蒽环类化疗药物所致心脏毒性的研究进展

蒽环类化疗药物是临床广泛应用的抗肿瘤药物之一,作为恶性肿瘤化疗方案的基础用药,其致命性的不良反应是心脏毒性,单位体表面积累积药物剂量引发的心脏毒性在很大程度上影响了肿瘤患者的治疗和预后,因此限制了其在恶性肿瘤治疗中的应用。随着医学水平的不断提高和医学技术的不断发展,与蒽环类化疗药物引起的心脏损害相关的药物结构、作用机制、病理改变、保护性制剂和监测方法的研究不断展开,早期亚临床心脏损害的出现逐渐引起了人们的重视。随着新型蒽环类化疗药物--脂质体制剂的研发与应用,心脏毒性的发生率和病死率均较传统蒽环类化疗药物有所下降,但仍无法避免由于多次低剂量的累积而引发的早期无症状的心脏损害。因此,本文对蒽环类化疗药物引起患者出现心脏损害的相关影响因素、表现形式和发生发展机制等作一综述,并通过对多种针对化疗后肿瘤患者的心功能检测和检查方式进行分析,评价早期监测蒽环类化疗药物对化疗后肿瘤患者的价值,从而为临床早期监测和诊疗蒽环类化疗药物引起的心脏毒性提供参考。     

化疗相关心脏毒性问题研究进展

化疗作为肿瘤治疗手段的基石之一,可引起心力衰竭、冠脉病变、瓣膜病、心律失常等心脏毒性事件,其相关近期、远期心脏毒性问题均需受到临床医生重视。近年随着肿瘤心脏病学交叉学科的发展,化疗药物相关心肌损伤问题在病理生理机制、诊断、治疗等方面均取得了一定进展,但仍然存在诸多问题。该综述从不同化疗药物引起心血管事件的流行病学、临床特点、机制、诊断及治疗策略方面简要介绍其心脏毒性的诊治问题,为临床实践提供参考。     

蒽环类抗肿瘤药物的心脏毒性及保护剂的研究进展

由于蒽环类药物显著的抗肿瘤作用和广泛的临床应用,其临床应用的安全性越来越受到重视.该类药物的心脏毒性表现为剂量限制性的特点.目前唯一获批的蒽环类药物心脏毒性保护剂只有右丙亚胺,其心脏保护作用已经得到了广泛认可,并被美国临床肿瘤实践指南及其他多种国内外指南推荐应用于蒽环类药物心脏毒性的预防和治疗.有关右丙亚胺的临床应用策略,目前仍存在一定争议.本文探讨了右丙亚胺对蒽环类药物抗肿瘤效价的影响、右丙亚胺用药时机的选择、右丙亚胺临床应用的安全性以及正在研究中的可能具有心脏保护功能的药物.     

肿瘤化疗药物心脏毒性的预防策略

化疗药物的心脏毒性越来越受到关注。在临床实践中,可以通过降低药物剂量、调整给药管理和使用低毒剂型等优化化疗方案对策降低心脏毒性反应的发生率和严重程度。心脏保护剂的应用也非常重要,目前常用的药物包括右丙亚胺、心血管药物和中药制剂等,但这些药物作为心脏保护剂的应用具有局限性,且其有效性和安全性尚需要进一步验证。     

蒽环类抗肿瘤抗生素心脏毒性防治研究进展

蒽环类抗肿瘤抗生素的化学结构中,均具有蒽及一个六元环为基础的侧链和一个氨基糖化合物,１９５７年分离出第一个蒽环类抗癌药柔红毒素（daunorubicin,DNR）,不久出现了第二代产品阿霉素（driamycin,ADM）,阿霉素自２０世纪７０年代进入临床试验以来,因具有抗瘤谱广、临床疗效高,对乏氧细胞有效的显著特点,已成为蒽环类抗癌药物的代表药物,临床主要用于乳腺癌、恶性淋巴瘤、胃癌、肺癌等实体瘤,但由于其剂量累积心脏毒性,严重限制了其在临床上的使用,现以ADM为代表就其心脏毒性及防治研究进展作一介绍。１蒽环类抗癌药的心…     

抗肿瘤化疗药物对心脏毒性的研究进展

摘 要：心脏毒性是抗肿瘤化疗过程中一种严重的并发症,对肿瘤患者的预后和生存有着显著的影响。如何降低化疗药物对心脏的毒副作用,提高患者生存质量,改善预后,已成为肿瘤科和心内科医生共同研究和探讨的课题。本文对常用化疗药物心脏毒副作用的临床表现和机制,化疗过程中产生心脏毒性的监测预防以及产生心脏毒性后的治疗方面进行综述,以期避免或减少抗肿瘤药物对肿瘤患者的心脏损伤,改善患者预后。     

抗肿瘤药物的心脏毒性

心脏毒性是部分化疗药物,特别是蒽环类药物常见的副反应,可出现各种各样的表现,从良性心律失常至致死性心肌缺血或梗死及心肌病。本文综述各种抗肿瘤药物相关的心脏毒性。     

超声心动图对化疗药所致心脏毒性的评估

摘 要：癌症治疗方法的改进延长了患者的生存期,但很多化疗药物会引起心脏并发症。尤为显著的是,化疗导致的心脏功能受损明显降低了癌症患者的生存质量,提高了死亡率。早期发现亚临床心脏毒性和左心室功能异常是非常重要的。目前,对于亚临床心脏毒性的检测缺乏准确的手段和方法。超声心动图是现有的一种有效评估心脏功能的方法,在心脏毒性诊断中起到重要作用。全文探讨超声心动图在检测心脏毒性中的作用,包括传统及超声心动图新技术对亚临床心脏毒性的评估。     

抗肿瘤治疗所致心脏毒性的研究进展

恶性肿瘤是目前社会的主要死亡原因之一,随着抗肿瘤治疗方法的不断进步,癌症患者的生存率显著提高。由于癌症患者的生存期延长,癌症治疗所引起的相关心血管不良事件的发生率明显升高,引起心脏病学家越来越多的关注。抗肿瘤治疗引起的主要心脏毒性包括左室收缩功能障碍和心功能不全,此外还可能产生其他心脏毒性,如高血压、心包疾病、心律失常、血栓栓塞及房颤等。心脏病学家已制定治疗策略,优化检测手段,预防和监测癌症治疗过程中的心脏毒性,以提高患者生活质量。本文主要对抗肿瘤治疗所致常见心脏毒性进行综述。     

miRNA在肿瘤治疗相关心脏毒性中的研究进展

因心脏毒性的发生使抗肿瘤药物的临床使用受限。化疗、放疗、靶向治疗和免疫治疗均表现出不同频度和程度的心脏毒性,严重者可发生心力衰竭,危及患者生命。不同抗肿瘤治疗导致的心脏毒性作用机制复杂,氧化应激、DNA损伤、细胞凋亡等均可能参与。miRNA（microRNA）是细胞增殖、死亡、凋亡和分化的关键调控因子,其失调还与心脏重塑和心脏毒性密切相关。本文将对miRNAs可能参与不同肿瘤治疗所致心脏毒性发生的作用机制,及其在监测和治疗中的作用进行综述。      

紫杉烷类抗肿瘤药物剂量个体化研究进展

紫杉烷类药物是治疗实体肿瘤的常用药物,临床常基于体表面积(body surface area,BSA)给药,但其无法降低个体间代谢差异以及化疗产生的毒副反应,已不再是最适宜的剂量算法,有必要对紫杉烷类药物采用剂量个体化给药。因此,现就紫杉烷类药物的代谢酶活性测定和治疗药物监测(TDM)的研究进展进行归纳和总结,以期为紫杉烷类药物剂量个体化的理论研究及临床应用提供参考。     

Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia. HCC is often resistant to chemotherapy and the mechanism remains unclear. Mitochondrion-mediated pathway is critical in hepatocyte apoptosis, which suggests Bcl-2 family genes may play a role in the regulation of chemotherapy in HCC. In the present study, we investigated the role of BH3 domain-only protein Bid in HCC tissues, HCC-derived cell lines and how the expression of Bid was related to chemotherapeutic agent-induced apoptosis. Bid was differently expressed in HCC tissues and hepatoma cell lines. Hep3B, a Bid-abundant HCC cell line, was more sensitive to drug-induced cytotoxicity than PLC/PRF/5, a Bid-insufficient HCC cell line. The level of caspase activity induced by 5-fluorouracil (5-FU) was higher in Hep3B than in PLC/PRF/5 and a significant increase in the activity occurred at a rather late stage, after 48 h of the treatment. Similar to the activation of caspase, Bid cleavage and activation was only significant at 72 h after the treatment. Overexpression of Bid or tBid sensitized HCC cells to 5-FU and doxorubicin (Dox) treatments. We further demonstrated that such a sensitive effect could be offset by Bcl-xL, as Bid- or tBid-induced apoptosis was completely blocked by the over-expression of Bcl-xL. These results indicate the level of Bid expression is closely associated with the sensitivity of HCC cells to chemotherapeutic drugs, suggesting that Bid plays an important role in HCC management.     

PD-1抑制剂心脏毒性研究进展

随着免疫疗法在肿瘤患者中的广泛应用,药物的多项不良反应逐步被人们所重视。本文结合当下最新研究进展,从临床特征、作用机制、监测与处理、亟待研究的若干问题等四个方面,对PD-1免疫抑制剂所介导的罕发却致命的心脏毒性效应进行综述。     

5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine

Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.     

蒽环类药物普通制剂及脂质体制剂的心脏毒性研究进展

蒽环类药物属于抗肿瘤抗生素,为细胞周期靶向非特异性药物,具有广谱、强效的特点,临床上广泛用于实体肿瘤和恶性血液系统肿瘤的治疗。但是,因为容易引起心脏毒性事件而使其临床应用受到了一定程度的限制。经多年研究表明,与蒽环类药物普通制剂相比,脂质体制剂不但疗效相当,而且能减轻心脏毒性。本文就蒽环类药物普通制剂和脂质体制剂心脏毒性的流行病学、发生机制和防治措施作一综述,以期为其临床应用提供指导。     

Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells.

PURPOSE: To test whether and how selenium enhances the apoptosis potency of selected chemotherapeutic drugs in prostate cancer (PCA) cells. EXPERIMENTAL DESIGN: DU145 and PC3 human androgen-independent PCA cells were exposed to minimal apoptotic doses of selenium and/or the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38), the topoisomerase II inhibitor etoposide or the microtubule inhibitor paclitaxel/taxol. Apoptosis was measured by ELISA for histone-associated DNA fragments, by flow cytometric analysis of sub-G(1) fraction, and by immunoblot analysis of cleaved poly(ADP-ribose)polymerase. Pharmacologic inhibitors were used to manipulate caspases and c-Jun-NH(2)-terminal kinases (JNK). RESULTS: The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide, or paclitaxel by several folds higher than the expected sum of the apoptosis induced by MSeA and each drug alone. The combination treatment did not further enhance JNK1/2 phosphorylation that was induced by each drug in DU145 cells. The JNK inhibitor SP600125 substantially decreased the activation of caspases and apoptosis induced by MSeA combination with SN38 or etoposide and completely blocked these events induced by MSeA/paclitaxel. The caspase-8 inhibitor zIETDfmk completely abolished apoptosis and caspase-9 and caspase-3 cleavage, whereas the caspase-9 inhibitor zLEHDfmk significantly decreased caspase-3 cleavage and apoptosis but had no effect on caspase-8 cleavage. None of these caspase inhibitors abolished JNK1/2 phosphorylation. A JNK-independent suppression of survivin by SN38 and etoposide, but not by paclitaxel, was also observed. In contrast to MSeA, selenite did not show any enhancing effect on the apoptosis induced by these drugs. CONCLUSIONS: MSeA enhanced apoptosis induced by cancer therapeutic drugs in androgen-independent PCA cells. In DU145 cells, the enhancing effect was primarily through interactions between MSeA and JNK-dependent targets to amplify the caspase-8-initiated activation cascades. The results suggest a novel use of methyl selenium for improving the chemotherapy of PCA.