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      Cardiac muscle wasting in individuals with cancer cachexia

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          Abstract

          Aims

          Cachexia is a severe complication of cancer that adversely affects the course of the disease and is associated with high rates of mortality. Patients with cancer manifest symptoms, such as fatigue, shortness of breath, and impaired exercise tolerance, which are clinical signs of chronic heart failure. The aim of this study was to evaluate cardiac muscle wasting in cancer individuals.

          Methods and results

          We retrospectively analysed 177 individuals who died of cancer, including 58 lung, 60 pancreatic, and 59 gastrointestinal (GI) cancers, and 42 cancer‐free controls who died of other, non‐cardiovascular reasons. Cancer cachexia (CC) was defined based on clinical and/or pathological diagnosis, body mass index (BMI) <20.0 kg/m 2 and/or oedema‐free body weight loss of 5.0% during the previous year or less. The pathology reports were analysed for BMI, heart weight (HW), and left and right ventricular wall thicknesses (LVWT and RVWT, respectively). The analysis of clinical data included recording of biochemical parameters and medication data of study patients. CC was detected in 54 (30.5%) subjects. Individuals with CC had a significantly lower HW than non‐cachectic subjects (363.1 ± 86.2 vs. 447.0 ± 128.9 g, P < 0.001) and control group (412.9 ± 75.8 g, P < 0.05). BMI correlated with HW in cases with GI cancer ( r = 0.44, P < 0.001), lung cancer ( r = 0.53, P < 0.0001), and pancreatic cancer ( r = 0.39, P < 0.01).

          Conclusions

          Body weight loss in individuals with lung, pancreatic, and GI cancers is accompanied by a decrease in HW. In patients with CC who receive cancer treatment, screening for cardiac muscle wasting may have clinical importance.

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          Most cited references32

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          Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival.

          Muscle wasting and cachexia have long been postulated to be key determinants of cancer-related death, but there has been no direct experimental evidence to substantiate this hypothesis. Here, we show that in several cancer cachexia models, pharmacological blockade of ActRIIB pathway not only prevents further muscle wasting but also completely reverses prior loss of skeletal muscle and cancer-induced cardiac atrophy. This treatment dramatically prolongs survival, even of animals in which tumor growth is not inhibited and fat loss and production of proinflammatory cytokines are not reduced. ActRIIB pathway blockade abolished the activation of the ubiquitin-proteasome system and the induction of atrophy-specific ubiquitin ligases in muscles and also markedly stimulated muscle stem cell growth. These findings establish a crucial link between activation of the ActRIIB pathway and the development of cancer cachexia. Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival. Copyright 2010 Elsevier Inc. All rights reserved.
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            Cachexia in cancer patients.

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              Cardiotoxicity of Anticancer Drugs: The Need for Cardio-Oncology and Cardio-Oncological Prevention

              Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications.
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                Author and article information

                Contributors
                wolfram.doehner@charite.de
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                Esc Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                15 July 2017
                November 2017
                : 4
                : 4 ( doiID: 10.1002/ehf2.v4.4 )
                : 458-467
                Affiliations
                [ 1 ] Clinic of General and Invasive Cardiology University Clinical Hospital No. 1 Yerevan Armenia
                [ 2 ] Center for Stroke Research Berlin Charite Universitätsmedizin Berlin Berlin Germany
                [ 3 ] German Centre for Cardiovascular Research (DZHK) Berlin Germany
                [ 4 ] Institute of Innovative Clinical Trials, Department of Cardiology and Pneumology University Medical Centre Göttingen (UMG) Göttingen Germany
                [ 5 ] Department of Cardiology and Berlin‐Brandenburg Center for Regenerative Therapies, Campus Virchow Charite Universitätsmedizin Berlin Berlin Germany
                Author notes
                [*] [* ] Correspondence to: Wolfram Doehner, Center for Stroke Research Berlin, Charite Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49 30 450 553507; Fax: +49 30 450 553507.

                Email: wolfram.doehner@ 123456charite.de

                [†]

                These authors contributed equally to the manuscript.

                Article
                EHF212184 ESCHF-16-00078
                10.1002/ehf2.12184
                5695173
                29154433
                62333f25-f946-4294-9b38-91b71cf96247
                © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 17 August 2016
                : 28 March 2017
                : 01 May 2017
                Page count
                Figures: 3, Tables: 3, Pages: 10, Words: 4597
                Funding
                Funded by: German Academic Exchange Service (DAAD)
                Award ID: A/08/76145
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                ehf212184
                November 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.6 mode:remove_FC converted:20.11.2017

                cancer cachexia,weight loss,heart weight,cardiac function

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