Background: Doxorubicin has been widely used to treat many cancers. It also induces cumulative and delayed cardiomyopathy. New biological markers to predict cardiac toxicity is needed.
Objectives: We identified novel markers and potential therapeutic targets of doxorubicin (DOX)-induced cardiac toxicity by proteomics approach.
Methods: The protein profiling of H9c2 cells in response to DOX at an apoptosis-induced concentration (0.5⃞M) were compared by two-dimensional electrophoresis (2-DE) and mass spectrometry.
Results: A total of nine differently expressed proteins were identified including six up-regulated and three downregulated proteins. We further confirmed the expression of two down-regulated proteins, prohibitin and endoplasmic reticulum protein ERp29 (ERp29), decreased in response to DOX induction by Western-blot, and over-expression of ERp29 also partially recovered the MTT reduction.
Conclusion: We first identified ERp29 and prohibitin as novel markers for DOX toxicity, and ERp29 might be a candidate target to develop novel therapeutic strategies to alleviate adverse effects of doxorubicin-based chemotherapies.
Rradiother Oncol. 2013;1(1):123-127.  Gagliardi G, Constine LS, Moiseenko V, et al . Radiation dose-volume effects in the heart. Int J Radiat Oncol Biol Phys. 2010;76(3):S77-S85.  Hahn E, Jiang H, Ng A, et al . Late CardiacToxicity After Mediastinal Radiation Therapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction. Int J Radiat Oncol Biol Phys. 2017;98(5):1116-1123.  Jakacki RI, Goldwein JW, Larsen RL, et al . Cardiac dysfunction following spinal irradiation during childhood. J Clin Oncol. 1993
-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495-502. 4. Palumbo A, Anderson K. Medical progress. Multiple myeloma. N Engl J Med 2011; 364 : 1046-60. 5. Zver S, Zadnik V, Cernelc P, Koželj M. Cardiactoxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation. Int J Haematology 2008; 88 : 227-36. 6. Braverman AC, Antin JH, Plappert MT. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin
Purpose: To investigate the cardio-pulmonary doses between Deep Inspiration Breath Hold (DIBH) and Free Breathing (FB) technique in left sided breast irradiation.
Materials & Methods: DIBH CT and FB CT were acquired for 10 left sided breast patients who underwent whole breast irradiation with or without nodal irradiation. Three fields single isocenter technique were used for patients with node positive patients along with two tangential conformal fields whereas only two tangential fields were used in node negative patients. All the critical structures like lungs, heart, esophagus, thyroid, etc., were delineated in both DIBH and FB scan. Both DIBH and FB scans were fused with the Dicom origin as they were acquired with the same Dicom coordinates. Plans were created in the DIBH scan for a dose range between 50 Gy in 25 fractions. Critical structures doses were recorded from the Dose Volume Histogram for both the DIBH and FB data set for evaluation.
Results: The average mean heart dose in DIBH vs FB was 13.18 Gy vs 6.97 Gy, (p = 0.0063) significantly with DIBH as compared to FB technique. The relative reduction in average mean heart dose was 47.12%. The relative V5 reduced by 14.70% (i.e. 34.42% vs 19.72%, p = 0.0080), V10 reduced by 13.83% (i.e. 27.79 % vs 13.96%, p = 0.0073). V20 reduced by 13.19% (i.e. 24.54 % vs 11.35%, p = 0.0069), V30 reduced by 12.38% (i.e. 22.27 % vs 9.89 %, p = 0.0073) significantly with DIBH as compared to FB. The average mean left lung dose reduced marginally by 1.43 Gy (13.73 Gy vs 12.30 Gy, p = 0.4599) but insignificantly with DIBH as compared to FB. Other left lung parameters (V5, V10, V20 and V30) shows marginal decreases in DIBH plans compare to FB plans.
Conclusion: DIBH shows a substantial reduction of cardiac doses but slight and insignificant reduction of pulmonary doses as compared with FB technique. Using the simple DIBH technique, we can effectively reduce the cardiac morbidity and at the same time radiation induced lung pneumonitis is unlikely to increase.
anticancer treatments: what the cardiologist needs to know. Nat Rev C ardiol 2010; 7: 564-75. 15. Chien AJ, Rugo HS. The cardiac safety of trastuzumab in the treatment of breast cancer. Expert Opin Drug Saf 2010; 9: 335-46. 16. Ewer MS, Tan-Chiu E. Reversibility of trastuzumab cardiotoxicity: is the concept alive and well? J Clin Oncol 2007; 25: 5532-3. Author reply: 5533-4. 17. Steinherz LJ, Steihherz PG, Tan CT, Heller G, Murphy ML. Cardiactoxicity 4-20 years after completing anthracycline therapy. JAMA 1991; 266: 1672-7. 18. Klein PM, Dybdal N. Trastuzumab and
investigations. Recently, in an experimental study in albino mice oedema and slight congestion were reported in the brain of affected animals. Up to now, data on the pathological changes of oleander poisoning in the brain has been rare. Moreover, no information about the changes of CK attributed to N . oleander toxicity was found, like troponin, and they were also measured in the current paper for the first time. In conclusion, the present investigations suggested that rats have a greater susceptibility to neurotoxicity and cardiactoxicity of N . oleander poisoning than
Previous studies have shown that palladium has toxic effects on the kidney and liver, leads to deterioration of the general condition of animals, and could cause allergy in animals and humans. Considering the limited data about the influence of palladium on the cardiovascular system, the aim of our study was to evaluate the effects of palladium on the heart from available published data, and to compare the toxicity of inorganic and organic palladium compounds. Relevant studies for our review were identified from PubMed and Scopus databases. The search terms included »palladium «, »palladium compound«, »cardiotoxicity«, »toxicity«, »heart«, »myocardium«, »oxidative stress« and »myocardial enzyme«, as well as combinations of these terms. There were only two published studies with the primary purpose to investigate the effect of palladium on the cardiovascular system, while others registered the side-effects of palladium compounds on the heart. Palladium could cause arrhythmias, a drop in blood pressure, decrease of the heart rate, as well as death of experimental animals. Based on the presented data it seems that palladium does not express significant cardiac toxicity when it is bound in an organic compound. Further investigation of the effects of palladium on the heart is necessary for a clear picture of the nature and extent of its cardiac toxicity.
References 1. Hoffmann R., Benz E.J.Jr. & Silberstein L.E. (2013). Hematology: basic principles and practice . (pp 1328-1334). Elsevier Saunders. Philadelphia, PA, USA. 2. The EBMT (2008). ESH Handbook Haematopoietic Stem Cell Transplantation (pp 112-128), from http://ebmtonline.forumservice.net/ 3. Zver S1., Zadnik V., Cernelc P. & Kozelj M. (2008). Cardiactoxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation. Int J Hematol. 88 (2),227-36. doi: 10.1007/s
. Tian S, Hirshfield KM, Jabbour SK, Toppmeyer D, Haffty BG, Khan AJ, Goyal S. Serum biomarkers for the detection of cardiactoxicity after chemotherapy and radiation therapy in breast cancer patients. Front Oncol. 2014;4:277. DOI: 10.3389/fonc.2014.00277 5. Christenson ES, James T, Agrawal V, Park BH. Use of biomarkers for the assessment of chemotherapy-induced cardiactoxicity. Clin Biochem. 2015;48(4-5):223-35. DOI: 10.1016/j.clinbiochem.2014.10.013 6. Van der Pal HJ, van Dalen EC, van Delden E, van Dijk IW, Kok WE, Geskus RB et al. High risk of symptomatic cardiac
of biomarkers for the assessment of chemotherapy-induced cardiactoxicity. Clin Biochem. 2014; 48(0):223-35 DOI: 10.1016/j.clinbiochem.2014.10.013 9. Mitry MA, Edwards JG. Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int J Cardiol Heart Vasc. 2015; 10:17-24 DOI: 10.1016/j. ijcha.2015.11.004 10. Wang GX, Wang YX, Zhou XB, Korth M. Effects of doxorubicinol on excitation-contraction coupling in guinea pig ventricular myocytes. Eur J Pharmacol. 2001; 423:99-107 DOI: 10.1016/S0014-2999(01)01096-2 11. Van der Pal HJ, Van Dalen EC. High risk of