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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
#1
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/m(2), 5-fluorouracil bolus 400 mg/m(2), oxaliplatin 85 mg/m(2) and 5-fluorouracil 2400 mg/m(2) 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/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#2
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/29121279/clinical-and-preclinical-perspectives-on-chemotherapy-induced-peripheral-neuropathy-cipn-a-narrative-review
#3
S J L Flatters, P M Dougherty, L A Colvin
This review provides an update on the current clinical and preclinical understanding of chemotherapy induced peripheral neuropathy (CIPN). The overview of the clinical syndrome includes a review of its assessment, diagnosis and treatment. CIPN is caused by several widely-used chemotherapeutics including paclitaxel, oxaliplatin, bortezomib. Severe CIPN may require dose reduction, or cessation, of chemotherapy, impacting on patient survival. While CIPN often resolves after chemotherapy, around 30% of patients will have persistent problems, impacting on function and quality of life...
October 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29117336/clinical-and-genetic-predictors-of-paclitaxel-neurotoxicity-based-on-patient-versus-clinician-reported-incidence-and-severity-of-neurotoxicity-in-the-icon7-trial
#4
S B Park, J B Kwok, R Asher, C K Lee, P Beale, F Selle, M Friedlander
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel, with no reliable method to identify at-risk patients. We investigated the incidence and risk factors including genetic polymorphisms associated with the development of CIPN based on clinician and patient reporting of neuropathic symptoms. Patients and methods: Risk factors for the development of CIPN were examined in 454 patients treated with paclitaxel/carboplatin from the International Collaboration on Ovarian Neoplasms 7 (ICON7) trial...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29084244/trpa1-activation-in-peripheral-sensory-neurons-underlies-the-ionic-basis-of-pain-hypersensitivity-in-response-to-vinca-alkaloids
#5
Nina Boiko, Geraldo Medrano, Elizabeth Montano, Nan Jiang, Claire R Williams, Ngonidzashe B Madungwe, Jean C Bopassa, Charles C Kim, Jay Z Parrish, Kenneth M Hargreaves, James D Stockand, Benjamin A Eaton
Chemotherapy induced peripheral neuropathy (CIPN), a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described...
2017: PloS One
https://www.readbyqxmd.com/read/29064553/n-acetylcysteine-versus-progesterone-on-the-cisplatin-induced-peripheral-neurotoxicity
#6
Sherif Mohamed Zaki, Enas Mohamed Ahmed, Ahmed Galal Motawie, Sheeren Abdel Fattah
BACKGROUND AND AIMS: Cisplatin-induced peripheral nerve neurotoxicity (CIPN) is the main obstacle in cisplatin treatment. The aim of this study was to compare the modulatory effects of N-acetylcysteine (NAC) and progesterone on CIPN; up to knowledge, the protective effect of the progesterone on the CIPN is scarce in the literature. METHODS: 24 rats were divided into four groups: control, cisplatin-treated, concomitant cisplatin and NAC, and concomitant cisplatin and progesterone-treated...
October 24, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/29055716/attenuation-of-mechanical-pain-hypersensitivity-by-treatment-with-peptide5-a-connexin-43-mimetic-peptide-involves-inhibition-of-nlrp3-inflammasome-in-nerve-injured-mice
#7
Ryan S Tonkin, Callum Bowles, Chamini J Perera, Brooke A Keating, Preet G S Makker, Samuel S Duffy, Justin G Lees, Collin Tran, Anthony S Don, Thomas Fath, Lu Liu, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Catherine Gorrie, Gila Moalem-Taylor
Connexin43 (Cx43) hemichannels in spinal cord astrocytes are implicated in the maintenance of neuropathic pain following peripheral nerve injury. Peptide5 is a Cx43 mimetic peptide that blocks hemichannels. In this study, we investigated the effects of spinal delivery of Peptide5 on mechanical pain hypersensitivity in two mouse models of neuropathic pain, peripheral nerve injury and chemotherapy-induced peripheral neuropathy (CIPN). We demonstrated that 10days following a chronic constriction injury (CCI) of the sciatic nerve, Cx43 expression, co-localised predominantly with astrocytes, was increased in the ipsilateral L3-L5 lumbar spinal cord...
October 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29053122/-clinical-and-electromyography-characteristics-of-chemotherapy-induced-polyneuropathy
#8
N B Kholodova, Yu A Ponkratova, M V Sinkin
AIM: The study aimed at determining clinical and electromyography characteristics and developing the methods of CIPN treatment. MATERIAL AND METHODS: A clinical and electromyographic examinations and treatment of 30 with CIPN symptoms developed after polychemotherapy were performed. The authors developed treatment schemes included allopathic, homeopathic drugs, hydrotherapy and pharmacopuncture. RESULTS AND CONCLUSION: Most of the patients were diagnosed with axonal polyneuropathy with affection of long nerves of the limbs, some patients had a combination of axonopathy with myelopathy...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29051087/triggering-receptor-expressed-on-myeloid-cells-2-trem2-dependent-microglial-activation-promotes-cisplatin-induced-peripheral-neuropathy-in-mice
#9
Lang-Yue Hu, Yang-Zhou, Wen-Qiang Cui, Xue-Ming Hu, Li-Xia Du, Wen-Li Mi, Yu-Xia Chu, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a "glove-and-stocking" distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs)...
October 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29042416/nicotine-prevents-and-reverses-paclitaxel-induced-mechanical-allodynia-in-a-mouse-model-of-cipn
#10
S Lauren Kyte, Wisam Toma, Deniz Bagdas, Julie A Meade, Lesley D Schurman, Aron H Lichtman, Zhi-Jian Chen, Egidio Del Fabbro, Xianjun Fang, John W Bigbee, M Imad Damaj, David A Gewirtz
Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate if nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the anti-tumor properties of paclitaxel...
October 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29042161/kinematic-evaluation-for-impairment-of-skilled-hand-function-in-chemotherapy-induced-peripheral-neuropathy
#11
Michihiro Osumi, Masahiko Sumitani, Hiroaki Abe, Yuko Otake, Shin-Ichiro Kumagaya, Shu Morioka
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) usually affects both sensory and motor function of hands and feet, resulting in impaired skilled hand function (e.g., typing a keyboard). However, quantitative and objective evaluations for this condition have not been established. PURPOSE OF THE STUDY: We evaluated skilled hand function using a kinematic analysis and investigated relationships among hand kinematic function and the clinical sensory and motor features of CIPN...
October 14, 2017: Journal of Hand Therapy: Official Journal of the American Society of Hand Therapists
https://www.readbyqxmd.com/read/29024661/paclitaxel-reduces-axonal-bclw-to-initiate-ip3r1-dependent-axon-degeneration
#12
Sarah E Pease-Raissi, Maria F Pazyra-Murphy, Yihang Li, Franziska Wachter, Yusuke Fukuda, Sara J Fenstermacher, Lauren A Barclay, Gregory H Bird, Loren D Walensky, Rosalind A Segal
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments. Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering IP3 receptor phosphorylation and intracellular calcium flux, and activating calcium-dependent calpain proteases...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28983799/b-vitamin-complex-and-chemotherapy-induced-peripheral-neuropathy
#13
REVIEW
Janet Schloss, Maree Colosimo
PURPOSE OF REVIEW: The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. RECENT FINDINGS: One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B6 and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B3 on paclitaxel administration with positive results...
October 5, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28963591/eight-week-multimodal-exercise-counteracts-a-progress-of-chemotherapy-induced-peripheral-neuropathy-and-improves-balance-and-strength-in-metastasized-colorectal-cancer-patients-a-randomized-controlled-trial
#14
Philipp Zimmer, Sina Trebing, Ursula Timmers-Trebing, Alexander Schenk, Rainer Paust, Wilhelm Bloch, Roland Rudolph, Fiona Streckmann, Freerk T Baumann
PURPOSES: Physical activity is supposed to decrease mortality of colorectal cancer (CRC) and is suggested to reduce side-effects of the disease and its treatment. However, the knowledge about the influence of exercise interventions on patients suffering from CRC and metastasized CRC (mCRC) is still sparse. One frequently observed side effect in mCRC is chemotherapy-induced peripheral neuropathy (CIPN). This randomized controlled trial investigated the influence of a supervised exercise program on CIPN in mCRC...
September 30, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28962077/the-flavonoid-6-methoxyflavone-allays-cisplatin-induced-neuropathic-allodynia-and-hypoalgesia
#15
Muhammad Shahid, Fazal Subhan, Nisar Ahmad, Robert D E Sewell
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side-effect of several commonly used chemotherapeutic agents (such as cisplatin) that profoundly impairs patient quality of life. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful in this condition. Flavonoids are found ubiquitously in fruits and vegetables and exert a multiplicity of beneficial effects. In this study, the antinociceptive activity of 6-methoxyflavone (6-MF) was investigated and evaluated in comparison with gabapentin in a rat model of CIPN...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28925884/prevention-and-treatment-for-chemotherapy-induced-peripheral-neuropathy-therapies-based-on-cipn-mechanisms
#16
Lang-Yue Hu, Wen-Li Mi, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory abnormities are common and the most suffering issues. The pathogenesis of CIPN has not been completely understood, and strategies for CIPN prevention and treatment are still open problems for medicine. OBJECTIVES: The objective of this paper is to review the mechanism-based therapies against sensory abnormities in CIPN...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28912674/a-mechanistic-understanding-of-axon-degeneration-in-chemotherapy-induced-peripheral-neuropathy
#17
REVIEW
Yusuke Fukuda, Yihang Li, Rosalind A Segal
Chemotherapeutic agents cause many short and long term toxic side effects to peripheral nervous system (PNS) that drastically alter quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to thermal or mechanical stimuli. This adverse side effect often requires a reduction in chemotherapy dosage or even discontinuation of treatment...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28868935/risk-reduction-and-treatment-of-chemotherapy-induced-peripheral-neuropathy
#18
REVIEW
Marios Bakogeorgos, Vassilis Georgoulias
Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years...
November 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28865678/gabapentin-and-its-salicylaldehyde-derivative-alleviate-allodynia-and-hypoalgesia-in-a-cisplatin-induced-neuropathic-pain-model
#19
Nisar Ahmad, Fazal Subhan, Nazar Ul Islam, Muhammad Shahid, Faiz Ur Rahman, Robert D E Sewell
Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. In this study, a gabapentin-salicylaldehyde derivative [gabapentsal (GPS)] was synthesized and evaluated to explore any potential benefit in comparison with GBP in a rat model of CIPN...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28843493/utilization-of-ipsc-derived-human-neurons-for-high-throughput-drug-induced-peripheral-neuropathy-screening
#20
Payal Rana, Gregory Luerman, Dietmar Hess, Elizabeth Rubitski, Karissa Adkins, Christopher Somps
As the number of cancer survivors continues to grow, awareness of long-term toxicities and impact on quality of life after chemotherapy treatment in cancer survivors has intensified. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of modern chemotherapy. Animal models are used to study peripheral neuropathy and predict human risk; however, such models are labor-intensive and limited translatability between species has become a major challenge. Moreover, the mechanisms underlying CIPN have not been precisely determined and few human neuronal models to study CIPN exist...
December 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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