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https://www.readbyqxmd.com/read/29456508/the-molecular-determinants-of-small-molecule-ligand-binding-at-p2x-receptors
#1
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29455872/-pd-l1-expression-and-pd-1-pd-l1-inhibitors-in-breast-cancer
#2
REVIEW
Audrey Monneur, Anthony Gonçalves, François Bertucci
The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing)...
February 15, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29455649/molecular-subtyping-of-nasopharyngeal-carcinoma-npc-and-a-microrna-based-prognostic-model-for-distant-metastasis
#3
Lan Zhao, Alvin H W Fong, Na Liu, William C S Cho
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a microRNA (miRNA)-based prognostic model for prediction of distant metastasis. METHODS: We retrieved two NPC datasets: GSE32960 and GSE70970 as training and validation cohorts, respectively. Consensus clustering was employed for cluster discovery, and support vector machine was used to build a classifier...
February 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29455562/spatiotemporal-characteristics-of-the-hiv-1-crf02_ag-crf63_02a1-epidemic-in-russia-and-central-asia
#4
Evangelia-Georgia Kostaki, Timokratis Karamitros, Marina Bobkova, Martha Oikonomopoulou, Gkikas Magiorkinis, Federico Garcia, Angelos Hatzakis, Dimitrios Paraskevis
BACKGROUND: Eastern European countries including Russia, Ukraine and other former Soviet Union (FSU) countries have experienced an HIV epidemic spreading mostly among people who inject drugs (PWID). We aimed to investigate the origin and the dispersal patterns of HIV-1 CRF02_AG in Russia and other FSU countries. METHODS: We studied 136 CRF02_AG sequences originating from Russia, and FSU countries along with a globally sampled dataset of 3,580 CRF02_AG sequences...
February 17, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29454759/chromosomal-numerical-aberration-pattern-in-papillary-renal-cell-carcinoma-review-article
#5
REVIEW
Tomas Pitra, Kristyna Pivovarcikova, Reza Alaghehbandan, Ondrej Hes
Traditionally, papillary renal cell carcinomas (PRCCs) have been divided in two subgroups - type 1 and type 2. Based on recent molecular and genetic developments in the understanding of RCCs, it seems that this traditional classification may not be adequate and that the spectrum of PRCCs is much wider than initially proposed. Small series of distinct types of PRCC which do not fit into the above mentioned categories have been described in the literature. Published studies investigating molecular genetic changes in various types of PRCCs have shown that the molecular genetic features are remarkably heterogeneous across the whole spectrum of PRCCs...
November 8, 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29454366/occurrence-of-blastocystis-sp-and-pentatrichomonas-hominis-in-sheep-and-goats-in-china
#6
Wen Chao Li, Kai Wang, Youfang Gu
BACKGROUND: Global data regarding the molecular epidemiology of Blastocystis sp. and Pentatrichomonas hominis in sheep and goats are sparse. China has one of the largest sheep and goat populations in the world. In this study we investigated the occurrence of Blastocystis sp. and P. hominis in domestic sheep and goats in China, and analyzed the genetic characterization of these two parasite species. METHODS: In total, we collected fresh fecal samples from 832 sheep and 781 goats located on seven and ten farms, respectively, in the central eastern region of China...
February 17, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#7
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29453814/preclinical-evaluation-of-a-semi-automated-and-rapid-commercial-electrophoresis-assay-for-von-willebrand-factor-multimers
#8
Marika Pikta, Galina Zemtsovskaja, Hector Bautista, Georges Nouadje, Timea Szanto, Margus Viigimaa, Valdas Banys
BACKGROUND: The von Willebrand factor (VWF) multimer test is required to correctly subtype qualitative type 2 von Willebrand disease (VWD). The current VWF multimer assays are difficult, nonstandardized, and time-consuming. The purpose of this study was to evaluate the clinical utility of the commercial VWF multimer kit by Sebia (Lisses, France), an electrophoresis technique yielding same-day results. METHODS: Ten healthy volunteer plasma samples, in-house reference plasma (IRP) and commercial normal plasma (CNP) samples, 10 plasma samples from patients with a known VWD type, 1 hemophilia A plasma sample, and 7 external quality assurance (EQA) samples were analyzed using the commercial VWF multimer kit...
February 17, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29453630/somatic-brca1-mutations-in-clinically-sporadic-breast-cancer-with-medullary-histological-features
#9
Markus Rechsteiner, Konstantin Dedes, Daniel Fink, Bernhard Pestalozzi, Bettina Sobottka, Holger Moch, Peter Wild, Zsuzsanna Varga
BACKGROUND: The role of somatic BRCA1/2 gene mutations in breast cancer is getting increasing attention in view of hereditary disease. The medullary phenotype and triple negative intrinsic subtypes are often, but not exclusively encountered in BRCA1 germline mutated breast cancer, whilst for BRCA2, no association to specific histological features are known. In this study, we addressed the relationship between morphological medullary phenotype and BRCA1/2 somatic mutations in breast cancer without known positive family anamnesis...
February 17, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29452217/gene-expression-screening-identifies-cdca5-as-a-potential-therapeutic-target-in-acral-melanoma
#10
Tianxiao Xu, Meng Ma, Jie Dai, Sifan Yu, Xiaowen Wu, Huan Tang, Jiayi Yu, Junya Yan, Huan Yu, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
Acral melanoma (AM) is a rapidly progressing subtype of melanoma with poor prognosis. The complete array of molecular changes that occur during AM metastasis remains unclear. In this study, we compared the gene expression profiles of six primary and 12 lymph node metastatic AM samples by tissue microarray analysis. We found that the expression levels of 396 genes were increased, and that of 766 genes were decreased in the metastatic tissues compared with that in the primary tumors. The top 19 genes upregulated in the metastatic tissue specimens were selected for high-content short interfering (si)RNA screening...
February 13, 2018: Human Pathology
https://www.readbyqxmd.com/read/29451855/in-vivo-labeling-by-cd73-marks-multipotent-stromal-cells-and-highlights-endothelial-heterogeneity-in-the-bone-marrow-niche
#11
Martin Breitbach, Kenichi Kimura, Tiago C Luis, Christopher J Fuegemann, Petter S Woll, Michael Hesse, Raffaella Facchini, Sarah Rieck, Katarzyna Jobin, Julia Reinhardt, Osamu Ohneda, Daniela Wenzel, Caroline Geisen, Christian Kurts, Wolfgang Kastenmüller, Michael Hölzel, Sten E W Jacobsen, Bernd K Fleischmann
Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP + MSCs in various organs. In vivo, EGFP + mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP + cells exhibited a perivascular distribution pattern. EGFP + cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential...
February 1, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29449460/pfn2-and-gamt-as-common-molecular-determinants-of-axonal-charcot-marie-tooth-disease
#12
Manisha Juneja, Abdelkrim Azmi, Jonathan Baets, Andreas Roos, Matthew J Jennings, Paola Saveri, Chiara Pisciotta, Nathalie Bernard-Marissal, Bernard L Schneider, Catherine Verfaillie, Roman Chrast, Pavel Seeman, Angelika F Hahn, Peter de Jonghe, Stuart Maudsley, Rita Horvath, Davide Pareyson, Vincent Timmerman
BACKGROUND: Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes. METHODS: A proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins...
February 15, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29446722/herbal-compounds-with-special-reference-to-gastrodin-as-potential-therapeutic-agents-for-microglia-mediated-neuroin%C3%AF-ammation
#13
Juan-Juan Li, Shun-Jin Liu, Xiao-Yu Liu, Eng-Ang Ling
BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-1bea (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446543/cyclin-dependent-kinase-inhibitor-2a-b-gene-deletions-are-markers-of-poor-prognosis-in-indian-children-with-acute-lymphoblastic-leukemia
#14
Manisha Agarwal, Sameer Bakhshi, Sadanand N Dwivedi, Madhulika Kabra, Rashmi Shukla, Rachna Seth
BACKGROUND: Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) genes are implicated in many malignancies including acute lymphoblastic leukemia (ALL). These tumor suppressor genes, with a key regulatory role in cell cycle are located on chromosome 9p21.3. Previous studies involving CDKN2A/B gene deletions have shown mixed associations with survival outcome in childhood ALL. PROCEDURE: Hundred and four newly diagnosed children with ALL (1-14 years) were enrolled in this study...
February 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29445290/molecular-features-of-giant-cell-carcinoma-of-the-lung-a-case-report-and-literature-review
#15
Xin Li, Zihe Zhang, Jinghao Liu, Dan Wang, Sen Wei, Jun Chen
Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 50-year-old Chinese male who presented with a pulmonary nodule in the right upper lobe of his lung. After thoracoscopic lobectomy, a histopathologic diagnosis of GCCL was made. He did well postoperatively, showing no local recurrence or distal disease in a 7-year follow-up period...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29445232/the-cerebellum-of-patients-with-steatohepatitis-shows-lymphocyte-infiltration-microglial-activation-and-loss-of-purkinje-and-granular-neurons
#16
Tiziano Balzano, Jerónimo Forteza, Pilar Molina, Juan Giner, Ana Monzó, Jennifer Sancho-Jiménez, Amparo Urios, Carmina Montoliu, Vicente Felipo
Peripheral inflammation contributes to minimal hepatic encephalopathy in chronic liver diseases, which could be mediated by neuroinflammation. Neuroinflammation in cerebellum of patients with chronic liver diseases has not been studied in detail. Our aim was to analyze in cerebellum of patients with different grades of liver disease, from mild steatohepatitis to cirrhosis and hepatic encephalopathy: (a) neuronal density in Purkinje and granular layers; (b) microglial activation; (c) astrocyte activation; (d) peripheral lymphocytes infiltration; (e) subtypes of lymphocytes infiltrated...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444670/breast-cancer-in-ethiopia-evidence-for-geographic-difference-in-the-distribution-of-molecular-subtypes-in-africa
#17
Endale Hadgu, Daniel Seifu, Wondemagegnhu Tigneh, Yonas Bokretsion, Abebe Bekele, Markos Abebe, Thomas Sollie, Sofia D Merajver, Christina Karlsson, Mats G Karlsson
BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2)...
February 14, 2018: BMC Women's Health
https://www.readbyqxmd.com/read/29444614/in-vitro-anti-influenza-virus-effect-of-total-flavonoid-from-trollius-ledebouri-reichb
#18
Yongping Liu, Jiming Tong, Ying Tong, Ping Li, Xiaolan Cui, Hongbao Cao
Objective To investigate the in vitro antivirus effect of total flavonoid from Trollius ledebouri Reichb (TFTLR). Methods Madin-Darby canine kidney (MDCK) and Human epithelial type 2 (HEp-2) cell lines were used to test the antivirus effect of TFTLR on nine virus subtypes: four H1N1, one H3N2, and four other subtypes prevalent in North China. Tamiflu, Ribavirin and Lianhua Qingwen were used as active comparators. Comprehensive molecular pathway analyses of TFTLR-H1N1 and TFTLR-H3N2 relationships were also conducted...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29444279/adult-brainstem-gliomas-with-h3k27m-mutation-radiology-pathology-and-prognosis
#19
Elena V Daoud, Veena Rajaram, Chunyu Cai, Robert J Oberle, Gregory R Martin, Jack M Raisanen, Charles L White, Chan Foong, Bruce E Mickey, Edward Pan, Kimmo J Hatanpaa
Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old...
February 10, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29443054/the-mouse-hindbrain-as-a-model-for-studying-embryonic-neurogenesis
#20
Mathew Tata, Christiana Ruhrberg
The mouse embryo forebrain is the most commonly employed system for studying mammalian neurogenesis during development. However, the highly folded forebrain neuroepithelium is not amenable to wholemount analysis to examine organ-wide neurogenesis patterns. Moreover, defining the mechanisms of forebrain neurogenesis is not necessarily predictive of neurogenesis in other parts of the brain; for example, due to the presence of forebrain-specific progenitor subtypes. The mouse hindbrain provides an alternative model for studying embryonic neurogenesis that is amenable to wholemount analysis, as well as tissue sections to observe the spatiotemporal distribution and behavior of neural progenitors...
January 29, 2018: Journal of Visualized Experiments: JoVE
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