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https://www.readbyqxmd.com/read/28108310/autophagic-dysregulation-in-doxorubicin-cardiomyopathy
#1
REVIEW
Jordan J Bartlett, Purvi C Trivedi, Thomas Pulinilkunnil
Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although prior research has mostly implicated disruptive events in the nucleus and mitochondria to be contributing to DOX cardiomyopathy, recent discoveries in the cellular waste management process, autophagy, have highlighted the role of the lysosome, an organelle central to autophagy, in this pathology. Indeed, dysregulation of lysosomal autophagy is observed in pre-clinical models of DOX cardiotoxicity...
January 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28105242/skin-toxicity-in-a-patient-with-ovarian-cancer-treated-with-pegylated-liposomal-doxorubicin-a-case-report-and-review-of-the-literature
#2
Joanna Kubicka-Wołkowska, Magdalena Kędzierska, Maja Lisik-Habib, Piotr Potemski
Pegylated liposomal doxorubicin (PLD) is a form of doxorubicin enclosed in pegylated liposomes. In contrast to conventional doxorubicin, PLD is characterized by a lower incidence of cardiotoxicity and myelosuppression. However, it induces specific mucocutaneous side effects, particularly palmar-plantar erythrodysesthesia (PPE). Other dermal manifestations, such as intertrigo-like dermatitis, diffuse follicular rash, melanotic macules, maculopapular rash or recall phenomenon are less common. Mechanisms that lead to skin toxicity remain unclear, however, certain reports indicate that drug excretion in sweat, host-vs...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104561/assessment-of-in-vitro-cardiotoxicity-of-extract-fractions-and-diterpene-alkaloids-from-aconitum-leucostomum-worosch-a-short-communication
#3
Jihong Nie, Fang Wang, Tengfei Ji, Jun Zhao, Feicui Zhao
Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C18-diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C19-diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A...
January 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#4
REVIEW
Christian Henninger, Gerhard Fritz
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#5
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#6
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28100487/doxorubicin-induced-nitrosative-stress-is-mitigated-by-vitamin-c-via-the-modulation-of-nitric-oxide-synthases
#7
Gauri Akolkar, Ashim K Bagchi, Prathapan Ayyappan, Davinder S Jassal, Pawan K Singal
An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox) -induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of Vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms and nitrosative stress as well as cytokines TNFα and IL-10 in isolated cardiomyocytes...
January 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28100352/-update-on-the-cardiotoxicity-of-noncardiovascular-drugs
#8
W X Peng, X J Shi, Y Lin
No abstract text is available yet for this article.
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28099878/screening-verification-and-analysis-of-biomarkers-for-drug-induced-cardiac-toxicity-in-vitro-based-on-rtca-coupled-with-pcr-array-technology
#9
Lu Zhang, Meng-Xi Xu, Qing-Sheng Yin, Cai-Ying Zhu, Xue-Lian Cheng, Yi-Ran Ren, Peng-Wei Zhuang, Yan-Jun Zhang
Cardiotoxicity is one of the most serious side effects of new drugs. Early detection of the drug induced cardiotoxicity based on the biomarkers provides an important preventative strategy for detecting potential cardiotoxicity of candidate drugs. In this study, we aim to identify the predictive genomics biomarkers for drug-induced cardiac toxicity based on the RTCA coupled with PCR Array technology in primary cells. Three prototypical cardiotoxic compounds (doxorubicin, isoproterenol, ouabain) with different mechanisms were firstly real-time monitored to diagnose the cytotoxicity by using the RTCA, while the functional alterations of cardiomyocytes were also monitored by analyzing the beating frequency of cardiomyocytes...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28099361/the-cardiotoxicity-of-cetuximab-as-single-therapy-in-chinese-chemotherapy-refractory-metastatic-colorectal-cancer-patients
#10
Xue-Miao Tang, Hao Chen, Yu Liu, Bin-Lian Huang, Xiu-Quan Zhang, Jian-Mei Yuan, Xia He
The cardiac safety of cetuximab, particularly as single approach, has not been investigated extensively. This trial was designed to evaluate the cardiac safety of cetuximab as salvage monotherapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients.Cetuximab was administrated at an initial dose of 400 mg/mon day 1 (week 1), followed by a maintenance dose of 250 mg/m on day 1 of each 7-day cycle. Electrocardiograph (ECG), routine laboratory tests, and troponin I (TNI) Ultra were performed at baseline, during, and after the cetuximab therapy...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28098511/hemodynamic-effects-of-hpma-copolymer-based-doxorubicin-conjugate-a-randomized-controlled-and-comparative-spectral-study-in-conscious-rats
#11
Hoay Yan Cheah, Olivera Šarenac, Juan J Arroyo, Marko Vasić, Maja Lozić, Sofija Glumac, See Ziau Hoe, Charles Colin Thomas Hindmarch, David Murphy, Lik Voon Kiew, Hong Boon Lee, Marίa J Vicent, Lip Yong Chung, Nina Japundžić-Žigon
Conjugation of Doxorubicin (DOX) to N-(2-Hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX...
January 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28098423/brain-derived-neurotrophic-factor-attenuates-doxorubicin-induced-cardiac-dysfunction-through-activating-akt-signalling-in-rats
#12
Pengzhou Hang, Jing Zhao, Li Sun, Minghui Li, Yu Han, Zhimin Du, Yue Li
The clinical application of doxorubicin (Dox) is limited by its adverse effect of cardiotoxicity. Previous studies have suggested the cardioprotective effect of brain-derived neurotrophic factor (BDNF). We hypothesize that BDNF could protect against Dox-induced cardiotoxicity. Sprague Dawley rats were injected with Dox (2.5 mg/kg, 3 times/week, i.p.), in the presence or absence of recombinant BDNF (0.4 μg/kg, i.v.) for 2 weeks. H9c2 cells were treated with Dox (1 μM) and/or BDNF (400 ng/ml) for 24 hrs. Functional roles of BDNF against Dox-induced cardiac injury were examined both in vivo and in vitro...
November 7, 2016: Journal of Cellular and Molecular Medicine
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
#13
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/28092839/effect-and-mechanism-of-sorbus-pohuashanensis-hante-hedl-flavonoids-protect-against-arsenic-trioxide-induced-cardiotoxicity
#14
Xiaojin Yu, Zhenyu Wang, Zunpeng Shu, Zhengqing Li, Yuan Ning, Keli Yun, Haina Bai, Ruihai Liu, Wenli Liu
The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS)...
January 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28092472/using-biomarkers-to-predict-and-to-prevent-cardiotoxicity-of-cancer-therapy
#15
Daniela Cardinale, Gina Biasillo, Michela Salvatici, Maria Teresa Sandri, Carlo Maria Cipolla
Cardiotoxicity is a common complication that may compromise the clinical effectiveness of anticancer therapy. The current standard for monitoring cardiac function detects cardiotoxicity only when a functional impairment has already occurred, not allowing for any early preventive strategy. Areas covered: A novel approach, based on the use of biomarkers has recently emerged, resulting in a very effective tool for early, real-time identification, and monitoring of cardiotoxicity. In particular, cardiac troponin elevation during chemotherapy allows to identify patients more prone to develop myocardial dysfunction and cardiac events...
January 16, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28087064/effect-of-cyp2d6-polymorphisms-on-the-pharmacokinetics-of-propafenone-and-its-two-main-metabolites
#16
Mohammad-Reza Rouini, Minoo Afshar
AIM OF THE STUDY: Propafenone (PPF) is an antiarrhythmic drug, metabolized mainly by CYP2D6 to 5-hydroxypropafenone (5OH-PPF) and by CYP3A4 to norpropafenone (NOR-PPF). CYP2D6 shows a high degree of genetic polymorphism which is associated with diminished antiarrhythmic efficacy or cardiac seizures/cardiotoxicity. This study aimed to investigate the effect of the CYP2D6 polymorphism on the pharmacokinetics of PPF and its two main metabolites. The usefulness of PPF/5OH-PPF ratio for CYP2D6 phenotyping in healthy adults was also evaluated...
December 19, 2016: Thérapie
https://www.readbyqxmd.com/read/28079007/novel-therapies-targeting-cardioprotection-and-regeneration
#17
Valeria Garrido, Evelyn Mendoza-Torres, Jaime A Riquelme, Ariel Díaz, Marcela Pizarro, Mario Bustamante, Myra N Chavez, María Paz Ocaranza, Rosemarie Mellado, Ramon Corbalan, Miguel L Allende, Sergio Lavandero
Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy...
January 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28078076/sex-dependent-alteration-of-cardiac-cytochrome-p450-gene-expression-by-doxorubicin-in-c57bl-6-mice
#18
Marianne K O Grant, Davis M Seelig, Leslie C Sharkey, Beshay N Zordoky
BACKGROUND: There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28074721/-capecitabine-induced-ventricular-fibrillation
#19
A V van Capelle, J de Valk, D Schakenraad, T Germans, D Ten Oever
BACKGROUND: Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of colorectal, gastric and breast carcinoma. Capecitabine has relatively mild side effects. Less known are its potential severe cardiotoxic effects. CASE DESCRIPTION: We report a case of a 61-year-old man recently diagnosed with rectal cancer. Six days after starting with capecitabine, he developed a cardiac arrest due to ventricular fibrillation (VF). Extensive additional diagnostics did not explain the cardiac arrest nor VF...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28073687/adverse-event-detection-using-the-fda-post-marketing-drug-safety-surveillance-system-cardiotoxicity-associated-with-loperamide-abuse-and-misuse
#20
Kimberley A Swank, Eileen Wu, Cindy Kortepeter, Jana McAninch, Robert L Levin
OBJECTIVE: The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016...
January 7, 2017: Journal of the American Pharmacists Association: JAPhA
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