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https://www.readbyqxmd.com/read/28448864/new-agents-for-endocrine-resistance-in-breast-cancer
#1
REVIEW
Christian Maurer, Samuel Martel, Dimitrios Zardavas, Michail Ignatiadis
Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is the most common BC subtype, defined by expression of the ER and absence of HER2 amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER signaling, represents the therapeutic mainstay for patients with both early and advanced disease. Despite its wide therapeutic efficacy, ET fails for a proportion of ER+, HER2- BC patients with early disease who develop endocrine resistance, resulting in disease recurrence...
April 24, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#2
Héctor A Rueda-Zárate, Iván Imaz-Rosshandler, Roberto A Cárdenas-Ovando, Juan E Castillo-Fernández, Julieta Noguez-Monroy, Claudia Rangel-Escareño
The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Drug Induced Liver Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not exhibit hepatotoxicity at early stages of development, so it is important to detect anomalies at gene expression level that could predict adverse reactions in later stages...
2017: PloS One
https://www.readbyqxmd.com/read/28447937/il17-factors-are-early-regulators-in-the-gut-epithelium-during-inflammatory-response-to-vibrio-in-the-sea-urchin-larva
#3
Katherine M Buckley, Eric Chun Hei Ho, Taku Hibino, Catherine S Schrankel, Nicholas W Schuh, Guizhi Wang, Jonathan Patrick Rast
IL17 cytokines are central mediators of mammalian immunity. In vertebrates, these factors derive from diverse cellular sources. Sea urchins share a molecular heritage with chordates that includes the IL17 system. Here, we characterize the role of epithelial expression of IL17 in the larval gut-associated immune response. The purple sea urchin genome encodes ten IL17 subfamilies (35 genes) and two IL17 receptors. Most of these subfamilies are conserved throughout echinoderms. Two IL17 subfamilies are sequentially strongly upregulated and attenuated in the gut epithelium in response to bacterial disturbance...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28447789/exploring-the-role-of-n-6-substituents-in-potent-dual-acting-5-c-ethyl-tetrazolyl-adenosine-derivatives-synthesis-binding-functional-assays-and-antinociceptive-effects-in-mice
#4
Riccardo Petrelli, Mirko Scortichini, Sonja Kachler, Serena Boccella, Carmen Cerchia, Ilaria Torquati, Fabio Del Bello, Daniela Salvemini, Ettore Novellino, Livio Luongo, Sabatino Maione, Kenneth A Jacobson, Antonio Lavecchia, Karl-Norbert Klotz, Loredana Cappellacci
Structural determinants of affinity of N(6)-substituted-5'-C-(ethyl-tetrazol-2-yl)-adenosine and 2-chloro-adenosine derivatives at adenosine receptor (AR) subtypes were studied with binding and molecular modeling. Small N(6)-cycloalkyl and 3-halo-benzyl groups furnished potent dual acting A1AR agonists and A3AR antagonists. 4 was the most potent dual acting human (h) A1AR agonist (Ki = 0.45 nM) and A3AR antagonist (Ki = 0.31 nM) and highly selective versus A2A; 11 and 26 were most potent at both h and rat (r) A3AR...
April 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28447218/pertuzumab-trastuzumab-ct-versus-trastuzumab-ct-therapy-for-her2-breast-cancer-results-from-the-prospective-neoadjuvant-breast-registry-symphony-trial-nbrst
#5
Peter Beitsch, Pat Whitworth, Paul Baron, Michael C Rotkis, Angela M Mislowsky, Paul D Richards, Mary K Murray, James V Pellicane, Carrie L Dul, Charles H Nash, Lisette Stork-Sloots, Femke de Snoo, Sarah Untch, Laura A Lee
BACKGROUND: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. METHODS: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U...
April 26, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#6
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446378/ceftriaxone-susceptibility-and-molecular-characteristics-of-neisseria-gonorrhoeae-isolates-in-changsha-china
#7
Ting Peng, Hui Lin, Qinglin Liu, Wei Cao, Hui Ding, Jianlin Chen, Lingli Tang
A total of 128 Neisseria gonorrhoeae isolates were consecutively obtained in Changsha, China, between April 2015 and June 2016. The minimum inhibitory concentrations (MICs) of ceftriaxone were measured by agar dilution method for each isolate. Ceftriaxone resistance determinants involving penA, mtrR, porB and ponA were amplified by PCR, and the PCR products were sequenced. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was conducted for genotyping. The results exhibited 11% (14/128) of isolates were reduced susceptibility or resistant to ceftriaxone...
April 23, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28446316/-prognostic-value-of-recurrent-molecular-genetics-and-epigenetics-abnormity-in-t-lymphoblastic-lymphoma-leukemia-review
#8
Wei Guan, Yu Jing, Li Yu
T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in pediatric patients to some extent. Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype. The incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes, which could be used as risk stratification factors...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445885/patterns-of-microglial-cell-activation-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#9
Ricardo Taipa, Paulo Brochado, Andrew Robinson, Inês Reis, Patrício Costa, David M Mann, Manuel Melo Pires, Nuno Sousa
AIMS: Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. In this study, we sought to characterize the distribution of microglial cell activation in 2 neurodegenerative dementias with distinct protein signatures, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to determine if there was an anatomical correlation with the phenotypes most commonly associated with these conditions...
April 27, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28445233/preclinical-models-for-translational-sarcoma-research
#10
Rainer Hamacher, Sebastian Bauer
PURPOSE OF REVIEW: Sarcoma is a basket term for mesenchymal tumors for which more than 75 genetically and histologically distinct subtypes are recognized. Therapeutic progress has largely been achieved with classical chemotherapeutic drugs that were tested in empirical clinical trials. However, outcome in metastatic patients remains poor and with few exceptions numerous trials have failed or only provided limited improvement in recent years. RECENT FINDINGS: Given the genomic heterogeneity, preclinical model systems will be indispensable to identify new molecular targets and to prioritize drugs and drug combinations...
April 25, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28443200/epidemiology-of-ovarian-cancer-a-review
#11
Brett M Reid, Jennifer B Permuth, Thomas A Sellers
Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles...
February 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28442525/korean-monozygotic-twins-with-lethal-acantholytic-epidermolysis-bullosa-caused-by-two-novel-dsp-mutations
#12
Se Jin Kim, Jung Min Ko, Seung Han Shin, Ee-Kyung Kim, Han-Suk Kim, Kyung-A Lee
Desmoplakin is an essential cytoplasmic plaque protein in desmosomes, and it is the major linker between intercellular junctions in the skin and heart. The role of desmoplakin is anchoring transmembrane cadherins to cytoplasmic intermediate filaments. The desmoplakin gene (DSP) is located on chromosome 6, and six common allelic disorders are associated with this gene, including autosomal-dominant or -recessive disorders that affect the skin, heart, hair, and nails. In particular, lethal acantholytic epidermolysis bullosa (LAEB) is an autosomal recessively inherited and extremely rare genetic skin disorder, and only three molecularly confirmed families with LAEB have been reported previously...
March 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28442298/how-to-study-and-overcome-tumor-heterogeneity-with-circulating-biomarkers-the-breast-cancer-case
#13
REVIEW
Valentina Appierto, Serena Di Cosimo, Carolina Reduzzi, Valentina Pala, Vera Cappelletti, Maria Grazia Daidone
Breast cancer ranks first among female cancer-related deaths in Western countries. As the primary tumor can often be controlled by surgical resection, the survival of women with breast cancer is closely linked to the incidence of distant metastases. Molecular screening by next generation sequencing highlighted the spatial and temporal heterogeneity of solid tumors as well as the clonal evolution of cancer cells during progression and under treatment pressure. Such findings question whether an optimal assessment of disease progression and a screening for druggable mutations should be based on molecular features of primary or recurrent/metastatic lesions and therefore represent a crucial element for failure or success of personalized medicine...
April 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28441873/identification-and-characterization-of-a-secondary-sodium-binding-site-and-the-main-selectivity-determinants-in-the-human-concentrative-nucleoside-transporter-3
#14
C Arimany-Nardi, A Claudio-Montero, A Viel-Oliva, P Schmidtke, C Estarellas, X Barril, A Bidon-Chanal, M Pastor-Anglada
The family of concentrative Na(+):nucleoside cotransporters in humans is constituted by three subtypes, namely hCNT1, hCNT2 and hCNT3. Besides their different nucleoside selectivity, hCNT1 and hCNT2 have a Na(+):nucleoside stoichiometry of 1:1, while for hCNT3 it is of 2:1. This distinct stoichiometry of subtype 3 might hint the existence of a secondary sodium-binding site that is not present in the other two subtypes, but to date their three-dimensional structures remain unknown and the residues implicated in Na(+) binding are unclear...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28441455/gene-expression-study-and-pathway-analysis-of-histological-subtypes-of-intestinal-metaplasia-that-progress-to-gastric-cancer
#15
Osmel Companioni, José Miguel Sanz-Anquela, María Luisa Pardo, Eulàlia Puigdecanet, Lara Nonell, Nadia García, Verónica Parra Blanco, Consuelo López, Victoria Andreu, Miriam Cuatrecasas, Maddi Garmendia, Javier P Gisbert, Carlos A Gonzalez, Núria Sala
BACKGROUND: Intestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC. METHODOLOGY: We used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress...
2017: PloS One
https://www.readbyqxmd.com/read/28441150/long-non-coding-rnas-in-leukemia-biology-and-clinical-impact
#16
Tim Lammens, Kaat Durinck, Annelynn Wallaert, Frank Speleman, Pieter Van Vlierberghe
PURPOSE OF REVIEW: Over the last years, long non-coding RNAs (lncRNAs) have emerged as putative regulators of malignant hematopoietic development. Here, we review recent literature on the involvement of lncRNAs in leukemia, including their role in driving or sustaining disease and their potential impact on diagnosis, classification, and prognosis. RECENT FINDINGS: Leukemogenesis is a complex process resulting from the accumulation of multiple genetic alterations...
April 22, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#17
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28440344/toxicogenomic-module-associations-with-pathogenesis-a-network-based-approach-to-understanding-drug-toxicity
#18
J J Sutherland, Y W Webster, J A Willy, G H Searfoss, K M Goldstein, A R Irizarry, D G Hall, J L Stevens
Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP')...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#19
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#20
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
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