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gene addiction

Hiroki Ishiguro, Kunio Miyake, Koichi Tabata, Chiaki Mochizuki, Takeshi Sakurai, Emmanuel S Onaivi
AIMS: The human NRCAM gene is associated with polysubstance use. Nrcam knockout mice do not acquire a preference for addictive substances. We aimed to elucidate the role of Nrcam in specific neural circuits underlying congenital preference for substances and the acquisition of addiction. METHODS: We analyzed gene expression patterns of neural molecules to find a common addiction pathway dependent on Nrcam function. We examined monoaminergic, glutamatergic, and GABAergic systems in the brains of Nrcam knockout mice following treatment with methamphetamine (METH) or saline (SAL) using micro-array gene expression analysis, which was replicated using TaqMan gene expression analysis...
December 13, 2018: Neuropsychopharmacology reports
Tiziana Triulzi, Luca Forte, Viola Regondi, Martina Di Modica, Cristina Ghirelli, Maria Luisa Carcangiu, Lucia Sfondrini, Andrea Balsari, Elda Tagliabue
Through whole-transcriptome profiling of HER2+ breast carcinomas (BCs), we previously showed that those sensitive to trastuzumab are addicted to this oncoprotein and are enriched in immune pathways, raising the hypothesis that HER2 itself regulates immune cell recruitment. In the present study we investigated the relationship between HER2 activity and the pro-trastuzumab tumor immune milieu. Gene expression profiling and immunohistochemistry analysis of 53 HER2+ BCs showed that trastuzumab-sensitive tumors expressed significantly higher levels of chemokines involved in immune cell recruitment, with higher infiltration of T cells and monocytes, and higher levels of PD-1 ligands than tumors that do not benefit from trastuzumab...
2019: Oncoimmunology
Huihui Qin, Jianmin Zeng, Hong Chen, Ling Deng, Li Su
Are we placing a bet by ourselves or has our DNA already made the decision for us? Previous research has suggested that some genes related to dopamine or serotonin can influence our non-bet-placing decision-making, but little is known about whether cannabinoid-related genes can impact how much people bet. To investigate this issue, we focused on rs1049353, a single-nucleotide polymorphism of the cannabinoid receptor 1 ( CNR1 ), because it is related to addictive behavior and reward processing. In this study ( N = 377), we used a modified Cambridge gambling task to test the effect of rs1049353 polymorphism on how much people bet...
2018: Frontiers in Human Neuroscience
Monica Ceccon, Mario Mauri, Luca Massimino, Giovanni Giudici, Rocco Piazza, Carlo Gambacorti-Passerini, Luca Mologni
Targeted therapy is an effective, rational, and safe approach to solid and hematological tumors treatment. Unfortunately, a significant fraction of patients treated with tyrosine kinase inhibitors (TKI) relapses mainly because of gene amplification, mutations, or other bypass mechanisms. Recently a growing number of papers showed how, in some cases, resistance due to oncogene overexpression may be associated with drug addiction: cells able to proliferate in the presence of high TKI doses become also TKI dependent, undergoing cellular stress, and apoptosis/death upon drug withdrawal...
December 12, 2018: Cancers
Sahika Cingir Koker, Ermira Jahja, Huma Shehwana, Ayse Gokce Keskus, Ozlen Konu
Cholinergic Receptor Nicotinic Alpha 5 (CHRNA5) is an important susceptibility locus for nicotine addiction and lung cancer. Depletion of CHRNA5 has been associated with reduced cell viability, increased apoptosis and alterations in cellular motility in different cancers yet not in breast cancer. Herein we first showed the expression of CHRNA5 was variable and positively correlated with the fraction of total genomic alterations in breast cancer cell lines and tumors indicating its potential role in DNA damage response (DDR)...
2018: PloS One
Meng-Li Zheng, Nai-Kang Zhou, Cheng-Hua Luo
Background: The exact molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still unknown, and the prognosis of ESCC has not been significantly improved. Objective: To understand the molecular mechanism of ESCC, differential modules (DMs) and key genes were identified through conducting analysis on the differential co-expression network (DCN) based on the gene expression profiles of ESCC and protein-protein interaction (PPI) data. Materials and Methods: First, gene expression profiles of ESCC and PPI data recruiting and preprocessing were conducted; then, a DCN was constructed based on the gene co-expression and gene differential expression in ESCC; in the following, candidate DMs were mined from DCN through a systemic module searching strategy, and significance analysis was performed on candidate DMs to identify DMs; moreover, significant genes contained in the DMs were analyzed to identify the underlying biomarkers for ESCC...
December 2018: Journal of Cancer Research and Therapeutics
Fiamma Mantovani, Licio Collavin, Giannino Del Sal
Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart...
December 11, 2018: Cell Death and Differentiation
Paula Bustamante, Jonathan R Iredell
Objectives: To identify toxin-antitoxin (TA)-like plasmid stability loci on IncX4 plasmids. Methods: TA-like loci were identified bioinformatically and their contribution to stability of the IncX4 plasmid pJIE143 was tested in optimal growth conditions in vitro. The conservation of the TA-like loci identified was analysed within an updated IncX plasmid database. Results: A novel TA-like locus, tsxAB, was identified on the IncX4 plasmid pJIE143, carrying the important plasmid-borne antibiotic resistance gene blaCTX-M-15...
December 6, 2018: Journal of Antimicrobial Chemotherapy
Wei Meng, Jiajia Wang, Baocheng Wang, Fang Liu, Meng Li, Yang Zhao, Chenran Zhang, Qifeng Li, Juxiang Chen, Liye Zhang, Yujie Tang, Jie Ma
Background: Glioblastoma multiforme (GBM) remains to be one of the top lethal cancer types for adult to date. Current GBM therapies suffer greatly from the highly heterogeneous and adaptable nature of GBM cells, indicating an urgent need of alternative therapeutic options. In this study, we focused on identifying novel epigenetic targeted strategy against GBM. Methods: A collection of epigenetic modulating small molecules were subjected to anti-GBM screening and the inhibitory effect of identified agent was validated both in vitro and in vivo...
2018: Cancer Management and Research
Raphael Saffroy, Genevieve Lafaye, Christophe Desterke, Elisabeth Ortiz-Tudela, Ammar Amirouche, Pasquale Innominato, Patrick Pham, Amine Benyamina, Antoinette Lemoine
Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes...
December 11, 2018: Chronobiology International
Farideh Jalali Mashayekhi, Mozhgan Rasti, Zahra Khoshdel, Ali Akbar Owji
BACKGROUND: Epigenetic mechanisms such as histone modifications may be involved in the structural and behavioral changes associated with addiction. We studied whether morphine-induced changes in mRNA levels of the catecholamine biosynthesis enzyme, tyrosine hydroxylase (TH), are associated with histone modifications around the promoter of this gene in the locus coeruleus (LC) and ventral tegmental area (VTA) of rats. METHODS: Dependence was induced in rats by intraperitoneal injections of morphine for 11 days...
December 5, 2018: European Addiction Research
Ana Canseco-Alba, Norman Schanz, Branden Sanabria, Juan Zhao, Zhicheng Lin, Qing-Rong Liu, Emmanuel S Onaivi
Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Here we report on the behavioral effects of psychostimulants in DAT-Cnr2 conditional knockout (cKO) mice with selective deletion of type 2 cannabinoid receptors in dopamine neurons...
November 30, 2018: Behavioural Brain Research
Sarah L Pollema-Mays, Maria Virginia Centeno, Zheng Chang, A Vania Apakarian, Marco Martina
The neuropathic pain phenotype is the consequence of functional and morphological reorganization of the PNS and CNS. This reorganization includes DRGs and the spinal cord, and extends to multiple supraspinal areas including the limbic and reward systems. Several recent papers show that acute manipulation of cortical and subcortical brain areas causally correlates with the cognitive, emotional and sensory components of neuropathic pain, yet mechanisms responsible for pain chronification remain largely unknown...
November 29, 2018: Neuroscience Letters
Bin Lu, Olaf Klingbeil, Yusuke Tarumoto, Tim D D Somerville, Yu-Han Huang, Yiliang Wei, Dorothy C Wai, Jason K K Low, Joseph P Milazzo, Xiaoli S Wu, Zhendong Cao, Xiaomei Yan, Osama E Demerdash, Gang Huang, Joel P Mackay, Justin B Kinney, Junwei Shi, Christopher R Vakoc
The Mixed Lineage Leukemia gene (MLL) is altered in leukemia by chromosomal translocations to produce oncoproteins composed of the MLL N-terminus fused to the C-terminus of a partner protein. Here, we used domain-focused CRISPR screening to identify ZFP64 as an essential transcription factor in MLL-rearranged leukemia. We show that the critical function of ZFP64 in leukemia is to maintain MLL expression via binding to the MLL promoter, which is the most enriched location of ZFP64 occupancy in the human genome...
November 15, 2018: Cancer Cell
Amna Zehra, Elsa Lindgren, Corinde E Wiers, Clara Freeman, Gregg Miller, Veronica Ramirez, Ehsan Shokri-Kojori, Gene-Jack Wang, Lori Talagala, Dardo Tomasi, Nora D Volkow
Numerous studies have documented cognitive impairments in multiple domains in patients with an alcohol use disorder (AUD), including perceptuomotor, executive, and visuospatial functions. Although the neural underpinnings of cognitive deficits in AUD have been studied extensively, the neural basis of attention deficits in AUD remains relatively unexplored. Here, we investigated neural responses to a visual attention task (VAT) in 19 recently abstinent patients with AUD and 23 healthy control participants (HC) using functional MRI (fMRI)...
November 24, 2018: Drug and Alcohol Dependence
Bo Xiang, Bao-Zhu Yang, Hang Zhou, Henry Kranzler, Joel Gelernter
Alcohol dependence (AD) and nicotine dependence (ND) co-occur frequently (AD+ND). We integrated SNP-based, gene-based, and protein-protein interaction network analyses to identify shared risk genes or gene subnetworks for AD+ND in African Americans (AAs, N = 2,094) and European Americans (EAs, N = 1,207). The DSM-IV criterion counts for AD and ND were modeled as two dependent variables in a multivariate linear mixed model, and analyzed separately for the two populations. The most significant SNP was rs6579845 in EAs (p < 1...
November 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
James M Kasper, Ashley E Smith, Jonathan D Hommel
Cocaine use disorder (CUD) is characterized by repeated cycles of drug seeking and drug taking. Currently, there are no available pharmacotherapies to treat CUD, partially due to a lack of a mechanistic understanding of cocaine-evoked alterations in the brain that drive drug-related behaviors. Repeated cocaine use alters expression of numerous genes in addiction-associated areas of the brain and these alterations are in part driven by inter-subject genetic variability. Recent findings have shown the neuropeptide neuromedin U (NMU) and its receptor NMU receptor 2 (NMUR2) decrease drug-related behaviors, but it is unknown if substances of abuse alter NMU or NMUR2 expression...
2018: Frontiers in Behavioral Neuroscience
Emily Petruccelli, Michael Feyder, Nicolas Ledru, Yanabah Jaques, Edward Anderson, Karla R Kaun
Drugs of abuse, like alcohol, modulate gene expression in reward circuits and consequently alter behavior. However, the in vivo cellular mechanisms through which alcohol induces lasting transcriptional changes are unclear. We show that Drosophila Notch/Su(H) signaling and the secreted fibrinogen-related protein Scabrous in mushroom body (MB) memory circuitry are important for the enduring preference of cues associated with alcohol's rewarding properties. Alcohol exposure affects Notch responsivity in the adult MB and alters Su(H) targeting at the dopamine-2-like receptor (Dop2R)...
October 23, 2018: Neuron
V Echeverry-Alzate, K M Bühler, J Calleja-Conde, E Huertas, R Maldonado, F Rodríguez de Fonseca, C Santiago, F Gómez-Gallego, A Santos, E Giné, J A López-Moreno
RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation...
November 23, 2018: Psychopharmacology
Benedetta Donati, Eugenia Lorenzini, Alessia Ciarrocchi
BRD4, member of the Bromodomain and Extraterminal (BET) protein family, is largely acknowledged in cancer for its role in super-enhancers (SEs) organization and oncogenes expression regulation. Inhibition of BRD4 shortcuts the communication between SEs and target promoters with a subsequent cell-specific repression of oncogenes to which cancer cells are addicted and cell death. To date, this is the most credited mechanism of action of BET inhibitors, a class of small molecules targeting BET proteins which are currently in clinical trials in several cancer settings...
November 22, 2018: Molecular Cancer
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