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Peripheral neurotoxicity

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https://www.readbyqxmd.com/read/29218692/euro-b-o-s-s-a-european-study-on-chemotherapy-in-bone-sarcoma-patients-aged-over-40-outcome-in-primary-high-grade-osteosarcoma
#1
Stefano Ferrari, Stefan S Bielack, Sigbjørn Smeland, Alessandra Longhi, Gerlinde Egerer, Kirsten Sundby Hall, Davide Donati, Matthias Kevric, Otte Brosjö, Alessandro Comandone, Mathias Werner, Odd Monge, Emanuela Palmerini, Wolfgang E Berdel, Bodil Bjerkehagen, Anna Paioli, Sylvie Lorenzen, Mikael Eriksson, Marco Gambarotti, Per-Ulf Tunn, Nina L Jebsen, Marilena Cesari, Thekla von Kalle, Virginia Ferraresi, Rudolf Schwarz, Rossella Bertulli, Anne-Katrin Kasparek, Giovanni Grignani, Fatime Krasniqi, Benjamin Sorg, Stefanie Hecker-Nolting, Piero Picci, Peter Reichardt
INTRODUCTION: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. METHODS: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study...
December 5, 2017: Tumori
https://www.readbyqxmd.com/read/29210293/phosphatidylcholine-attenuated-docetaxel-induced-peripheral-neurotoxicity-in-rats
#2
Sung Tae Kim, Eun Jung Kyung, Jung Sook Suh, Ho Sung Lee, Jun Ho Lee, Soo In Chae, Eon Sub Park, Yoon Hee Chung, Jinhyung Bae, Tae Jin Lee, Won Mo Lee, Uy Dong Sohn, Ji Hoon Jeong
Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold...
December 6, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29205357/hexokinase-2-dependent-hyperglycolysis-driving-microglial-activation-contributes-to-ischemic-brain-injury
#3
Yuan Li, Bingzheng Lu, Longxiang Sheng, Zhu Zhu, Hongjiaqi Sun, Yuwei Zhou, Yang Yang, Dongdong Xue, Wenli Chen, Xuyan Tian, Yun Du, Min Yan, Wenbo Zhu, Fan Xing, Kai Li, Suizhen Lin, Pengxin Qiu, Xingwen Su, Yijun Huang, Guangmei Yan, Wei Yin
Hyperglycolysis, observed within the penumbra zone during brain ischemia, was shown to be detrimental for tissue survival due to lactate accumulation and reactive oxygen species (ROS) overproduction in clinical and experimental settings. Recently, mounting evidence suggests that glycolytic reprogramming and induced metabolic enzymes can fuel the activation of peripheral immune cells. However, the possible roles and details regarding hyperglycolysis in neuroinflammation during ischemia are relatively poorly understood...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29197621/inhibition-of-histone-deacetylase-6-hdac6-protects-against-vincristine-induced-peripheral-neuropathies-and-inhibits-tumor-growth
#4
Lawrence Van Helleputte, Mandy Kater, Dana P Cook, Caroline Eykens, Elisabeth Rossaert, Wanda Haeck, Tom Jaspers, Natasja Geens, Pieter Vanden Berghe, Conny Gysemans, Chantal Mathieu, Wim Robberecht, Philip Van Damme, Guido Cavaletti, Matthew Jarpe, Ludo Van Den Bosch
As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy...
November 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29191802/peripheral-neuropathy-induced-by-microtubule-targeted-chemotherapies-insights-into-acute-injury-and-long-term-recovery
#5
Krystyna M Wozniak, James J Vornov, Ying Wu, Ying Liu, Valentina A Carozzi, Virginia Rodriquez-Menendez, Elisa Ballarini, Paola Alberti, Eleonora Pozzi, Sara Semperboni, Brett M Cook, Bruce A Littlefield, Kenichi Nomoto, Krista Condon, Sean Eckley, Christopher DesJardins, Leslie Wilson, Mary Ann Jordan, Stuart C Feinstein, Guido Cavaletti, Michael Polydefkis, Barbara S Slusher
Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the anti-tubulin cancer drugs eribulin (ERIB), ixabepilone (IXA), paclitaxel (PACLI) or vinorelbine (VINO) at maximal tolerated doses...
November 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/29173832/the-psychometric-properties-of-the-turkish-version-of-the-chemotherapy-induced-peripheral-neuropathy-assessment-tool-cipnat
#6
Sevinç Kutlutürkan, Elif Sözeri Öztürk, Fatma Arıkan, Burcu Bayrak Kahraman, Keziban Özcan, Mürvet Artuk Uçar
PURPOSE: Chemotherapy-induced peripheral neuropathy is a common treatment-related adverse effect. It adversely affects the quality of life. Therefore, it is important to evaluate symptoms. The purpose of this study was to evaluate the validity and reliability of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool in Turkish patients. METHODS: A convenience sample of 327 patients, being treated with peripheral neurotoxic chemotherapeutic agents were asked to fill in the questionnaire...
December 2017: European Journal of Oncology Nursing: the Official Journal of European Oncology Nursing Society
https://www.readbyqxmd.com/read/29166931/elevated-lrrk2-autophosphorylation-in-brain-derived-and-peripheral-exosomes-in-lrrk2-mutation-carriers
#7
Shijie Wang, Zhiyong Liu, Tao Ye, Omar S Mabrouk, Tyler Maltbie, Jan Aasly, Andrew B West
Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease (PD). LRRK2 mutations increase LRRK2 kinase activities that may increase levels of LRRK2 autophosphorylation at serine 1292 (pS1292) and neurotoxicity in model systems. pS1292-LRRK2 protein can be packaged into exosomes and measured in biobanked urine. Herein we provide evidence that pS1292-LRRK2 protein is robustly expressed in cerebral spinal fluid (CSF) exosomes. In a novel cohort of Norwegian subjects with and without the G2019S-LRRK2 mutation, with and without PD, we quantified levels of pS1292-LRRK2, total LRRK2, and other exosome proteins in urine from 132 subjects and in CSF from 82 subjects...
November 22, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29163177/assessment-of-pharmacogenomic-panel-assay-for-prediction-of-taxane-toxicities-preliminary-results
#8
Raffaele Di Francia, Luigi Atripaldi, Salvo Di Martino, Carla Fierro, Tommaso Muto, Anna Crispo, Sabrina Rossetti, Gaetano Facchini, Massimiliano Berretta
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163145/insulin-like-growth-factor-1-and-neuroinflammation
#9
REVIEW
Jose L Labandeira-Garcia, Maria A Costa-Besada, Carmen M Labandeira, Begoña Villar-Cheda, Ana I Rodríguez-Perez
Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results on effects of IGF-1 in neuroinflammation...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29159762/p2y12-receptor-upregulation-in-satellite-glial-cells-is-involved-in-neuropathic-pain-induced-by-hiv-glycoprotein-120-and-2-3-dideoxycytidine
#10
Zhihua Yi, Lihui Xie, Congfa Zhou, Huilong Yuan, Shuai Ouyang, Zhi Fang, Shanhong Zhao, Tianyu Jia, Lifang Zou, Shouyu Wang, Yun Xue, Bing Wu, Yun Gao, Guilin Li, Shuangmei Liu, Hong Xu, Changshui Xu, Chunping Zhang, Shangdong Liang
The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine)...
November 20, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29154036/inhibition-of-cathepsin-l-alleviates-the-microglia-mediated-neuroinflammatory-responses-through-caspase-8-and-nf-%C3%AE%C2%BAb-pathways
#11
Shaoqing Xu, Hui Zhang, Xiaodong Yang, Yiwei Qian, Qin Xiao
Cathepsin L (CTSL) has been shown to participate in the microglia-mediated neuroinflammation. However, the role of CTSL in neuroinflammation remains to be elucidated. In this study, CTSL was found to be upregulated on lipopolysaccharide (LPS) stimulation. The neuroinflammatory responses on LPS stimulation were ameliorated by inhibition or deficiency of CTSL in vitro or vivo. Treatment with conditioned medium of activated BV2 cells in SH-SY5Y cells showed that CTSL inhibition reduced microglia-mediated neurotoxicity...
October 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29151170/the-function-of-the-cellular-prion-protein-in-health-and-disease
#12
REVIEW
Joel C Watts, Matthew E C Bourkas, Hamza Arshad
The essential role of the cellular prion protein (PrP(C)) in prion disorders such as Creutzfeldt-Jakob disease is well documented. Moreover, evidence is accumulating that PrP(C) may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer's disease. Although the pathological roles of PrP(C) have been thoroughly characterized, a general consensus on its physiological function within the brain has not yet been established. Knockout studies in various organisms, ranging from zebrafish to mice, have implicated PrP(C) in a diverse range of nervous system-related activities that include a key role in the maintenance of peripheral nerve myelination as well as a general ability to protect against neurotoxic stimuli...
November 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29145874/peripheral-immune-tolerance-alleviates-the-intracranial-lipopolysaccharide-injection-induced-neuroinflammation-and-protects-the-dopaminergic-neurons-from-neuroinflammation-related-neurotoxicity
#13
Yang Liu, Xin Xie, Li-Ping Xia, Hong Lv, Fan Lou, Yan Ren, Zhi-Yi He, Xiao-Guang Luo
BACKGROUND: Neuroinflammation plays a critical role in the onset and development of neurodegeneration disorders such as Parkinson's disease. The immune activities of the central nervous system are profoundly affected by peripheral immune activities. Immune tolerance refers to the unresponsiveness of the immune system to continuous or repeated stimulation to avoid excessive inflammation and unnecessary by-stander injury in the face of continuous antigen threat. It has been proved that the immune tolerance could suppress the development of various peripheral inflammation-related diseases...
November 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29144959/induction-of-innervation-by-encapsulated-adipocytes-with-engineered-vitamin-a-metabolism
#14
Qiwen Shen, Rumana Yasmeen, Jessica Marbourg, Lu Xu, Lianbo Yu, Paolo Fadda, Alan Flechtner, L James Lee, Phillip G Popovich, Ouliana Ziouzenkova
Innervation is a fundamental basis for function and survival of tissues. In the peripheral tissues, degenerative diseases create a neurotoxic metabolic milieu that either causes neurodegeneration or fails to sustain regenerative growth and reinnervation of injured/diseased tissues. Encapsulation of cells producing neurotrophic factors can augment axon growth and neuron survival; however, sustained innervation in vivo requires a combination of factors promoting axon growth and guidance pathway that are released in a tissue-specific context...
October 28, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29142460/efficacy-and-safety-of-duloxetine-in-chinese-breast-cancer-patients-with-paclitaxel-induced-peripheral-neuropathy
#15
Jiani Wang, Qing Li, Binghe Xu, Tongtong Zhang, Shanshan Chen, Yang Luo
Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy (PIPN) in Chinese breast cancer patients. Methods: A total of 102 patients with a median age of 50 (range, 25-60) years, treated in the Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, between November 2014 and January 2017 were finally enrolled...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#16
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29140155/persistent-prevention-of-oxaliplatin-induced-peripheral-neuropathy-using-calmangafodipir-pledox%C3%A2-a-placebo-controlled-randomised-phase-ii-study-pliant
#17
Bengt Glimelius, Nebojsa Manojlovic, Per Pfeiffer, Baadur Mosidze, Galina Kurteva, Mia Karlberg, Devalingam Mahalingam, Peter Buhl Jensen, Jan Kowalski, Marie Bengtson, Malin Nittve, Jacques Näsström
PURPOSE: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC). PATIENT AND METHODS: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible...
November 15, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29131611/synthesis-and-in-vitro-evaluation-of-monodisperse-amino-functional-polyester-dendrimers-with-rapid-degradability-and-antibacterial-properties
#18
Patrik Stenström, Erik Hjorth, Yuning Zhang, Oliver C J Andrén, Simon Guette-Marquet, Marianne Schultzberg, Michael Malkoch
Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents...
November 22, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#19
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29122704/comparing-the-different-response-of-pns-and-cns-injured-neurons-to-mesenchymal-stem-cell-treatment
#20
Marianna Monfrini, Maddalena Ravasi, Daniele Maggioni, Elisabetta Donzelli, Giovanni Tredici, Guido Cavaletti, Arianna Scuteri
Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking...
November 6, 2017: Molecular and Cellular Neurosciences
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