Doxorubicin and its proarrhythmic effects: a comprehensive review of the evidence from experimental and clinical studies

Publication date: Available online 13 November 2019Source: Pharmacological ResearchAuthor(s): Juthipong Benjanuwattra, Natthaphat Siri-Angkul, Siriporn C. Chattipakorn, Nipon C. hattipakornAbstractThe cancer burden on health and socioeconomics remains exceedingly high, with more than ten million new cases reported worldwide in 2018. The financial cost of managing cancer patients has great economic impact on both an individual and societal levels. Currently, many chemotherapeutic agents are available to treat various malignancies. One of these agents is doxorubicin, which was isolated from Streptomyces peucetius in the 1960s. Doxorubicin is frequently administered in combination with other agents as a mainstay chemotherapeutic regimen in many settings, since there is well-documented evidence that it is effective in eliminating malignant cells. Doxorubicin exerts its anti-tumor properties through DNA intercalation and topoisomerase inhibition. It also contains a quinone moiety which is susceptible to redox reaction with certain intracellular molecules, thereby leading to the production of reactive oxygen species. The oxidative stress following doxorubicin exposure is responsible for its well-documented cardiotoxicity, impairing cardiac contractility, ultimately resulting in congestive heart failure. Despite the cumulative evidence noting its adverse effects on the heart, limited information is available regarding the mechanistic association between doxorubicin and cardiac arrhy...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 21 December 2018Source: Pharmacological ResearchAuthor(s): Hesham R. El-Seedi, Shaden A.M. Khalifa, Eman A. Taher, Mohamed A. Farag, Aamer Saeed, Mohamed Gamal, Mohamed-Elamir F. Hegazy, Diaa Youssef, Syed G. Musharraf, Muaaz M. Alajlani, Jianbo Xiao, Thomas EfferthAbstractCardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of ...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Introduction. Recent research in lymphoma has resulted in better outcomes for clinical trial populations. Population studies have suggested that some real-world patients (pts) have not benefited. We hypothesized that one reason for this discrepancy is the difference between trial participants and real-world pts. We aimed to: 1) Compare demographics and baseline clinical characteristics of real-world and clinical trial pts receiving first-line therapy for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL); and 2) Compare demographics and baseline clinical characteristics of real-...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Poster II Source Type: research
Authors: He Y, Khan M, Yang J, Yao M, Yu S, Gao H Abstract Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
Publication date: July 2018Source: Epilepsy &Behavior, Volume 84Author(s): Yang Si, Xiaoqiang Xiao, Hongbin SunAbstractPurposeThe purpose of this study was to investigate the current condition of mortality-specific comorbidity among hospitalized patients with epilepsy (PWE).MethodsThe discharge abstract records of PWE from over 730,000 admissions were extracted from the hospital medical database. Fourteen mortality-related comorbidities from an epilepsy-specific index (ESI) were selected for the present assessment. The hospital-based prevalence of these comorbidities was estimated. The distributions of PWE with an ESI-...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
Abstract PURPOSE: The purpose of this study was to investigate the current condition of mortality-specific comorbidity among hospitalized patients with epilepsy (PWE). METHODS: The discharge abstract records of PWE from over 730,000 admissions were extracted from the hospital medical database. Fourteen mortality-related comorbidities from an epilepsy-specific index (ESI) were selected for the present assessment. The hospital-based prevalence of these comorbidities was estimated. The distributions of PWE with an ESI-based prognostic score were calculated. RESULTS: A cohort of 11,422 PWE (male 58.5%) was i...
Source: Epilepsy and Behaviour - Category: Neurology Authors: Tags: Epilepsy Behav Source Type: research
Conclusions and implicationsOur results show that therapeutic concentrations of digitoxin inhibit angiogenesis and FAK activation by diverse pro‐angiogenic stimuli. These novel findings suggest a potential repositioning of digitoxin as a broad‐spectrum antiangiogenic drug for diseases where pathological angiogenesis is involved.
Source: British Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: RESEARCH PAPER Source Type: research
Conclusions The results of this study suggest trametinib has no significant effect on QT prolongation at supratherapeutic exposure.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionsThe NEJM study was accompanied by an editorial by Stone and Lloyd-Jones(2) which documented that drugs previously shown to lower cholesterol were never proved to do any good for patients, and concluded,it would be premature to endorse these drugs for widespread use before the ongoing randomized trials, appropriately powered for primary end-point analysis and safety assessment, are available. After an FDA advisory committee recommended approval of aliromucab and another PCSK9 inhibitor in June, 2015, John Mandrola entitled a Medscape article,Dear FDA: Resist the Urge on PCSK9 DrugsHis reasons included lack o...
Source: Health Care Renewal - Category: Health Management Tags: aliromucab evidence-based medicine health care prices manipulating clinical research PCSK9 inhibitor Praluent Regeneron Sanofi-Aventis Source Type: blogs
This study will evaluate the cardiac safety of two anthracycline-based neoadjuvant regimens in combination with P+T. Following surgery, all pts will receive adjuvant P+T. Trial design: In this non-randomized, open-label, phase II study, two parallel cohorts of pts receive different P-based neoadjuvant treatment regimens. In Cohort A, pts receive four 2-weekly cycles of ddAC, followed by 12 doses of weekly Ptx, plus four 3-weekly (q3w) cycles of P+T from the start of Ptx. In Cohort B, pts receive four q3w cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by four q3w cycles of D, plus four q3w cycles of P+...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Ongoing Clinical Trials Source Type: research
The objectives of the study were to estimate the incidence of Wernicke's encephalopathy (WE) and cardiac disorders among patients with myeloproliferative neoplasms (MPN), and compare it with those without MPN. A total of 39,761 MPN patients were identified from the US Marketscan database. Approximately 27% of them were 65+ years of age, and 51% were male. Patients with MPN had higher rates of WE, compared to those without MPN (MPN vs. non-MPN: 1.09 vs. 0.39/1000 person-year, adjusted HR=2.19, 95%CI 1.43–3.34). Patients with MPN also had higher rates of cardiac events (congestive heart failure: MPN vs. non-MPN: 9.27 v...
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
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