Cardiotoxicity

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS)...

BACKGROUND: Anthracyclines are one of the most effective chemotherapeutic agents in management of Breast cancer, however Anthracycline induced cardiotoxicity remains a matter of special concern. Detection of early toxicity by use of biomarkers like Troponins has been the focus of interest in recent years. We measured Troponin I levels after chemotherapy with anthracyclines and correlated it with ECG, Echocardiography and clinical findings. METHODS: Patients with early Breast cancer eligible for chemotherapy were included in the study...

Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential...

Cardiotoxicity is a well-established complication of oncology therapies. Cardiomyopathy resulting from anthracyclines is a classic example. In the past decade, an explosion of novel cancer therapies, often targeted and more specific than traditional therapies, has revolutionized oncology therapy and dramatically changed cancer prognosis. However, some of these therapies have introduced an assortment of cardiovascular (CV) complications. At times, these devastating outcomes have only become apparent after drug approval and have limited the use of potent therapies...

OBJECTIVE: To identify the salient issues of young adults (YAs) diagnosed with multiple myeloma (MM), a hematologic disease of older adults, that is rare in patients 19-40 years of age. DATA SOURCES: Peer-reviewed journal articles, case reports, single-institution series, and national guidelines. CONCLUSION: Compared to older adults with MM, YAs live longer and are at higher risk for survivorship-related issues, which include treatment adherence, infertility, reproductive concerns, risk of second primary cancers, treatment-related cardiotoxicity, and higher risk of non-cancer-related mortality...

BACKGROUND: Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QTc interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QTc interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy...

PURPOSE: Trastuzumab improves overall survival for women with HER2-positive breast cancer but is associated with cardiotoxicity, especially when administered after anthracyclines. Use of non-anthracycline trastuzumab-based regimens is rising, particularly for patients with low-risk disease or with multiple cardiovascular risk factors. We performed a single-center retrospective cohort study to assess the cardiac safety of trastuzumab without anthracyclines outside of a clinical trial setting...

The anticancer efficacy of anthracyclines is limited by congestive heart failure. Clinically established markers of early onset of cardiotoxicity following anthracycline treatment and preventive measures are missing. Although statins are reported to alleviate anthracycline-induced cardiotoxicity in vivo, the molecular mechanisms involved remain elusive. In vitro data point to Rac1 as major target of the cytoprotective statin effects. Here we investigated whether specific inhibition of Rac1 by NSC23766 is as effective as lovastatin in preventing subacute cardiotoxicity following doxorubicin treatment...

Takotsubo cardiomyopathy (TTC) is associated with acute, reversible left ventricular (LV) dysfunction, while transient global amnesia (TGA) is a reversible disorder of the brain characterised by anterograde amnesia. We report an unusual case of TTC occurring concurrently in a patient with TGA, and propose that catecholamine surge induced cerebral venous congestion and cardiotoxicity is the shared aetiology that leads to the concurrent manifestation of these conditions. TTC and TGA are reversible disorders that can occur concurrently in a subset of patients due to a unifying aetiology, catecholamine excess, leading to pathophysiological changes within the brain and the myocardium...

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to Doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by Vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction and Vit C transporter proteins...

Over the past 20 years, cancer treatments have become more effective, leading to significant improvements in survival rates. However, anticancer drugs can have several possible cardiovascular side effects; in particular, the development of left ventricular dysfunction with chemoradiation therapy can negatively affect patients' cardiac outcome, and can limit anticancer treatments. This is an ongoing issue that will continue to persist, due to the ongoing development of new antitumor agents with potential cardiotoxic effects, and the prolonged life expectancy of long-term cancer survivors...

The primary aim of this study was to find the potential modulatory roles of quercetin (QUE) against Adriamycin (ADR)-induced cardiotoxicity. A total of 50 rats were assigned to five groups: a control group, an ADR-treated group, a QUE-treated group, a prophylaxis-cotreated group, and a therapeutic-cotreated group, respectively. QUE exhibited a significant cardioprotective effect, particularly, when it was administered prior to and concurrently with ADR treatment (prophylaxis-cotreated group). This effect was biochemically evident by the significant decreases in the serum levels of myocardial injury biomarkers such as troponin, creatine kinase-myocardium bound, and creatine phosphokinase...

Trastuzumab-induced cardiotoxicity (TIC) is the primary adverse event that limits the use of trastuzumab in HER2-positive breast cancer patients. However, the incidence and risk factors of TIC in HER2-positive gastric cancer are not known. Therefore, we evaluated the incidence and predictive factors of TIC in gastric cancer patients treated with trastuzumab in clinical practice. We reviewed cardiac dysfunction in HER2-positive gastric cancer patients between December 2005 and April 2015 in a prospectively-collected database that included prospective clinical trials at Yonsei Cancer Center, Republic of Korea...

Backgrounds: Despite their clear therapeutic benefits, anthracycline-induced cardiotoxicity is a major concern limiting the ability to reduce morbidity and mortality associated with cancers. The early identification of anthracycline-induced cardiotoxicity is of vital importance to assess the cardiac risk against the potential cancer treatment. Objective: To investigate whether speckle-tracking analysis can provide a sensitive and accurate measurement when detecting doxorubicin-induced left ventricular injury...

Progress in cancer therapy has led to improved prognosis of patients with cancer and thus to a continuous rise of cancer survivors. However, it has simultaneously increased cardiovascular morbidity and mortality rates due to direct and/or indirect side effects of anticancer treatment. Similar to the rapid rise of patients with adult congenital disease, the number of patients suffering or at risk of cardiotoxicity has been steeply increasing and getting an emerging issue. Among the many facets of chemotherapy-induced cardiovascular toxicity, this review attempts to summarize echocardiographic evaluation of cardiac function after cancer chemotherapy by reviewing the definition, risk factors, brief history, limitation of left ventricular ejection fraction and myocardial strain imaging, as well as the limitations of this technique...

Breast cancer is the most frequent cancer affecting women worlwide. In every setting, the majority of women are treated with an evergrowing arsenal of therapeutic agents that have greatly improved their outcomes. However, these therapies can also be associated with significant adverse events. Areas covered: This review aims to thoroughly describe the current state of the evidence regarding the potential cardiotoxicity of agents commonly used in the treatment of breast cancer. These include chemotherapeutic agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors...

With major oil spills in Korea, the United States, and China in the past decade, there has been a dramatic increase in the number of studies characterizing the developmental toxicity of crude oil and its associated polycyclic aromatic compounds (PACs). The use of model fish species with associated tools for genetic manipulation, combined with high throughput genomics techniques in nonmodel fish species, has led to significant advances in understanding the cellular and molecular bases of functional and morphological defects arising from embryonic exposure to crude oil...

Cefazolin sodium is an essential drug that is widely used in clinical therapy for certain infective diseases caused by bacteria. As drug impurities are considered to be one of the most important causes of drug safety issues, we studied embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazolin sodium impurities in zebrafish embryo and larvae for the objective control of impurity profiling. LC-MS/MS was employed to analyze the compound absorbance in vivo, and the structure-toxicity relationship was approached...

PURPOSE: The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low-cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur. METHODS: Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire...

Cane toads are an invasive pest species in which all life stages employ cardiotoxic bufagenins as a chemical defense against predators. Curiously, the bufagenin profiles of eggs and tadpoles are more complex than those of parotoid secretion, the principle mechanism of toxin delivery in adult toads. In an effort to understand this complexity, we determined that selected strains of adult toad parotoid-gland-associated Gram-positive bacteria, Bacillus spp., were capable of biotransforming secreted bufagenins, marinobufagenin (1), telocinobufagenin (2), bufalin (3), and resibufagenin (4), to hydroxylated scaffolds commonly encountered in cane toad eggs and tadpoles...