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https://www.readbyqxmd.com/read/28346757/commentary-extraordinary-environments-extreme-neuroplasticity-and-mental-disorder-reflections-on-pathways-from-adversity-to-mental-disorder-prompted-by-mccrory-gerin-and-viding-2017
#1
Edmund J S Sonuga-Barke
Neuroplasticity, the brain's capacity to be shaped in response to environmental experience, has been claimed to resemble a double-edged sword - potentiating growth and healing when individuals are exposed to normative, benign or therapeutic environments on the one hand, mediating mental disorder development in those exposed to adversity, on the other. However, questions about the scope and limits of neuroplasticity and, especially, its clinical significance, remain unanswered.
April 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28346462/wnt-tcf1-pathway-restricts-embryonic-stem-cell-cycle-through-activation-of-the-ink4-arf-locus
#2
Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346412/vista-is-an-inhibitory-immune-checkpoint-that-is-increased-after-ipilimumab-therapy-in-patients-with-prostate-cancer
#3
Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#4
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28346008/wnt-%C3%AE-catenin-signaling-is-required-for-distraction-osteogenesis-in-rats
#5
Xuemei Wang, En Luo, Ruiye Bi, Bin Ye, Jing Hu, Shujuan Zou
OVERVIEW: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized. MATERIALS AND METHODS: We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process...
March 1, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28345812/reduced-expression-of-let-7f-activates-tgf-%C3%AE-alk5-pathway-and-leads-to-impaired-ischaemia-induced-neovascularization-after-cigarette-smoke-exposure
#6
Wahiba Dhahri, Sylvie Dussault, Paola Haddad, Julie Turgeon, Sophie Tremblay, Kevin Rolland, Michel Desjarlais, Katia Y Cáceres-Gorriti, Raphael Mathieu, Alain Rivard
This study sought to determine the potential role of microRNAs (miRNAs) in the detrimental effects of cigarette smoke on angiogenesis and neovascularization. Using large-scale miRNA profiling and qRT-PCR analyses, we identified let-7f as a pro-angiogenic miRNA which expression is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischaemia, intramuscular injection of let-7f mimic restored ischaemia-induced neovascularization in MES...
March 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28345497/scoping-the-role-and-education-needs-of-practice-nurses-in-london
#7
Susan Procter, Lauren Griffiths, Agnes Fanning, Lizzie Wallman, Heather P Loveday
Aims To identify education priorities for practice nursing across eight London Clinical Commissioning Groups (CCGs); to identify the education, training, development and support needs of practice nurses in undertaking current and future roles. BACKGROUND: The education needs of practice nurses have long been recognised but their employment status means that accessing education requires the support of their GP employer. This study scopes the educational requirements of the practice nurse workforce and working with educational providers and commissioners describes a coherent educational pathway for practice nurses...
March 27, 2017: Primary Health Care Research & Development
https://www.readbyqxmd.com/read/28345280/otoprotective-effects-of-mouse-nerve-growth-factor-in-dba-2j-mice-with-early-onset-progressive-hearing-loss
#8
Qingzhu Wang, Hongchun Zhao, Tihua Zheng, Wenjun Wang, Xiaolin Zhang, Andi Wang, Bo Li, Yanfei Wang, Qingyin Zheng
As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth...
March 27, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28345253/attending-and-avoiding-dental-appointments-do-bright-and-dark-motivational-paths-have-a-role
#9
A E Münster Halvari, H Halvari, E L Deci
OBJECTIVE: The aim of this study was to test a self-determination theory (SDT) process model of the "bright" and the "dark" motivational pathways through dental attendance or avoidance to oral health. METHODS: A cross-sectional study was conducted among 322 students from all study disciplines at the University of Oslo. Participants responded to a survey with validated questionnaires. Structural equation modelling was used to test the SDT model, and a bootstrapping procedure was used to test the indirect links in the model...
March 26, 2017: International Journal of Dental Hygiene
https://www.readbyqxmd.com/read/28345021/oncolytic-group-b-adenovirus-enadenotucirev-mediates-non-apoptotic-cell-death-with-membrane-disruption-and-release-of-inflammatory-mediators
#10
Arthur Dyer, Ying Di, Hugo Calderon, Sam Illingworth, Gray Kueberuwa, Alison Tedcastle, Phil Jakeman, Suet Lin Chia, Alice Brown, Michael A Silva, David Barlow, John Beadle, Terry Hermiston, David J P Ferguson, Brian Champion, Kerry D Fisher, Leonard W Seymour
Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#11
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#12
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344862/expression-profiles-of-immune-related-genes-are-associated-with-neoadjuvant-ipilimumab-clinical-benefit
#13
Ahmad A Tarhini, Yan Lin, Hui-Min Lin, Priyanka Vallabhaneni, Cindy Sander, William LaFramboise, Lana Hamieh
Purpose: Patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab in a previously reported study (PLOS One 2014). Gene expression profiles of tumors of treated patients were investigated for their association with immunotherapeutic benefit. Methods: Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks × 2 doses) before and after surgery. Tumor specimens were obtained at baseline and at definitive surgery (weeks 6-8). Gene expression profiling was performed on the tumor biopsies of 27 patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344859/hla-class-ii-antigen-processing-pathway-in-tumors-molecular-defects-and-clinical-relevance
#14
REVIEW
Barbara Seliger, Matthias Kloor, Soldano Ferrone
The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4(+) T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4(+) T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344765/new-insights-on-thyroid-hormone-mediated-regulation-of-herpesvirus-infections
#15
REVIEW
Robert W Figliozzi, Feng Chen, S Victor Hsia
Thyroid hormone (T3) has been suggested to participate in the regulation of herpesvirus replication during reactivation. Clinical observations and in vivo experiments suggest that T3 are involved in the suppression of herpes virus replication. In vitro, differentiated LNCaP cells, a human neuron-like cells, further resisted HSV-1 replication upon addition of T3. Previous studies indicate that T3 controlled the expression of several key viral genes via its nuclear receptors in differentiated LNCaP cells. Additional observation showed that differentiated LNCaP cells have active PI3K signaling and inhibitor LY294002 can reverse T3-mediated repression of viral replication...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28344746/cpg-island-methylator-phenotype-in-adenocarcinomas-from-the-digestive-tract-methods-conclusions-and-controversies
#16
EDITORIAL
Francisco Sánchez-Vega, Valer Gotea, Yun-Ching Chen, Laura Elnitski
Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype (CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using cross-platform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas...
March 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28344663/everolimus-treatment-for-neuroendocrine-tumors-latest-results-and-clinical-potential
#17
REVIEW
Sara Pusceddu, Elena Verzoni, Natialie Prinzi, Alessia Mennitto, Daniela Femia, Paolo Grassi, Laura Concas, Claudio Vernieri, Giuseppe Lo Russo, Giuseppe Procopio
Neuroendocrine tumors (NETs) are a heterogeneous class of diseases characterized by challenging management. Preclinical evidence shows that the PI3K/AKT/mTOR signaling pathway plays a central role in the pathogenesis and progression of NETs. Everolimus is a direct inhibitor of this pathway, and therefore this molecule appears to be a well-grounded strategy for the treatment of NETs, capable of changing clinical practice. The efficacy and safety of everolimus was demonstrated in the RADIANT trials. In this work, we comment on the results of the RADIANT trials, and other recent key evidence from fully published clinical trials on everolimus, and we discuss the current role of everolimus in the treatment of NETs...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#18
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344472/prevalence-of-udp-glucuronosyltransferase-polymorphisms-ugt1a6%C3%A2-2-1a7%C3%A2-12-1a8%C3%A2-3-1a9%C3%A2-3-2b7%C3%A2-2-and-2b15%C3%A2-2-in-a-saudi-population
#19
Khalid M Alkharfy, Basit L Jan, Sibtain Afzal, Fahad I Al-Jenoobi, Abdullah M Al-Mohizea, Saleh Al-Muhsen, Rabih Halwani, Mohammad K Parvez, Mohammed S Al-Dosari
Glucuronidation is an important phase II pathway responsible for many endogenous substances and drug metabolism. The present work evaluated allele frequencies of certain UDP-glucuronosyl-transferases (UGT 1A6∗2, A7∗12, A8∗3, A9∗3, 2B7∗2, and 2B15∗2) in Saudi Arabians that could provide essential ethnic information. Blood samples from 192 healthy unrelated Saudi males of various geographic regions were collected. Genomic DNA was isolated and genotyping of various UGTs was carried out using polymerase chain reaction (PCR) followed by direct sequencing...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344323/new-knowledge-of-the-mechanisms-of-sorafenib-resistance-in-liver-cancer
#20
REVIEW
Yan-Jing Zhu, Bo Zheng, Hong-Yang Wang, Lei Chen
Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems...
March 27, 2017: Acta Pharmacologica Sinica
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