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https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#1
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28811127/attenuation-of-sunitinib-induced-cardiotoxicity-through-the-a3-adenosine-receptor-activation
#2
Hardip Sandhu, Samantha Cooper, Afthab Hussain, Christopher Mee, Helen Maddock
Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28810591/dual-character-of-flavonoids-in-attenuating-and-aggravating-ischemia-reperfusion-induced-myocardial-injury
#3
Wenqiang Li, Yun Li, Ruifang Sun, Sumei Zhou, Meifeng Li, Mingchen Feng, Yingguang Xie
The concept that flavonoids exert cardioprotection against myocardial ischemia-reperfusion (I/R) injury has been acknowledged by a large body of evidence. However, recent studies reported cardiotoxic effects of certain flavonoids, while the underlying mechanisms have remained largely elusive. Flavonoids have been demonstrated to activate aryl hydrocarbon receptor (Ahr), which is implicated in an array of cell signaling processes. The present study examined the cardioprotective roles of quercetin (Qu) and β-naphthoflavone (β-NF) against I/R injury and explored whether the underlying mechanism proceeds via molecular signaling downstream of Ahr...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808936/-envenomation-by-micrurus-psyches-in-french-guiana
#4
X Heckmann, C Marty, F Starace, J-D Louembé, S Larréché
We report here the first known envenomation by Micrurus psyches, the so-called Carib coral snake, which occurred on April 2016 in the surroundings of Saint- Laurent-du-Maroni, Western French Guiana. Besides local neurological symptoms, it featured unexpected electrocardiogram changes, which were emergence of a first-degree atrioventricular block and biphasic T waves, both transient. NewWorld elapid venoms were not known for being cardiotoxic so far. The possible reasons of this cardiac injury are discussed.
August 14, 2017: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/28807827/the-endotoxemia-cardiac-dysfunction-is-attenuated-by-ampk-mtor-signaling-pathway-regulating-autophagy
#5
Jie Zhang, Peng Zhao, Nanhu Quan, Lin Wang, Xu Chen, Courtney Cates, Thomas Rousselle, Ji Li
AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK on lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway against autophagy in young and aged mice...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhance-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#6
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28807058/role-of-metabolites-of-cyclophosphamide-in-cardiotoxicity
#7
Koichiro Kurauchi, Takuro Nishikawa, Emiko Miyahara, Yasuhiro Okamoto, Yoshifumi Kawano
BACKGROUND: The dose-limiting toxic effect of cyclophosphamide (CY) is cardiotoxicity. The pathogenesis of myocardial damage is poorly understood, and there is no established means of prevention. In previous studies, we suggested that for CY-induced cardiotoxicity, whereas acrolein is the key toxic metabolite, carboxyethylphosphoramide mustard (CEPM) is protective. We sought to verify that acrolein is the main cause of cardiotoxicity and to investigate whether aldehyde dehydrogenase (ALDH), which is associated with greater CEPM production, is involved in the protective effect for cardiotoxicity...
August 14, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#8
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28804553/sirt3-attenuates-doxorubicin-induced-cardiac-hypertrophy-and-mitochondrial-dysfunction-via-suppression-of-bnip3
#9
Qiong Du, Bin Zhu, Qing Zhai, Bo Yu
Doxorubicin (Dox) is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by development of cardiotoxicity. Sirtuin-3 (Sirt3) is the major deacetylase within the mitochondrial matrix that plays an important role in regulation of cardiac function. This study was performed to identify the regulatory role of Sirt3 on Dox-induced cardiac hypertrophy and mitochondrial dysfunction in rats in vivo and in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801766/absence-of-cardiotoxicity-with-prolonged-treatment-and-large-accumulating-doses-of-pegylated-liposomal-doxorubicin
#10
N Blank, I Laskov, R Kessous, L Kogan, S Lau, I A Sebag, Walter H Gotlieb, L Rudski
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]...
August 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28801545/cardiotoxicity-and-mechanism-of-particulate-matter-2-5-pm2-5-exposure-in-offspring-rats-during-pregnancy
#11
Hongling Wang, Xiangwen Peng, Fenglin Cao, Ying Wang, Huijie Shi, Shuai Lin, Weijie Zhong, Jingxia Sun
BACKGROUND The aim of this study was to investigate the cardiotoxicity and mechanism of particulate matter 2.5 (PM2.5) exposure on offspring rats during pregnancy. MATERIAL AND METHODS Wistar rats were used to establish a PM2.5 exposure animal model during pregnancy, and they were divided into a control group, a low-dose group, a middle-dose group, and a high-dose group according to PM2.5 exposure dose. The pathological changes of heart tissue, the rate of myocardial cell apoptosis, the levels of LDH, AST, and CM-KB in serum, and the difference in mitochondrial fusion genes (OPA1 and Mfn1) and mitochondrial genes (Drp1 and Fis1) were compared among groups...
August 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28795750/supramolecular-alleviation-of-cardiotoxicity-of-a-small-molecule-kinase-inhibitor
#12
Xue Yang, Qiaoxian Huang, David Bardelang, Chunming Wang, Simon M Y Lee, Ruibing Wang
Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO by a synthetic receptor cucurbit[7]uril (CB[7]) alleviated the inherent cardiotoxicity of SO, as demonstrated in an in vivo zebrafish model. Moreover, the anti-cancer activity of SO was well preserved, upon its encapsulation by CB[7], as demonstrated by both in vitro and in vivo cancer/angiogenesis models...
August 10, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28795306/lung-cancer-as-a-cardiotoxic-state-a-review
#13
REVIEW
David Pérez-Callejo, María Torrente, María Auxiliadora Brenes, Beatriz Núñez, Mariano Provencio
As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed...
August 9, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28791609/cardiac-imaging-multimodality-advances-and-surveillance-strategies-in-detection-of-cardiotoxicity
#14
REVIEW
Marie Moonen, Cécile Oury, Patrizio Lancellotti
Contemporary cancer management has increased the overall number of cancer survivors, but cardiotoxicity remains a subject of concern, which is a major cause of noncancer mortality among survivors. Among the potential cardiovascular complications, left ventricular (LV) systolic dysfunction is a poor prognostic factor. The importance of its early detection is based on the principle that the likelihood of response to heart failure (HF) treatment is temporally related to the initiation of HF treatment. For these reasons, cardiac monitoring is commonly applied in general practice, based on serial measurements of LV ejection fraction (LVEF); transthoracic echocardiography (TTE) is generally used...
August 8, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28783581/high-doses-of-s-methylcysteine-cause-hypoxia-induced-cardiomyocyte-apoptosis-accompanied-by-engulfment-of-mitochondaria-by-nucleus
#15
Mohammed A El-Magd, Walied S Abdo, Mustafa El-Maddaway, Nasr M Nasr, Rasha A Gaber, Eman S El-Shetry, Ayman A Saleh, Faisal Abdulrahman Ali Alzahrani, Doaa H Abdelhady
Despite its important role as a medicinal plant, some studies reported a toxic effect for garlic (Allium sativum) when given in higher doses. Herein, we investigated the possible cardiotoxic effects of high doses of S-methylcysteine (SMC), a water soluble organosulfur compound present in garlic. Rats were orally administered SMC at a low dose (50mg), high dose (150mg) and very high dose (300mg)/kg body weight, or saline (control) for 10days. High and very high doses of SMC resulted in a significant increase in serum cardiac injury biomarkers [aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin T (cTnT)], as well as oxidative stress marker nitric oxide (NO) concentration in heart and a significant decrease in cardiac superoxide dismutase (SOD) activity...
August 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28781723/developing-a-comprehensive-cardio-oncology-program-at-a-cancer-institute-the-moffitt-cancer-center-experience
#16
REVIEW
Michael G Fradley, Allen C Brown, Bernadette Shields, Federico Viganego, Rongras Damrongwatanasuk, Aarti A Patel, Gregory Hartlage, Natalee Roper, Julie Jaunese, Larry Roy, Roohi Ismail-Khan
Cardio-oncology is a multidisciplinary field focusing on the management and prevention of cardiovascular complications in cancer patients and survivors. While the initial focus of this specialty was on heart failure associated with anthracycline use, novel anticancer agents are increasingly utilized and are associated with many other cardiotoxicities including hypertension, arrhythmias and vascular disease. Since its inception, the field has developed at a rapid pace with the establishment of programs at many major academic institutions and community practices...
June 14, 2017: Oncology Reviews
https://www.readbyqxmd.com/read/28780919/anthracycline-induced-cardiotoxicity-in-patients-with-paediatric-bone-sarcoma-and-soft-tissue-sarcoma
#17
Ilaria Bini, Sebastian D Asaftei, Chiara Riggi, Elisa Tirtei, Rosaria Manicone, Eleonora Biasin, Maria Eleonora Basso, Gabriella Agnoletti, Franca Fagioli
OBJECTIVES: Anthracycline cardiotoxicity is an important side-effect in long-term childhood cancer survivors. We evaluated the incidence of and factors associated with anthracycline cardiotoxicity in a population of patients diagnosed with bone or soft tissue sarcoma. Materials and methods We retrospectively enrolled patients diagnosed with bone or soft tissue sarcoma, from 1995 to 2011, treated with anthracycline chemotherapy at our Centre and with a follow-up echocardiography carried out ⩾3 years from cardiotoxic therapy completion...
August 7, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/28780599/liraglutide-ameliorates-cardiotoxicity-induced-by-doxorubicin-in-rats-through-the-akt-gsk-3%C3%AE-signaling-pathway
#18
Noha A T Abbas, Soad L Kabil
Doxorubicin (Dox)-induced cardiotoxicity constitutes the major adverse effect that limited its use. We investigated the possible protective effects of liraglutide on Dox-induced cardiotoxicity in rats. Rats were divided into the following groups: control group rats received normal saline [1 ml/kg, intraperitoneal (i.p.)]; doxorubicin group rats received doxorubicin (1.25 mg/kg, i.p.), four times per week for 4 weeks; and liraglutide group rats received doxorubicin (1.25 mg/kg, i.p.) four times per week for 4 weeks then received liraglutide (100 μg/kg, i...
August 5, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28777443/use-of-human-pluripotent-stem-cell-derived-cardiomyocytes-to-study-drug-induced-cardiotoxicity
#19
Agnes Maillet, Kim Peng Tan, Liam R Brunham
Drug-induced cardiotoxicity is the one of the most common causes of drug withdrawal from market. A major barrier in managing the risk of drug-induced cardiotoxicity has been the lack of relevant models to study cardiac safety. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in drug discovery and cardiotoxcity screens as they display many characteristics of the human myocardium and offer unlimited supply. This unit describes how to use pluripotent stem cells derived cardiomyocytes to study drug-induced cardiotoxicty using doxorubicin as an example...
August 4, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28774277/novel-approaches-to-the-prediction-diagnosis-and-treatment-of-cardiac-late-effects-in-survivors-of-childhood-cancer-a-multi-centre-observational-study
#20
Amy Skitch, Seema Mital, Luc Mertens, Peter Liu, Paul Kantor, Lars Grosse-Wortmann, Cedric Manlhiot, Mark Greenberg, Paul C Nathan
BACKGROUND: Anthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity...
August 3, 2017: BMC Cancer
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