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https://www.readbyqxmd.com/read/28735026/regulated-viral-bdnf-delivery-in-combination-with-schwann-cells-promotes-axonal-regeneration-through-capillary-alginate-hydrogels-after-spinal-cord-injury
#1
Shengwen Liu, Beatrice Sandner, Thomas Schackel, LaShae Nicholson, Abdelwahed Chtarto, Liliane Tenenbaum, Radhika Puttagunta, Rainer Müller, Norbert Weidner, Armin Blesch
Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally...
July 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28734937/longitudinal-examination-of-resilience-after-traumatic-brain-injury-a-traumatic-brain-injury-model-systems-study
#2
Jennifer H Marwitz, Adam P Sima, Jeffrey S Kreutzer, Laura E Dreer, Thomas F Bergquist, Ross Zafonte, Douglas Johnson-Greene, Elizabeth R Felix
OBJECTIVE: To evaluate the trajectory of resilience during the first year following a moderate-severe TBI, factors associated with resilience at 3, 6 and 12-months post-injury, and changing relationships over time between resilience and other factors. DESIGN: Longitudinal analysis of an observational cohort. SETTING: Five inpatient rehabilitation centers. PARTICIPANTS: Patients with TBI (N = 195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3, 6, and 12-month follow-up...
July 19, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#3
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#4
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28733998/quiescent-oct4-neural-stem-cells-nscs-repopulate-ablated-glial-fibrillary-acidic-protein-nscs-in-the-adult-mouse-brain
#5
Rachel L Reeve, Samantha Z Yammine, Cindi M Morshead, Derek van der Kooy
Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP)(-) Oct4(+) cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP(+) NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months...
July 21, 2017: Stem Cells
https://www.readbyqxmd.com/read/28733520/the-ketogenic-diet-is-not-feasible-as-a-therapy-in-a-cd-1-nu-nu-mouse-model-of-renal-cell-carcinoma-with-features-of-stauffer-s-syndrome
#6
Silvia Vidali, Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Renaud Vatrinet, Andreas Koller, Felix Locker, Tricia Rutherford, Maura O'Donnell, Andrea Stöger-Kleiber, Bridget Lambert, Thomas Klaus Felder, Wolfgang Sperl, Barbara Kofler
The ketogenic diet (KD), a high-fat low-carbohydrate diet, has shown some efficacy in the treatment of certain types of tumors such as brain tumors and neuroblastoma. These tumors are characterized by the Warburg effect. Because renal cell carcinoma (RCC) presents similar energetic features as neuroblastoma, KD might also be effective in the treatment of RCC. To test this, we established xenografts with RCC 786-O cells in CD-1 nu/nu mice and then randomized them to a control diet or to KDs with different triglyceride contents...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733442/-89-zr-lumretuzumab-pet-imaging-before-and-during-her3-antibody-lumretuzumab-treatment-in-patients-with-solid-tumors
#7
Frederike Bensch, Laetitia E Lamberts, Michaël M Smeenk, Annelies Jorritsma-Smit, Marjolijn N Lub-de Hooge, Anton G T Terwisscha van Scheltinga, Johan R de Jong, Jourik A Gietema, Carolina P Schröder, Marlene Thomas, Wolfgang Jacob, Keelara Abiraj, Celine Adessi, Georgina Meneses-Lorente, Ian James, Martin Weisser, Adrienne H Brouwers, Elisabeth G de Vries
Purpose: We evaluated biodistribution and tumor targeting of (89)Zr-lumretuzumab before and during treatment with lumretuzumab, a human epidermal growth factor receptor 3 (HER3)-targeting monoclonal antibody. <p>Experimental design: 20 patients with histologically confirmed HER3-expressing tumors received (89)Zr-lumretuzumab and underwent Positron Emission Tomography (PET). In Part A, (89)Zr-lumretuzumab was given with additional, escalating doses of unlabeled lumretuzumab and scans were performed 2, 4 and 7 days postinjection to determine optimal imaging conditions...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#8
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729735/the-wnt-receptor-ryk-is-a-negative-regulator-of-mammalian-dendrite-morphogenesis
#9
Vanessa Lanoue, Michael Langford, Amanda White, Kai Sempert, Lily Fogg, Helen M Cooper
The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726571/primary-blast-causes-delayed-effects-without-cell-death-in-shell-encased-brain-cell-aggregates
#10
Thomas Sawyer, Yushan Wang, David V Ritzel, Tyson Josey, Mercy Villanueva, Cory Vair, Yanfeng Song, Yimin Shei, Steven Parks, Peggy Nelson, Grant Hennes, Lori McLaws, Changyan Fan
Previous work used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. This current study has utilized simulated air blast to expose aggregates in suspension and enclosed within a spherical shell, enabling the examination of a much more complex biomechanical insult. Culture medium-filled spheres were exposed to single pulse overpressures of 15-30 psi (6-7 msec duration) and measurements within the sphere at defined sites showed complex and spatially dependent pressure changes...
July 20, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#11
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#12
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724170/circulating-insulin-like-growth-factor-1-and-insulin-like-growth-factor-binding-protein-3-predict-three-months-outcome-after-ischemic-stroke
#13
Moritz Armbrust, Hans Worthmann, Reinhard Dengler, Helmut Schumacher, Ralf Lichtinghagen, Christoph Cyrill Eschenfelder, Matthias Endres, Martin Ebinger
Reports on neuroprotective effects of Insulin-like growth factor-1 (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) in ischemic brain tissue are inconsistent. The aim of this study was to determine if plasma levels of IGF-1 and IGFBP-3 in acute stroke patients are indicative of 3 months functional outcome. Plasma levels were measured via chemiluminescence immunoassay in heparin blood samples of patients included in the EARLY trial (NCT00562588). Plasma samples were drawn on admission and 8 days post-stroke...
July 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28723550/induced-pluripotent-stem-cell-derived-primitive-macrophages-provide-a-platform-for-modeling-tissue-resident-macrophage-differentiation-and-function
#14
Kazuyuki Takata, Tatsuya Kozaki, Christopher Zhe Wei Lee, Morgane Sonia Thion, Masayuki Otsuka, Shawn Lim, Kagistia Hana Utami, Kerem Fidan, Dong Shin Park, Benoit Malleret, Svetoslav Chakarov, Peter See, Donovan Low, Gillian Low, Marta Garcia-Miralles, Ruizhu Zeng, Jinqiu Zhang, Chi Ching Goh, Ahmet Gul, Sandra Hubert, Bernett Lee, Jinmiao Chen, Ivy Low, Nurhidaya Binte Shadan, Josephine Lum, Tay Seok Wei, Esther Mok, Shohei Kawanishi, Yoshihisa Kitamura, Anis Larbi, Michael Poidinger, Laurent Renia, Lai Guan Ng, Yochai Wolf, Steffen Jung, Tamer Önder, Evan Newell, Tara Huber, Eishi Ashihara, Sonia Garel, Mahmoud A Pouladi, Florent Ginhoux
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28721825/biomarkers-associated-with-stroke-risk-in-atrial-fibrillation
#15
Adam Ioannou, Nikolaos Papageorgiou, Debbie Falconer, Onkar Rehal, Emma Sewart, Effimia Zacharia, Konstantinos Toutouzas, Charalampos Vlachopoulos, Gerasimos Siasos, Constantinos Tsioufis, Dimitris Tousoulis
Atrial fibrillation is associated with increased risk for cardioembolic stroke. The risk of cardioembolism is not adequately reduced with the administration of oral anticoagulants, since a number of patients continue to experience thromboembolic events despite receiving anti-thrombotic treatment. Several biomarkers have been proposed to predict cardioembolic stroke in patients with atrial fibrillation. Some of them are already used in the clinical practice, such as D-Dimers, Troponin and brain natriuretic peptide...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28720534/tgf-%C3%AE-signaling-regulates-p-akt-levels-via-pp2a-during-diapause-entry-in-the-cotton-bollworm-helicoverpa-armigera
#16
Hai-Yin Li, Tao Wang, Yong-Pan Yang, Shao-Lei Geng, Wei-Hua Xu
Akt, which is a key kinase in the insulin signaling pathway, plays important roles in glucose metabolism, cell proliferation, transcription and cell migration. Our previous studies indicated that low insulin levels and high p-Akt levels are present in diapause-destined individuals. Here, we show that PI3K, which is upstream of Akt, is low in diapause-destined pupal brains but high in p-Akt levels, implying that p-Akt is modified by factors other than the insulin signaling pathway. Protein phosphatase 2A (PP2A), which is a key regulator in the TGF-β signaling pathway, can directly bind to and dephosphorylate Akt...
July 15, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28718326/cns-anticancer-drug-discovery-and-development-2016-conference-insights
#17
Victor A Levin, Lauren E Abrey, Timothy P Heffron, Peter J Tonge, Arvin C Dar, William A Weiss, James M Gallo
CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas...
July 18, 2017: CNS Oncology
https://www.readbyqxmd.com/read/28717762/epidermal-growth-factor-receptor-mutational-status-and-brain-metastases-in-non-small-cell-lung-cancer
#18
Vijaya Raj Bhatt, Sanyo P D'Souza, Lynette M Smith, Allison M Cushman-Vokoun, Vanita Noronha, Vivek Verma, Amit Joshi, Anuradha Chougule, Nirmala Jambhekar, Anne Kessinger, Alissa Marr, Vijay Patil, Sripad D Banavali, Apar Kishor Ganti, Kumar Prabhash
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables. METHODS: This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India)...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717667/haploinsufficiency-of-bcl11a-associated-with-cerebellar-abnormalities-in-2p15p16-1-deletion-syndrome
#19
Hiroko Shimbo, Takayuki Yokoi, Noriko Aida, Seiji Mizuno, Hiroshi Suzumura, Junichi Nagai, Kazumi Ida, Yumi Enomoto, Chihiro Hatano, Kenji Kurosawa
BACKGROUND: Chromosome 2p15p16.1 deletion syndrome is a rare genetic disorder characterized by intellectual disability (ID), neurodevelopmental delay, language delay, growth retardation, microcephaly, structural brain abnormalities, and dysmorphic features. More than 30 patients with 2p15p16.1 microdeletion syndrome have been reported in the literature. METHODS: Molecular analysis was performed using microarray-based comparative genomic hybridization (array CGH)...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28715593/physical-exercise-improves-total-antioxidant-capacity-and-gene-expression-in-rat-hippocampal-tissue
#20
F Franzoni, G Federighi, J Fusi, E Cerri, R Banducci, A Petrocchi, A Innocenti, C Pruneti, S Daniele, S Pellegrini, C Martini, R Scuri, F Galetta
Exercise may exert beneficial effects on cognitive functions and play an important role in the prevention of neurodegenerative diseases. Such effects seem to be mediated by changes in anti-oxidative status, but limited information is available on the nature of molecular pathways supporting the antioxidant effects of exercise in the brain. In this study 3-5-month-old male Wistar albino rats were subjected to three times/week moderate intensity exercise on a rodent treadmill for a period of 6 weeks. The tissue antioxidant activity towards various reactive oxygen species (ROS) was determined in the hippocampus...
July 1, 2017: Archives Italiennes de Biologie
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