides (DRPs) are found throughout nature. They are suitable scaffolds for drug development due to their small cores, whose disulfide bonds impart extraordinary chemical and biological stability. A challenge in developing a DRP therapeutic is to engineer binding to a specific target. This challenge can be overcome by (i) sampling the large sequence space of a given scaffold through a phage display library and by (ii) panning multiple libraries encoding structurally distinct scaffolds...
November 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27872081/novel-effects-of-lapatinib-revealed-in-the-african-trypanosome-using-hypothesis-generating-proteomics-and-chemical-biology-strategies
#3
Paul J Guyett, Ranjan Behera, Yuko Ogata, Michael Pollastri, Kojo Mensa-Wilmot
Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei Lapatinib, a human epidermal growth factor receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases associate with lapatinib, suggesting the drug may be a multi-targeted inhibitor of phosphoprotein signaling in the bloodstream trypanosome. Phosphoprotein signaling pathways in T. brucei have diverged significantly from those in humans...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27871234/a-genome-wide-bac-end-sequence-survey-provides-first-insights-into-sweetpotato-ipomoea-batatas-l-lam-genome-composition
#4
Zengzhi Si, Bing Du, Jinxi Huo, Shaozhen He, Qingchang Liu, Hong Zhai
BACKGROUND: Sweetpotato, Ipomoea batatas (L.) Lam., is an important food crop widely grown in the world. However, little is known about the genome of this species because it is a highly heterozygous hexaploid. Gaining a more in-depth knowledge of sweetpotato genome is therefore necessary and imperative. In this study, the first bacterial artificial chromosome (BAC) library of sweetpotato was constructed. Clones from the BAC library were end-sequenced and analyzed to provide genome-wide information about this species...
November 21, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27853960/phase-ii-study-of-tivozanib-an-oral-vegfr-inhibitor-in-patients-with-recurrent-glioblastoma
#5
Jayashree Kalpathy-Cramer, Vyshak Chandra, Xiao Da, Yangming Ou, Kyrre E Emblem, Alona Muzikansky, Xuezhu Cai, Linda Douw, John G Evans, Jorg Dietrich, Andrew S Chi, Patrick Y Wen, Stephen Stufflebeam, Bruce Rosen, Dan G Duda, Rakesh K Jain, Tracy T Batchelor, Elizabeth R Gerstner
Targeting tumor angiogenesis is a potential therapeutic strategy for glioblastoma because of its high vascularization. Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. We conducted a phase II study to test the effectiveness of tivozanib in patients with recurrent glioblastoma. Ten adult patients were enrolled and treated with tivozanib 1.5 mg daily, 3 weeks on/1 week off in 28-day cycles. Brain MRI and blood biomarkers of angiogenesis were performed at baseline, within 24-72 h of treatment initiation, and monthly thereafter...
November 16, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#6
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27806312/systematic-approach-identifies-rhoa-as-a-potential-biomarker-therapeutic-target-for-asian-gastric-cancer
#7
Hae Ryung Chang, Seungyoon Nam, Jinhyuk Lee, Jin-Hee Kim, Hae Rim Jung, Hee Seo Park, Sungjin Park, Young Zoo Ahn, Iksoo Huh, Curt Balch, Ja-Lok Ku, Garth Powis, Taesung Park, Jin-Hyun Jeong, Yon Hui Kim
Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27788488/serum-exosomal-mir-4772-3p-is-a-predictor-of-tumor-recurrence-in-stage-ii-and-iii-colon-cancer
#8
Chang Liu, Cathy Eng, Jianjun Shen, Yue Lu, Takata Yoko, Amir Mehdizadeh, George J Chang, Miguel A Rodriguez-Bigas, Yanan Li, Ping Chang, Yixiang Mao, Manal M Hassan, Fangyu Wang, Donghui Li
PURPOSE: The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer. RESULTS: 145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27759029/a-cross-ethnic-survey-of-cfb-and-slc44a4-indian-ulcerative-colitis-gwas-hits-underscores-their-potential-role-in-disease-susceptibility
#9
Aditi Gupta, Garima Juyal, Ajit Sood, Vandana Midha, Keiko Yamazaki, Arnau Vich Vila, Motohiro Esaki, Toshiyuki Matsui, Atsushi Takahashi, Michiaki Kubo, Rinse K Weersma, B K Thelma
The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case-control genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P=1...
October 19, 2016: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/27735867/modulation-of-autophagy-by-a-thioxanthone-decreases-the-viability-of-melanoma-cells
#10
Raquel T Lima, Diana Sousa, Ana M Paiva, Andreia Palmeira, João Barbosa, Madalena Pedro, Madalena M Pinto, Emília Sousa, M Helena Vasconcelos
(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to N(10)-substituted phenoxazines (isosteres of thioxanthones, and autophagy inducers), this study aimed at further assessing its cytotoxic mechanism and evaluating its potential as an autophagy modulator in A375-C5 melanoma cells; (2) Methods: Flow cytometry with propidium iodide (PI) for cell cycle profile analysis; Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry with Annexin V/PI labeling and Western blot for apoptosis analysis were conducted...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27701688/-direct-oral-anticoagulants-doac-in-tumor-patients
#11
Ralf Ulrich Trappe, Marianne Sinn, Hanno Riess
There is only limited data for the use of direct oral anticoagulants (DOACs) in tumor patients and no data from prospective randomised trials comparing DOACs to the current standard care: low molecular weight heparine (LMWH). Therefore, DOACs must be used with caution and should be restricted to tumor patients with (1) contraindications for LMWH (e.g. HIT II, phobia of syringe) or (2) to the situations of prolonged anticoagulation after initial therapy with LMWH. Cancer-associated disorders as well as side effects of chemotherapy as nausea and emesis have to be considered as well as potential substance-specific interactions...
September 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27688957/are-sites-with-multiple-single-nucleotide-variants-in-cancer-genomes-a-consequence-of-drivers-hypermutable-sites-or-sequencing-errors
#12
Thomas C A Smith, Antony M Carr, Adam C Eyre-Walker
Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation...
2016: PeerJ
https://www.readbyqxmd.com/read/27687602/-ants-a-chemical-library-of-anticancer-molecules
#13
Angélique Vétillard, Wafa Bouzid
Animal venoms are complex mixtures containing simple organic molecules, proteins, peptides, and other bioactive elements with extraordinary biological properties associated with their ability to act on a number of molecular receptors in the process of incapacitating their target organisms. In such a context, arthropod venoms are invaluable sources of bioactive substances, with therapeutic interest but the limited availability of some venom such as those from ants, has restricted the potential that these biomolecules could represent...
2016: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/27662418/elevations-on-select-conners-cpt-ii-scales-indicate-noncredible-responding-in-adults-with-traumatic-brain-injury
#14
Laszlo A Erdodi, Chantalle L Pelletier, Robert M Roth
Elevations on certain Conners' CPT-II scales are known to be associated with invalid responding. However, scales and cutoffs vary across studies. In addition, the methodology behind developing performance validity tests (PVTs) has been challenged for mistaking true impairment for noncredible presentation. Using ability-based tests as a PVT makes clinicians especially vulnerable to this criticism. The present study examined the ability of CPT-II to dissociate effort from impairment in 47 adults clinically referred for neuropsychological assessment...
September 23, 2016: Applied Neuropsychology. Adult
https://www.readbyqxmd.com/read/27622946/bacterial-transcription-inhibitor-of-rna-polymerase-holoenzyme-formation-by-structure-based-drug-design-from-in-silico-screening-to-validation
#15
Cong Ma, Xiao Yang, Peter J Lewis
Bacterial transcription is a proven target for antibacterial research. However, most of the known inhibitors targeting transcription are from natural extracts or are hits from screens where the binding site remains unidentified. Using an RNA polymerase holoenzyme homology structure from the model Gram-positive organism Bacillus subtilis, we created a pharmacophore model and used it for in silico screening of a publicly available library for compounds able to inhibit holoenzyme formation. The hits demonstrated specific affinity to bacterial RNA polymerase and excellent activity using in vitro assays and showed no binding to the equivalent structure from human RNA polymerase II...
January 8, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27621141/do-we-need-updated-guidelines-on-the-use-of-insulin-pump-therapy-in-type-2-diabetes-a-review-of-national-and-international-practice-guidelines
#16
Ohad Cohen, William Valentine
BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is used less for type 2 than for type 1 diabetes because of inconsistencies in evidence of effectiveness. We reviewed published guidelines on intensive insulin therapy in type 2 diabetes to assess whether updating of guidance is needed with respect to evidence used and recommendations for CSII in diabetes management. METHODS: A literature review was performed to identify published national and international guidelines on type 2 diabetes management...
November 2016: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/27620627/not-all-differences-between-patients-with-schizophrenia-and-healthy-subjects-are-pathological-performance-on-the-conners-continuous-performance-test
#17
Beatriz López-Luengo, Alejandro González-Andrade, Miguel García-Cobo
OBJECTIVE: This study analyzed attentional performance in patients with schizophrenia during a continuous performance task requiring a high response rate. METHOD: The Conners' Continuous Performance Test-II (CPT-II) was administered to 64 patients with schizophrenia and 64 healthy comparison subjects. A cross-sectional design was used in order to allow analysis of the means between patients and healthy subjects. Differences in performance were assessed for significance using ANCOVA...
September 12, 2016: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
https://www.readbyqxmd.com/read/27607590/changes-in-the-heart-rate-recovery-to-endurance-effort-after-high-intensity-interval-strength-and-concurrent-exercise-training-in-patients-with-insulin-resistance
#18
Cristian Álvarez, Rodrigo Ramírez-Campillo, Cristian Martínez, Mauricio Castro-Sepúlveda, Johnattan Cano-Montoya, Rodrigo Mancilla, Marcelo Flores-Opazo
BACKGROUND: The aim of this study was to assess the effects of three exercise training program in the adaptation of the heart rate recovery of patients with insulin resistance. METHODS: We studied 43 women with insulin resistance, which were assigned to three training groups: i) high intensity interval training (HIT, age 39.0 ± 10 y), ii) strength training (ST, age 33.9 ± 9.4 y), iii) mixed training of HIT+ST (MIXT, age 43.3 ± 8.1 y), and iv) and control group (CG, age 40...
September 8, 2016: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/27574993/mice-survival-and-plasmatic-cytokine-secretion-in-a-two-hit-model-of-sepsis-depend-on-intratracheal-pseudomonas-aeruginosa-bacterial-load
#19
Damien Restagno, Fabienne Venet, Christian Paquet, Ludovic Freyburger, Bernard Allaouchiche, Guillaume Monneret, Jeanne-Marie Bonnet, Vanessa Louzier
Sepsis is characterized by pro- and anti-inflammatory responses following infection. While inflammation is responsible for widespread organ damage, anti-inflammatory mediators lead to immunoparalysis increasing susceptibility to secondary infections (nosocomial pneumonia). We aimed to investigate the impact of bacterial load on survival and cytokine release in a two-hit murine (C57BL/6J) model of CLP followed by P. aeruginosa pneumonia. Plasmatic TNFα, IL-6, IL-10, sTNFr I and II were quantified until 13 days...
2016: PloS One
https://www.readbyqxmd.com/read/27574401/novel-glyoxalase-i-inhibitors-possessing-a-zinc-binding-feature-as-potential-anticancer-agents
#20
Qosay A Al-Balas, Mohammad A Hassan, Nizar A Al-Shar'i, Nizar M Mhaidat, Ammar M Almaaytah, Fatima M Al-Mahasneh, Israa H Isawi
BACKGROUND: The glyoxalase system including two thiol-dependent enzymes, glyoxalase I (Glo-I) and glyoxalase II, plays an important role in a ubiquitous metabolic pathway involved in cellular detoxification of cytotoxic 2-oxoaldehydes. Tumor cells have high glycolytic activity, leading to increased cellular levels of these toxic metabolites. The increased activity of the detoxification system in cancerous cells makes this pathway a viable target for developing novel anticancer agents...
2016: Drug Design, Development and Therapy
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