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https://www.readbyqxmd.com/read/29932116/targeting-mtor-as-a-therapeutic-approach-in-medulloblastoma
#1
REVIEW
Juncal Aldaregia, Ainitze Odriozola, Ander Matheu, Idoia Garcia
Mechanistic target of rapamycin (mTOR) is a master signaling pathway that regulates organismal growth and homeostasis, because of its implication in protein and lipid synthesis, and in the control of the cell cycle and the cellular metabolism. Moreover, it is necessary in cerebellar development and stem cell pluripotency maintenance. Its deregulation has been implicated in the medulloblastoma and in medulloblastoma stem cells (MBSCs). Medulloblastoma is the most common malignant solid tumor in childhood. The current therapies have improved the overall survival but they carry serious side effects, such as permanent neurological sequelae and disability...
June 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29930758/prognostic-values-of-the-mrna-expression-of-natural-killer-receptor-ligands-and-their-association-with-clinicopathological-features-in-breast-cancer-patients
#2
Ali Abouelghar, Reem Hasnah, Ghina Taouk, Mohamad Saad, Manale Karam
Background: Natural killer (NK) cells are lymphocytes of the innate immune system that have potent cytotoxic activity against tumor cells. NK cell recognition and activity towards cancer cells are regulated by an integrated interplay between numerous inhibitory and activating receptors acting in concert to eliminate tumor cells expressing cognate ligands. Despite strong evidence supporting the role of NK cells in breast cancer (BC) control, BC still develops and progresses to form large tumors and metastases...
June 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29930089/three-dimensional-intact-tissue-sequencing-of-single-cell-transcriptional-states
#3
Xiao Wang, William E Allen, Matthew A Wright, Emily L Sylwestrak, Nikolay Samusik, Sam Vesuna, Kathryn Evans, Cindy Liu, Charu Ramakrishnan, Jia Liu, Garry P Nolan, Felice-Alessio Bava, Karl Deisseroth
Retrieving high-content gene-expression information while retaining 3D positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. Here we develop and apply a technology for 3D intact-tissue RNA sequencing, termed STARmap (Spatially-resolved Transcript Amplicon Readout Mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1,020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy and reproducibility...
June 21, 2018: Science
https://www.readbyqxmd.com/read/29929545/systematic-analyses-reveal-long-non-coding-rna-ptaf-mediated-promotion-of-emt-and-invasion-metastasis-in-serous-ovarian-cancer
#4
Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
BACKGROUND: A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. METHODS: We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels...
June 21, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29929361/genetic-diversity-of-bovine-mycobacterium-avium-subsp-paratuberculosis-discriminated-by-is-1311-pcr-rea-miru-vntr-and-mlssr-genotyping
#5
Hong-Tae Park, Hyun-Eui Park, Woo Bin Park, Suji Kim, Young-Hoon Jung, Han Sang Yoo
The aim of this study was to describe the genetic diversity of Mycobacterium avium subsp. paratuberculosis (MAP) obtained from individual cows in Korea. Twelve MAP-positive fecal DNA samples and 19 MAP isolates were obtained from 10 cattle herds located in 5 provinces in Korea. In addition to this, 5 MAP isolates were obtained from the Czech Republic and Slovakia, and 3 were from Australia were used for typing to compare with the domestic isolates. The most prevalent strains in Korea were the "bison-type" genotype (23 out of the 31 fecal DNA/isolates) and distributed nationwide...
June 21, 2018: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29928425/correlation-of-socs-1-gene-with-onset-and-prognosis-of-breast-cancer
#6
Yuetao Lv, Ge Song, Peng Li
The aim of the present study is to study the expressions of suppressor of cytokine signaling (SOCS)-1 in the tumor tissues and adjacent normal tissues of patients with breast cancer. The study was also planned to investigate the association of SOCS-1 gene expression with patients' clinical pathology, molecular subtype and prognosis. A total of 60 cases of frozen and paraffin-embedded specimens of tumor tissues and corresponding adjacent normal tissues of patients with breast cancer were selected. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of SOCS-1 messenger RNA (mRNA) in the patients' tumor tissues and adjacent normal tissues...
July 2018: Oncology Letters
https://www.readbyqxmd.com/read/29928032/activation-of-trek-currents-by-riluzole-in-three-subgroups-of-cultured-mouse-nodose-ganglion-neurons
#7
Diego Fernández-Fernández, Alba Cadaveira-Mosquera, Lola Rueda-Ruzafa, Salvador Herrera-Pérez, Emma L Veale, Antonio Reboreda, Alistair Mathie, J Antonio Lamas
Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG)...
2018: PloS One
https://www.readbyqxmd.com/read/29927639/microcalcification-associated-breast-cancer-her2-enriched-molecular-subtype-is-associated-with-mammographic-features
#8
Zhong Nie, Jian Wang, Xiao-Chun Ji
PURPOSE: To investigate whether the mammographic features were different between breast cancer HER2-enriched molecular subtype and non-HER2-enriched molecular subtype. METHODS: 283 microcalcification-associated breast cancers were identified (HER2-enriched: n = 57; non-HER2-enriched: n = 226). Mammographic tumor mass and calcification features in relation to HER2 molecular subtype were analyzed. RESULTS: On univariate analysis, HER2-enriched molecular subtype rates were significantly higher (a) in tumor size <= 2 cm 33 of 57 [57...
June 21, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29926531/arnt-hif-1%C3%AE-links-high-risk-1q21-gain-and-microenvironmental-hypoxia-to-drug-resistance-and-poor-prognosis-in-multiple-myeloma
#9
Chuan Wu, Ting Yang, Yingmin Liu, Yicheng Lu, Yanping Yang, Xiaobo Liu, Xuelian Liu, Long Ye, Yue Sun, Xue Wang, Qingchao Li, Peiyu Yang, Xiaoyuan Yu, Sujun Gao, Shaji Kumar, Fengyan Jin, Yun Dai, Wei Li
1q21 gain is a common cytogenetic abnormality featuring high-risk multiple myeloma (HRMM). However, the molecular mechanism underlying the adverse prognostic effect of 1q21 gain remains largely unclear. Here, we report that ARNT/HIF-1β, a 1q21 gene, is highly expressed in HRMM and induced by microenvironmental hypoxia, which confers drug resistance and correlates with inferior outcome. Analysis of the gene expression profile database revealed that ARNT expression was upregulated in MM and increased with disease progression or in HRMM subtypes (particularly 1q21 gain), while correlated to shorter overall survival...
June 21, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29925955/a-multiprotein-supercomplex-controlling-oncogenic-signalling-in-lymphoma
#10
James D Phelan, Ryan M Young, Daniel E Webster, Sandrine Roulland, George W Wright, Monica Kasbekar, Arthur L Shaffer, Michele Ceribelli, James Q Wang, Roland Schmitz, Masao Nakagawa, Emmanuel Bachy, Da Wei Huang, Yanlong Ji, Lu Chen, Yandan Yang, Hong Zhao, Xin Yu, Weihong Xu, Maryknoll M Palisoc, Racquel R Valadez, Theresa Davies-Hill, Wyndham H Wilson, Wing C Chan, Elaine S Jaffe, Randy D Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M Rimsza, Fausto J Rodriguez, Fayez Estephan, Matthias Holdhoff, Michael J Kruhlak, Stephen M Hewitt, Craig J Thomas, Stefania Pittaluga, Thomas Oellerich, Louis M Staudt
B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1 . Gene expression profiling identified two major DLBCL subtypes, known as germinal center (GC) B cell-like (GCB) and activated B cell-like (ABC)2,3 , with inferior outcomes following immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 (CBM) adapter complex that recruits and activates IκB kinase (IKK)4-6 ...
June 20, 2018: Nature
https://www.readbyqxmd.com/read/29925945/structure-of-the-adenosine-bound-human-adenosine-a-1-receptor-g-i-complex
#11
Christopher J Draper-Joyce, Maryam Khoshouei, David M Thal, Yi-Lynn Liang, Anh T N Nguyen, Sebastian G B Furness, Hariprasad Venugopal, Jo-Anne Baltos, Jürgen M Plitzko, Radostin Danev, Wolfgang Baumeister, Lauren T May, Denise Wootten, Patrick M Sexton, Alisa Glukhova, Arthur Christopoulos
The class A adenosine A1 receptor (A1 R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human A1 R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A1 R, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2...
June 20, 2018: Nature
https://www.readbyqxmd.com/read/29925760/effect-of-methionine-oxidation-and-substitution-of-%C3%AE-conotoxin-txid-on-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptor
#12
Jie Ren, Rui Li, Jiong Ning, Xiaopeng Zhu, Dongting Zhangsun, Yong Wu, Sulan Luo
&alpha;-Conotoxin TxID was discovered from Conus textile by gene cloning, which has 4/6 inter-cysteine loop spacing and selectively inhibits &alpha;3&beta;4 nicotinic acetylcholine receptor (nAChR) subtype. However, TxID is susceptible to modification due to it containing a methionine (Met) residue that easily forms methionine sulfoxide (MetO) in oxidative environment. In this study, we investigated how Met-11 and its derivatives affect the activity of TxID using a combination of electrophysiological recordings and molecular modelling...
June 20, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29925689/deep-phenotyping-of-human-induced-pluripotent-stem-cell-derived-atrial-and-ventricular-cardiomyocytes
#13
Lukas Cyganek, Malte Tiburcy, Karolina Sekeres, Kathleen Gerstenberg, Hanibal Bohnenberger, Christof Lenz, Sarah Henze, Michael Stauske, Gabriela Salinas, Wolfram-Hubertus Zimmermann, Gerd Hasenfuss, Kaomei Guan
Generation of homogeneous populations of subtype-specific cardiomyocytes (CMs) derived from human induced pluripotent stem cells (iPSCs) and their comprehensive phenotyping is crucial for a better understanding of the subtype-related disease mechanisms and as tools for the development of chamber-specific drugs. The goals of this study were to apply a simple and efficient method for differentiation of iPSCs into defined functional CM subtypes in feeder-free conditions and to obtain a comprehensive understanding of the molecular, cell biological, and functional properties of atrial and ventricular iPSC-CMs on both the single-cell and engineered heart muscle (EHM) level...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29925470/factors-that-influence-survival-in-high-grade-serous-ovarian-cancer-a-complex-relationship-between-molecular-subtype-disease-dissemination-and-operability
#14
Diogo Torres, Chen Wang, Amanika Kumar, Jamie N Bakkum-Gamez, Amy L Weaver, Michaela E McGree, Gottfried E Konecny, Ellen L Goode, William A Cliby
OBJECTIVE: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC). METHODS: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0...
June 17, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29925409/sexual-dimorphism-in-bacterial-infections
#15
REVIEW
Edgar Ricardo Vázquez-Martínez, Elizabeth García-Gómez, Ignacio Camacho-Arroyo, Bertha González-Pedrajo
BACKGROUND: Sex differences are important epidemiological factors that impact in the frequency and severity of infectious diseases. A clear sexual dimorphism in bacterial infections has been reported in both humans and animal models. Nevertheless, the molecular mechanisms involved in this gender bias are just starting to be elucidated. In the present article, we aim to review the available data in the literature that report bacterial infections presenting a clear sexual dimorphism, without considering behavioral and social factors...
June 20, 2018: Biology of Sex Differences
https://www.readbyqxmd.com/read/29925043/molecular-characterization-and-putative-pathogenic-pathways-of-tuberous-sclerosis-complex-associated-renal-cell-carcinoma
#16
Jeong Hwan Park, Cheol Lee, Mee Soo Chang, Kwangsoo Kim, Seongmin Choi, Hyunjung Lee, Hyun-Seob Lee, Kyung Chul Moon
Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...
June 17, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29924962/prognostic-value-of-aldehyde-dehydrogenase-1-aldh1-in-invasive-breast-carcinomas
#17
Hale Demir, Ozgecan Dulgar, Bugra Taygun Gulle, Hande Turna, Sennur Ilvan
Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival...
June 11, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29923243/gold-nanoparticles-functionalized-with-rgd-semipeptides-a-simple-yet-highly-effective-targeting-system-for-%C3%AE-v%C3%AE-3-integrins
#18
Vito Maggi, Francesca Bianchini, Elisabetta Portioli, Silvia Peppicelli, Matteo Lulli, Daniele Bani, Roberta Del Sole, Franca Zanardi, Andrea Sartori, Roberto Fiammengo
Effective and selective targeting of the αVβ3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, αVβ3-targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis...
June 19, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29923159/dynamics-of-spontaneous-activity-in-random-networks-with-multiple-neuron-subtypes-and-synaptic-noise-spontaneous-activity-in-networks-with-synaptic-noise
#19
Rodrigo F O Pena, Michael A Zaks, Antonio C Roque
Spontaneous cortical population activity exhibits a multitude of oscillatory patterns, which often display synchrony during slow-wave sleep or under certain anesthetics and stay asynchronous during quiet wakefulness. The mechanisms behind these cortical states and transitions among them are not completely understood. Here we study spontaneous population activity patterns in random networks of spiking neurons of mixed types modeled by Izhikevich equations. Neurons are coupled by conductance-based synapses subject to synaptic noise...
June 19, 2018: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29921827/differential-expression-and-pathway-analysis-in-drug-resistant-triple-negative-breast-cancer-cell-lines-using-rnaseq-analysis
#20
Safa Shaheen, Febin Fawaz, Shaheen Shah, Dietrich Büsselberg
Triple-negative breast cancer (TNBC) is among the most notorious types of breast cancer, the treatment of which does not give consistent results due to the absence of the three receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as well as high amount of molecular variability. Drug resistance also contributes to treatment unresponsiveness. We studied differentially expressed genes, their biological roles, as well as pathways from RNA-Seq datasets of two different TNBC drug-resistant cell lines of Basal B subtype SUM159 and MDA-MB-231 treated with drugs JQ1 and Dexamethasone, respectively, to elucidate the mechanism of drug resistance...
June 19, 2018: International Journal of Molecular Sciences
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