scholarly journals The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

2016 ◽  
Vol 8s2 ◽  
pp. BIC.S31798 ◽  
Author(s):  
Christine Henri ◽  
Therese Heinonen ◽  
Jean-Claude Tardif
Keyword(s):  
Cancer Therapy ◽  
Natriuretic Peptides ◽  
Cardiac Toxicity ◽  
Myocardial Damage ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cancer Therapies ◽  
Lv Dysfunction ◽  
After Cancer

With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab), and multikinase inhibitors (sunitinib). The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV) ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

Abstract P050: Novel Mechanism of Ser-496 ERK5 Phosphorylation and Association with p90RSK Is Critical for Regulating C Terminus of Hsc70-Interacting Protein (CHIP) Ubiquitin E3 Ligase Activity in Diabetes-Mediated Exacerbation of Cardiomyocyte Apoptosis and Left Ventricular Dysfunction After Myocardial Infarction

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Nhat-Tu Le ◽  
Yuichiro Takei ◽  
Chang-Hoon Woo ◽  
Tetsuro Shishido ◽  
Yan Lu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Active Form ◽  
E3 Ligase ◽  
Left Ventricular ◽  
Ang Ii ◽  
Lv Dysfunction ◽  
On Chip

Rationale: Cardiac dysfunction is accelerated in DM patients after MI. Previously, we reported the critical role of ERK5 and CHIP association on CHIP Ub E3 ligase activity, which inhibits inducible cAMP early repressor (ICER)-mediated apoptosis and left ventricle (LV) dysfunction after MI in DM (DM + MI). Yet the regulatory mechanism of ERK5-CHIP has not been established. Objective: Since we found that p90RSK activation was increased in DM heart, we investigated whether p90RSK activation may inhibit ERK5-mediated CHIP activation, and subsequent ICER induction and apoptosis. Methods and Results: The inhibition of p90RSK activation prevented the reduction of ERK5-CHIP binding, CHIP activity, as well as ICER induction and cardiac apoptosis both in vitro after angiotensin II (ang II) stimulation and in vivo after DM + MI. p90RSK and CHIP share a same binding site with ERK5 C-terminal domain (aa571–807), and overexpression of both p90RSK and ERK5 (aa571–807) fragment, but not kinase dead mutant of p90RSK, inhibited ERK5-CHIP association, suggesting the critical role of p90RSK activation on ERK5-CHIP interaction, and competitive nature of p90RSK and CHIP against ERK5 association. Furthermore. LC-MS/MS analysis identified ERK5-S496 as being directly phosphorylated by p90RSK, and ERK5 S496A mutant significantly impaired ang II-mediated inhibition of CHIP Ub ligase activity, suggesting the critical role of Ser-496 phoaphorylation of ERK5 on CHIP activity. Therefore, p90RSK activation is critical for both p90RSK-ERK5 association as well as ERK5-Ser496 phosphorylation, and following disruption of ERK5-CHIP interaction and subsequent inhibition of CHIP Ub ligase activity. The reduction of CHIP Ub ligase activity and LV dysfunction were accelerated both in cardio-specific ERK5 knock out and wild type p90RSK transgenic mice (WT-p90RSK-Tg). Furthermore, double transgenic mice of WT-p90RSK and constitutively active form of MEK5α (specific ERK5 activator) inhibited single WT-p90RSK-Tg-medaited reduction of CHIP Ub ligase activity, LV dysfunction, and improved mortality after MI. Conclusions: These data strongly suggested that p90RSK activation accelerated cardiac dysfunction and apoptosis after DM + MI via inhibiting ERK5-CHIP module.

Abstract 3474: Cardiac -Specific SOCS3 Dificient Mice Shows Resistance to Lipopolysaccharide-Induced Cardiac Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Futamata Nobuyoshi ◽  
Hldeo Yasukawa ◽  
Toyoharu Ohba ◽  
Kazutoshi Mawatari ◽  
Daisuke Fukui ◽  
...  
Keyword(s):  
Western Blot ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Left Ventricular Ejection ◽  
Cytokine Signaling ◽  
Rt Pcr ◽  
Lv Dysfunction ◽  
Stat3 Signaling ◽  
Cardiomyocyte Survival

Background : Lypopolysaccharide (LPS)-induced left ventricular (LV) dysfunction is a well-established model for sepsis-induced acute heart failure. STAT3 signaling in the heart has been shown to promote cardiomyocyte survival during LPS-induced LV dysfunction. Little is known, however, about the role of negative regulation of STAT3 signaling during LPS-induced LV dysfunction. Suppressor of cytokine signaling 3 (SOCS3) is an intrinsic negative regulator of gp130 cytokine-induced STAT3 signaling that plays an important role in cardiomyocyte survival. In this study, we determined whether STAT3 signaling and its negative regulator SOCS3 would play a role in LPS-induced LV dysfunction. Methods and Results : We examined the activation of STAT3 and inductions of gp130 cytokines and SOCS3 in the wild-type (WT) mice hearts after LPS injection by western blot and real-time PCR (RT-PCR). RT-PCR revealed that gp130 cytokines were markedly increased after AMI. Western blot revealed that STAT3 was markedly phosphorylated and SOCS3 was induced in WT mice hearts after LPS injection. To investigate the role of STAT3 signaling and SOCS3 in LPS-induced LV dysfunction, we generated cardiac-specific SOCS3 knockout mice (SOCS3-CKO). Left ventricular ejection fraction (LVEF) of SOCS3-CKO mice was similar to that of WT mice at baseline (64.2 ± 6.1 vs. 62.4 ± 4.4%). LPS (30mg/kg) elicited a significant and robust reduction of LVEF in both SOCS3-CKO mice and WT mice 3 hr after LPS injection (18 ± 4.5 vs. 16 ± 5.2%, p <0.01). LVEF in WT mice was further reduced 6 hr after LPS injection. On the other hand, interestingly, LVEF was restored to the baseline in SOCS3-CKO mice 6 hr after LPS injection (10.4 ± 3.9 vs. 62.2 ± 8.1%, p <0.01). Also the duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Furthermore, SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection ( p <0.01). Conclusion : Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice, possibly by augmenting the STAT3-mediated gp130 cytokine signaling.

scholarly journals Advanced cardiac magnetic resonance imaging in takotsubo cardiomyopathy

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200514
Author(s):  
Vineeta Ojha ◽  
Rishabh Khurana ◽  
Kartik P Ganga ◽  
Sanjeev Kumar
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Takotsubo Cardiomyopathy ◽  
Left Ventricular ◽  
Diagnostic Modality ◽  
Coronary Syndrome ◽  
Lv Dysfunction ◽  
Reversible Condition

Takotsubo cardiomyopathy (TC) is a reversible condition in which there is transient left ventricular (LV) dysfunction characterised most commonly by basal hyperkinesis and mid-apical LV ballooning and hypokinesia. It is said to be triggered by stress and mimics, such as acute coronary syndrome (ACS) clinically. Diagnosis is usually suspected on echocardiography due to the characteristic contraction pattern in a patient with symptoms and signs of ACS but normal coronary arteries on catheter angiography. Cardiac magnetic resonance (CMR), with its latest advancements, is the diagnostic modality of choice for diagnosis, prognosis and follow-up of patients. The advances in CMR (including T1, T2, ECV mapping and threshold-based late gadolinium enhancement (LGE) measurements have revolutionised the role of CMR in tissue characterisation and prognostication in patients with TC. In this review, we highlight the current role of CMR in management of TC and enumerate the CMR findings in TC as well the current advances in the field of CMR, which could help in prognosticating these patients.

scholarly journals Machine Learning–Based Risk Assessment for Cancer Therapy–Related Cardiac Dysfunction in 4300 Longitudinal Oncology Patients

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Yadi Zhou ◽  
Yuan Hou ◽  
Muzna Hussain ◽  
Sherry‐Ann Brown ◽  
Thomas Budd ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
De Novo ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Oncology Patients ◽  
Relevant Variables ◽  
After Cancer

Background The growing awareness of cardiovascular toxicity from cancer therapies has led to the emerging field of cardio‐oncology, which centers on preventing, detecting, and treating patients with cardiac dysfunction before, during, or after cancer treatment. Early detection and prevention of cancer therapy–related cardiac dysfunction (CTRCD) play important roles in precision cardio‐oncology. Methods and Results This retrospective study included 4309 cancer patients between 1997 and 2018 whose laboratory tests and cardiovascular echocardiographic variables were collected from the Cleveland Clinic institutional electronic medical record database (Epic Systems). Among these patients, 1560 (36%) were diagnosed with at least 1 type of CTRCD, and 838 (19%) developed CTRCD after cancer therapy (de novo). We posited that machine learning algorithms can be implemented to predict CTRCDs in cancer patients according to clinically relevant variables. Classification models were trained and evaluated for 6 types of cardiovascular outcomes, including coronary artery disease (area under the receiver operating characteristic curve [AUROC], 0.821; 95% CI, 0.815–0.826), atrial fibrillation (AUROC, 0.787; 95% CI, 0.782–0.792), heart failure (AUROC, 0.882; 95% CI, 0.878–0.887), stroke (AUROC, 0.660; 95% CI, 0.650–0.670), myocardial infarction (AUROC, 0.807; 95% CI, 0.799–0.816), and de novo CTRCD (AUROC, 0.802; 95% CI, 0.797–0.807). Model generalizability was further confirmed using time‐split data. Model inspection revealed several clinically relevant variables significantly associated with CTRCDs, including age, hypertension, glucose levels, left ventricular ejection fraction, creatinine, and aspartate aminotransferase levels. Conclusions This study suggests that machine learning approaches offer powerful tools for cardiac risk stratification in oncology patients by utilizing large‐scale, longitudinal patient data from healthcare systems.

Results of randomized study on dexrazoxane administration in children with de novo acute leukemia

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9037-9037
Author(s):  
E. De Berranger ◽  
G. Vaksmann ◽  
E. Thebaud-Leculee ◽  
I. Wyckaert ◽  
F. Mazingue ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cardiac Function ◽  
Cardiac Toxicity ◽  
De Novo ◽  
Randomized Study ◽  
Wall Stress ◽  
Left Ventricular ◽  
Grade 3 ◽  
Mean Time

9037 Background: Anthracyclins and anthracenediones represent major drugs for both AML and ALL. Among other mechanisms, these drugs induce free radical production responsible of cardiac toxicity. It appeared very important to protect cardiomyocytes. Dexrazoxane (DZ) was developed in this goal. In adult patients, its efficiency was demonstrated both to protect heart and to respect anticancer therapy. We conducted a prospective single bind randomized study using DZ in pediatric acute leukemia. Methods: From Dec 00 to Sept 03, 16 patients (pts) were enrolled for receiving or not DZ (1g for 50mg of doxorubicin equivalent dose) with chemotherapy. Cardiac function was evaluated by echocardiogram before induction and after each chemotherapy course of either EORTC 58951 (arm VHR) or LAME01 trials and each year after treatment completion. The cardiologist operator did not know if child received DZ or not. The cumulative equivalent doxorubicin doses were 310 and 450mg/m2 for EORTC 58951 and LAME01, respectively. The primary end-point was cardiac function evolution. The secondary end points were OS, EFS and the respect of therapy schedule. Results: 16 pts (9M/7F, 11AML/5ALL), median age 8.5y (2.4 - 16.1) were enrolled. 5 AML and 3 ALL pts received DZ. Median f-up was 28.5 months (10–47). Mean left ventricular shortening fractions were 39 and 35% in pts without DZ and 40 and 39% in pts with DZ before chemotherapy and 1 year after diagnosis, respectively. Mean wall stress values were 50 and 50g/cm2 for patients without DZ and 39 and 38g/cm2 for pts with DZ. All these values were comparable. 12 pts were alive, 6 in each arm. 1 pt relapsed in DZ arm and 3 in the other arm. 2 pts died of disease and 2 from infection equally dispatched in the 2 arms. Mean time between successive chemotherapy courses was identical in different groups. 2 patients given DZ presented severe hepatic toxicity (≥grade 3 of WHO classification) followed by quick and spontaneous regression. None other toxicity > grade 1 were observed. Conclusions: DZ may be used safely in children receiving anthracycline. No difference in OS and DFS appear in our study. Median follow-up was probably too short for distinguishing any cardiac alteration, and patient number was low. No significant financial relationships to disclose.

scholarly journals Getting to the Heart of the Matter: An Overview of Cardiac Toxicity Related to Cancer Therapy

2015 ◽  
Vol 9s2 ◽  
pp. CMC.S19704 ◽  
Author(s):  
Carine E. Hamo ◽  
Michelle Weisfelner Bloom
Keyword(s):  
Radiation Therapy ◽  
Side Effects ◽  
Cancer Therapy ◽  
Patient Outcomes ◽  
Cancer Survival ◽  
Cardiac Toxicity ◽  
Early Recognition ◽  
Cancer Therapies ◽  
Cardiovascular Side Effects

With the improvement in cancer survival, long-term cardiotoxicity has become an area of increased interest. Various cancer therapies, including chemotherapy and radiation therapy can lead to cardiac toxicities with both acute and chronic manifestations. Awareness and early recognition can lead to improvement in cardiac survival and patient outcomes. The focus of this review is to summarize the cancer therapy agents most often associated with cardiovascular side effects, highlighting their mechanism of action and strategies for surveillance and prevention.

scholarly journals The Role of Natriuretic Peptides for the Diagnosis of Left Ventricular Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alberto Palazzuoli ◽  
Matteo Beltrami ◽  
Gaetano Ruocco ◽  
Marco Pellegrini ◽  
Ranuccio Nuti
Keyword(s):  
Natriuretic Peptides ◽  
Potential Role ◽  
Low Cost ◽  
Pressure Overload ◽  
High Specificity ◽  
Left Ventricular ◽  
Cardiac Insufficiency ◽  
Cardiac Condition ◽  
Measurement Biases

Natriuretic peptides (NPs) are entered in current guidelines for heart failure (HF) diagnosis and management because of their high specificity and sensibility in screening patients with acute dyspnea. Due to their availability and relatively low cost, they became the first step examinations in HF patients evaluation at hospital admission together with clinical and chest radiography examination. NPs are released following any cardiac haemodynamic stress due to volume or pressure overload and should be considered as a mirror of cardiac condition helping in recognizing patients with poor outcome. Moreover, the exact role of NPs in early HF stages, in isolated diastolic dysfunction, and in general population is questioned. Several promising reports described their potential role; however, the wide cut-off definition, inclusion criteria, and intrinsic measurement biases do not actually consent to their clinical application in these settings. A multimodality strategy including both NPs and imaging studies appears to be the best strategy to define the cardiac dysfunction etiology and its severity as well as to identify patients with higher risk. In this review, we describe the current and potential role of NPs in patients with asymptomatic cardiac insufficiency, evaluating the requirement to obtain a better standardization for imaging as for laboratory criteria.

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