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https://www.readbyqxmd.com/read/28214420/prevention-of-radiotherapy-induced-neurocognitive-dysfunction-in-survivors-of-paediatric-brain-tumours-the-potential-role-of-modern-imaging-and-radiotherapy-techniques
#1
REVIEW
Thankamma Ajithkumar, Stephen Price, Gail Horan, Amos Burke, Sarah Jefferies
Neurocognitive dysfunction is the leading cause of reduced quality of life in long-term survivors of paediatric brain tumours. Radiotherapy is one of the main contributors to neurocognitive sequelae. Current approaches for prevention and reduction of neurocognitive dysfunction include avoidance of radiotherapy in young children and reduction of the radiotherapy dose and volume of brain irradiated. Substantial advances have been made in brain imaging, especially with functional imaging and fibre tracking with the use of diffusion tensor imaging...
February 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#2
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#3
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28213520/cholesterol-up-regulates-neuronal-g-protein-gated-inwardly-rectifying-potassium-girk-channel-activity-in-the-hippocampus
#4
Anna N Bukiya, Serdar Durdagi, Sergei Noskov, Avia Rosenhouse-Dantsker
Hypercholesterolemia is a well-known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#5
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213110/effect-of-chinese-herbal-medicine-on-stroke-patients-with-type-2-diabetes
#6
Fuu-Jen Tsai, Tsung-Jung Ho, Chi-Fung Cheng, Xiang Liu, Hsinyi Tsang, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Ju-Pi Li, Cheng-Wen Lin, Jaung-Geng Lin, Jung-Chun Lin, Chih-Chien Lin, Wen-Miin Liang, Ying-Ju Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Complications of type 2 diabetes (T2D) include stroke, which is a cerebrovascular disturbance characterized by reduced blood flow in the brain, leading to death or physical disability. Chinese herbal medicine (CHM) has been widely used in ancient China for the treatment of diabetes and stroke by supplementing Qi and activating blood circulation. AIM OF THE STUDY: This study aimed to investigate the frequencies and patterns of CHM treatment for stroke patients with T2D and the outcomes of long-term use in Taiwan...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28212927/patients-with-chronic-dizziness-following-traumatic-head-injury-typically-have-multiple-diagnoses-involving-combined-peripheral-and-central-vestibular-dysfunction
#7
Q Arshad, R E Roberts, H Ahmad, R Lobo, M Patel, T Ham, D J Sharp, B M Seemungal
OBJECTIVE: We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted...
February 7, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28212850/human-astrocytes-in-the-diseased-brain
#8
Elena Dossi, Flora Vasile, Nathalie Rouach
Astrocytes are key active elements of the brain that contribute to information processing. They not only provide neurons with metabolic and structural support, but also regulate neurogenesis and brain wiring. Furthermore, astrocytes modulate synaptic activity and plasticity in part by controlling the extracellular space volume, as well as ion and neurotransmitter homeostasis. These findings, together with the discovery that human astrocytes display contrasting characteristics with their rodent counterparts, point to a role for astrocytes in higher cognitive functions...
February 13, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28212737/gene-delivery-of-apoptin-derived-peptide-using-an-adeno-associated-virus-vector-inhibits-glioma-and-prolongs-animal-survival
#9
Xiuli Zhong, Hengyu Zhao, Songhe Liang, DanYang Zhou, Wenjia Zhang, Lijie Yuan
Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212619/brain-and-liver-pathology-amyloid-deposition-and-interferon-responses-among-older-hiv-positive-patients-in-the-late-haart-era
#10
Isaac H Solomon, Umberto De Girolami, Sukrutha Chettimada, Vikas Misra, Elyse J Singer, Dana Gabuzda
BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons...
February 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28212618/clinical-features-and-outcome-in-patients-with-osseomuscular-type-of-wilson-s-disease
#11
Hao Yu, Juan-Juan Xie, Yu-Chao Chen, Qin-Yun Dong, Yi Dong, Wang Ni, Zhi-Ying Wu
BACKGROUND: Wilson's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. METHODS: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated...
February 17, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28212563/progression-of-motor-deficits-in-glioma-bearing-mice-impact-of-cnf1-therapy-at-symptomatic-stages
#12
Eleonora Vannini, Federica Maltese, Francesco Olimpico, Alessia Fabbri, Mario Costa, Matteo Caleo, Laura Baroncelli
Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212562/overexpression-of-mir-29a-reduces-the-oncogenic-properties-of-glioblastoma-stem-cells-by-downregulating-quaking-gene-isoform-6
#13
Zhuo Xi, Ping Wang, Yixue Xue, Chao Shang, Xiaobai Liu, Jun Ma, Zhiqing Li, Zhen Li, Min Bao, Yunhui Liu
Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212546/precursor-n-cadherin-mediates-glial-cell-line-derived-neurotrophic-factor-promoted-human-malignant-glioma
#14
Ye Xiong, Liyun Liu, Shuang Zhu, Baole Zhang, Yuxia Qin, Ruiqin Yao, Hao Zhou, Dian Shuai Gao
As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#15
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212323/low-intensity-extracorporeal-shock-wave-therapy-enhances-brain-derived-neurotrophic-factor-expression-through-perk-atf4-signaling-pathway
#16
Bohan Wang, Hongxiu Ning, Amanda B Reed-Maldonado, Jun Zhou, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Lia Banie, Guiting Lin, Tom F Lue
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212278/the-effect-of-the-human-peptide-ghk-on-gene-expression-relevant-to-nervous-system-function-and-cognitive-decline
#17
Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions...
February 15, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#18
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211988/intrathecal-enzyme-replacement-therapy-reverses-cognitive-decline-in-mucopolysaccharidosis-type-i
#19
Igor Nestrasil, Elsa Shapiro, Alena Svatkova, Patricia Dickson, Agnes Chen, Amy Wakumoto, Alia Ahmed, Edward Stehel, Sarah McNeil, Curtis Gravance, Elizabeth Maher
Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211910/link-between-plasminogen-activator-inhibitor-1-and-cardiovascular-risk-in-chronic-hepatitis-c-after-viral-clearance
#20
Ming-Ling Chang, Yu-Sheng Lin, Li-Heng Pao, Hsin-Chih Huang, Cheng-Tang Chiu
The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy...
February 13, 2017: Scientific Reports
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