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https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#1
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#2
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
March 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28316027/validation-of-dopamine-receptor-drd1-and-drd2-antibodies-using-receptor-deficient-mice
#3
Tamara Stojanovic, Michaela Orlova, Fernando J Sialana, Harald Höger, Stanislav Stuchlik, Ivan Milenkovic, Jana Aradska, Gert Lubec
Dopamine receptors 1 and 2 (DRD1, DRD2) are essential for signaling in the brain for a multitude of brain functions. Previous work using several antibodies against these receptors is abundant but only the minority of antibodies used have been validated and, therefore, the results of these studies remain uncertain. Herein, antibodies against DRD1 (Merck Millipore AB1765P, Santa Cruz Biotechnology sc-14001, Sigma Aldrich D2944, Alomone Labs ADR-001) and DRD2 (Abcam ab21218, Merck Millipore AB5084P, Santa Cruz Biotechnology sc-5303) have been tested using western blotting and immunohistochemistry on mouse striatum (wild type and corresponding knock-out mice) and when specific, they were further evaluated on rat and human striatum...
March 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28264500/geneanalytics-pathway-analysis-and-genetic-overlap-among-autism-spectrum-disorder-bipolar-disorder-and-schizophrenia
#4
Naveen S Khanzada, Merlin G Butler, Ann M Manzardo
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28264032/interactions-of-adolescent-social-experiences-and-dopamine-genes-to-predict-physical-intimate-partner-violence-perpetration
#5
Laura M Schwab-Reese, Edith A Parker, Corinne Peek-Asa
OBJECTIVES: We examined the interactions between three dopamine gene alleles (DAT1, DRD2, DRD4) previously associated with violent behavior and two components of the adolescent environment (exposure to violence, school social environment) to predict adulthood physical intimate partner violence (IPV) perpetration among white men and women. METHODS: We used data from Wave IV of the National Longitudinal Study of Adolescent to Adult Health, a cohort study following individuals from adolescence to adulthood...
2017: PloS One
https://www.readbyqxmd.com/read/28259861/-investigation-of-cntf-comt-ddr1-disc1-drd2-drd3-and-dtnbp1-candidate-genes-in-schizophrenia-results-from-the-hungarian-schizobank-consortium
#6
Judit Benkovits, Szilvia Magyarosi, Attila J Pulay, Zoltan Makkos, Aniko Egerhazi, Nora Balogh, Peter Almos, Istvan Liko, Hungarian Schizobank Consortium, Gyorgy Nemeth, Judit Maria Molnar, Laszlo Nagy, Janos M Rethelyi
Schizophrenia is a chronic, debilitating psychiatric disorder characterized by heterogeneous clinical symptoms. Although the pathogenesis of this disorder is poorly understood, several lines of evidence support the role of both common and rare genetic variants in the etiology of schizophrenia. Common variants, single nucleotide polymorphisms can be investigated by candidate gene association studies or genome-wide association studies, while rare variants, single nucleotide variants are assessable by means of candidate gene resequencing or whole-exome and genome sequencing using next generation sequencing...
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28259004/age-dependent-role-of-pre-and-perinatal-factors-in-interaction-with-genes-on-adhd-symptoms-across-adolescence
#7
Djûke M Brinksma, Pieter J Hoekstra, Barbara van den Hoofdakker, Annelies de Bildt, Jan K Buitelaar, Catharina A Hartman, Andrea Dietrich
Little is known about the effects of risk factors on attention-deficit/hyperactivity disorder (ADHD) symptom over time. Here, we longitudinally studied the role of candidate genes, pre- and perinatal factors, and their interactions on ADHD symptoms between ages 10 and 18 years. Subjects were part of the general population or clinic-referred cohort of the TRacking Adolescents' Individual Lives Survey (n = 1667). At mean ages of 11.1 (T1), 13.4 (T2), and 16.2 years (T3), ADHD symptoms were assessed with the Child Behavior Checklist...
February 21, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28257413/uncovering-precision-phenotype-biomarker-associations-in-traumatic-brain-injury-using-topological-data-analysis
#8
Jessica L Nielson, Shelly R Cooper, John K Yue, Marco D Sorani, Tomoo Inoue, Esther L Yuh, Pratik Mukherjee, Tanya C Petrossian, Jesse Paquette, Pek Y Lum, Gunnar E Carlsson, Mary J Vassar, Hester F Lingsma, Wayne A Gordon, Alex B Valadka, David O Okonkwo, Geoffrey T Manley, Adam R Ferguson
BACKGROUND: Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. METHODS AND FINDINGS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28241982/association-of-the-dopamine-d2-receptor-rs1800497-polymorphism-and-eating-behavior-in-chilean-children
#9
Ana M Obregón, Macarena Valladares, Gary Goldfield
OBJECTIVES: Studies have established a strong genetic component in eating behavior. The TaqI A1 polymorphism (rs1800497) has previously been associated with obesity and eating behavior. Additionally, this polymorphism has been associated with diminished dopamine D2 receptor (DRD2) density, higher body mass, and food reinforcement. The aim of this study was to evaluate the association between the DRD2 rs1800497 polymorphism and eating behavior in Chilean children. METHODS: This was a cross-sectional study in which we selected 258 children (44% girls, 56% boys; ages 8-14 y) with a wide variation in body mass index...
March 2017: Nutrition
https://www.readbyqxmd.com/read/28237458/inattention-and-reaction-time-variability-are-linked-to-ventromedial-prefrontal-volume-in-adolescents
#10
Matthew D Albaugh, Catherine Orr, Bader Chaarani, Robert R Althoff, Nicholas Allgaier, Nicholas D'Alberto, Kelsey Hudson, Scott Mackey, Philip A Spechler, Tobias Banaschewski, Rüdiger Brühl, Arun L W Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Robert Goodman, Penny Gowland, Yvonne Grimmer, Andreas Heinz, Viola Kappel, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Jani Penttila, Luise Poustka, Tomáš Paus, Michael N Smolka, Maren Struve, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, Alexandra S Potter
BACKGROUND: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28223337/functional-expression-of-dopamine-d2-receptor-is-regulated-by-tetraspanin-7-mediated-postendocytic-trafficking
#11
Seol-Ae Lee, Yeongjun Suh, Saebom Lee, Jaehoon Jeong, Soo Jeong Kim, So Jung Kim, Sang Ki Park
The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28222164/comt-and-drd2-ankk-1-gene-gene-interaction-account-for-resetting-of-gamma-neural-oscillations-to-auditory-stimulus-driven-attention
#12
Manuel Garcia-Garcia, Marc Via, Katarzyna Zarnowiec, Iria SanMiguel, Carles Escera, Immaculada C Clemente
Attention capture by potentially relevant environmental stimuli is critical for human survival, yet it varies considerably among individuals. A large series of studies has suggested that attention capture may depend on the cognitive balance between maintenance and manipulation of mental representations and the flexible switch between goal-directed representations and potentially relevant stimuli outside the focus of attention; a balance that seems modulated by a prefrontostriatal dopamine pathway. Here, we examined inter-individual differences in the cognitive control of attention through studying the effects of two single nucleotide polymorphisms regulating dopamine at the prefrontal cortex and the striatum (i...
2017: PloS One
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#13
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
February 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28202054/increase-of-urinary-malondialdehyde-level-by-bisphenol-a-exposure-a-longitudinal-panel-study
#14
Jin Hee Kim, Yun-Chul Hong
BACKGROUND: To verify oxidative stress as a possible mechanism that establishes a relationship between exposure to bisphenol A (BPA) and adverse health outcomes in the elderly Korean population, we evaluated the relation between visit-to-visit variations in urinary BPA and oxidative stress biomarker. METHODS: To assess the relation between BPA and urinary malondialdehyde (MDA) as an oxidative stress biomarker, we used a mixed effect model after controlling for age, sex, BMI, drinking status, exercise, urinary cotinine level, PM10 on lag day 2, and mean temperature and dew point on the day...
February 15, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28192769/disorganization-at-the-stage-of-schizophrenia-clinical-outcome-clinical-biological-study
#15
A Nestsiarovich, V Obyedkov, H Kandratsenka, M Siniauskaya, I Goloenko, N Waszkiewicz
BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality...
December 30, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28190415/a-potential-role-of-the-5-httlpr-polymorphism-in-self-reported-executive-functioning
#16
Margarita V Alfimova, Vera Golimbet, Tatyana Lezheiko, Galina Korovaitseva
Intense effort is directed toward searching for associations between genes and neuropsychological measures of executive functions. In contrast, the impact of genetic polymorphisms on self-rating of everyday executive functioning has not been investigated so far. This study was designed to test associations of self-reported executive functioning, measured with the Behavior Rating Inventory of Executive Function (BRIEF-A), with dopaminergic and serotoninergic genes in non-clinical population and to assess impact of neuropsychological and personality characteristics on these associations...
February 13, 2017: Spanish Journal of Psychology
https://www.readbyqxmd.com/read/28152448/high-frequency-of-the-drd2-ankk1-a1-allele-in-mexican-native-amerindians-and-mestizos-and-its-association-with-alcohol-consumption
#17
Arturo Panduro, Omar Ramos-Lopez, Octavio Campollo, Eloy Alfonso Zepeda-Carrillo, Karina Gonzalez-Aldaco, Rafael Torres-Valadez, Sonia Roman
BACKGROUND: Mexico has an ancient tradition of alcohol drinking influenced by genetic and sociocultural factors. This study aimed to determine the distribution of the DRD2/ANKK1 TaqIA polymorphism in Mexican populations and to analyze its association with heavy drinking. METHODS: In a cross-sectional and analytical study, 680 unrelated subjects including two Native Amerindians groups (87 Nahuas and 139 Huicholes), and two Mestizos groups (158 subjects from Tepic, Nayarit and 296 subjects from Guadalajara, Jalisco) were enrolled...
January 18, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28128287/striatal-neurons-expressing-d1-and-d2-receptors-are-morphologically-distinct-and-differently-affected-by-dopamine-denervation-in-mice
#18
D Gagnon, S Petryszyn, M G Sanchez, C Bories, J M Beaulieu, Y De Koninck, A Parent, M Parent
The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123032/role-of-dorsomedial-striatum-neuronal-ensembles-in-incubation-of-methamphetamine-craving-after-voluntary-abstinence
#19
Daniele Caprioli, Marco Venniro, Michelle Zhang, Jennifer M Bossert, Brandon L Warren, Bruce T Hope, Yavin Shaham
We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28120505/dopamine-receptor-type-2-drd2-and-somatostatin-receptor-type-2-sstr2-agonists-are-effective-in-inhibiting-proliferation-of-progenitor-stem-like-cells-isolated-from-nonfunctioning-pituitary-tumors
#20
E Peverelli, E Giardino, D Treppiedi, M Meregalli, M Belicchi, V Vaira, S Corbetta, C Verdelli, E Verrua, A L Serban, M Locatelli, G Carrabba, G Gaudenzi, E Malchiodi, L Cassinelli, A G Lania, S Ferrero, S Bosari, G Vitale, Y Torrente, A Spada, G Mantovani
The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins...
January 24, 2017: International Journal of Cancer. Journal International du Cancer
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