zarello G
Abstract
Since it came into being as a discipline, cardio-oncology has focused on the prevention and treatment of cardiotoxicity induced by antitumor chemotherapy and radiotherapy. Over time, it has been proved that even more detrimental is the direct effect generated by cancer cells that release pro-cachectic factors in the bloodstream. Secreted molecules target different organs at a distance, including the heart. Inflammatory and neuronal modulators released by the tumor bulk, either as free molecules or through exosomes, contribute to the pathogenesis of cardiac disease. Progressive cancer causes cachexia and severe cardiac muscle wasting accompanied by cardiomyocyte atrophy, tissue fibrosis, and several functional impairments up to heart failure. The molecular mechanisms responsible for such a cardiac muscle wasting have been partially elucidated in animal models, but minimally investigated in humans, although severe cardiac dysfunction exacerbates global cachexia and hampers efficient anti-cancer treatments. This review provides an overview of cancer-induced structural cardiac and functional damage, drawing on both clinical and scientific research. We start by looking at the pathophysiological mechanisms and evolving epidemiology and go on to discuss prevention, diagnosis, and a multimodal policy of intervention aimed at providing overall prognosis and global care for patients. Despite much interest in the cardiotoxicity of cancer therapies, the direct tumor effect on the heart remains poorly explored. There is still a lack of diagnostic criteria for the identification of the early stages of cardiac disease in cancer patients, while the possibilities that there are for effective prevention are largely underestimated. Research on innovative therapies has claimed considerable advances in preclinical studies, but none of the molecular targets suitable for clinical application has been approved for therapy. These issues are critically discussed here.
PMID: 32152913 [PubMed - as supplied by publisher]
12 March 2020
11:25
Cardiotoxicity News
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Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors.
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Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors.
Immune Netw. 2020 Feb;20(1):e9
Authors: Choi J, Lee SY
Abstract
Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.
PMID: 32158597 [PubMed]
13 March 2020
13:15
Cardiotoxicity News
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Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio.
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Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio.
J Pharm Biomed Anal. 2020 Mar 04;185:113231
Authors: Pippa LF, Oliveira ML, Rocha A, de Andrade JM, Lanchote VL
Abstract
Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer. The cardiotoxicity of DOX is related to the accumulation of its main metabolite doxorubicinol (DOXOL) in the cardiac tissue. Although the pharmacokinetics of DOX shows high interindividual variability, there are no significant covariates to improve dose adjustment. The present study reports the pharmacokinetics of both DOX and DOXOL in a homogeneous population of young female patients with breast cancer (n = 12) making use of a standardized drug association, evaluated in the very first chemotherapy cycle, using plasma and urine data that allowed the calculation of the renal clearance of DOX, the formation clearance of DOXOL and the hepatic clearance of DOX. The extensive data availability also made it possible to estimate the hepatic extraction ratio of DOX for the investigated population, as well as to determine DOXOL unbound fraction in plasma for the first time in humans. DOX and DOXOL simultaneous analysis in plasma, plasma ultrafiltrate, and urine were performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The pharmacokinetics profile of both DOX and DOXOL showed high variability (geometric coefficient of variation of area under the plasma concentration versus time curve extrapolated to infinity was approximately 215 %). The geometrics means were 0.26 for DOXOL/DOX AUC ratio, 15 % and 17 % for unbound fractions of DOX and DOXOL, respectively, 30.70 L⋅h-1 for total clearance, 0.66 L⋅h-1 for renal clearance, 29.97 L⋅h-1 for hepatic clearance and 0.39 L⋅h-1 for the formation clearance of the metabolite DOXOL. The 95 % confidence interval of the estimated hepatic extraction ratio of DOX ranged from 0.14 to 0.79, which characterizes DOX as a drug of low, intermediate or high hepatic extraction ratio.
PMID: 32163849 [PubMed - as supplied by publisher]
13:15
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[Сurrent views on predictors and biomarkers of early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer (review of literature).]
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[Сurrent views on predictors and biomarkers of early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer (review of literature).]
Klin Lab Diagn. 2020;65(3):141-148
Authors: Kit OI, Gvaldin DY, Omelchuk EP, Timoshkina NN
Abstract
Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.
PMID: 32163687 [PubMed - as supplied by publisher]
17 March 2020
14:35
Cardiotoxicity News
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Cytotoxic-induced heart failure among breast cancer patients in Nigeria: A call to prevent today's cancer patients from being tomorrow's cardiac patients.
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Cytotoxic-induced heart failure among breast cancer patients in Nigeria: A call to prevent today's cancer patients from being tomorrow's cardiac patients.
Ann Afr Med. 2020 Jan-Mar;19(1):1-7
Authors: Anakwue R
Abstract
We report three cases of heart failure (HF) associated with the use of cytotoxic drugs such as anthracycline, cyclophosphamide, and 5-fluorouracil in the treatment of breast cancer in Nigerians. The patients had systolic and diastolic HF: HF with reduced ejection fraction and preserved ejection fraction. The prevalence of breast cancer is increasing across Africa, and cytotoxics are some of the most common and best drugs used during management. The cardiotoxicity caused by these drugs limits their use as chemotherapeutic agents. Cytotoxic-induced HF is a preventable and manageable cause of cardiovascular disease (CVD) in Nigeria and Africa. This article discusses the pathophysiology of cytotoxic-induced HF and presents the risk factors that impair cardiovascular function. The importance of proper assessment and the prophylactic and therapeutic measures in the management of cytotoxic-induced HF are emphasized. The peculiar challenges in the management of cytotoxic-induced HF in Nigeria were also discussed. The need for early involvement of cardiologists by oncologists to improve on the chemotherapeutic and cardiovascular outcome in the management of patients with breast cancer was stressed. Perhaps, it is time to birth a new discipline of cardiooncology in Nigeria.
PMID: 32174608 [PubMed - in process]
14:35
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Clusterin is regulated by IGF1-PI3K signaling in the heart: implications for biomarker and drug target discovery, and cardiotoxicity.
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Clusterin is regulated by IGF1-PI3K signaling in the heart: implications for biomarker and drug target discovery, and cardiotoxicity.
Arch Toxicol. 2020 Mar 14;:
Authors: Bass-Stringer S, Ooi JYY, McMullen JR
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