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Cardiac Toxicity

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https://www.readbyqxmd.com/read/28098907/synergistic-combination-of-ys-1-and-adriamycin-inhibits-human-renal-cancer-through-erk1-2-signaling-pathway-in%C3%A2-vitro-and-in%C3%A2-vivo
#1
Xiaowen Yu, Qingqing Yang, Sensen Lin, Shengtao Yuan, Li Sun
Adriamycin (ADM) is a principal drug for the treatment of renal cell cancer (RCC). Due to its limited response and high renal and cardiac toxicity, synergistic effects of ADM in combination with other drugs have been widely researched. In this study, we found the combination between YS-1 and ADM, performed higher anticancer activity on 786-O human RCC cells in vitro and in vivo, than that reported on its anti-angiogenesis effect compared with monotherapy of ADM. Our data showed that when combined with ADM, YS-1 promoted the sensitivity of 786-O cells to ADM...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#2
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28094454/boosting-the-reserves-additive-regulation-of-cardiac-repolarisation
#3
Adam P Hill
Since the first description of the mechanism of digitalis toxicity in this journal in 1978 (Kass et al. 1978), abnormal calcium handling has been established as a key player across a spectrum of ventricular arrhythmias. This article is protected by copyright. All rights reserved.
January 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28090366/bosutinib-therapy-in-patients-with-chronic-myeloid-leukemia-practical-considerations-for-management-of-side-effects
#4
REVIEW
Patricia S Ault, John Rose PharmD, Lisa A Nodzon PhD, Elizabeth S Kaled
The past decade has witnessed great advances in the treatment of chronic myeloid leukemia (CML), brought about in large part by the development of BCR-ABL tyrosine kinase inhibitors (TKIs). Bosutinib joins the armamentarium of approved TKIs for the treatment of chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome (Ph)-positive CML resistant to or intolerant of prior therapy. Bosutinib has an adverse-event (AE) profile distinct from that of other TKIs. Diarrhea is the predominant toxicity associated with bosutinib treatment; other commonly reported nonhematologic AEs include rash and liver enzyme elevations...
March 2016: Journal of the Advanced Practitioner in Oncology
https://www.readbyqxmd.com/read/28089476/serum-asymmetric-and-symmetric-dimethylarginine-and-morbidity-and-mortality-in-hemodialysis-patients
#5
Tariq Shafi, Thomas H Hostetter, Timothy W Meyer, Seungyoung Hwang, Xin Hai, Michal L Melamed, Tanushree Banerjee, Josef Coresh, Neil R Powe
BACKGROUND: Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. STUDY DESIGN: Post hoc analysis of the Hemodialysis (HEMO) Study. SETTING & PARTICIPANTS: 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization...
January 12, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28089158/cardiac-dose-and-survival-after-stereotactic-body-radiotherapy-for-early-stage-non-small-cell-lung-cancer
#6
Amode R Tembhekar, Cari L Wright, Megan E Daly
INTRODUCTION: Recent analyses have identified cardiac dose as an important predictor of overall survival (OS) after chemoradiation for locally advanced non-small-cell lung cancer (NSCLC). However, the survival influence of the cardiac dose after stereotactic body radiotherapy (SBRT) is unknown. We performed a dose-volume histogram (DVH) analysis of patients treated with SBRT for early stage NSCLC to examine survival and cardiac toxicity. MATERIALS AND METHODS: We reviewed the medical records of patients who had undergone SBRT for early-stage NSCLC from June 2007 to June 2015 and documented the cardiac DVH parameters, including the maximum and mean dose and percentage of volume receiving >5, >10, >20, and >30 Gy (V5, V10, V20, and V30, respectively)...
December 22, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28081170/an-alpha-1a-adrenergic-receptor-agonist-prevents-acute-doxorubicin-cardiomyopathy-in-male-mice
#7
Megan D Montgomery, Trevor Chan, Philip M Swigart, Bat-Erdene Myagmar, Rajesh Dash, Paul C Simpson
Alpha-1 adrenergic receptors mediate adaptive effects in the heart and cardiac myocytes, and a myocyte survival pathway involving the alpha-1A receptor subtype and ERK activation exists in vitro. However, data in vivo are limited. Here we tested A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide), a selective imidazoline agonist for the alpha-1A. A61603 was the most potent alpha-1-agonist in activating ERK in neonatal rat ventricular myocytes. A61603 activated ERK in adult mouse ventricular myocytes and protected the cells from death caused by the anthracycline doxorubicin...
2017: PloS One
https://www.readbyqxmd.com/read/28079735/incidence-of-local-anesthetic-systemic-toxicity-in-orthopedic-patients-receiving-peripheral-nerve-blocks
#8
Eva E Mörwald, Nicole Zubizarreta, Crispiana Cozowicz, Jashvant Poeran, Stavros G Memtsoudis
BACKGROUND AND OBJECTIVES: Peripheral nerve blocks are increasingly used. However, despite low complication rates, concerns regarding local anesthetic systemic toxicity remain. Although recent studies suggest that this severe complication has decreased considerably, there is a paucity of data about it on a national level. We sought to elucidate the incidence of local anesthetic systemic toxicity on a national level and therefore provide guidance toward the need for preparedness in daily anesthetic practice...
January 9, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28076319/impact-of-nutrition-on-pollutant-toxicity-an-update-with-new-insights-into-epigenetic-regulation
#9
Jessie B Hoffman, Michael C Petriello, Bernhard Hennig
Exposure to environmental pollutants is a global health problem and is associated with the development of many chronic diseases, including cardiovascular disease, diabetes and metabolic syndrome. There is a growing body of evidence that nutrition can both positively and negatively modulate the toxic effects of pollutant exposure. Diets high in proinflammatory fats, such as linoleic acid, can exacerbate pollutant toxicity, whereas diets rich in bioactive and anti-inflammatory food components, including omega-3 fatty acids and polyphenols, can attenuate toxicant-associated inflammation...
January 11, 2017: Reviews on Environmental Health
https://www.readbyqxmd.com/read/28071742/core-transcription-factors-micrornas-and-small-molecules-drive-transdifferentiation-of-human-fibroblasts-towards-the-cardiac-cell-lineage
#10
Nicolas Christoforou, Syandan Chakraborty, Robert D Kirkton, Andrew F Adler, Russell C Addis, Kam W Leong
Transdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071613/clinical-and-pathologic-response-following-taxane-based-neoadjuvant-chemotherapy-in-locally-advanced-breast-cancer-patients-in-a-tertiary-care-centre-in-india
#11
Masillamany Sivasanker, S C Sistla, S Ali Manwar, S Vivekanandam
BACKGROUND: Neoadjuvant chemotherapy has become the standard recommendation in the management of patients with locally advanced breast cancer. At present anthracycline based regimen such as CAF (cyclophosphamide, adriamycin and 5-FU) is widely used in clinical practice. The introduction of taxanes has revolutionized this field because of superior results. AIMS AND OBJECTIVES: This study is designed to compare the efficacy of paclitaxel plus doxorubicin regimen and CAF (cyclophosphamide, doxorubicin and 5-fluorouracil) regimen as neoadjuvant treatment of locally advanced breast cancer and to compare their toxicity profiles and also to correlate the hormonal receptor status in predicting response to the NACT...
April 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28070113/pharmacological-characterization-of-microminipig-as-a-model-to-assess-the-drug-induced-cardiovascular-responses-for-non-clinical-toxicity-and-or-safety-pharmacology-studies
#12
Hirofumi Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, Kiyotaka Hoshiai, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Yasuki Akie, Atsushi Sugiyama
We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28059036/reduction-of-doxorubicin-induced-cardiotoxicity-using-nanocarriers-a-review
#13
Michaela Fojtu, Jaromir Gumulec, Tibor Stracina, Martina Raudenska, Anna Skotakova, Marketa Vaculovicova, Vojtech Adam, Petr Babula, Marie Novakova, Michal Masarik
BACKGROUND: Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of haematological and solid tumours, although its administration is commonly accompanied with several severe side effects. The most serious one is a development of dose-dependent and cumulative cardiotoxicity. In the course of time, many strategies have been investigated in order to avoid or at least to diminish DOX-induced cardiac dysfunction; these include reduction of toxic effect by co-administration with iron chelators (dexrazoxane), trastuzumab, taxanes, statins, and ACE-inhibitors...
January 5, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28056568/in-vitro-metabolite-formation-in-human-hepatocytes-and-cardiomyocytes-and-metabolism-and-tissue-distribution-in-monkeys-of-the-2-c-methylguanosine-prodrug-bms-986094
#14
Wenying Li, Kevin J Trouba, Li Ma, Jae Kwagh, Christopher Storck, Yongxin Zhu, Oliver Flint, William G Humphreys, Jian Wang, Ang Liu, Bonnie Wang, Michael J Graziano, Marc H Davies, Thomas P Sanderson
BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28049396/oxidative-stress-and-antioxidant-potential-of-one-hundred-medicinal-plants
#15
Waseem Hassan, Hamsa Noreen, Shakila Rehman, Shehnaz Gul, Mohammad Amjad Kamal, Jean Paul Kamdem, Bakht Zaman, Joao B T da Rocha
Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc...
January 2, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28047965/tu-h-campus-jep2-05-can-automatic-delineation-of-cardiac-substructures-on-noncontrast-ct-be-used-for-cardiac-toxicity-analysis
#16
Y Luo, Z Liao, W Jiang, D Gomez, R Williamson, L Court, J Yang
PURPOSE: To evaluate the feasibility of using an automatic segmentation tool to delineate cardiac substructures from computed tomography (CT) images for cardiac toxicity analysis for non-small cell lung cancer (NSCLC) patients after radiotherapy. METHODS: A multi-atlas segmentation tool developed in-house was used to delineate eleven cardiac substructures including the whole heart, four heart chambers, and six greater vessels automatically from the averaged 4DCT planning images for 49 NSCLC patients...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047823/we-de-209-00-practical-implementation-of-deep-inspiration-breath-hold-techniques-for-breast-radiation-therapy
#17
Rebecca Howell
: Breast radiation therapy is associated with some risk of lung toxicity as well as cardiac toxicity for left-sided cases. Radiation doses to the lung and heart can be reduced by using the deep inspiration breath hold (DIBH) technique, in which the patient is simulated and treated during the deep inspiration phase of the breathing cycle. During DIBH, the heart is usually displaced posteriorly, inferiorly, and to the right, effectively expanding the distance between the heart and the breast/chest wall...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047632/we-de-209-03-spirometric-motion-management-system
#18
S Hadley
: Breast radiation therapy is associated with some risk of lung toxicity as well as cardiac toxicity for left-sided cases. Radiation doses to the lung and heart can be reduced by using the deep inspiration breath hold (DIBH) technique, in which the patient is simulated and treated during the deep inspiration phase of the breathing cycle. During DIBH, the heart is usually displaced posteriorly, inferiorly, and to the right, effectively expanding the distance between the heart and the breast/chest wall...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047209/su-c-brc-01-a-monte-carlo-study-of-out-of-field-doses-from-cobalt-60-teletherapy-units-intended-for-historical-correlations-of-dose-to-normal-tissue
#19
H Petroccia, E Olguin, W Culberson, B Bednarz, N Mendenhall, W Bolch
PURPOSE: Innovations in radiotherapy treatments, such as dynamic IMRT, VMAT, and SBRT/SRS, result in larger proportions of low-dose regions where normal tissues are exposed to low doses levels. Low doses of radiation have been linked to secondary cancers and cardiac toxicities. The AAPM TG Committee No.158 entitled, 'Measurements and Calculations of Doses outside the Treatment Volume from External-Beam Radiation Therapy', has been formed to review the dosimetry of non-target and out-of-field exposures using experimental and computational approaches...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047169/we-de-209-01-dosimetric-benefits-of-dibh
#20
R Howell
: Breast radiation therapy is associated with some risk of lung toxicity as well as cardiac toxicity for left-sided cases. Radiation doses to the lung and heart can be reduced by using the deep inspiration breath hold (DIBH) technique, in which the patient is simulated and treated during the deep inspiration phase of the breathing cycle. During DIBH, the heart is usually displaced posteriorly, inferiorly, and to the right, effectively expanding the distance between the heart and the breast/chest wall...
June 2016: Medical Physics
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