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      Radiation-Induced Cardiovascular Toxicity: Mechanisms, Prevention, and Treatment

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          Abstract

          Ionizing radiation is a highly effective treatment for a wide range of malignancies, yet the cardiovascular (CV) toxicity that can result from chest radiotherapy impairs the long-term health of cancer survivors and can be a limiting factor for its use. Despite over 100 years of successful clinical use, the mechanisms by which high-energy photons damage critical components within cells of the heart’s myocardium, pericardium, vasculature and valves remain unclear. Recent studies exploring the acute and chronic effects of radiation therapy on cardiac and vascular tissue have provided new insights into the development and progression of heart disease, including the identification and understanding of age- and complication-associated risk factors. However, key questions relating to the connection from upstream signaling to fibrotic changes remain. In addition, advances in the delivery of chest radiotherapy have helped to limit heart exposure and damage, but additional refinements to delivery techniques and cardioprotective therapeutics are absolutely necessary to reduce patient mortality and morbidity. Radiation therapy (RT)-driven CV toxicity remains a major issue for cancer survivors and more research is needed to define the precise mechanisms of toxicity. However, recent findings provide meaningful insights that may help improve patient outcomes.

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          Most cited references49

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          Melatonin as a natural ally against oxidative stress: a physicochemical examination.

          Oxidative stress has been proven to be related to the onset of a large number of health disorders. This chemical stress is triggered by an excess of free radicals, which are generated in cells because of a wide variety of exogenous and endogenous processes. Therefore, finding strategies for efficiently detoxifying free radicals has become a subject of a great interest, from both an academic and practical points of view. Melatonin is a ubiquitous and versatile molecule that exhibits most of the desirable characteristics of a good antioxidant. The amount of data gathered so far regarding the protective action of melatonin against oxidative stress is overwhelming. However, rather little is known concerning the chemical mechanisms involved in this activity. This review summarizes the current progress in understanding the physicochemical insights related to the free radical-scavenging activity of melatonin. Thus far, there is a general agreement that electron transfer and hydrogen transfer are the main mechanisms involved in the reactions of melatonin with free radicals. However, the relative importance of other mechanisms is also analyzed. The chemical nature of the reacting free radical also has an influence on the relative importance of the different mechanisms of these reactions. Therefore, this point has also been discussed in detail in the current review. Based on the available data, it is concluded that melatonin efficiently protects against oxidative stress by a variety of mechanisms. Moreover, it is proposed that even though it has been referred to as the chemical expression of darkness, perhaps it could also be referred to as the chemical light of health. © 2011 John Wiley & Sons A/S.
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            Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association.

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              Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics.

              It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage. While expression of the apoptotic protein machinery is nearly absent by adulthood, in young tissues its expression is driven by c-Myc, linking developmental growth to cell death. These differences may explain why pediatric cancer patients have a higher risk of developing treatment-associated toxicities.
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                Author and article information

                Journal
                Current Treatment Options in Cardiovascular Medicine
                Curr Treat Options Cardio Med
                Springer Nature
                1092-8464
                1534-3189
                April 2018
                March 20 2018
                April 2018
                : 20
                : 4
                Article
                10.1007/s11936-018-0627-x
                7325164
                29556748
                5ba664c3-a2ed-48a3-a9aa-c5053b0e214b
                © 2018

                http://www.springer.com/tdm

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