TRIPASS XR تري باس

 

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of patients with relapsed and refractory hematologic malignancies and is increasingly investigated as a therapeutic option of other malignancies. The main adverse effect of CAR T-cell therapy is potentially life-threatening cytokine release syndrome (CRS). Clinical cardiovascular (CV) manifestations of CRS include tachycardia, hypotension, troponin elevation, reduced left ventricular ejection fraction, pulmonary edema, and cardiogenic shock. Although insults related to CRS toxicity might be transient and reversible in most instances in patients with adequate CV reserve, they can be particularly challenging in higher-risk, often elderly patients with pre-existing CV disease. As the use of CAR T-cell therapy expands to include a wider patient population, careful patient selection, pre-treatment cardiac evaluation, and CV risk stratification should be considered within the CAR T-cell treatment protocol. Early diagnosis and management of CV complications in patients with CRS require awareness and multidisciplinary collaboration.

PMID: 31856973 [PubMed - in process]

22 December 2019

14:55

Cardiotoxicity News

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

14:55

In reply to this message

pubmed: tutte cardiotoxicity...

Current functioning of cardio-oncology units in Spain.

Related Articles

Current functioning of cardio-oncology units in Spain.

Clin Transl Oncol. 2019 Dec 20;:

Authors: Mitroi C, Martín-García A, Mazón Ramos P, Virizuela Echaburu JA, Arenas-Prat M, García-Sanz R, Arrarte Esteban V, García-Pinilla JM, Cosín-Sales J, López-Fernández T

Abstract

PURPOSE: The aim of the current survey was to describe the functioning of cardio-oncology (C-O) units in Spain.

METHODS: All members of the Spanish Society of Cardiology pertaining to scientific communities related to C-O received questionnaires on the existence of specific programs at their institutions. A second, more extensive questionnaire was sent to the centers which reported C-O organization.

RESULTS: We identified 56 centers with C-O programs of which 32 (62.5%) replied to the extended questionnaire. 28% of all centers reported having a multidisciplinary unit involving specialists in several areas. More than 80% of the centers developed surveillance protocols locally adapted which included advanced echocardiographic techniques (68%) or troponin (82%).

CONCLUSIONS: The number of institutions with C-O programs is still limited but higher than reported in a survey in 2017. Development of multidisciplinary units of C-O should be promoted to improve the cardiovascular health of cancer patients.

PMID: 31863353 [PubMed - as supplied by publisher]

14:55

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

14:55

In reply to this message

pubmed: tutte cardiotoxicity...

ST2 levels increased and were associated with changes in left ventricular systolic function during a three-year follow-up after adjuvant radiotherapy for breast cancer.

Related Articles

ST2 levels increased and were associated with changes in left ventricular systolic function during a three-year follow-up after adjuvant radiotherapy for breast cancer.

Breast. 2019 Dec 06;49:183-186

Authors: Aula H, Skyttä T, Tuohinen S, Luukkaala T, Hämäläinen M, Virtanen V, Raatikainen P, Moilanen E, Kellokumpu-Lehtinen PL

Abstract

OBJECTIVES: To search for biomarkers of RT-induced cardiotoxicity, we studied the behavior of ST2 during RT and three years after RT, and the associations with echocardiographic changes.

MATERIALS AND METHODS: We measured soluble ST2 (ng/ml) in serum samples from 63 patients receiving RT for early breast cancer. Sampling and echocardiography were performed at baseline, after RT and at the three-year follow-up. Patients were grouped by >15% (group 1) and ≤15% (group 2) relative worsening in global longitudinal strain (GLS).

RESULTS: ST2 levels tended to increase during RT, from a median (interquartile range; IQR) of 17.9 (12.4-22.4) at baseline to 18.2 (14.1-23.5) after RT (p = 0.075). By the three-year follow up, ST2 levels increased to 18.7 (15.8-24.2), p = 0.018. The increase in ST2 level was associated with worsening cardiac systolic function at three-year follow-up, GLS (rho = 0.272, p = 0.034) and left ventricular ejection fraction (LVEF) (rho = ─0.343, p = 0.006). Group 1 (n = 14) had a significant increase in ST2 levels from 17.8 (12.3-22.5) at baseline to 18.4 (15.6-22.6) after RT, p = 0.035 and to 19.9 (16.0-25.1) three years after RT, p = 0.005. ST2 levels were stable in group 2 (n = 47): 17.8 (12.3-22.0) at baseline, 17.7 (12.6-23.5) after RT and 18.0 (15.5-22.4) at three years.

CONCLUSION: ST2 may be useful for determining which patients are at risk for long-term cardiovascular toxicity following adjuvant breast cancer RT, but prospective clinical studies are needed to confirm this hypothesis.

PMID: 31862685 [PubMed - as supplied by publisher]

23 December 2019

15:26

Cardiotoxicity News

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

15:26

In reply to this message

pubmed: tutte cardiotoxicity...

Can Quantitative CMR Tissue Characterization Adequately Identify Cardiotoxicity During Chemotherapy?: Impact of Temporal and Observer Variability.

Related Articles

Can Quantitative CMR Tissue Characterization Adequately Identify Cardiotoxicity During Chemotherapy?: Impact of Temporal and Observer Variability.

JACC Cardiovasc Imaging. 2019 Dec 13;:

Authors: Altaha MA, Nolan M, Marwick TH, Somerset E, Houbois C, Amir E, Yip P, Connelly KA, Michalowska M, Sussman MS, Wintersperger BJ, Thavendiranathan P

Abstract

OBJECTIVES: The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T1, T2, and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD).

BACKGROUND: Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability.

METHODS: A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T1 and T2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM.

RESULTS: Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T1 (29 ms), T2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T1. The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%).

CONCLUSIONS: The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.

PMID: 31864977 [PubMed - as supplied by publisher]

15:26

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

15:26

In reply to this message

pubmed: tutte cardiotoxicity...

Longitudinal and quantitative assessment platform for concurrent analysis of anti-tumor efficacy and cardiotoxicity of nano-formulated medication in vivo.

Related Articles

Longitudinal and quantitative assessment platform for concurrent analysis of anti-tumor efficacy and cardiotoxicity of nano-formulated medication in vivo.

Anal Chim Acta. 2020 Jan 25;1095:129-137

Authors: Tu WM, Huang XC, Chen YL, Luo YL, Liau I, Hsu HY

Abstract

Increasing nanomedicinal approaches have been developed to effectively inhibit tumor growth; however, critical questions such as whether a nanomedicinal approach can mitigate latent side effects are barely addressed. To this end, we established a zebrafish xenograft tumor model, combining pseudodynamic three-dimensional cardiac imaging and image analysis to enable simultaneous and quantitative determination of the change of tumor volume and cardiac function of zebrafish upon specific nanoformulation treatment. Doxorubicin (DOX), a well-known chemotherapeutic agent with cardiotoxicity, and a recently developed DOX-loaded nanocomposite were employed as two model drugs to demonstrate the effectiveness to utilize the proposed evaluation platform for rapid validation. The nanoformulation significantly mitigated DOX-associated cardiotoxicity, while retaining the efficacy of DOX in inhibiting tumor growth compared to administration of carrier-free DOX at the same dose. We anticipate that this platform possesses the potential as an efficient assessment system for nanoformulated cancer therapeutics with suspected toxicity and side effects to vital organs such as the heart.

PMID: 31864613 [PubMed - in process]

24 December 2019

15:54

Cardiotoxicity News

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

15:54

In reply to this message

pubmed: tutte cardiotoxicity...

Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study.

Related Articles

Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study.

PLoS Med. 2019 Dec;16(12):e1002989

Authors: Kaboré EG, Guenancia C, Vaz-Luis I, Di Meglio A, Pistilli B, Coutant C, Cottu P, Lesur A, Petit T, Dalenc F, Rouanet P, Arnaud A, Arsene O, Ibrahim M, Wassermann J, Boileau-Jolimoy G, Martin AL, Lemonnier J, André F, Arveux P

Abstract

BACKGROUND: In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.

METHODS AND FINDINGS: Using prospective data collected from 2012-2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I-III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10-8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6-40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.

CONCLUSIONS: In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).

TRIAL REGISTRATION: ClinicalTrials.gov NCT01993498.

PMID: 31869400 [PubMed - in process]

15:55

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

15:55

In reply to this message

pubmed: tutte cardiotoxicity...

Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells.

Related Articles

Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells.

Front Pharmacol. 2019;10:1434

Authors: Wang X, Hui R, Chen Y, Wang W, Chen Y, Gong X, Jin J

Abstract

Doxorubicin (DOX) is metabolized to a variety of metabolites in vivo, which has been shown to be associated with cardiotoxicity. We speculate that metabolic processes are also present in tumor cells. A LC-MS/MS method was developed to detect intracellular metabolites. Drug resistant tumor cells with high drug stress tolerance and metabolically active are suitable as materials for this study. Our results show difference in drug metabolites between the wild-type and drug-resistant cells. Three novel doxorubicin metabolites were discovered after the LC-MS/MS analysis. All these metabolites and their profiles of metabolites are totally different from that in liver or kidney in vivo. Our results suggest that tumor cells and drug-resistant tumor cells have a unique drug metabolism pathway for doxorubicin.

PMID: 31866863 [PubMed]

15:55

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

15:55

In reply to this message

pubmed: tutte cardiotoxicity...

Atorvastatin protects cardiomyocyte from doxorubicin toxicity by modulating survivin expression through FOXO1 inhibition.

Related Articles

Atorvastatin protects cardiomyocyte from doxorubicin toxicity by modulating survivin expression through FOXO1 inhibition.

J Mol Cell Cardiol. 2019 Dec 19;:

Authors: Oh J, Lee BS, Lim G, Lim H, Lee CJ, Park S, Lee SH, Chung JH, Kang SM

Abstract

BACKGROUND: Survivin has an anti-apoptotic effect against anthracycline-induced cardiotoxicity. Clinically, statin use is associated with a lower risk for heart failure in breast cancer patients with anthracycline chemotherapy. So, the purpose of our study was to investigate whether survivin mediates the protective effect of statin against anthracycline-induced cardiotoxicity.

METHODS: Mice were treated once a week with 5 mg/kg doxorubicin for 4 weeks with or without atorvastatin 20 mg/kg every day then heart tissues were analyzed. Molecular and cellular biology analyses were performed with H9c2 cell lysates.

RESULTS: Doxorubicin suppressed survivin expression via activation of FOXO1 in H9c2 cardiomyocytes. Whereas, atorvastatin inhibited FOXO1 by increasing phosphorylation and inhibiting nuclear localization. Doxorubicin induced FOXO1 binding to STAT3 and prevented STAT3 from interacting with Sp1. However, atorvastatin inhibited these interactions and stabilized STAT3/Sp1 transcription complex. Chromatin immunoprecipitation analysis demonstrated that doxorubicin decreased STAT3/Sp1 complex binding to survivin promoter, whereas atorvastatin stabilized this binding. In mouse model, atorvastatin rescued doxorubicin-induced reduction of survivin expression and of heart function measured by cardiac magnetic resonance imaging.

CONCLUSIONS: Our study suggested a new pathophysiologic mechanism that survivin mediated protective effect of atorvastatin against doxorubicin-induced cardiotoxicity via FOXO1/STAT3/Sp1 transcriptional network.

PMID: 31866378 [PubMed - as supplied by publisher]

15:55

Animation

Not included, change data exporting settings to download.

2.7 KB

15:55

In reply to this message

pubmed: tutte cardiotoxicity...

An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.plos.org-plosone-resource-img-external-pone_120x30.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques.