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Targeting MDR-1 gene expression, BAX/BCL2, caspase-3 and Ki-67 by nano-encapsulated imatinib and hesperidin to enhance anticancer activity and ameliorate cardiotoxicity.
Fundam Clin Pharmacol. 2020 Feb 21;:
Authors: El-Sisi AE, Sokkar SS, Ibrahim HA, Hamed MF, Abu-Risha SE
Abstract
There is a great demand to introduce new approaches into cancer treatment field due to incidence increase of breast cancer all over the world. The current study was designed to evaluate the role of imatinib mesylate (IM) and/or hesperidin (HES) nanoparticles alone or in combination in enhancing the anti-cancer activity, and to investigate the ability of nanoencapsulation to reduce cardiotoxicity of IM in Solid Ehrlich Carcinoma (SEC)-bearing mice. IM and HES were loaded into PLGA (poly(lactic-co-glycolic acid) polymer. SEC was induced in female albino mice as a model for experimentally induced breast cancer. Mice were randomly divided into eight groups (n =10). On day 28 from tumor inoculation, mice were sacrificed and blood samples were collected in heparinized tubes for hematological studies, biochemical determination of lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) levels. In addition, tumor and cardiac tissues were utilized for histopathological examination as well as determination of MDR-1 gene expression. Immunohistochemical staining of BAX and BCL-2 was done. Nano IM and/or Nano HES treated groups showed a significant reduction in tumor volume, weight, hematological, cardiac markers and tumor MDR-1 gene down regulation compared to free conventional treated groups. In conclusion, the use of HES as an adjuvant therapy with IM could improve its cytotoxic effects and limit its cardiac toxicity. Furthermore, nano-encapsulation of IM and/or HES with PLGA polymer showed a remarkable anti-cancer activity.
PMID: 32080901 [PubMed - as supplied by publisher]
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Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials.
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Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials.
ESMO Open. 2020 Feb;5(1):
Authors: Eiger D, Franzoi MA, Pondé N, Brandão M, de Angelis C, Schmitt Nogueira M, de Hemptinne Q, de Azambuja E
Abstract
BACKGROUND: Treatment de-escalation in early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been attempted in order to decrease costs and toxicities. One of the strategies pursued is decreasing trastuzumab treatment duration, with mixed results thus far. Trastuzumab-associated cardiotoxicity, however, may be more frequent with 12 months of trastuzumab compared with shorter treatment lengths. Therefore, we have conducted a meta-analysis to address this question.
MATERIALS AND METHODS: A meta-analysis of trials testing 12 months of adjuvant trastuzumab versus shorter regimens, reporting cardiac outcomes in patients with HER2-positive BC was performed with the random effects model with inverse variance weighting.
RESULTS: Clinical cardiac dysfunction associated with 12 months of trastuzumab versus shorter trastuzumab regimens, including 11 250 patients, showed a pooled OR (pOR) of 1.90 (95% CI 1.37 to 2.64; p value <0.001;<0.001;<0.001;
CONCLUSIONS: Compared to shorter treatment durations, there is sufficient evidence that 12 months of trastuzumab yields higher odds for the occurrence of relevant cardiac events. An individual patient-level data meta-analysis is needed in order to provide adequate data on risk factors for cardiotoxicity.
PMID: 32079624 [PubMed - in process]
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Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats.
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Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats.
Antioxidants (Basel). 2020 Feb 16;9(2):
Authors: Alanazi AM, Fadda L, Alhusaini A, Ahmad R, Hasan IH, Mahmoud AM
Abstract
Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.
PMID: 32079097 [PubMed]
23 February 2020
13:30
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Human Amnion Membrane Proteins Prevent Doxorubicin-Induced Oxidative Stress Injury and Apoptosis in Rat H9c2 Cardiomyocytes.
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Human Amnion Membrane Proteins Prevent Doxorubicin-Induced Oxidative Stress Injury and Apoptosis in Rat H9c2 Cardiomyocytes.
Cardiovasc Toxicol. 2020 Feb 21;:
Authors: Faridvand Y, Haddadi P, Vahedian V, Nozari S, Nejabati HR, Pezeshkian M, Afrasiabi A, Safaie N, Jodati A, Nouri M
Abstract
Doxorubicin (DOX) is widely used as an effective chemotherapy agent in cancer treatment. Cardiac toxicity in cancer treatment with DOX demand urgent attention and no effective treatment has been established for DOX-induced cardiomyopathy. It has been well documented that human amniotic membrane proteins (AMPs), extracted from amnion membrane (AM), have antioxidant, anti-apoptotic, and cytoprotective properties. Therefore, in this study, we aimed to investigate the protective effects of AMPs against cardiotoxicity induced by DOX in cultured rat cardiomyocyte cells (H9c2). DOX-induced cell injury was evaluated using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT), the release of lactic dehydrogenase (LDH), intracellular Ca2+ , reactive oxygen species (ROS) levels, cellular antioxidant status, mitochondrial membrane potential (ΔΨm), malondialdehyde (MDA), and NF-κB p65 DNA-binding activity. Moreover, expression profiling of apoptosis-related genes (P53, Bcl-2, and Bax) and Annexin V by flow cytometry were used for cell apoptosis detection. It was shown that AMPs pretreatment inhibited the cell toxicity induced by DOX. AMPs effectively attenuated the increased levels of LDH, Ca2+ , ROS, and MDA and also simultaneously elevated the ΔΨm and antioxidant status such as superoxide dismutase (SOD) and Catalase (CAT) in pretreated H9c2 cardiomyocytes. Besides, the activity of NF-kB p65 was reduced and the p53 and Bax protein levels were inhibited in these myocardial cells subjected to DOX. These findings provide the first evidence that AMPs potently suppressed DOX-induced toxicity in cardiomyocytes through inhibition of oxidative stress and apoptosis. Thus, AMPs can be a potential therapeutic agent against DOX cardiotoxicity.
PMID: 32086724 [PubMed - as supplied by publisher]
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Trastuzumab related cardiotoxicity in nonmetastatic breast cancer: A real-world scenario.
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Trastuzumab related cardiotoxicity in nonmetastatic breast cancer: A real-world scenario.
Ann Oncol. 2019 May;30 Suppl 3:iii69
Authors: Shrivastva S, Prasad SK, Chennamaneni R, Stalin B, Konatam ML, Gundeti S
PMID: 32084902 [PubMed - as supplied by publisher]
24 February 2020
14:03
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Trastuzumab-Related Cardiotoxicity and Cardiac Care in Patients With HER2 Positive Metastatic Breast Cancer.
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Trastuzumab-Related Cardiotoxicity and Cardiac Care in Patients With HER2 Positive Metastatic Breast Cancer.
Am J Cardiol. 2020 Jan 27;:
Authors: Calvillo-Argüelles O, Abdel-Qadir H, Suntheralingam S, Michalowska M, Amir E, Thavendiranathan P
Abstract
Prolonged trastuzumab therapy is the standard of care for women with metastatic HER2 positive (HER2+) breast cancer. There are limited data on the incidence of cardiotoxicity, its treatment implication, and cardiac care in these patients. We retrospectively identified consecutive women who received >12 months of trastuzumab treatment at Princess Margaret Cancer Centre (Toronto, ON) from 2007 to 2012 for metastatic HER2 positive breast cancer and followed them until death or August 2018. Patients were included if a pretherapy multigated acquisition scan and ≥2 subsequent follow-up scans were available. The Cardiac Review and Evaluation Committee Criteria were used to identify cardiotoxicity. Baseline characteristics and outcomes (final left ventricular ejection fraction, change in LVEF, trastuzumab interruption) were compared in patients with and without cardiotoxicity. Cardiac care and treatment received were recorded. Sixty patients (mean age 52 ± 10.4 years) were included. The median trastuzumab exposure was 37 cycles (interquartile range 23 to 56) over 28 months (interquartile range 19 to 49) and 48% received previous anthracycline therapy. The cumulative incidence of cardiotoxicity was 35% (95% CI 23 to 48) at 3 years. Patients who developed cardiotoxicity were more likely to receive third-line cancer treatments and had lower final LVEF than patients without (54.9% ± 6.3% vs 64% ± 4.9%, p <0.001).
PMID: 32087998 [PubMed - as supplied by publisher]
25 February 2020
16:02
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Case of pembrolizumab-induced myocarditis presenting as torsades de pointes with safe re-challenge.
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Case of pembrolizumab-induced myocarditis presenting as torsades de pointes with safe re-challenge.
J Oncol Pharm Pract. 2020 Feb 23;:1078155220904152
Authors: Lee DH, Armanious M, Huang J, Jeong D, Druta M, Fradley MG
PMID: 32089073 [PubMed - as supplied by publisher]
26 February 2020
13:40
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Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper.
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Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper.
Blood Adv. 2020 Feb 25;4(4):762-775
Authors: Neuendorff NR, Loh KP, Mims AS, Christofyllakis K, Soo WK, Bölükbasi B, Oñoro-Algar C, Hundley WG, Klepin HD
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