Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Humans ; Cardiologists ; Neoplasms/drug therapy* ; Medical Oncology ; Heart ; Oncologists

Humans ; Cardiotoxicity/etiology* ; Antineoplastic Agents/adverse effects* ; Oncologists ; Neoplasms/drug therapy*

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
Humans ; Rats ; Animals ; Benzhydryl Compounds/toxicity* ; Phenols/toxicity* ; Auditory Perception/physiology* ; Neurons/physiology*

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/drug therapy* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Receptor, ErbB-2

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Cardiovascular toxicity of cancer patients in antineoplastic therapy is gradually paid widespread attention. Although many high-risk factors of cardiovascular toxicity associated with chemotherapy, targeted therapy or immunotherapy have been identified, it is still difficult to establish accurate risk prediction model. Traditional risk prediction model cannot adequately explain the differences in cardiovascular toxicity susceptibility among patients, makes it difficult to accurately screen high-risk groups, early diagnose and prevent cardiovascular toxicity. Finding susceptible genes of cardiovascular toxicity associated with antineoplastic therapy and incorporating single-nucleotide polymorphisms into risk prediction model can significantly improve the identification of high-risk population of cardiovascular toxicity.

Objective:To verify the risk prediction efficacies of COMPASS-cancer associated thrombosis (COMPASS-CAT) risk assessment model and the new prediction probability model established based on COMPASS-CAT for venous thromboembolism (VTE) in hospitalized patients with non-small cell lung cancer (NSCLC).Methods:We retrospectively collected the clinical data of 373 patients with NSCLC admitted to National Clinical Research Center for Cancer/Cancer Hospital from March 2013 to June 2017. All of them were divided into VTE group (63 cases) and non-VTE group (310 cases) according to VTE occurred or not. According to the COMPASS-CAT risk assessment model, all patients were scored and classified by risk. Chi-square test was used to compare the clinical features between two groups, and multivariate logistic regression analysis was used to evaluate the independent risk factors of VTE in NSCLC patients. Based on the COMPASS-CAT risk assessment model, D-dimer≥1.03 mg/L and hemoglobin<10 g/dl were included to construct a new COMPASS-CAT prediction probability model, the ROC curve was also drawn. We used MedCalc software to compare the difference of ROC curves and analyze the application value of different risk assessment models in predicting VTE risk of NSCLC patients.Results:The incidence of VTE was 16.9% (63/373). The COMPASS-CAT score of VTE group was 6.37±3.40, which was higher than 2.74±2.04 of non-VTE group ( P<0.001). Univariate analysis showed that the proportion of patients with KPS≤80, COMPASS-CAT≥7, D-dimer≥1.03 mg/L, central venous catheter (CVC), hemoglobin<10 g/L, cardiovascular complications≥2, hyperlipidemia, clinical stages Ⅲ and Ⅳ, KPS≤80 in VTE group was significantly higher than that in non-VTE group ( P<0.05). Logistic regression analysis showed that D-dimer≥1.03 mg/L, compass-cat score≥7 and hemoglobin <10 g/dL were independent risk factors for VTE. Based on the COMPASS-CAT risk assessment model, a new risk assessment model of COMPASS-CAT was constructed by incorporating the variables of D-dimer ≥1.03 mg/L and hemoglobin <10 g/dl. The area under ROC curve (AUC) of COMPASS-CAT model and new COMPASS-CAT prediction probability model were 0.745 and 0.804, respectively. Compared with COMPASS-CAT model, AUC of new COMPASS-CAT prediction probability model increased by 0.059, with statistically significant difference( P=0.007). Conclusion:COMPASS-CAT risk assessment model can predict the risk of VTE in NSCLC patients, and the new COMPASS-CAT prediction probability model constructed by COMPASS-CAT model combined with D-dimer and hemoglobin variables can improve the accuracy of screening VTE risk factors in NSCLC patient.

Objective:To analyze the metabolism of blood glucose and lipid in breast cancer patients after the first chemotherapy.Methods:Breast cancer patients who received chemotherapy for the first time from December 2016 to January 2020 were collected in our hospital, and their blood glucose and lipid levels were monitored. Patients were grouped according to different treatment plans. Non-parametric rank sum test was used for statistical analysis on SPSS software.Results:There were 1 356 female breast cancer patients were enrolled, blood glucose and lipid levels were compared before and after chemotherapy. Our results showed that baseline medium blood glucose was 5.2 mmol/L, lower than 5.3 mmol/L after chemotherapy ( P<0.05). The baseline triglyceride (TG) was 1.2 mmol/L, lower than 1.6 mmol/L after chemotherapy ( P<0.05). The baseline small dense low-density lipoprotein (sdLDL) was 0.7 mmol/L, lower than 0.8 mmol/L after chemotherapy ( P<0.05). The baseline high density lipoprotein (HDL) was 1.3 mmol/L, higher than 1.2 mmol/L after chemotherapy ( P<0.05). Patients′ menstrual status and body mass index were related with blood glucose, TG, LDL and sdLDL (all P< 0.05). Conclusions:Abnormal metabolism of blood glucose and lipid are observed in breast cancer patients after the first chemotherapy. More awareness of cardiovascular disease in breast cancer patients might ensure their overall clinical benefits.