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Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.  相似文献   
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目的:探讨自动心肌运动定量(aCMQ)技术评价急性淋巴细胞白血病(ALL)儿童使用蒽环类药物化疗后亚临床左室功能损害的价值。方法:选取2021年11月至2022年1月在温州医科大学附属第二医院育英儿童医院采用DVLD方案诱导化疗的30例ALL患儿作为白血病组,在化疗前和化疗3个月后行超声心动图检查。同期选取性别匹配的26例健康者作为对照组。运用常规超声心动图获取左室射血分数(LVEF)、左室短轴缩短率(LVFS)、二尖瓣口舒张早期峰值流速(E)与晚期最大峰值流速(A)比值(E/A)、E与二尖瓣环舒张早期血流峰值(e’)比值(E/e’)、e’与二尖瓣环舒张晚期血流峰值(a’)比值e’/a’。运用aCMQ技术获得两腔心纵向应变(AP2LS)、三腔心纵向应变(AP3LS)、四腔心纵向应变(AP4LS)及整体纵向应变(LVGLS),左室短轴基底段环向应变(SAXBCS)、左室短轴中间段环向应变(SAXMCS)、左室短轴心尖段环向应变(SAXACS)及整体环向应变(LVGCS),并进行比较分析。结果:白血病组与对照组年龄差异无统计学意义(P >0.05);对照组、化疗前组及化疗后组LVEF、LVFS、E/A、E/e’、e’/a’差异无统计学意义(P >0.05),化疗前组AP4LS、AP3LS、AP2LS、GLS、SAXBCS、SAXMCS、SAXACS及GCS值与对照组比较,差异无统计学意义(均P >0.05);化疗后组SAXBCS、SAXMCS值与化疗前和对照组比较,差异无统计学意义(P >0.05);化疗后组AP4LS、AP3LS、AP2LS、GLS、SAXACS及GCS参数绝对值低于对照组和化疗前组,差异有统计学意义(P <0.05)。结论:aCMQ技术能早期发现儿童ALL蒽环类药物化疗所致亚临床左室功能损害,可作为一种评估左室收缩功能相对准确的方法。  相似文献   
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细胞周期蛋白依赖性激酶(cyclin-dependent kinases, CDKs)在细胞周期的调控中起着至关重要的作用,是干扰肿瘤细胞分裂和增殖的特异治疗靶点。帕博西尼是全球首个CDK4/6特异性抑制剂,临床疗效显著,毒性可控,被批准联合来曲唑治疗绝经后ER+、HER2-的晚期乳腺癌患者,作为转移性疾病的初始内分泌治疗。目前已经开始研究这种抑制剂对其他恶性肿瘤的疗效。本文综述了帕博西尼的作用机制及其在不同肿瘤治疗中的研究进展,并对帕博西尼的发展前景进行了展望。  相似文献   
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Carfilzomib (CFZ) is an inhibitor of proteasome that is generally used in the treatment of multiple myeloma but due to its cardiotoxicity clinical use may be limited. Dexrazoxane (DZR), an inhibitor of topoisomerase-II, prevents cardiac damage by reducing the formation of reactive oxygen species and hypertrophic gene expression. This study evaluated the protective effect of DZR on CFZ-induced cardiotoxicity. Thirty-two male Albino rats were randomly divided into four groups (n?=?8). Group I received DMSO, Group II received CFZ (4?mg/kg, intraperitoneally [i.p.]) twice weekly up to day 16, Group III received DZR (20?mg/kg, i.p.) for 16 days and CFZ twice weekly for 16, Group IV received DZR (40?mg/kg, i.p.) for 16 days and CFZ twice weekly for 16. CFZ-induced cardiotoxicity was assessed by hematological, biochemical, mRNA expression, oxidative stress and histopathological studies. CFZ-induced significant changes have been observed in blood parameters including red blood cells, white blood cells, hemoglobin and hematocrit concentrations which were associated with increase in cardiac enzymes markers like creatine kinase (CK), CK-MB and lactate dehydrogenase. Treatment with DZR reversed the hematological statistics and the biochemical markers of CFZ-induced cardiotoxicity. Furthermore, DZR also attenuated the effects of CFZ-induced toxic effect on redox markers such as malondialdehyde and reduced glutathione. Above findings were further confirmed by beta-myosin heavy chain (β-MHC) and alpha-MHC (α-MHC) gene expression. Histopathological reports suggested that DZR ameliorates CFZ-induced changes in cardiac cellular architecture in rats. These results confirm that DZR protects heart from CFZ-induced cardiotoxicity.  相似文献   
8.
Cardiotoxicity limits the clinical applications of doxorubicin (Dox), which mechanism might be excess generation of intracellular ROS. Quercetin (Que) is a flavonoid that possesses anti-oxidative activities, exerts myocardial protection. We hypothesized that the cardioprotection against Dox injury of Que involved 14-3-3γ, and mitochondria. To investigate the hypothesis, we treated primary cardiomyocytes with Dox and determined the effects of Que pretreatment with or without 14-3-3γ knockdown. We analyzed various cellular and molecular indexes. Our data showed that Que attenuated Dox-induced toxicity in cardiomyocytes by upregulating 14-3-3γ expression. Que pretreatment increased cell viability, SOD, catalase, and GPx activities, GSH levels, MMP and the GSH/GSSG ratio; decreased LDH and caspase-3 activities, MDA and ROS levels, mPTP opening and the percentage of apoptotic cells. However, Que’s cardioprotection were attenuated by knocking down 14-3-3γ expression using pAD/14-3-3γ-shRNA. In conclusion, Que protects cardiomyocytes against Dox injury by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ.  相似文献   
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目的:探讨常规超声心动图对蒽环类化疗药物所致心脏毒性的诊断价值。方法:选取2014年2月至2017年6月在我院接受蒽环类药物化疗的乳腺癌术后患者136例,给予吡柔比星+环磷酰胺+多西他赛方案化疗6个周期。疗程结束后,根据患者是否发生心脏毒性分为心脏毒性组(N=48)和无心脏毒性组(N=76),对比患者化疗前后的超声心动图参数,分析常规超声心动图参数在早期心脏毒性诊断中的价值。结果:心脏毒性组TAPSE、E/A和E/a,值显著低于无心脏毒性组(P0.05)。ROC曲线分析,TAPSE、E/A和E/e'对应的曲线下面积分别为0.917(0.874,0.962)、0.902(0.853,0.957)、0.845(0.823,0.921)。TAPSE的截断值为20.78 mm、E/A的截断值为1.19、E/e'的截断值为8.59,Youden指数分别为0.842、0.761、0.712。结论:常规超声心动图在蒽环类药物心脏毒性诊断中具有一定价值。  相似文献   
10.
Survival rates of patients with non‐Hodgkin lymphoma (NHL) have improved over the last decade. However, cardiotoxicities remain important adverse consequences of treatment with chemotherapy and radiation, although the burden of cardiovascular mortality (CVM) in such patients remains unknown. We conducted a retrospective cohort study of patients greater than or equal to 20 years of age diagnosed with diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) between 2000 and 2013 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. Our primary endpoint was CVM. The association between NHL and CVM was evaluated using multivariable Cox regression analysis after adjusting for other patient characteristics. We calculated standardized mortality ratios (SMRs) for CVM, comparing NHL patients with the general population. We identified 153 983 patients who met the inclusion criteria (69 329 with DLBCL, 48 650 with CLL/SLL, and 36 004 with FL). The median follow‐up was 37 months (interquartile range, 10‐78 months); the mean patient age was 66.24 (±14.69) years; 84 924 (55.2%) were men; 134 720 (87.5%) were White, and 131 912 (85.7%) did not receive radiation therapy. Overall, 9017 patients (5.8%) died from cardiovascular disease, and we found that NHL patients had a higher risk of CVM than the general population, after adjusting for age (SMR 15.2, 95% confidence interval: 14.89‐15.52). The rates of CVM were 5.1%, 8%, and 4.4% in patients with DLBCL, CLL/SLL, and FL, respectively. Furthermore, across all NHL subtypes, older age, higher stage at the time of diagnosis (particularly stage 4), male sex, and living in the south were associated with higher risks of CVM. Our data suggest that risk assessment and careful cardiac monitoring are recommended for NHL patients, particularly those with the CLL/SLL subtypes.  相似文献   
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