蒽环类药物对白血病细胞的细胞毒作用与活性氧的关系研究进展

蒽环类抗生素用于白血病的治疗已30余年历史,已成为化疗不可缺少的药物之一。近年来研究显示,蒽环类抗生素对白血病细胞的细胞毒作用包括凋亡。而活性氧(reactive oxygen species,ROS)是细胞增殖、分化、成熟及凋亡过程中的重要介质;同时它与细胞耐药、心脏毒性有关。研究其作用机制将更好地了解白血病化疗的机制,更好地指导临床治疗。文章简述了蒽环类药物的作用机制及ROS与蒽环类药物细胞毒作用的关系,以期为临床研究提供参考。     

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL

Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m², V 1.4mg/m² (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m² i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC <500/mm³ for >5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m²,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m²in the COP-X regimen was well tolerated with little non-hematologic toxicity.     

Early detection of cardiotoxicity by 3D speckle tracking imaging of area strain in breast cancer patients receiving chemotherapy

Eighty‐three breast cancer patients who underwent six cycles of EC chemotherapy regimen (epirubicin + cyclophosphamide) without symptoms and signs of heart disease were enrolled in the study. Three‐dimensional speckle tracking imaging technique (3D‐STI) was used to measure left ventricular global area strain (GAS), overall annular strain (GCS), overall longitudinal strain (GLS), and overall radial strain (GRS). Meanwhile, serum troponin T (Hs‐cTnT) was measured. The clinical value of each index on cardiotoxicity after chemotherapy was analyzed using the receiver operating characteristic (ROC) curve. Hs‐cTnT increased from the early stage to the end during chemotherapy, but it was still in the normal range. During the mid‐chemotherapy and the end‐chemotherapy, GAS, GLS, GCS, and E/A significantly reduced, while the changes in LVESV, LVEDV, LVEF, and GRS were not significant after chemotherapy. Pearson correlation analysis showed a significant negative correlation between GAS and anthracycline doses (r = ?.772, P < .01); GAS and Hs‐cTnT were significantly negatively correlated (P < .05). The area under the curve (AUC) of GAS, GLS, GCS, and GRS are 0.815, 0.683, 0.645, and 0.585, respectively. A GAS of ?31.5% was used as the cutoff value for diagnosing left ventricular systolic dysfunction after receiving chemotherapy. The sensitivity of the previous parameters was 81.9%, and the specificity was 80.3%. Interobserver consistency analysis showed that 3D‐STI strain parameter measurement has good repeatability. GAS has greater value in predicting early myocardial damage after anthracycline chemotherapy.     

Apoptosis of cardiomyocytes as extreme manifestation of regeneration and plastic insufficiency of myocardium

Alkaline dissociation of the myocardium from rats with modeled anthracycline cardiomyopathy revealed decreased absolute number of cardiomyocytes, disturbances in their intracellular regeneration, although no sings of necrosis were observed. Regeneration and plastic insufficiency of the myocardium due to structural changes in the nuclei and disturbances in myofibril reproduction resulting from selective suppression of synthesis of contractile proteins in the cardiomyocytes leads to the death of up to 30% cardiomyocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 336–341, September, 2000     

常规超声心动图对蒽环类化疗药物致心脏毒性的诊断价值

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。     

Use of non-anthracycline regimens in early stage breast cancer in Australia

Various factors have recently prompted a re-evaluation of the role of non-anthracycline regimens in early stage breast cancer (ESBC). Since 1990 anthracyclines have been a key component of chemotherapy regimens. However, there is increased understanding of the long-term, irreversible toxicities associated with these therapies, including cardiac failure and secondary leukemia. The development of the taxanes in the 1990s led to new adjuvant chemotherapy regimens and trials of various combinations in an effort to further increase survival and reduce toxicity. Concerns about cardiac toxicity were reinforced with the emergence of trastuzumab for the treatment of HER2-positive breast cancer. Trastuzumab alone causes cardiac toxicity and increases the risk of cardiac toxicity when combined with anthracyclines. These data, combined with recent results demonstrating the efficacy of non-anthracycline regimens in various disease settings, have generated interest in utilizing these therapies in patients with both HER2-positive and -negative tumors. This review outlines the evidence for the use of non-anthracycline adjuvant regimens in ESBC, including cyclophosphamide, methotrexate and 5-fluoruoracil, docetaxel, carboplatin and trastuzumab and docetaxel and cyclophosphamide, which have demonstrated equivalent efficacy and reduced toxicity compared to anthracycline-based regimens in various trials. The review also examines evidence for the use of non-anthracycline regimens in patients who previously had restricted access to these therapies due to their negative lymph node status. The wider availability of these regimens increases options when deciding upon adjuvant chemotherapy for patients with ESBC, especially in patients with a high risk of cardiac toxicity.     

蒽环类抗肿瘤抗生素脂质体制剂的研究现状与进展述评

脂质体作为一种微粒类靶向制剂载体具有许多优良的特性,近年来在肿瘤化学治疗中的应用日益广泛。主要介绍几种具有代表性的蒽环类抗肿瘤抗生素多柔比星、表柔比星、柔红霉素、伊达比星、吡柔比星及米托蒽醌的脂质体制剂的上市或研发情况。