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https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#1
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28644490/potentiating-role-of-copper-on-spatial-memory-deficit-induced-by-beta-amyloid-and-evaluation-of-mitochondrial-function-markers-in-the-hippocampus-of-rats
#2
Ladan Behzadfar, Mohammad Abdollahi, Omid Sabzevari, Rohollah Hosseini, Ahmad Salimi, Parvaneh Naserzadeh, Mohammad Sharifzadeh, Jalal Pourahmad
Mounting evidence suggests that copper, a crucial element in normal brain function, plays an important role in the etiology of Alzheimer's disease, which is known as a neurodegenerative mitochondrial disorder. However, the precise mechanisms of its effects on cognitive and mitochondrial functions through the CNS have not been thoroughly recognized yet. In this study, we aimed to investigate the long-term (3-week) effects of copper sulfate (50, 100 and 200 mg kg(-1) day(-1)) exposure on learning and memory as well as on mitochondrial function in the hippocampus of rats in the presence and absence of beta amyloid (1 μg μl(-1) per side) intrahippocampally (IH)...
June 23, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28643358/maximizing-functional-axon-repair-in-the-injured-cns-lessons-from-neuronal-development
#3
Andrew Kaplan, Mardja Bueno, Luyang Hua, Alyson E Fournier
The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors, however it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviours. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system...
June 23, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28643038/prevalence-of-cerebral-cavernous-malformations-associated-with-developmental-venous-anomalies-increases-with-age
#4
Waleed Brinjikji, Ali El-Rida El-Masri, John T Wald, Kelly D Flemming, Giuseppe Lanzino
BACKGROUND AND PURPOSE: To test the hypothesis that the prevalence of cerebral cavernous malformation (CCM) associated with developmental venous anomalies (DVAs) increases with age, we studied the age-related prevalence of DVA-associated CCM among patients with DVAs. MATERIALS AND METHODS: Patients with DVAs on contrast-enhanced MRI exams performed over a 2-year period were included in this study. A single neuroradiologist reviewed all imaging exams for the presence of CCMs...
June 22, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28642887/dynamic-regulation-of-serum-aryl-hydrocarbon-receptor-agonists-in-ms
#5
Veit Rothhammer, Davis M Borucki, Maria Isabel Garcia Sanchez, Maria Antonietta Mazzola, Christopher C Hemond, Keren Regev, Anu Paul, Pia Kivisäkk, Rohit Bakshi, Guillermo Izquierdo, Howard L Weiner, Francisco J Quintana
OBJECTIVE: Several factors influence the clinical course of autoimmune inflammatory diseases such as MS and inflammatory bowel disease. Only recently, the complex interaction between the gut microbiome, dietary factors, and metabolism has started to be appreciated with regard to its potential to modulate acute and chronic inflammation. One of the molecular sensors that mediates the effects of these environmental signals on the immune response is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with key functions in immune cells...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28642339/establishment-of-a-novel-three-dimensional-primary-culture-model-for-hippocampal-neurogenesis
#6
Tatsuya Usui, Masashi Sakurai, Hideyoshi Kawasaki, Takashi Ohama, Hideyuki Yamawaki, Koichi Sato
New neurons are generated in the adult hippocampus throughout life and contribute to the functions of learning and memory. Nevertheless, the mechanisms by which disrupted neurogenesis regulates central nervous system (CNS) disorders are not fully understood. Here, we established a novel 3D culture system of hippocampal neurogenesis using air liquid interface (ALI) culture and Matrigel culture from mouse hippocampus tissues. After isolated mouse hippocampus tissue fragments were seeded into ALI wells and cultured in stemness-stimulated media containing Wnt, EGF, Noggin and R-spondin for 7 days, small spheres gradually appeared in the tissues...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28642179/analysis-of-outcomes-of-multidisciplinary-management-of-gliosarcoma-a-single-centre-study-2000-2013
#7
Abhinav Jain, Jason Correia, Patrick Schweder, Adele McMahon, Joseph Merola, Robert Aspoas
BACKGROUND: Gliosarcoma is a rare CNS tumour with a reported incidence of ∼2-8% of all gliomas. We reviewed the outcomes of patients treated at our institution over a 14-year period from 2000-2013 to characterize overall and progression free survival as well as to elucidate the additive effect of chemo-radiotherapy. METHODS: For the duration of 01/01/2000 to 31/12/2013, we retrospectively reviewed the clinical notes of all patients treated at our institution with a histopathological diagnosis of Gliosarcoma...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28642128/immunomodulation-of-parkinson-s-disease-using-mucuna-pruriens-mp
#8
REVIEW
Sachchida Nand Rai, Hareram Birla, Walia Zahra, Saumitra Sen Singh, Surya Pratap Singh
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2)...
June 19, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#9
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28641926/targeting-the-gm-csf-receptor-for-the-treatment-of-cns-autoimmunity
#10
Igal Ifergan, Todd S Davidson, Hania Kebir, Dan Xu, Daphne Palacios-Macapagal, Jennifer Cann, Jane M Rodgers, Zoe N Hunter, Camille L Pittet, Sara Beddow, Clare A Jones, Alexandre Prat, Matthew A Sleeman, Stephen D Miller
In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes...
June 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28641623/-analysis-of-clinical-characteristics-and-therapeutic-efficacy-in-61-adult-patients-with-acute-lymphoblastic-leukemia
#11
Xiao-Ping Zhang, Bao-An Chen, Zheng Ge, Ran Liu, Xiao-Yan Ma, Chong Gao
OBJECTIVE: To investigate the clinical characteristics and curative effect in 61 adult patients with acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 61 patients (≥15 years old) with ALL enrolled from January 2010 to December 2014 were studied retrospectively. The relationship between clinical characteristics and curative effect was analyzed. The univariate and multivariate analyses related with the overall survival (OS) and disease free survival (DFS) were conducted by using the method of COX regression analysis...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641606/solving-the-challenge-of-the-blood-brain-barrier-to-treat-infections-caused-by-trypanosoma-evansi-evaluation-of-nerolidol-loaded-nanospheres-in-mice
#12
Matheus D Baldissera, Carine F Souza, Aline A Boligon, Thirssa H Grando, Mariângela F DE Sá, Aleksandro S DA Silva, Lenita M Stefani, Bernardo Baldisserotto, Silvia G Monteiro
Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood-brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T...
June 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28641519/neural-stem-cells-and-human-induced-pluripotent-stem-cells-to-model-rare-cns-diseases
#13
Lidia De Filippis, Cristina Zalfa, Daniela Ferrari
Despite the great effort spent over the last decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them remain still unclear. In particular, the study of rare brain diseases is hurdled by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue has efficiently allowed to model several neurological diseases "in a dish" and has also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting...
June 15, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28641242/arrhythmia-mechanism-and-scaling-effect-on-the-spectral-properties-of-electroanatomical-maps-with-manifold-harmonics
#14
Margarita Sanroman-Junquera, Inmaculada Mora-Jimenez, Arcadi Garcia-Alberola, Antonio J Caamano, Beatriz Trenor, Jose Luis Rojo-Alvarez
Spatial and temporal processing of intracardiac electrograms provides relevant information to support the arrhythmia ablation during electrophysiological studies. Current Cardiac Navigation Systems (CNS) and Electrocardiographic Imaging (ECGI) build detailed three-dimensional electroanatomical maps (EAM), which represent the spatial anatomical distribution of bioelectrical features, such as activation time or voltage. We present a principled methodology for spectral analysis of both EAM geometry and bioelectrical feature in CNS or ECGI, including their spectral representation, cut-off frequency, or spatial sampling rate (SSR)...
June 15, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28640909/hiv-tat-regulates-macrophage-gene-expression-in-the-context-of-neuroaids
#15
Loreto Carvallo, Lillie Lopez, Jorge E Fajardo, Matias Jaureguiberry-Bravo, Andras Fiser, Joan W Berman
Despite the success of cART, greater than 50% of HIV infected people develop cognitive and motor deficits termed HIV-associated neurocognitive disorders (HAND). Macrophages are the major cell type infected in the CNS. Unlike for T cells, the virus does not kill macrophages and these long-lived cells may become HIV reservoirs in the brain. They produce cytokines/chemokines and viral proteins that promote inflammation and neuronal damage, playing a key role in HIV neuropathogenesis. HIV Tat is the transactivator of transcription that is essential for replication and transcriptional regulation of the virus and is the first protein to be produced after HIV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28640707/response-assessment-in-neuro-oncology-clinical-trials
#16
Patrick Y Wen, Susan M Chang, Martin J Van den Bent, Michael A Vogelbaum, David R Macdonald, Eudocia Q Lee
Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640704/immunotherapy-for-brain-tumors
#17
John H Sampson, Marcela V Maus, Carl H June
Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide a basis for new approaches of cellular therapies for tumors that involve the CNS. The ultimate success of immunotherapy in the CNS will require improved imaging technologies and methods for analysis of the tumor microenvironment in patients with GBM. It is likely that combinatorial approaches with targeted immunotherapies will be required to exploit the vulnerabilities of GBM and other brain tumors...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640701/primary-cns-lymphoma
#18
Christian Grommes, Lisa M DeAngelis
Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640700/cns-tumors-in-neurofibromatosis
#19
Jian Campian, David H Gutmann
Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640698/pediatric-gliomas-current-concepts-on-diagnosis-biology-and-clinical-management
#20
Dominik Sturm, Stefan M Pfister, David T W Jones
Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs)...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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