Abstract
: Cancer patients are increasingly referred for cardiology evaluations. These patients differ from those routinely seen in cardiology clinics because of their psychological burden and because the therapies and cancer itself can cause cardiac symptoms. A humane approach is critical to managing these patients. Cardiologists may see patients who are newly diagnosed with cancer or are in various phases of treatment; these patients may or may not have preexisting cardiac disease, and may develop cardiotoxicity from chemoimmunotherapy or radiotherapy. Each of these situations presents unique communication challenges for cardiologists. Although some oncology centers provide training in communication skills for their personnel, including cardiologists, this training is not widely available to physicians in general hospitals or private practice. This article examines the psychological aspects of cardio-oncology. It offers practical suggestions on how to best communicate with cancer patients in different phases of oncology care, and discusses when professional psychological help is needed.
PMID: 31977538 [PubMed - as supplied by publisher]
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Cardiotoxicity and Cardioprotection by Artesunate in Larval Zebrafish.
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Cardiotoxicity and Cardioprotection by Artesunate in Larval Zebrafish.
Dose Response. 2020 Jan-Mar;18(1):1559325819897180
Authors: Zheng C, Shan L, Tong P, Efferth T
Abstract
Although artesunate (ART) is generally accepted as a safe and well-tolerated first-line treatment of severe malaria, cases of severe side effects and toxicity of this compound are also documented. This study applied larval zebrafishes to determine the acute toxicity and efficacy of ART and performed RNA-sequencing analyses to unravel the underlying signaling pathways contributing to ART's activities. Results from acute toxicity assay showed that a single-dose intravenous injection of ART from 3.6 ng/fish (1/9 maximum nonlethal concentration) to 41.8 ng/fish (lethal dose 10%) obviously induced pericardial edema, circulation defects, yolk sac absorption delay, renal edema, and swim bladder loss, indicating acute cardiotoxicity, nephrotoxicity, and developmental toxicity of ART. Efficacy assay showed that ART at 1/2 lowest observed adverse effect level (LOAEL) exerted cardioprotective effects on zebrafishes with verapamil-induced heart failure. Artesunate significantly restored cardiac malformation, venous stasis, cardiac output decrease, and blood flow dynamics reduction. No adverse events were observed with this treatment, indicating that ART at doses below LOAEL was effective and safe. These results indicate that ART at low doses was cardioprotective, but revealed cardiotoxicity at high doses. RNA-sequencing analysis showed that gene expression of frizzled class receptor 7a (fzd7a) was significantly upregulated in zebrafishes with verapamil-induced heart failure and significantly downregulated if ART at 1/2 LOAEL was coadministrated, indicating that fzd7a-modulated Wnt signaling may mediate the cardioprotective effect of ART. For the first time, this study revealed the biphasic property of ART, providing in-depth knowledge on the pharmacological efficacy-safety profile for its therapeutic and safe applications in clinic.
PMID: 31975974 [PubMed]
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Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride.
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Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride.
J Pharm Pharmacol. 2020 Jan 24;:
Authors: Zha L, Wang B, Qian J, Fletcher B, Zhang C, Dong Q, Chen W, Hong L
Abstract
OBJECTIVES: Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein-DOX NPs) to improve its pH-sensitive release, bioavailability and decrease cardiotoxicity.
METHODS: HA/Zein-DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X-ray diffraction and Fourier-transform infrared spectroscopy of HA/Zein-DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo.
KEY FINDINGS: The small PDI and high Zeta potential demonstrated that HA/Zein-DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein-DOX NPs. HA/Zein-DOX NPs showed pH-sensitive release. Compared with free DOX, HA/Zein-DOX NPs increased cellular uptake which caused 7 times higher in-vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t1/2β and AUC0- t of HA/Zein-DOX NPs were 2.73- and 3.12-fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein-DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%).
CONCLUSION: In this study, HA/Zein-DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.
PMID: 31975457 [PubMed - as supplied by publisher]
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The Limits of the Linear Quadratic (LQ) Model for Late Cardiotoxicity Prediction: Example of Hypofractionated Rotational Intensity Modulated Radiation Therapy (IMRT) for Breast Cancer.
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The Limits of the Linear Quadratic (LQ) Model for Late Cardiotoxicity Prediction: Example of Hypofractionated Rotational Intensity Modulated Radiation Therapy (IMRT) for Breast Cancer.
Int J Radiat Oncol Biol Phys. 2020 Jan 20;:
Authors: Loap P, Fourquet A, Kirova Y
PMID: 31973883 [PubMed - as supplied by publisher]
26 January 2020
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Genetic Polymorphisms Affecting Cardiac Biomarker Concentrations in Children with Cancer: an Analysis from the "European Paediatric Oncology Off-patents Medicines Consortium" (EPOC) Trial.
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Genetic Polymorphisms Affecting Cardiac Biomarker Concentrations in Children with Cancer: an Analysis from the "European Paediatric Oncology Off-patents Medicines Consortium" (EPOC) Trial.
Eur J Drug Metab Pharmacokinet. 2020 Jan 24;:
Authors: Hellmann F, Völler S, Krischke M, Jamieson D, André N, Bisogno G, Boddy A, Hempel G
Abstract
BACKGROUND AND OBJECTIVES: Doxorubicin plays an essential role in the treatment of paediatric cancers. Defining genotypes with a higher risk for developing anthracycline-induced cardiotoxicity could help to reduce cardiotoxicity.
METHODS: Data originated from a phase II study assessing the pharmacokinetics of doxorubicin in 100 children. Studied patients (0-17 years) were treated for solid tumours or leukaemia. Two cycles of doxorubicin were studied. Concentrations of natriuretic peptides proANP, BNP and NT-proBNP and cardiac troponins T and I were measured at five time points before, during and after two cycles of doxorubicin treatment. Genotypes of 17 genetic polymorphisms in genes encoding for anthracycline metabolizing enzymes and drug transporters were determined for each patient. We analysed the influence of genotypes on cardiac biomarker concentrations at different time points by a Kruskal-Wallis test. To perform a pairwise comparison significant genetic polymorphisms with more than two genotypes were analysed by a post hoc test.
RESULTS: The Kruskal-Wallis tests and the post hoc-tests showed a significant association for seven genetic polymorphisms (ABCB1-rs1128503, ABCB1-rs1045642, ABCC1-rs4148350, CBR3-rs8133052, NQO2-in/del, SLC22A16-rs714368 and SLC22A16-rs6907567) with the concentration of at least one biomarker at one or more time points. We could not identify any polymorphism with a consistent effect on any biomarker over the whole treatment period.
CONCLUSIONS: In this study of patients treated with doxorubicin for different tumour entities, seven genetic polymorphisms possibly influencing the pharmacokinetics and pharmacodynamics of doxorubicin could lead occasionally to differences in the concentration of cardiac biomarkers. Since, the role of cardiac biomarkers for monitoring anthracycline-induced cardiotoxicity has not yet been clarified, further trials with a long follow-up time are required to assess the impact of these genetic polymorphisms on chemotherapy-related cardiotoxicity.
TRIAL REGISTRATION: EudraCT number: 2009-011454-17.
PMID: 31981210 [PubMed - as supplied by publisher]
28 January 2020
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Rehabilitation Needs in Cancer Treatment-Related Cardiotoxicity.
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Rehabilitation Needs in Cancer Treatment-Related Cardiotoxicity.
Semin Oncol Nurs. 2020 Jan 23;:150986
Authors: Pituskin E, Kirkham AA, Cox-Kennett N, Dimitry R, Dimitry J, Paterson I, Gyenes GT
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