TRIPASS XR تري باس

 

Abstract

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

PMID: 30543051 [PubMed - indexed for MEDLINE]

7 May 2020

12:44

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Pegylated liposomal doxorubicin in patients with metastatic triple-negative breast cancer: 8-year experience of a single center.

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Pegylated liposomal doxorubicin in patients with metastatic triple-negative breast cancer: 8-year experience of a single center.

J Egypt Natl Canc Inst. 2020 Apr 27;32(1):20

Authors: Khallaf SM, Roshdy J, Ibrahim A

Abstract

BACKGROUND: The known efficacy of doxorubicin in metastatic breast cancer is countered by its dose-limiting myelosuppression and cardiotoxicity. Pegylated liposomal doxorubicin (PLD) was discovered to overcome these problems. But the data regarding its use in metastatic TNBC (triple-negative breast cancer) is still insufficient. Our study aimed to assess the factors affecting the outcome of the patients with metastatic TNBC who received PLD.

RESULTS: During a period of 8 years (January 2011-December 2018), we analyzed 39 eligible patients. The disease control rate (DCR) was 51.3%. Among all the analyzed factors, two of them significantly affected DCR. The first factor was the chemosensitivity to prior anthracycline. As patients with chemosensitive disease had higher DCR than those with the chemoresistant disease (P = .001). The second factor was the number of prior lines of chemotherapy. As the patients who received two prior lines had a higher DCR than those who received three lines or more (P = .023). Chemosensitivity was the only significant independent factor for DCR (odds ratio = .095, P = .008). For the studied patients, the median progression-free survival (PFS) was 7 months. The anthracycline-chemosensitivity was the only significant independent prognostic factor for PFS (P = .002). The median overall survival (OS) was 12 months. There was a marginally significant effect of anthracycline-chemosensitivity on OS (P = .052).

CONCLUSION: The anthracycline-chemosensitivity is an independent predictive and prognostic factor for the patients with metastatic TNBC receiving PLD. In developing countries, PLD should be reserved for the patients whose tumors are anthracycline-chemosensitive.

PMID: 32372114 [PubMed - in process]

12:44

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Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies.

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Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies.

Antioxidants (Basel). 2020 May 02;9(5):

Authors: Pepe G, Salviati E, Rapa SF, Ostacolo C, Cascioferro S, Manfra M, Autore G, Marzocco S, Campiglia P

Abstract

Abstract: The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line (MCF-7) exposed to doxorubicin. Interestingly, we found that the mix resulting from Citrus sinensis and Vitis vinifera association in ratio 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines, without significantly interfering with the pro-apoptotic activity of the drug on breast cancer cells. These results point out the potential use of vegetable smoothies as adjuvants functional foods for chemotherapeutic anticancer protocols.

PMID: 32370308 [PubMed]

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EGFR Inhibitor Gefitinib Induces Cardiotoxicity through the Modulation of Cardiac PTEN/Akt/FoxO3a Pathway and Reactive Metabolites Formation: In Vivo and In Vitro Rat Studies.

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EGFR Inhibitor Gefitinib Induces Cardiotoxicity through the Modulation of Cardiac PTEN/Akt/FoxO3a Pathway and Reactive Metabolites Formation: In Vivo and In Vitro Rat Studies.

Chem Res Toxicol. 2020 May 06;:

Authors: Alhoshani A, Alanazi FE, Alotaibi MR, Attwa M, Kadi AA, Aldhfyan A, Akhtar S, Hourani S, Agouni A, Zeidan A, Korashy H

Abstract

Gefitinib (GEF) is a selective inhibitor of the epidermal growth factor receptor (EGFR) used to treat non-small cell lung cancer. Yet, few cases of cardiotoxicity have been reported. However, the role of PTEN/Akt/FoxO3a pathway, which is mediating GEF anticancer activity, in GEF cardiotoxicity remains unclear. For this purpose, in vitro H9c2 cell and in vivo rat cardiomyocyte were utilized as study models. Treatment of H9c2 cells and Sprague Dawley rats with GEF significantly induced the expression of hypertrophic and apoptotic markers at mRNA and protein levels with increased plasma level of troponin. This was accompanied with induction of autophagy and mitochondrial dysfunction in H9c2 cells. Inhibition of cardiac EGFR activity and Akt cellular content in vitro and in vivo rat cardiomyocyte by GEF increased PTEN and FoxO3a genes expression and cellular content. In addition, by using LC-MS/MS, GEF is metabolized in the rat heart microsomes into one cyanide- and two methoxylamine-adducts reactive metabolites, where their formation was entirely blocked by CYP1A1 inhibitor, -naphthoflavone. Importantly, treatment of H9c2 cells with PI3K/Akt inhibitor increased PTEN and FoxO3a mRNA expression associated with potentiation of GEF cardiotoxicity. The current study concluded that GEF induces cardiotoxicity through modulating the expression/function of cardiac PTEN/AKT/FoxO3a pathway and formation of CYP1A1-mediated reactive metabolites.

PMID: 32370496 [PubMed - as supplied by publisher]

8 May 2020

13:18

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Cardiotoxicity and myocardial hypoperfusion associated with anti-vascular endothelial growth factor therapies: prospective cardiac magnetic resonance imaging in patients with cancer.

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Cardiotoxicity and myocardial hypoperfusion associated with anti-vascular endothelial growth factor therapies: prospective cardiac magnetic resonance imaging in patients with cancer.

Eur J Heart Fail. 2020 May 07;:

Authors: Dobbin SJH, Mangion K, Berry C, Roditi G, Basak S, Sourbron S, White J, Venugopal B, Touyz RM, Jones RJ, Petrie MC, Lang NN

PMID: 32379945 [PubMed - as supplied by publisher]

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Development of stimuli-responsive intelligent polymer micelles for the delivery of doxorubicin.

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Development of stimuli-responsive intelligent polymer micelles for the delivery of doxorubicin.

J Drug Target. 2020 May 07;:1-52

Authors: Yang F, Xu J, Fu M, Ji J, Chi L, Zhai G

Abstract

Doxorubicin is still used as a first-line drug in current therapeutics for numerous types of malignant tumors (including lymphoma, transplantable leukemia and solid tumor). Nevertheless, to overcome the serious side effects like cardiotoxicity and myelosuppression caused by effective doses of doxorubicin remains as a world-class puzzle. In recent years, the usage of biocompatible polymeric nanomaterials to form an intelligently sensitive carrier for the targeted release in tumor microenvironment has attracted wide attention. These different intelligent polymeric micelles could change the pharmacokinetics process of drugs or respond in the special microenvironment of tumor site to maximize the efficacy and reduce the toxicity of doxorubicin in other tissues and organs. Several intelligent polymeric micelles have already been in the clinical research stage and planned for market. Therefore, related research remains active, and the latest nanotechnology approaches for doxorubicin delivery are always in the spotlight. Centering on the model drugs doxorubicin, this review summarized the mechanisms of polymeric micelles, classified the polymers used in the application of doxorubicin delivery and discussed some interesting and imaginative smart polymeric micelles in recent years.

PMID: 32378974 [PubMed - as supplied by publisher]

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Genome-Wide Association Study of Genetic Variants Related to Anthracycline-Induced Cardiotoxicity in Early Breast Cancer.

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Genome-Wide Association Study of Genetic Variants Related to Anthracycline-Induced Cardiotoxicity in Early Breast Cancer.

Cancer Sci. 2020 May 07;:

Authors: Park B, Sim SH, Lee KS, Kim HJ, Park IH

Abstract

We performed a genome-wide association study to investigate the association between single nucleotide polymorphisms and anthracycline-induced cardiotoxicity (ACT) in patients diagnosed with early breast cancer. From January 2000 to December 2015, 8,490 patients underwent breast surgery at the National Cancer Center in Korea. Patients who received doxorubicin (cumulative dose 240 mg/m2 ~300 mg/m2 ) with or without trastuzumab as a neoadjuvant/adjuvant therapy were included in our cohort. Sixty-seven patients in our cohort were diagnosed with ACT. Clinical data, including age, body weight, height, cancer stage, trastuzumab treatment, co-morbidities, and concomitant medications were retrospectively collected. Patients were classified as having either persistent or transient ACT based on their clinical course. A total of 346,946 single nucleotide polymorphisms in 42 cases and 215 controls were tested in this study. Body mass index (BMI) ≥25kg/m2 [odds ratio (OR)=2.45, 95% confidence interval (CI), 1.23-4.88, p=0.011] and trastuzumab use (OR=2.40, 95% CI, 1.11-5.17, p=0.026) were identified as significant risk factors. We found 7 genetic variants for ACT including rs17530621 (SHISA3, p=3.10E-06), rs11894115 (MPP4, p=4.71E-06), rs58328254 (RPL7, p=6.09E-06), and rs117299725 (PRUNE2, p=8.53E-06), though none of these variants reached the Bonferroni-corrected significance level when adjusted with BMI and trastuzumab use α=1.44E-07 based on 0.05/346,946). rs117299725 was a common variant when only the persistent ACT group was analyzed separately. It is meaningful that our study comprehensively analyzed the influence of genetic variation on ACT, along with a number of clinical factors in Asian breast cancer patients who received anthracycline with or without trastuzumab. Further research will be needed on candidate genetic variants found in this study.

PMID: 32378780 [PubMed - as supplied by publisher]

13:18

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[Clinical pharmacology of cardio-oncology: a novel interdisciplinary platform for basic and translational research].

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[Clinical pharmacology of cardio-oncology: a novel interdisciplinary platform for basic and translational research].

Nihon Yakurigaku Zasshi. 2020;155(3):179-184

Authors: Sase K

Abstract

Advances in cancer treatment have led to dramatic increase in cancer survivors. In addition to cardiotoxicity resulting from anthracyclines and radiation therapy, the emergence of novel cancer treatment-related cardiovascular disease (CTRCD) with molecularly targeted therapies and immune checkpoint inhibitors has been recognized as an unmet medical need. Cardio-oncology is a new interdisciplinary research opportunity at the intersection of cardiovascular disease and cancer. Research priorities need to be identified for diagnosis, treatment, and prevention of previously unknown CTRCD(s), including (a) cardiac dysfunction and heart failure, (b) coronary artery disease, (c) valvular disease, (d) arrhythmias and QT-prolongation, (e) arterial hypertension, (f) thromboembolic disease, and (g) other cardiovascular disorders. In particular, understanding the fundamental mechanisms underlying CTRCD is essential for developing new methods. Applying more appropriate disease models and more effective methods for toxicity screening will help to better understand CTRCD. Although animal models have been used to predict potential problems, more advanced predictive models are also needed. Biobanks and other specimens with patient registries are expected to facilitate the validation of new biomarkers, genomic analysis, and imaging methods.

PMID: 32378640 [PubMed - in process]

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Deep Learning-Based Prediction of Drug-Induced Cardiotoxicity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc-MS.gif Related Articles

Deep Learning-Based Prediction of Drug-Induced Cardiotoxicity.

J Chem Inf Model. 2019 03 25;59(3):1073-1084

Authors: Cai C, Guo P, Zhou Y, Zhou J, Wang Q, Zhang F, Fang J, Cheng F

Abstract

Blockade of the human ether-à-go-go-related gene (hERG) channel by small molecules induces the prolongation of the QT interval which leads to fatal cardiotoxicity and accounts for the withdrawal or severe restrictions on the use of many approved drugs. In this study, we develop a deep learning approach, termed deephERG, for prediction of hERG blockers of small molecules in drug discovery and postmarketing surveillance. In total, we assemble 7,889 compounds with well-defined experimental data on the hERG and with diverse chemical structures. We find that deephERG models built by a multitask deep neural network (DNN) algorithm outperform those built by single-task DNN, naı̈ve Bayes (NB), support vector machine (SVM), random forest (RF), and graph convolutional neural network (GCNN). Specifically, the area under the receiver operating characteristic curve (AUC) value for the best model of deephERG is 0.967 on the validation set. Furthermore, based on 1,824 U.S. Food and Drug Administration (FDA) approved drugs, 29.6% drugs are computationally identified to have potential hERG inhibitory activities by deephERG, highlighting the importance of hERG risk assessment in early drug discovery. Finally, we showcase several novel predicted hERG blockers on approved antineoplastic agents, which are validated by clinical case reports, experimental evidence, and the literature. In summary, this study presents a powerful deep learning-based tool for risk assessment of hERG-mediated cardiotoxicities in drug discovery and postmarketing surveillance.

PMID: 30715873 [PubMed - indexed for MEDLINE]

9 May 2020

21:52

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Risk of cardiovascular disease after radiotherapy in survivors of breast cancer: A case-cohort study.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png Related Articles

Risk of cardiovascular disease after radiotherapy in survivors of breast cancer: A case-cohort study.

J Cardiol. 2019 04;73(4):280-291

Authors: Hamood R, Hamood H, Merhasin I, Keinan-Boker L