Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 611
Filtrar
1.
Ann Med ; 53(1): 117-134, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33095083

RESUMO

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.


Assuntos
Antimaláricos/uso terapêutico , Cardiotoxicidade/etiologia , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antimaláricos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Hidroxicloroquina/farmacologia , Pandemias
2.
Isr Med Assoc J ; 9(22): 498-502, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954696

RESUMO

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Feminino , Humanos , Israel , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente
3.
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
4.
BMB Rep ; 53(10): 545-550, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958120

RESUMO

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].


Assuntos
Azitromicina/efeitos adversos , Cardiotoxicidade/etiologia , Cloroquina/efeitos adversos , Células-Tronco Embrionárias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação , Animais , Arritmias Cardíacas/induzido quimicamente , Azitromicina/administração & dosagem , Diferenciação Celular , Cloroquina/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Humanos , Camundongos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
5.
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
6.
Ecotoxicol Environ Saf ; 204: 111040, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798748

RESUMO

Tebuconazole (TEB) is a common triazole fungicide that is widely used throughout the world in agriculture applications. We previously reported that TEB induces cardiac toxicity in rats. The aim of this study was to investigate the underlying mechanism of the toxicity induced by TEB in cardiac cells. TEB induced dose-dependent cell death in H9c2 cardiomyoblasts and in adult rat ventricular myocytes (ARVM). The comet assay and western blot analysis showed a concentration-dependent increase in DNA damage and in p53 and p21 protein levels 24 h after TEB treatment. Our findings also showed that TEB triggered the mitochondrial pathway of apoptosis as evidenced by a loss of mitochondrial transmembrane potential (ΔΨm), an increase in Bax/Bcl-2 ratio, an activation of caspase-9 and caspase-3, a cleavage of poly (ADP-ribose) polymerase (PARP) and an increase in the proportion of cells in the sub-G1 phase. In addition, TEB promoted ROS production in cardiac cells and consequently increased the amounts of MDA, the end product of lipid peroxidation. Treatment of cardiomyocytes with the ROS scavenger N-acetylcysteine reduced TEB-induced DNA damage and activation of the mitochondrial pathway of apoptosis. These results indicate that the genotoxic and cytotoxic effects of TEB are mediated through a ROS-dependent pathway in cardiac cells.


Assuntos
Apoptose , Cardiotoxicidade/metabolismo , Dano ao DNA , Fungicidas Industriais/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Triazóis/toxicidade , Animais , Cardiotoxicidade/etiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Ratos , Ratos Wistar
7.
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
8.
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
9.
S Afr Med J ; 110(4): 271-273, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32657737

RESUMO

Trastuzumab was added to the South African Essential Medicines List (EML) in 2017 for the adjuvant management of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. However, access has remained inconsistent, as some provinces continue to regard trastuzumab as unaffordable within the contexts of their respective oncology budgets. The intention of providing access to trastuzumab through its inclusion on the EML, therefore, has not been met. The National EML Committee (NEMLC) recently reviewed newly published peer-reviewed information investigating the impact of a shorter trastuzumab treatment period on both clinical efficacy and safety. On account of this review, and with a view to improving access while reducing cost and toxicity, the NEMLC has revised the duration of trastuzumab therapy, i.e. from 12 months to 6 months in the adjuvant management of early HER2-positive breast cancer. This article explores and reports on the data used to make this policy amendment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Medicamentos Essenciais , Duração da Terapia , Política de Saúde , Mastectomia , Formulação de Políticas , Trastuzumab/uso terapêutico , Antineoplásicos Imunológicos/economia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Orçamentos , Cardiotoxicidade/etiologia , Quimioterapia Adjuvante , Feminino , Acesso aos Serviços de Saúde , Humanos , Mastectomia Segmentar , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , África do Sul , Trastuzumab/economia
10.
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
11.
Life Sci ; 257: 118074, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673667

RESUMO

AIM: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy. MAIN METHODS: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later. KEY FINDINGS: The DOX group showed a poorer 6-day survival and decreased cardiac function than the DOX + STS group. The DOX group showed a marked increase in the plasma creatine kinase isoenzyme myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels 10 h after DOX injection, while the DOX + STS group showed suppression of DOX-induced elevation of CK-MB and LDH levels. The DOX group showed increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the heart, whereas the DOX + STS group showed increased catalase and superoxide dismutase (SOD) activities and decreased 8-OHdG levels in the heart compared with DOX group, suggesting that STS reduces DOX-induced DNA damage by improving antioxidant enzymes activities in cardiomyocytes. Additionally, the DOX + STS group showed attenuation of cleaved caspase-3 and DNA fragmentation in cardiomyocytes compared with the DOX group, suggesting that STS suppresses DOX-induced apoptosis in cardiomyocytes. SIGNIFICANCE: STS exerts cardioprotective effects against DOX-induced cardiac dysfunction partly by improving antioxidant defense and suppressing apoptosis, indicating the therapeutic potential of STS against DOX-induced cardiomyopathy.


Assuntos
Cardiotoxicidade/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Tiossulfatos/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
12.
Rev Med Suisse ; 16(696): 1165-1168, 2020 Jun 03.
Artigo em Francês | MEDLINE | ID: mdl-32496706

RESUMO

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer.


Assuntos
Cardiotoxicidade/etiologia , Imunoterapia/efeitos adversos , Miocardite/induzido quimicamente , Neoplasias/tratamento farmacológico , Humanos , Neoplasias/imunologia , Neoplasias/patologia
13.
Adv Exp Med Biol ; 1257: 181-192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483740

RESUMO

Doxorubicin is an anthracycline and one of the more effective chemotherapy agents used in the treatment of children, adolescents, and adults with osteosarcoma. Despite its effectiveness, cardiotoxicity is a major late effect that compromises the survival and quality of life of survivors of this and other cancers. Cardiotoxicity is the inability of the heart to pump blood through the body effectively. Doxorubicin-induced cardiotoxicity is dose dependent. Additionally, the age of the patients plays a role in susceptibility with younger patients having a greater risk for cardiotoxicity and heart failure years after treatment is complete. The exact mechanism(s) responsible for doxorubicin-induced cardiotoxicity is poorly understood, and further research needs to be done to elucidate the mechanisms. This chapter summarizes the identified mechanisms that may play a role in anthracycline-induced cardiotoxicity. We will also summarize the types of cardiomyopathies that have been described in survivors treated with doxorubicin and the current recommendations for monitoring survivor for the development of cardiomyopathies. Included will be the important search for defining early biomarkers to identify patients and survivors at risk. Finally, we will summarize some of the interventions proposed for decreasing anthracycline-induced cardiotoxicity.


Assuntos
Antraciclinas , Cardiotoxicidade , Osteossarcoma , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Humanos , Neoplasias/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Qualidade de Vida
14.
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
16.
Top Magn Reson Imaging ; 29(3): 135-148, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32568976

RESUMO

The delivery of radiation therapy shares many of the challenges encountered in imaging procedures. As in imaging, such as MRI, organ motion must be reduced to a minimum, often for lengthy time periods, to effectively target the tumor during imaging-guided therapy while reducing radiation dose to nearby normal tissues. For patients, radiation therapy is frequently a stress- and anxiety-provoking medical procedure, evoking fear from negative perceptions about irradiation, confinement from immobilization devices, claustrophobia, unease with equipment, physical discomfort, and overall cancer fear. Such stress can be a profound challenge for cancer patients' emotional coping and tolerance to treatment, and particularly interferes with advanced radiation therapy procedures where active, complex and repetitive high-level cooperation is often required from the patient.In breast cancer, the most common cancer in women worldwide, radiation therapy is an indispensable component of treatment to improve tumor control and outcome in both breast-conserving therapy for early-stage disease and in advanced-stage patients. High technological complexity and high patient cooperation is required to mitigate the known cardiac toxicity and mortality from breast cancer radiation by reducing the unintended radiation dose to the heart from left breast or left chest wall irradiation. To address this, radiation treatment in daily deep inspiration breath hold (DIBH), to create greater distance between the treatment target and the heart, is increasingly practiced. While holding the promise to decrease cardiac toxicity, DIBH procedures often augment patients' baseline stress and anxiety reaction toward radiation treatment. Patients are often overwhelmed by the physical and mental demands of daily DIBH, including the nonintuitive timed and sustained coordination of abdominal thoracic muscles for prolonged breath holding.While technologies, such as DIBH, have advanced to millimeter-precision in treatment delivery and motion tracking, the "human factor" of patients' ability to cooperate and perform has been addressed much less. Both are needed to optimally deliver advanced radiation therapy with minimized normal tissue effects, while alleviating physical and cognitive distress during this challenging phase of breast cancer therapy.This article discusses physical training and psychotherapeutic integrative health approaches, applied to radiation oncology, to leverage and augment the gains enabled by advanced technology-based high-precision radiation treatment in breast cancer. Such combinations of advanced technologies with training and cognitive integrative health interventions hold the promise to provide simple feasible and low-cost means to improve patient experience, emotional outcomes and quality of life, while optimizing patient performance for advanced imaging-guided treatment procedures - paving the way to improve cardiac outcomes in breast cancer survivors.


Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/radioterapia , Cardiotoxicidade/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Coração/efeitos da radiação , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Suspensão da Respiração , Cardiotoxicidade/etiologia , Feminino , Humanos , Qualidade de Vida , Doses de Radiação , Lesões por Radiação/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
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
19.
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
20.
Cancer Sci ; 111(7): 2579-2587, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32378780

RESUMO

We performed a genome-wide association study to investigate the association between single nucleotide polymorphisms and anthracycline-induced cardiotoxicity (ACT) in patients diagnosed with early breast cancer. From January 2000 to December 2015, 8490 patients underwent breast surgery at the National Cancer Center in Korea. Patients who received doxorubicin (cumulative dose 240 mg/m2 -300 mg/m2 ) with or without trastuzumab as a neoadjuvant/adjuvant therapy were included in our cohort. Sixty-seven patients in our cohort were diagnosed with ACT. Clinical data, including age, body weight, height, cancer stage, trastuzumab treatment, comorbidities, and concomitant medications, were collected retrospectively. Patients were classified as having either persistent or transient ACT based on their clinical course. In total, 346 946 single nucleotide polymorphisms in 42 cases and 215 controls were tested in this study. Body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) = 2.45, 95% confidence interval (CI), 1.23-4.88, P = .011] and trastuzumab use (OR = 2.40, 95% CI, 1.11-5.17, P = .026) were identified as significant risk factors. We found 7 genetic variants for ACT including rs17530621 (SHISA3, P = 3.10E-06), rs11894115 (MPP4, P = 4.71E-06), rs58328254 (RPL7, P = 6.09E-06), and rs117299725 (PRUNE2, P = 8.53E-06), although none of these variants reached the Bonferroni-corrected significance level when adjusted for BMI and trastuzumab use ( = α1.44E-07 based on 0.05/346 946). rs117299725 was a common variant when only the persistent ACT group was analyzed separately. It is meaningful that our study analyzed comprehensively the influence of genetic variation on ACT, along with some clinical factors in Asian breast cancer patients who received anthracycline with or without trastuzumab. Further research will be needed on candidate genetic variants found in this study.


Assuntos
Antraciclinas/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Cardiotoxicidade/etiologia , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/epidemiologia , Estudos de Casos e Controles , Comorbidade , Feminino , Estudos de Associação Genética/métodos , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , República da Coreia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA