Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin\'s diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated.

Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower anthracycline-induced cardiotoxicity. Methods: PubMed and Google Scholar were searched until September 2023 for studies regarding SGLT2i for treating anthracycline-induced cardiotoxicity. Overall mortality and cardiovascular events were considered. Using a random-effects model, data pooled RR and HR at a 95% confidence interval (CI). Results: 3 cohort studies were identified, analyzing 2817 patients. Results display a significant reduction in overall mortality [RR = 0.52 (0.33-0.82); p = 0.005; I2= 32%], HF hospitalization [RR = 0.20 (0.04-1.02); p = 0.05; I2= 0%] and no significant reduction in HF incidence [RR = 0.50 (0.20-1.16); p = 0.11, I2= 0%]. Conclusion: SGLT2i mitigates mortality and hospitalization due to heart failure, improving cancer patient\'s chances of survival by undergoing anthracycline treatment.
What is this article about? This article explores the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a solution for reducing anthracycline-induced cardiotoxicity. Anthracycline is an established subclass of chemotherapeutic drugs which has been known to cause harm to the heart. The study, conducted a systematic search of PubMed and Google Scholar up until September 2023, assessing the effects of SGLT2i on overall mortality and cardiovascular events in cancer patients, regardless of the presence or absence of diabetes mellitus and the effectiveness of SGLT2i as a cardiotoxic therapy in cancer patients.What were the results? The analysis of studies involving 2817 patients showed findings indicating that giving SGLT2i could lower the chances of anthracycline-induced heart problems in cancer patients undergoing treatment. The findings showed a striking decrease in hospitalization due to heart failure and overall mortality whereas the findings for the effect of SGLT2i on incidence of heart failure were insignificant. The encouraging outcomes offer valuable insights that could help enhance the outlook and chances of survival for individuals with cancer.What do the results of the study mean? These findings indicate that SGLT2i notably reduces the risk of death and cardiovascular issues, like being hospitalized due to heart failure, in cancer patients undergoing anthracycline treatment. This has significant implications for how doctors might treat cancer patients in practice. Including SGLT2i in the treatment plan could improve the survival prospects of these patients, offering a promising advancement in handling anthracycline-induced heart issues with side effects that can be managed.

Left ventricular dysfunction in dogs after the administration of doxorubicin (DOX) has been extensively examined. However, the effects of DOX on right ventricular (RV) function remain unknown. Therefore, the present study investigated whether the chemotherapy treatment with DOX decreases RV function. Twelve dogs (five with multicentric lymphoma, four with hemangiosarcoma, two with thyroid cancer, and one with lung adenocarcinoma) that received at least two doses of DOX were prospectively enrolled. Echocardiography and the measurement of troponin I were performed prior to each administration of DOX and approximately one month after the last administration. Right ventricular function was assessed by the RV fractional area change and RV Tei index. Two (n=4), three (n=3), four (n=3), and five (n=2) doses of DOX were administered. While no significant differences were observed in the RV fractional area change, the RV Tei index was significantly impaired after two doses of DOX. Troponin I level significantly increased after four doses. Cumulative doses of DOX correlated with the RV Tei index (r=0.77, P<0.001). The present results demonstrated that the chemotherapy treatment with DOX decreased RV function in a dose-dependent manner in dogs.

UNASSIGNED: Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties.
UNASSIGNED: This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model.
UNASSIGNED: Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis.
UNASSIGNED: DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (*p = 0.0199), (**p = 0.0077), respectively. A significant reduction (***p = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (****p < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*p=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results.
UNASSIGNED: Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.

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UNASSIGNED: Anthracycline administration in children is associated with cardiac dysfunction. Speckle-tracking echocardiography (STE) can detect subclinical cardiac damage that may go undetected by conventional two-dimensional (2D) echocardiography. This study aims to investigate medium-term anthracycline cardiotoxicity using STE and determine a safer administrable level of anthracyclines (ACs).
UNASSIGNED: This observational case-control study enrolled 37 healthy controls and 78 pediatric cancer survivors who received chemotherapy. The patients were divided into two groups: cardiotoxic received (CR) and cardiotoxic free (CF). Data on segmental longitudinal strain (LS), global LS (GLS), and 2D echocardiographic parameters were collected after a drug-free period of at least one year.
UNASSIGNED: A total of 115 children with a mean age of 108 ± 55 months, of whom 66% were males, were included in the study. Both the groups of cancer survivors exhibited significantly reduced GLS compared to healthy controls (CR vs. controls, P = 0.001; CF vs. controls, P = 0.013), but no significant difference in left ventricular ejection fraction (LVEF) was observed (P = 0.75). Overall, cancer survivors treated with ACs demonstrated a significant reduction in strain in 10 left ventricular segments, particularly in the basal segments (P < 0.05). Among CR patients, those with impaired GLS (n = 43, GLS worse than -21.9) had significantly higher mean age and cumulative anthracycline dose compared to CR patients with normal GLS (age, P = 0.024; anthracycline dosage, P = 0.036). Using an anthracycline cutoff of 223 mg/m2 resulted in a higher detection rate (49% vs. 25%) and fewer missed cases (51% vs. 74%) compared to the 360 mg/m2 anthracycline cutoff.
UNASSIGNED: Childhood cancer survivors demonstrate significantly reduced GLS while preserving a normal LVEF, which does not differ significantly from reference values of healthy children. The reduction in strain appears to be associated with higher anthracycline doses and older age. Lowering the anthracycline threshold to 223 mg/m2 may improve the predictability of a decline in cardiac function using strain imaging at medium-term follow-up.

BACKGROUND: Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database.
METHODS: Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate (MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints.
RESULTS: Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293).
CONCLUSIONS: Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

BACKGROUND: Doxorubicin (DXR) is an effective chemotherapeutic agent. DOX-induced cardiomyopathy (DICM), a major limitation of DXR, is a complication with limited treatment options. We previously reported that Red Ginseng (steamed and dried the root of Panax Ginseng cultivated for over six years; RGin) is beneficial for the treatment of DICM. However, the mechanism underlying the action of RGin remains unclear. In this study, we investigated the mechanism of action underlying the efficacy of RGin in the treatment of DICM.
METHODS: Four-week-old DBA/2 mice were divided into: vehicle, DXR, RGin, and DXR + RGin (n = 10/group). Mice were treated with DXR (4 mg/kg, once a week, accumulated 20 mg/kg, i.p.) or RGin (0.5 g/kg, three times a week, i.p.). To evaluate efficacy, the survival rate and left ventricular ejection fraction (LVEF) were measured as a measure of cardiac function, and cardiomyocytes were subjected to Masson trichrome staining. To investigate the mechanism of action, western blotting was performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, transferrin receptor (TfR), and other related proteins. Data were analyzed using the Easy R software. Between-group comparisons were performed using one-way analysis of variance and analyzed using a post-hoc Tukey test. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. P < 0.05 was considered statistically significant in all analyses.
RESULTS: RGin treatment prolongs survival and protects against reduced LVEF. In the DXR group, Nrf2 was not activated and cell death was accelerated. Furthermore, there was an increase in the TfR levels, suggesting abnormal iron metabolism. However, the DXR + RGin group showed activation of the Nrf2 pathway and suppression of myocardial cell death. Furthermore, there was no increase in TfR expression, suggesting that there were no abnormalities in iron metabolism. Therefore, the mechanism of action of RGin in DICM involves an increase in antioxidant activity and inhibition of cell death through activation of the Nrf2 pathway.
CONCLUSIONS: RGin is a useful therapeutic candidate for DICM. Its efficacy is supported by the activation of the Nrf2 pathway, which enhances antioxidant activity and inhibits cell death.

UNASSIGNED: Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.
UNASSIGNED: 1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m2/biweekly IV, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT.
UNASSIGNED: In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses.
UNASSIGNED: In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.

Background: During the physiological cardiac cycle, the helix orientation of the muscle fibres induces the rotation of the apex relative to the base of the left ventricular (LV). In heart failure, LV torsion is impaired, and rotation at basal and apical levels occurs in the same direction, a phenomenon called rigid body rotation (RBR). We aimed to evaluate whether the RBR pattern and GLS together could improve the diagnosis of cardiotoxicity in patients treated with anthracyclines and/or anti-HER2. Methods: With an observational, retrospective study involving 175 patients (mean age 55 ± 12 years, 94% females), we evaluated the development of cancer therapeutic-related cardiac dysfunction (CTRCD) defined according to ESC guidelines. We characterised LV dysfunction by echocardiographic standard and speckle-tracking (GLS and RBR pattern) measurements. Patients with a previous diagnosis of structural heart disease or atrial fibrillation were excluded. Results: At the time of enrolment, the chemotherapy regimen included trastuzumab (96%), pertuzumab (21%), and anthracyclines (13%). Twenty-two patients (12.5%) developed cardiotoxicity, and thirteen patients developed an RBR within 6 months of follow-up. In all cases, the RBR pattern was associated with cardiotoxicity (p < 0.001), reporting an optimal specificity but poor sensitivity at three and six months. However, the addition of the RBR pattern to the global longitudinal strain (GLS) ≥ -16% increased the odds ratio (OR) from 25.6 to 32.6 at three months and from 32.5 to 49.6 at six months rather than GLS alone. Conclusions: The RBR pattern improves the diagnostic accuracy of GLS for the detection of cardiotoxicity secondary to anthracyclines and anti-HER2-based treatments.