Modulation of cardiovascular toxicity in Hodgkin lymphoma: Potential role and mechanisms of aerobic training

Future Cardiology

Volumn 11, Issue 4, 2015, Pages 441-452

  Yu, Anthony F ^a   Jones, Lee W ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Aerobic training; Anthracycline; Cardiotoxicity; Exercise; Hodgkin lymphoma; Mediastinal radiotherapy

Indexed keywords

AEROBIC EXERCISE; CANCER SURVIVOR; CARDIOTOXICITY; FATIGUE; HEART FAILURE; HODGKIN DISEASE; HUMAN; ISCHEMIC HEART DISEASE; MODULATION; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME; VALVULAR HEART DISEASE; CARDIOVASCULAR DISEASES; EXERCISE; MORTALITY;

CARDIOTOXICITY; CARDIOVASCULAR DISEASES; EXERCISE; HODGKIN DISEASE; HUMANS;

EID: 84939443073     PISSN: 14796678     EISSN: 17448298     Source Type: Journal    
DOI: 10.2217/fca.15.29     Document Type: Review

References (113)

1. Howlader NNoone AM Krapcho M et al. (Eds). Seer Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD, USA. http://seer. cancer. gov/csr/1975-2012/
2. Diehl V, Thomas RK, Re D. Part II. Hodgkin's lymphoma-diagnosis and treatment. Lancet Oncol. 5(1), 19-26 (2004).
3. Herbst C, Rehan FA, Skoetz N et al. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma. Cochrane Database Syst. Rev. (2), CD007110 (2011).
4. Ng AK. Review of the cardiac long-term effects of therapy for Hodgkin lymphoma. Br. J. Haematol. 154(1), 23-31 (2011).
5. Aleman BM, Van Den Belt-Dusebout AW, De Bruin ML et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood 109(5), 1878-1886 (2007).
6. Castellino SM, Geiger AM, Mertens AC et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 117(6), 1806-1816 (2011).
7. Ng AK, Bernardo MP, Weller E et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger. J. Clin. Oncol. 20(8), 2101-2108 (2002).
8. Aleman BM, Van Den Belt-Dusebout AW, Klokman WJ, Van't Veer MB, Bartelink H, Van Leeuwen FE. Long-term cause-specific mortality of patients treated for Hodgkin's disease. J. Clin. Oncol. 21(18), 3431-3439 (2003).
9. Hancock SL, Tucker MA, Hoppe RT. Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA 270(16), 1949-1955 (1993).
10. Reulen RC, Winter DL, Frobisher C et al. Long-term cause-specific mortality among survivors of childhood cancer. JAMA 304(2), 172-179 (2010).
11. Hoppe BS, Flampouri S, Li Z, Mendenhall NP. Cardiac sparing with proton therapy in consolidative radiation therapy for Hodgkin lymphoma. Leuk. Lymphoma 51(8), 1559-1562 (2010).
12. Metzger ML, Weinstein HJ, Hudson MM et al. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA 307(24), 2609-2616 (2012).
13. Bartlett NL, Niedzwiecki D, Johnson JL et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann. Oncol. 18(6), 1071-1079 (2007).
14. Tebbi CK, London WB, Friedman D et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J. Clin. Oncol. 25(5), 493-500 (2007).
15. Johnson PW. Management of early-stage Hodgkin lymphoma: is there still a role for radiation? Hematology Am. Soc. Hematol. Educ. Program 2013, 400-405 (2013).
16. Swain SM, Whaley FS, Gerber MC et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J. Clin. Oncol. 15(4), 1318-1332 (1997).
17. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 100(2), 126-131 (1985).
18. Briones AM, Touyz RM. Moderate exercise decreases inflammation and oxidative stress in hypertension: but what are the mechanisms? Hypertension 54(6), 1206-1208 (2009).
19. Di Francescomarino S, Sciartilli A, Di Valerio V, Di Baldassarre A, Gallina S. The effect of physical exercise on endothelial function. Sports Med. 39(10), 797-812 (2009).
20. Van Nimwegen FA, Schaapveld M, Janus CPM et al. Cardiovascular diseases after Hodgkin lymphoma treatment: 35-year disease risk and sequence of events. J. Clin. Oncol. 32(Suppl. 5s), Abstract 9505 (2014).
21. Stewart JR, Fajardo LF, Gillette SM, Constine LS. Radiation injury to the heart. Int. J. Radiat. Oncol. Biol. Phys. 31(5), 1205-1211 (1995).
22. Lee CK, Aeppli D, Nierengarten ME. The need for long-term surveillance for patients treated with curative radiotherapy for Hodgkin's disease: University of Minnesota experience. Int. J. Radiat. Oncol. Biol. Phys. 48(1), 169-179 (2000).
23. Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin's disease in children and adolescents. J. Clin. Oncol. 11(7), 1208-1215 (1993).
24. Piovaccari G, Ferretti RM, Prati F et al. Cardiac disease after chest irradiation for Hodgkin's disease: incidence in 108 patients with long follow-up. Int. J. Cardiol. 49(1), 39-43 (1995).
25. Boivin JF, Hutchison GB, Lubin JH, Mauch P. Coronary artery disease mortality in patients treated for Hodgkin's disease. Cancer 69(5), 1241-1247 (1992).
26. Swerdlow AJ, Higgins CD, Smith P et al. Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J. Natl Cancer Inst. 99(3), 206-214 (2007).
27. Heidenreich PA, Schnittger I, Strauss HW et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J. Clin. Oncol. 25(1), 43-49 (2007).
28. Van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD et al. Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat. Rev. 37(5), 391-403 (2011).
29. Daniels LA, Krol AD, De Graaf MA et al. Screening for coronary artery disease after mediastinal irradiation in Hodgkin lymphoma survivors: Phase II study of indication and acceptancedagger. Ann. Oncol. 25(6), 1198-1203 (2014).
30. Heidenreich PA, Hancock SL, Lee BK, Mariscal CS, Schnittger I. Asymptomatic cardiac disease following mediastinal irradiation. J. Am. Coll. Cardiol. 42(4), 743-749 (2003).
31. Adams MJ, Lipsitz SR, Colan SD et al. Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy. J. Clin. Oncol. 22(15), 3139-3148 (2004).
32. Cutter DJ, Schaapveld M, Darby SC et al. Risk of valvular heart disease after treatment for Hodgkin lymphoma. J. Natl Cancer Inst. 107(4), pii: djv008 (2015).
33. Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am. J. Med. 62(2), 200-208 (1977).
34. Bristow MR, Mason JW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann. Intern. Med. 88(2), 168-175 (1978).
35. Tsai HR, Gjesdal O, Wethal T et al. Left ventricular function assessed by twodimensional speckle tracking echocardiography in long-term survivors of Hodgkin's lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy. Am. J. Cardiol. 107(3), 472-477 (2011).
36. Myrehaug S, Pintilie M, Tsang R et al. Cardiac morbidity following modern treatment for Hodgkin lymphoma: supra-additive cardiotoxicity of doxorubicin and radiation therapy. Leuk. Lymphoma 49(8), 1486-1493 (2008).
37. Mock V, Atkinson A, Barsevick A et al. NCCN practice guidelines for cancer-related fatigue. Oncology 14(11A), 151-161 (2000).
38. Loge JH, Abrahamsen AF, Ekeberg O, Kaasa S. Hodgkin's disease survivors more fatigued than the general population. J. Clin. Oncol. 17(1), 253-261 (1999).
39. Hjermstad MJ, Fossa SD, Oldervoll L, Holte H, Jacobsen AB, Loge JH. Fatigue in long-term Hodgkin's Disease survivors: a follow-up study. J. Clin. Oncol. 23(27), 6587-6595 (2005).
40. Van Leeuwen-Segarceanu EM, Dorresteijn LD, Pillen S, Biesma DH, Vogels OJ, Van Alfen N. Progressive muscle atrophy and weakness after treatment by mantle field radiotherapy in Hodgkin lymphoma survivors. Int. J. Radiat. Oncol. Biol. Phys. 82(2), 612-618 (2012).
41. Henry-Amar M, Joly F. Late complications after Hodgkin's disease. Ann. Oncol. 7(Suppl. 4), 115-126 (1996).
42. Bower JE. Cancer-related fatigue-mechanisms, risk factors, and treatments. Nat. Rev. Clin. Oncol. 11(10), 597-609 (2014).
43. Van Weert E, Hoekstra-Weebers J, Otter R, Postema K, Sanderman R, Van Der Schans C. Cancer-related fatigue: predictors and effects of rehabilitation. Oncologist 11(2), 184-196 (2006).
44. Courneya KS, Sellar CM, Stevinson C et al. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. J. Clin. Oncol. 27(27), 4605-4612 (2009).
45. Vallance JK, Courneya KS, Jones LW, Reiman T. Differences in quality of life between non-Hodgkin's lymphoma survivors meeting and not meeting public health exercise guidelines. Psychooncology 14(11), 979-991 (2005).
46. Page E, Assouline D, Durand C et al. Stage-related changes in functional capacity in Hodgkin's disease: assessment by cardiopulmonary exercise testing before initiation of treatment. Ann. Hematol. 85(12), 857-861 (2006).
47. Vermaete N, Wolter P, Verhoef G, Gosselink R. Physical activity and physical fitness in lymphoma patients before, during, and after chemotherapy: a prospective longitudinal study. Ann. Hematol. 93(3), 411-424 (2014).
48. Groarke JD, Tanguturi VK, Hainer J et al. Abnormal exercise response in long-term survivors of Hodgkin lymphoma treated with thoracic irradiation. JACC 65(6), 573-583 (2015).
49. Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW. Coronary heart-disease and physical activity of work. Lancet 265(6796), 1111-1120; concl (1953).
50. Nocon M, Hiemann T, Muller-Riemenschneider F, Thalau F, Roll S, Willich SN. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur. J. Cardiovasc. Prev. Rehabil. 15(3), 239-246 (2008).
51. Wendel-Vos GC, Schuit AJ, Feskens EJ et al. Physical activity and stroke. A meta-analysis of observational data. Int. J. Epidemiol. 33(4), 787-798 (2004).
52. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann. Intern. Med. 136(7), 493-503 (2002).
53. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 325(3), 147-152 (1991).
54. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ 174(6), 801-809 (2006).
55. Sesso HD, Paffenbarger RS Jr, Lee IM. Physical activity and coronary heart disease in men: The Harvard Alumni Health Study. Circulation 102(9), 975-980 (2000).
56. Lee IM, Sesso HD, Oguma Y, Paffenbarger RS Jr. Relative intensity of physical activity and risk of coronary heart disease. Circulation 107(8), 1110-1116 (2003).
57. Sattelmair J, Pertman J, Ding EL, Kohl HW 3rd, Haskell W, Lee IM. Dose response between physical activity and risk of coronary heart disease: a meta-analysis. Circulation 124(7), 789-795 (2011).
58. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N. Engl. J. Med. 346(11), 793-801 (2002).
59. Kokkinos P, Faselis C, Myers J, Sui X, Zhang J, Blair SN. Age-specific exercise capacity threshold for mortality risk assessment in male veterans. Circulation 130(8), 653-658 (2014).
60. Blair SN, Kohl HW 3rd, Paffenbarger RS Jr, Clark DG, Cooper KH, Gibbons LW. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA 262(17), 2395-2401 (1989).
61. Blair SN, Kampert JB, Kohl HW 3rd et al. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA 276(3), 205-210 (1996).
62. Mora S, Redberg RF, Cui Y et al. Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study. JAMA 290(12), 1600-1607 (2003).
63. Manson JE, Hu FB, Rich-Edwards JW et al. A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N. Engl. J. Med. 341(9), 650-658 (1999).
64. Gulati M, Pandey DK, Arnsdorf MF et al. Exercise capacity and the risk of death in women: the St James Women Take Heart Project. Circulation 108(13), 1554-1559 (2003).
65. Weintraub MS, Rosen Y, Otto R, Eisenberg S, Breslow JL. Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels. Circulation 79(5), 1007-1014 (1989).
66. Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N. Engl. J. Med. 325(7), 461-466 (1991).
67. Kraus WE, Houmard JA, Duscha BD et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N. Engl. J. Med. 347(19), 1483-1492 (2002).
68. Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. N. Engl. J. Med. 339(1), 12-20 (1998).
69. Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 46(4), 667-675 (2005).
70. Jeon CY, Lokken RP, Hu FB, Van Dam RM. Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care30(3), 744-752 (2007).
71. Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 286(10), 1218-1227 (2001).
72. Ford ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among U. S. adults. Epidemiology 13(5), 561-568 (2002).
73. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J. Am. Coll. Cardiol. 45(10), 1563-1569 (2005).
74. Paoletti R, Gotto AM Jr, Hajjar DP. Inflammation in atherosclerosis and implications for therapy. Circulation 109(23 Suppl. 1), III20-III26 (2004).
75. Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J. Am. Coll. Cardiol. 54(23), 2129-2138 (2009).
76. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 454(7203), 463-469 (2008).
77. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation 122(12), 1221-1238 (2010).
78. Thorogood A, Mottillo S, Shimony A et al. Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials. Am. J. Med. 124(8), 747-755 (2011).
79. Joyner MJ, Green DJ. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J. Physiol. 587(Pt 23), 5551-5558 (2009).
80. Hambrecht R, Gielen S, Linke A et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 283(23), 3095-3101 (2000).
81. Giannuzzi P, Temporelli PL, Corra U, Tavazzi L, Group E-CS. Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial. Circulation 108(5), 554-559 (2003).
82. Arbab-Zadeh A, Dijk E, Prasad A et al. Effect of aging and physical activity on left ventricular compliance. Circulation 110(13), 1799-1805 (2004).
83. Hambrecht R, Wolf A, Gielen S et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N. Engl. J. Med. 342(7), 454-460 (2000).
84. Gokce N, Vita JA, Bader DS et al. Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am. J. Cardiol. 90(2), 124-127 (2002).
85. Hambrecht R, Adams V, Erbs S et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107(25), 3152-3158 (2003).
86. Monahan KD, Dinenno FA, Tanaka H, Clevenger CM, Desouza CA, Seals DR. Regular aerobic exercise modulates ageassociated declines in cardiovagal baroreflex sensitivity in healthy men. J. Physiol. 529(Pt 1), 263-271 (2000).
87. Davy KP, Miniclier NL, Taylor JA, Stevenson ET, Seals DR. Elevated heart rate variability in physically active postmenopausal women: a cardioprotective effect? Am. J. Physiol. 271(2 Pt 2), H455-H460 (1996).
88. Physical Activity Guidelines Committee. Physical Activity Guidelines Advisory Committee Report. Washington DDOHaHS. www. health. gov/paguidelines/report/
89. Eckel RH, Jakicic JM, Ard JD et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 63(25 Pt B), 2960-2984 (2014).
90. Courneya KS. Exercise in cancer survivors: an overview of research. Med. Sci. Sports Exerc. 35(11), 1846-1852 (2003).
91. Schmitz KH, Courneya KS, Matthews C et al. American College of Sports Med. roundtable on exercise guidelines for cancer survivors. Med. Sci. Sports Exerc. 42(7), 1409-1426 (2010).
92. Courneya KS, Segal RJ, Mackey JR et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J. Clin. Oncol. 25(28), 4396-4404 (2007).
93. Demark-Wahnefried W, Case LD, Blackwell K et al. Results of a diet/exercise feasibility trial to prevent adverse body composition change in breast cancer patients on adjuvant chemotherapy. Clin. Breast Cancer 8(1), 70-79 (2008).
94. Jones LW, Courneya KS, Fairey AS, Mackey JR. Effects of an oncologist's recommendation to exercise on self-reported exercise behavior in newly diagnosed breast cancer survivors: a single-blind, randomized controlled trial. Ann. Behav. Med. 28(2), 105-113 (2004).
95. Windsor PM, Nicol KF, Potter J. A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma. Cancer 101(3), 550-557 (2004).
96. Segal RJ, Reid RD, Courneya KS et al. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J. Clin. Oncol. 27(3), 344-351 (2009).
97. Scott JM, Khakoo A, Mackey JR, Haykowsky MJ, Douglas PS, Jones LW. Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms. Circulation 124(5), 642-650 (2011).
98. Mcneely ML, Campbell KL, Rowe BH, Klassen TP, Mackey JR, Courneya KS. Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis. CMAJ 175(1), 34-41 (2006).
99. Gardner JR, Livingston PM, Fraser SF. Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J. Clin. Oncol. 32(4), 335-346 (2014).
100. Jones LW, Liu Q, Armstrong GT et al. Exercise and risk of major cardiovascular events in adult survivors of childhood hodgkin lymphoma: a report from the childhood cancer survivor study. J. Clin. Oncol. 32(32), 3643-3650 (2014).
101. Oldervoll LM, Kaasa S, Knobel H, Loge JH. Exercise reduces fatigue in chronic fatigued Hodgkins disease survivors-results from a pilot study. Eur. J. Cancer 39(1), 57-63 (2003).
102. Courneya KS, Friedenreich CM, Franco-Villalobos C et al. Effects of supervised exercise on progression-free survival in lymphoma patients: an exploratory follow-up of the HELP Trial. Cancer Causes Control 26(2), 269-276 (2015).
103. Streckmann F, Kneis S, Leifert JA et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann. Oncol. 25(2), 493-499 (2014).
104. Soloviev AI, Tishkin SM, Parshikov AV, Ivanova IV, Goncharov EV, Gurney AM. Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endotheliumdependent vasodilation. Br. J. Pharmacol. 138(5), 837-844 (2003).
105. Lipshultz SE, Adams MJ, Colan SD et al. 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. Circulation 128(17), 1927-1995 (2013).
106. Gaya AM, Ashford RF. Cardiac complications of radiation therapy. Clin. Oncol. 17(3), 153-159 (2005).
107. Hambrecht R, Fiehn E, Weigl C et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98(24), 2709-2715 (1998).
108. Kojda G, Hambrecht R. Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc. Res. 67(2), 187-197 (2005).
109. Ascensao A, Ferreira R, Magalhaes J. Exercise-induced cardioprotection-biochemical, morphological and functional evidence in whole tissue and isolated mitochondria. Int. J. Cardiol. 117(1), 16-30 (2007).
110. Ascensao A, Magalhaes J, Soares J et al. Endurance training attenuates doxorubicininduced cardiac oxidative damage in mice. Int. J. Cardiol. 100(3), 451-460 (2005).
111. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J. Am. Coll. Cardiol. 64(9), 938-945 (2014).
112. Zhang S, Liu X, Bawa-Khalfe T et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med. 18(11), 1639-1642 (2012).
113. Carver JR, Shapiro CL, Ng A et al. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J. Clin. Oncol. 25(25), 3991-4008 (2007).