可溶性ST-2对接受阿霉素化疗乳腺癌患者的左心功能及结构变化预测价值的研究

目的通过检测乳腺癌患者接受阿霉素化疗后的可溶性致癌抑制因子2(sST-2)水平以及心脏功能指标,评估sST-2水平对左心功能损害的预测价值。方法回顾性收集2016年9月至2018年6月期间于郑州大学第五附属医院乳腺外科接受阿霉素(吡柔比星)化疗的90例乳腺癌患者的临床病理资料。所有患者均于化疗前以及接受蒽环类化疗药物治疗1年时抽取外周静脉血血样检测sST-2水平和心功能指标,同时行超声心动图检查。结果与化疗前比较,化疗1年时的sST-2、左心室收缩末期容积(left ventricular end-systolic volume,LVESV)、左心室舒张末期容积(left ventricular end diastolic volume,LVEDV)、左心室收缩末期内径(left ventricular systolic diameter,LVESD)、左心室舒张末期内径(left ventricular diastolic internal diameter,LVEDD)和二尖瓣舒张早期血流峰值速度与二尖瓣环舒张早期运动峰值速度比值(E/e’)升高,LVEF值降低,差异均有统计学意义(P<0.05)。sST-2水平与LVEF值存在负相关关系(r=–0.618,P<0.05)。受试者工作特征曲线结果显示,sST-2水平为11.9 ng/mL时为最佳临界值,以此预测左心室功能损害的灵敏度和特异度分别为90.6%和69.2%,ROC曲线下面积为0.836(P<0.05)。结论 sST-2对预测接受阿霉素类化疗的乳腺癌患者的左心功能有一定的辅助诊断价值。     

Doxorubicin concentrations in plasma and myocardium and their respective roles in cardiotoxicity

Summary Three hours after the intravenous infusion of doxorubicin (3 mg/kg over 15 min) to anesthetized dogs, the drug concentration was found much higher in the myocardium than in the plasma (about 4,000 ng/g, i.e., 50 times higher). After the intravenous infusion of doxorubicin (1.5 mg/kg over 15 min) to conscious dogs, the drug concentration appeared to decline very slowly in the myocardium, since it was close to 200 ng/g at the 7th day, whereas the plasma concentration had fallen to zero, and the drug was still detected in the cardiac tissue 21 days after the administration. As myocardial concentrations of doxorubicin persist long after plasma clearance is complete, the hazards of repeated administration, based on plasma kinetic patterns, must be emphasized.     

Anthracycline—Induced Congestive Heart Failure in two Pediatric Leukemia Cases and Long Term Follow—Up

Endomyocardial biopsy was performed on two leukemia patients who had recovered from severe congestive heart failure (CHF) due to anthracycline cardiomyopathy at 41 months and 47 months after CHF. Microscopic myocardial findings in both patients revealed that myocytes were hypertrophic, but interstitial fibrosis was not observed, suggesting a compensatory mechanism for the damaged heart muscle during the acute episode of CHF. The improvement of clinical symptoms and the normalization of cardiac function, including fractional shortening and ECG changes, is thought to have been associated with this myocardial repairing process.     

Cardiotoxicity of a new anthracycline derivative (SM-5887) following intravenous administration to rabbits: Comparative study with doxorubicin

The degree of cardiotoxicity of SM-5887 compared with that of doxorubicin was investigated in rabbits.Two experimental groups were administered high and low doses of SM-5887, respectively. One group was administered doxorubicin and another group was administered the vehicle only were prepared as positive and negative controls, respectively. Drugs were intravenously administered 3 times a week for 8 weeks.At terminus, electrocardiograms were recorded under anesthesia. The blood was collected for haematology and blood biochemistry analyses. Myocardial tissue damage was evaluated using light and electron microscopy.In the electrocardiogram study, prolongation of QTc interval and ST-T change were observed in rabbits administered SM-5887 and doxorubicin.Morphological studies showed that myocardial tissue damage in animals administered SM-5887 was comparable to that in the negative controls, and less than that observed in the positive controls.The general toxicological investigations uniformly indicated lower toxicity in the SM-5887 group than in the doxorubicin group at equivalent dosages.In total, considering the results of antitumor efficacy studies comparing SM-5887 with doxorubicin, these results indicate that the cardiotoxicity of SM-5887 is very slight, and that the general toxicity of SM-5887 is lower than that of doxorubicin.     

新的蒽环类抗生素80334B、C和F的研究~△Ⅴ.高产菌株的选育

采用紫外光诱变、自然分离纯化、自身耐药菌株筛选及耐浅蓝菌素菌株筛选等复合处理的方法,获得了几株高产菌株,建立了一个极为简便而有效的选育蒽环类抗生素产生菌的方法。用此法找到的一突变株UV 162,产量比原株提高了5.7倍。     

神经激肽1受体拮抗剂预防蒽环类药物所致恶心呕吐的研究进展

神经激肽-1受体（NK1R）拮抗剂联合5羟色胺3（5-HT3）抑制剂和地塞米松的标准三联止吐方案广泛用于预防蒽环类药物所致的恶心呕吐。近年不同NK1R拮抗剂及其给药方式,与不同5-HT3抑制剂和其他止吐药物联合用于防治蒽环类化疗所致恶心呕吐的研究进展迅速。本文就NK1R拮抗剂在预防蒽环类药物所致恶心呕吐中的作用及机制作一综述。     

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post‐HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait‐list and post‐HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait‐list survival was higher in the ACM group, post‐HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long‐term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group.     

Cytarabine and daunorubicin for the treatment of acute myeloid leukemia

Introduction: Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as ‘3 + 7? has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally.

Areas covered: This paper will briefly review clinically important trials related to ‘3 + 7?. Somatic mutations in AML that are linked to chemoresistance to ‘3 + 7?will be discussed. Other topics covered include the novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and midostaurin in FLT3 mutated AML.

Expert opinion: ‘3 + 7? continues to be the backbone of therapy for AML. However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy and hence, should be enrolled onto a clinical trial upfront. This will facilitate development of newer effective treatment strategies in AML. Patients with mutations that are associated with chemoresistance should be offered therapies which may circumvent or overcome these pathways.