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1.
Food Chem Toxicol ; 145: 111742, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32916218

RESUMO

SARS-CoV-2 (Covid-19) infection has recently become a worldwide challenge with dramatic global economic and health consequences. As the pandemic is still spreading, new data concerning Covid-19 complications and related mechanisms become increasingly available. Accumulating data suggest that the incidence of cardiac arrest and its outcome are adversely affected during the Covid-19 period. This may be further exacerbated by drug-related cardiac toxicity of Covid-19 treatment regimens. Elucidating the underlying mechanisms that lead to Covid-19 associated cardiac arrest is imperative, not only in order to improve its effective management but also to maximize preventive measures. Herein we discuss available epidemiological data on cardiac arrest during the Covid-19 pandemic as well as possible associated causes and pathophysiological mechanisms and highlight gaps in evidence warranting further investigation. The risk of transmission during cardiopulmonary resuscitation (CPR) is also discussed in this review. Finally, we summarize currently recommended guidelines on CPR for Covid-19 patients including CPR in patients with cardiac arrest due to suspected drug-related cardiac toxicity in an effort to underscore the most important common points and discuss discrepancies proposed by established international societies.


Assuntos
Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/complicações , Parada Cardíaca/epidemiologia , Parada Cardíaca/fisiopatologia , Pneumonia Viral/complicações , Arritmias Cardíacas/etiologia , Reanimação Cardiopulmonar/normas , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Transmissão de Doença Infecciosa/prevenção & controle , Parada Cardíaca/etiologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico
3.
Medicine (Baltimore) ; 99(32): e21613, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769920

RESUMO

BACKGROUND: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors are immune therapies that have shown great promise in the treatment of multiple cancers. However, immune-related adverse events of PD-1 and PD-L1 inhibitors may limit their use in non-small cell lung cancer (NSCLC). Given the rising number of clinical trials in recent years, it is essential to perform a meta-analysis to provide assess the cardiotoxicity of PD-1/ PD-L1 inhibitors in NSCLC therapy. METHOD AND ANALYSIS: The ClinicalTrials.gov, Embase, PubMed, and Cochrane Central Register of Controlled Trials repositories will be searched from their inception to December 2019. The bibliography of the searching process will be imported into Endnote X9 software. Two reviewers independently will screen the literature, extract data, and conduct the risk of bias for every added study. The data analysis will be analyzed using Stata15.0 software. Specific adverse cardiac events will be identified, with particular attention on atrial fibrillation, cardiac arrest, cardiac failure, and pericarditis. This review will be performed as per the Preferred Reporting Item for Systematic Review and meta-analysis statement recommendations. ETHICS AND DISSEMINATION: This study will provide support for the cardiotoxicity linked to the treatment of NSCLC using PD-1/PD-L1 inhibitors. The data in the meta-analysis will be retrieved from completed and published clinical trials; therefore, ethical review and patient informed consent will not be required. PROSPERO NUMBER: CRD42020156397.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cardiotoxicidade/etiologia , Protocolos Clínicos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/complicações , Cardiotoxicidade/fisiopatologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
4.
Cancer Radiother ; 24(6-7): 576-585, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32830054

RESUMO

Cancer and cardiovascular disease (CVD) are the leading cause of mortality worldwide, and breast cancer (BC) the most common malignancy affecting women worldwide. Radiotherapy is an important component of BC treatment and participates in CVD occurrence. It seems, therefore, crucial to gather both radiation oncology and cardiology medical fields to improve the follow-up quality of our BC patients. This review aims at updating our knowledge regarding cardiotoxicities risk factors, and consequently, doses constraints in case of 3D-conformal and IMRT treatment planning. Then we will develop how to reduce cardiac exposure and what kind of cardiac follow-up we could recommend to our breast cancer patients.


Assuntos
Neoplasias da Mama/radioterapia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Assistência ao Convalescente , Feminino , Humanos , Planejamento de Assistência ao Paciente , Guias de Prática Clínica como Assunto , Doses de Radiação , Radioterapia Conformacional , Fatores de Risco
5.
Life Sci ; 261: 118346, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32853656

RESUMO

Doxorubicin is an antineoplastic in the anthracycline class widely used for the treatment of several solid tumors and blood cancers. Cardiotoxicity is the major dose-limiting adverse effect of the drug. Chronic and accumulated doxorubicin administration cause myocyte damage and myocardial fibrosis. Doxorubicin-associated cardiotoxicity can be also observed after a short-course drug treatment even without clinical evidence of cardiac disease. Nevertheless, acute underlying mechanisms involved in the initiation of drug-induced cardiotoxicity remain poorly explored despite their similarities with pathophysiological conditions where cardiac TRH (cTRH) plays a central role. We showed that cTRH mediates myocardial injury induced by hypertension, and angiotensin II. Further, cTRH overexpression induces cardiac apoptosis, hypertrophy and fibrosis. AIM: To demonstrate that cTRH could mediate acute doxorubicin cardiotoxicity. MAIN METHOD: A single injection of doxorubicin (10 mg kg/day i.p.) was used to evaluate acute cardiac damage in a short-term experimental model of doxorubicin-induced cardiotoxicity. While inhibiting cTRH by small interfering RNA (siRNA), we evaluated the progression of cardiotoxicity. KEY FINDINGS: We found a doxorubicin-induced TRH overexpression in the LV, which was associated with apoptosis, hypertrophy and fibrosis. siRNA-mediated cTRH suppression prevented the doxorubicin-associated cardiac histological lesions. SIGNIFICANCES: doxorubicin requires an active cardiac TRH system to promote heart injury.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/etiologia , Doxorrubicina/toxicidade , Hormônio Liberador de Tireotropina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Cardiotoxicidade/fisiopatologia , Progressão da Doença , Fibrose/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno , Hormônio Liberador de Tireotropina/genética
6.
Life Sci ; 257: 118084, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663572

RESUMO

Since an outbreak of vaping-related deaths in the US has been reported as a public health crisis, the cardiovascular safety of nicotine nowadays receives increasing attention due to use of tobacco cigarette alternatives, such as electronic cigarettes. However, whether and how nicotine contributes to cardiac detrimental effects are in great controversy, especially less understood in young adult population. We report that chronic nicotine exposure, a major component of Electronic cigarettes, resulted in directly inhibited cardiomyocytes viability, increased cardiac fibrosis, and markedly suppressed cardiac function compared with sham. Gene array combined with bioinformatics analysis identified cardiac apoptosis and mitophagy were the key signals responsible for nicotine induced cardiac detrimental effect. Mechanistically, nicotine exposure markedly increased cleaved Caspase 3 and cleaved Caspase 9 indicating the involvement of intrinsic apoptotic pathway (mitochondrial cell death pathway). Meanwhile, nicotine-induced ROS outbreak promoted lysomal alkalization, furthermore blocked mitophagic degradation, thereby disrupted mitophagic flux promoted mitochondrial cell death cascade. Taken together, these findings indicate that nicotine confers cardiotoxicity via ROS-induced mitophagic flux blockage and provide the first demonstration of a causative link between nicotine and cardiac toxicity in young adult rat which may suggest nicotine induces cardiomyocytes impairment leading to cardiotoxicity in young adult population.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Mitofagia/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Nicotina/toxicidade , Animais , Cardiotoxicidade/fisiopatologia , Sistemas Eletrônicos de Liberação de Nicotina , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Vaping/efeitos adversos
7.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188383, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535158

RESUMO

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/administração & dosagem , Androgênios/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , GMP Cíclico/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Longevidade/fisiologia , Masculino , Estudos Observacionais como Assunto , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptores LHRH/agonistas , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
9.
Life Sci ; 255: 117843, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464123

RESUMO

Metabolic diseases, such as obesity and type 2 diabetes, are known risk factors for cardiovascular (CV) diseases. Thus, patients with those comorbidities could be at increased risk of experiencing cardiotoxicity related to treatment with Anthracyclines and the other new generation targeted anticancer drugs. However, investigations addressing the mechanisms underlying the development of CV complications and poor outcome in such cohort of patients are still few and controversial. Given the importance of a personalized approach against chemotherapy-induced cardiomyopathy, this review summarizes our current knowledge on the pathophysiology of chemotherapy-induced cardiomyopathy and its association with obesity and type 2 diabetes. Along with clinical evidences, future perspectives of preclinical research around this field and its role in addressing important open questions, including the development of more proactive strategies for prevention, and treatment of cardiotoxicity during and after chemotherapy in the presence of metabolic diseases, is also presented.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Doenças Metabólicas/complicações , Animais , Antineoplásicos/administração & dosagem , Cardiotoxicidade/fisiopatologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Neoplasias/tratamento farmacológico , Obesidade/complicações , Fatores de Risco
10.
Life Sci ; 255: 117844, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464124

RESUMO

AIMS: Interleukin (IL) 9 is a pleiotropic cytokine, and recent studies have demonstrated that IL-9 is associated with several cardiovascular diseases, via regulation of the inflammatory response. Doxorubicin (DOX) is known to induce severe cardiac injury and dysfunction by enhancing inflammation. This study aimed to investigate the role of IL-9 in DOX-induced cardiotoxicity. MATERIALS AND METHODS: DOX was used to induce cardiac dysfunction and the expression of IL-9 in the murine cardiac tissues was measured. The mice were intraperitoneally injected with recombinant mouse IL-9 (rmIL-9) or anti-IL-9 neutralizing antibody (IL-9nAb) for investigating the effect of IL-9 on DOX-induced cardiac injury and dysfunction. The messenger ribonucleic acid (mRNA) expression levels of the pro-inflammatory cytokines were determined in each group by quantitative real-time polymerase chain reaction (RT-qPCR). The effect of rmIL-9 or IL-9nAb on DOX-induced apoptosis was determined both in vivo and vitro. KEY FINDINGS: IL-9 levels significantly increased in the heart following DOX injection. Cardiac injury and dysfunction were induced by DOX, and treatment with IL-9nAb significantly alleviated DOX-induced injury, whereas rmIL-9 administration aggravated the cardiac damage. IL-9nAb decreased the expression of pro-inflammatory cytokines in the DOX-treated mice, while rmIL-9 administration increased the levels of pro-inflammatory cytokines. IL-9nAb reduced DOX-induced myocardial apoptosis, whereas rmIL-9 administration produced the opposite results. Additionally, IL-9nAb mitigated the DOX-induced apoptosis in H9C2 cells, while administration of rmIL-9 produced the opposite effect. SIGNIFICANCE: Our results demonstrated that IL-9 aggravated DOX-induced cardiac injury and dysfunction by promoting the inflammatory response and cardiomyocyte apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Doxorrubicina/toxicidade , Inflamação/induzido quimicamente , Interleucina-9/metabolismo , Animais , Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/fisiopatologia , Linhagem Celular , Citocinas/metabolismo , Inflamação/patologia , Interleucina-9/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos
11.
Oxid Med Cell Longev ; 2020: 4965171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454939

RESUMO

The chemotherapeutic and immunosuppressive agent cyclophosphamide has previously been shown to induce complications within the setting of bone marrow transplantation. More recently, cardiotoxicity has been shown to be a dose-limiting factor during cyclophosphamide therapy, and cardiooncology is getting wider attention. Though mechanism of cyclophosphamide-induced cardiotoxicity is not completely understood, it is thought to encompass oxidative and nitrative stress. As such, this review focuses on antioxidants and their role in preventing or ameliorating cyclophosphamide-induced cardiotoxicity. It will give special emphasis to the cardioprotective effects of natural, plant-derived antioxidants that have garnered significant interest in recent times.


Assuntos
Antioxidantes/farmacologia , Cardiotoxicidade/patologia , Ciclofosfamida/efeitos adversos , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/fisiopatologia , Humanos
13.
Life Sci ; 251: 117631, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251635

RESUMO

Initially, the selective COX-2 inhibitors were developed as safer alternatives to the conventional NSAIDs, but later on, most of them were withdrawn from the market due to the risk of heart attack and stroke. Celecoxib, the first selective COX-2 inhibitor, was approved by the Food and Drug Administration (FDA) in December 1998 and was taken back from the market in 2004. Since then, many coxibs have been discontinued one by one due to adverse cardiovascular events. United States (US), Australian and European authorities related to Therapeutic Goods Administration (TGA) implemented the requirements to carry the "Black box" warning on the labels of COX-2 drugs highlighting the risks of serious cardiovascular events. These facts encouraged the researchers to explore them well and find out the biochemical basis behind the cardiotoxicity. From the last few decades, the molecular mechanisms behind the coxibs have regained the attention, especially the specific structural features of the selective COX-2 inhibitors that are associated with cardiotoxicity. This review discusses the key structural features of the selective COX-2 inhibitors and underlying mechanisms that are responsible for the cardiotoxicity. This report also unfolds different strategies that have been reported in the last 10 years to combat the problem of selective COX-2 inhibitors mediated cardiotoxicity.


Assuntos
Cardiotoxicidade/etiologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/química , Rotulagem de Medicamentos , Humanos
14.
Nat Rev Cardiol ; 17(8): 474-502, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32231332

RESUMO

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.


Assuntos
Antineoplásicos/efeitos adversos , Arritmias Cardíacas , Cardiotoxicidade , Animais , Antineoplásicos/uso terapêutico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioterapia/efeitos adversos
15.
Nat Rev Cardiol ; 17(8): 503-522, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32218531

RESUMO

Cancer therapies can lead to a broad spectrum of cardiovascular complications. Among these, cardiotoxicities remain of prime concern, but vascular toxicities have emerged as the second most common group. The range of cancer therapies with a vascular toxicity profile and the clinical spectrum of vascular toxic effects are quite broad. Historically, venous thromboembolism has received the greatest attention but, over the past decade, the arterial toxic effects, which can present as acute vasospasm, acute thrombosis and accelerated atherosclerosis, of cancer therapies have gained greater recognition. This Review focuses on these types of cancer therapy-related arterial toxicity, including their mechanisms, and provides an update on venous thromboembolism and pulmonary hypertension associated with cancer therapies. Recommendations for the screening, treatment and prevention of vascular toxic effects of cancer therapies are outlined in the context of available evidence and society guidelines and consensus statements. The shift towards greater awareness of the vascular toxic effects of cancer therapies has further unveiled the urgent needs in this area in terms of defining best clinical practices. Well-designed and well-conducted clinical studies and registries are needed to more precisely define the incidence rates, risk factors, primary and secondary modes of prevention, and best treatment modalities for vascular toxicities related to cancer therapies. These efforts should be complemented by preclinical studies to outline the pathophysiological concepts that can be translated into the clinic and to identify drugs with vascular toxicity potential even before their widespread clinical use.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade , Neoplasias/terapia , Radioterapia/efeitos adversos , Doenças Vasculares , Animais , Antineoplásicos/uso terapêutico , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Humanos , Camundongos , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia
16.
Food Chem Toxicol ; 137: 111134, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006631

RESUMO

Tebuconazole is an effective systemic fungicide that belongs to the triazoles family. It has been widely used in both agricultural and medical sectors for the control of fungal diseases. Although TEB poses serious threats to mammals health, studies regarding its cardiotoxicity are very limited. Thus, we aimed to evaluate the effects of TEB on some biochemical parameters, the induction of apoptosis and DNA damage in the heart tissue. Male Wistar rats were treated with TEB at varied oral doses for 28 consecutive days. This study demonstrates that TEB decreased cardiac acetylcholinesterase, increased serum marker enzymes such as creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH), and altered the lipid profile by increasing serum levels of total cholesterol (T-CHOL), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, TEB increased levels of p53 and Bax/Bcl2 ratio, released the cytochrome c into the cytosol and activated caspase-9 and caspase-3. Besides, our results showed that TEB induced genotoxic effects. TEB induced DNA fragmentation and increased the frequency of micronucleated bone marrow cells. Moreover, TEB treatment developed fibrosis in the myocardium. Our results suggest that TEB exposure may affect myocardial cells normal functioning and triggers apoptosis.


Assuntos
Cardiotoxicidade/etiologia , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Cardiotoxicidade/fisiopatologia , LDL-Colesterol/metabolismo , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
17.
Curr Cardiol Rep ; 22(1): 1, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932992

RESUMO

PURPOSE OF REVIEW: Cardiac regeneration has received much attention as a possible means to treat various forms of cardiac injury. This review will explore the field of cardiac regeneration by highlighting the existing animal models, describing the involved molecular pathways, and discussing attempts to harness cardiac regeneration to treat cardiomyopathies. RECENT FINDINGS: Light chain cardiac amyloidosis is a degenerative disease characterized by progressive heart failure due to amyloid fibril deposition and light chain-mediated cardiotoxicity. Recent findings in a zebrafish model of light chain amyloidosis suggest that cardiac regenerative confers a protective effect against this disease. Cardiac regeneration remains an intriguing potential tool for treating cardiovascular disease. Degenerative diseases, such as light chain cardiac amyloidosis, may be particularly suited for therapeutic interventions that target cardiac regeneration. Further studies are needed to translate preclinical findings for cardiac regeneration into effective therapies.


Assuntos
Amiloidose/diagnóstico , Cardiomiopatias/metabolismo , Cardiotoxicidade/fisiopatologia , Insuficiência Cardíaca/etiologia , Cadeias Leves de Imunoglobulina/metabolismo , Miocárdio/patologia , Regeneração , Amiloidose/complicações , Animais , Cardiomiopatias/complicações , Cardiomiopatias/terapia , Insuficiência Cardíaca/diagnóstico , Humanos , Peixe-Zebra
18.
Eur J Cancer ; 126: 65-73, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31923729

RESUMO

INTRODUCTION: T-DM1 has been approved for the treatment of HER2+ breast cancer. Cardiac dysfunction is a side effect of trastuzumab, a component of T-DM1. However, little is known about T-DM1-associated cardiotoxicity. METHODS: We have conducted a pooled analysis of T-DM1 trials in advanced HER2+ breast cancer cases to understand the incidence, clinical presentation as well as to establish possible risk factors for T-DM1-associated cardiotoxicity. The primary endpoint was the incidence of cardiac events (CEs). CEs were categorized as follows: (1) congestive heart failure (CHF) or grade 3/4 LVEF drop; (2) cardiac ischemia, (3) cardiac arrhythmia, (4) grade 1/2 LVEF drop. Secondary endpoints included CE recovery rate and impact of CEs on treatment discontinuation. Logistic regression was used to assess possible risk factors for CEs. RESULTS: Individual patient-level data from 1961 patients exposed to T-DM1 in seven trials were pooled. Of these, 1544 received T-DM1 and 417 T-DM1 + pertuzumab. CHF/LVEF drop grade 3/4 was reported in 0.71%, cardiac ischemia in 0.1%, cardiac arrhythmia in 0.71% and grade 1/2 LVEF drop in 2.04%. The total CE rate was 3.37% (95% confidence interval (CI), 2.6%-4.3%). Multivariate analysis showed patient's age ≥65 (OR 3.0; 95% CI, 1.77-5.14; P-value <0.001) and baseline LVEF<55% (OR 2.62; 95% CI, 1.29-5.32; P-value 0.008) as risk factors. CEs resolved in most (79%) patients after treatment discontinuation. CONCLUSION: The incidence of CEs in patients receiving T-DM1 was low. Older patients receiving T-DM1 should be carefully followed for cardiac safety during treatment.


Assuntos
Ado-Trastuzumab Emtansina/efeitos adversos , Arritmias Cardíacas/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Isquemia Miocárdica/diagnóstico , Ado-Trastuzumab Emtansina/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Neoplasias da Mama/metabolismo , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Isquemia Miocárdica/induzido quimicamente , Receptor ErbB-2/metabolismo
19.
Breast ; 49: 183-186, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862685

RESUMO

OBJECTIVES: To search for biomarkers of RT-induced cardiotoxicity, we studied the behavior of ST2 during RT and three years after RT, and the associations with echocardiographic changes. MATERIALS AND METHODS: We measured soluble ST2 (ng/ml) in serum samples from 63 patients receiving RT for early breast cancer. Sampling and echocardiography were performed at baseline, after RT and at the three-year follow-up. Patients were grouped by >15% (group 1) and ≤15% (group 2) relative worsening in global longitudinal strain (GLS). RESULTS: ST2 levels tended to increase during RT, from a median (interquartile range; IQR) of 17.9 (12.4-22.4) at baseline to 18.2 (14.1-23.5) after RT (p = 0.075). By the three-year follow up, ST2 levels increased to 18.7 (15.8-24.2), p = 0.018. The increase in ST2 level was associated with worsening cardiac systolic function at three-year follow-up, GLS (rho = 0.272, p = 0.034) and left ventricular ejection fraction (LVEF) (rho = â”€0.343, p = 0.006). Group 1 (n = 14) had a significant increase in ST2 levels from 17.8 (12.3-22.5) at baseline to 18.4 (15.6-22.6) after RT, p = 0.035 and to 19.9 (16.0-25.1) three years after RT, p = 0.005. ST2 levels were stable in group 2 (n = 47): 17.8 (12.3-22.0) at baseline, 17.7 (12.6-23.5) after RT and 18.0 (15.5-22.4) at three years. CONCLUSION: ST2 may be useful for determining which patients are at risk for long-term cardiovascular toxicity following adjuvant breast cancer RT, but prospective clinical studies are needed to confirm this hypothesis.


Assuntos
Neoplasias da Mama/radioterapia , Cardiotoxicidade/fisiopatologia , Ecocardiografia , Radioterapia Adjuvante/efeitos adversos , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico/efeitos da radiação , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/efeitos da radiação
20.
Med Sci Sports Exerc ; 52(1): 25-36, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318716

RESUMO

PURPOSE: Endurance exercise (EXE) preconditioning before DOX treatment confers cardioprotection; however, whether EXE postconditioning (i.e., EXE intervention after the completion of DOX treatment) is cardioprotective remains unknown. Thus, the aim of the present study was to investigate if EXE postconditioning provides cardioprotection by testing the hypothesis that EXE-autophagy upregulation and NADPH oxidase 2 (NOX2) downregulation would be linked to cardioprotection against DOX-induced cardiotoxicity. METHODS: C57BL/6 male mice were assigned into three groups: control (CON, n = 10), doxorubicin (DOX, n = 10), and doxorubicin + endurance exercise (DOX + EXE, n = 10). Animals assigned to DOX and DOX + EXE groups were intraperitoneally injected with DOX (5 mg·kg each week for 4 wk). Forty-eight hours after the last DOX treatment, the mice assigned to DOX + EXE performed EXE on a motorized treadmill at a speed of 13-15 m·min for 60 min·d for 4 wk. RESULTS: EXE prevented DOX-induced apoptosis and mitigated tissue damages. Although DOX did not modulate auto/mitophagy, EXE significantly enhanced its flux (increased LC3-II levels, reduced p62 levels, and increased autophagosomes with mitochondria) along with increased mitochondrial fission (DRP1) and reduced fusion markers (OPA1 and MFN2). Interestingly, EXE-induced autophagy against DOX occurred in the absence of alterations of autophagy inducer AMPK or autophagy inhibitor mTOR signaling. EXE prohibited DOX-induced oxidative damages by suppressing NOX2 levels but without modulating other key antioxidant enzymes including MnSOD, CuZnSOD, catalase, and GPX1/2. CONCLUSION: Our data provide novel findings that EXE-induced auto/mitophagy promotion and NOX2 downregulation are linked to cardioprotection against DOX-induced cardiotoxicity. Importantly, our study shows that EXE postconditioning intervention is effective and efficacious to prevent DOX-induced cardiac injuries.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Condicionamento Físico Animal/fisiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/fisiologia , Cardiotoxicidade/fisiopatologia , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , Mitofagia/efeitos dos fármacos , NADPH Oxidase 2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Resistência Física/efeitos dos fármacos , Regulação para Cima
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