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      Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects

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          Abstract

          (1) Background: Cancer is one of the leading causes of mortality worldwide. Radiotherapy and chemotherapy attempt to kill tumor cells by different mechanisms mediated by an intracellular increase of free radicals. However, free radicals can also increase in healthy cells and lead to oxidative stress, resulting in further damage to healthy tissues. Approaches to prevent or treat many of these side effects are limited. Ozone therapy can induce a controlled oxidative stress able to stimulate an adaptive antioxidant response in healthy tissue. This review describes the studies using ozone therapy to prevent and/or treat chemotherapy-induced toxicity, and how its effect is linked to a modification of free radicals and antioxidants. (2) Methods: This review encompasses a total of 13 peer-reviewed original articles (most of them with assessment of oxidative stress parameters) and some related works. It is mainly focused on four drugs: Cisplatin, Methotrexate, Doxorubicin, and Bleomycin. (3) Results: In experimental models and the few existing clinical studies, modulation of free radicals and antioxidants by ozone therapy was associated with decreased chemotherapy-induced toxicity. (4) Conclusions: The potential role of ozone therapy in the management of chemotherapy-induced toxicity merits further research. Randomized controlled trials are ongoing.

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          Most cited references72

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          NRF2 and the Hallmarks of Cancer

          The transcription factor NRF2 is the master regulator of the cellular antioxidant response. Though recognized originally as a target of chemopreventive compounds that help prevent cancer and other maladies, accumulating evidence has established the NRF2 pathway as a driver of cancer progression, metastasis, and resistance to therapy. Recent studies have identified new functions for NRF2 in the regulation of metabolism and other essential cellular functions, establishing NRF2 as a truly pleiotropic transcription factor. In this review, we explore the roles of NRF2 in the hallmarks of cancer, indicating both tumor suppressive and tumor-promoting effects.
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            Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.

            To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted. © 2014 by American Society of Clinical Oncology.
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              Preventing and Managing Toxicities of High-Dose Methotrexate

              High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury. This article provides comprehensive recommendations for prevention of toxicity from HDMTX, along with detailed treatment guidance to mitigate acute kidney injury and subsequent toxicity.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                26 November 2019
                December 2019
                : 8
                : 12
                : 588
                Affiliations
                [1 ]Research Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain; frodesp@ 123456gobiernodecanarias.org
                [2 ]Chronic Pain Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
                [3 ]Radiation Oncology Department, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
                [4 ]Universitary Institute for Research in Biomedicine and Health (IUIBS), Molecular and Translational Pharmacology Group, University of Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain; leandrofco.fernandez@ 123456ulpgc.es (L.F.-P.); norbesanrod@ 123456gmail.com (N.S.-R.)
                [5 ]Spanish Group of Clinical Research in Radiation Oncology (GICOR), 28290 Madrid, Spain
                [6 ]Medical Oncology Department, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, University of Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain; delvysra@ 123456yahoo.com
                [7 ]Scientific Advisor, Freelance, 60126 Ancona, Italy; gregorcuba@ 123456yahoo.it
                [8 ]Experimental Medicine and Surgery Unit of Hospital Gregorio Marañon and the Health Research Institute of Hospital Gregorio Marañon (IiSGM), 28007 Madrid, Spain; perollonsa@ 123456gmail.com
                [9 ]Medical Oncology Department, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain; dagubuj@ 123456gobiernodecanarias.org
                [10 ]Thoracic Surgery, Department of Surgery, King Faisal Specialist Hospital and Research Center, 12713 Riyadh, Saudi Arabia
                [11 ]College of Medicine, Department of Surgery, Alfaisal University, 11533 Riyadh, Saudi Arabia
                Author notes
                [* ]Correspondence: bernardinoclavo@ 123456gmail.com ; Tel.: +34-928-449-278
                Author information
                https://orcid.org/0000-0003-2522-1064
                https://orcid.org/0000-0003-1663-3673
                https://orcid.org/0000-0002-4469-1099
                https://orcid.org/0000-0002-5623-9315
                https://orcid.org/0000-0001-7802-465X
                Article
                antioxidants-08-00588
                10.3390/antiox8120588
                6943601
                31779159
                4bb401f4-d0f8-404b-8579-fa0f2028ea97
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 October 2019
                : 23 November 2019
                Categories
                Review

                antioxidants,bleomycin,cancer treatment,chemotherapy-induced toxicity,cisplatin,doxorubicin,free radicals,methotrexate,oxidative stress,ozone therapy

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