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。     

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。      

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。     

麻醉处理对蒽环类抗肿瘤药物心脏毒性影响的研究进展

蒽环类抗肿瘤药物是一类对造血系统和实体肿瘤具有高效作用的广谱抗癌药物，是临床化疗方案中常用的药物之一。该类药物有一个严重的不良反应，即随着剂量的增加会产生显著的心脏毒性。临床上应用具有心肌保护作用的药物是安全使用蒽环类药物的重要策略之一。很多癌症患者在化疗期间还要进行手术治疗，全身麻醉是患者手术时主要的麻醉方法。对术前已行蒽环类药物化疗的患者实施全麻手术时，可能正处于蒽环类药物所致心肌损害的急性或慢性期，而麻醉药物对蒽环类药物所致心脏毒性的影响，将对患者术后心肺功能的恢复产生重要作用。目前，有关麻醉药物对蒽环类药物心脏毒性的影响已开始受到关注，本文即从蒽环类抗肿瘤药物的心脏毒性、心肌保护以及麻醉药物对其心脏毒性影响的研究现况进行综述。      

新型抗肿瘤药物的肺毒性

0 引言 肿瘤的化学治疗是肿瘤治疗的重要手段之一.由于肿瘤细胞与正常组织细胞间缺乏根本性的代谢差异,化疗中使用的多数抗肿瘤药物在抑制或杀伤肿瘤细胞的同时,会对机体的某些正常细胞、组织和器官造成损害,抗肿瘤药物诱导的肺毒性就是其中之一.本文对一些新型抗肿瘤药物所致的肺毒性的发生机制、临床诊断及防治进行总结.     

恶性肿瘤药物治疗相关性神经毒性诊治进展

随着诊疗技术的提高及新药物的快速发展目前肿瘤治疗药物包括化疗药物、靶向药物、免疫药物。随着抗肿瘤药物的广泛应用,会引起严重不良反应,神经毒性不良反应导致患者生存质量及依从性下降。因此肿瘤内科医生在使用抗肿瘤药物前必须了解神经毒性不良反应的相关症状,治疗前对易引起神经毒性不良反应的药物进行预处理及预防,出现神经毒性不良反应后积极治疗,从而提高患者生存质量及依从性。本文对肿瘤内科治疗常见药物所致神经毒性的诊治进展作一综述,以提高临床医生对该类不良反应的认识。     

细胞毒抗癌药物肾脏毒性研究现状

细胞毒化学药物治疗(化疗)是癌症主要治疗手段之一，在提高癌症患者治愈率和改善生存质量的同时，不可避免地会产生许多毒副作用，如肾毒性、心脏毒性、骨髓毒性等。如何防治毒副作用的发生发展，是肿瘤内科治疗的重要研究课题之一。现将近年来对细胞毒抗癌药物所致肾脏毒性的防治概况作一简要回顾。……     

辅酶Q10治疗蒽环类药物致心脏毒性的疗效

目的：研究辅酶Q10（CoQ10）对使用蒽环类化疗药物致心脏毒性的保护作用,并探讨可能的机理。方法：60例肿瘤患者随机分为治疗组（30例）和对照组（30例）,化疗同时分别予CoQ10及大剂量维生素E治疗,治疗前后行心电图、心肌酶检查。结果：化疗后CoQ10组心电图和血清心肌酶学指标均优于对照组（P〈0.05）。结论：CoQ10对蒽环类化疗药物所致心脏毒性有保护作用。     

乳腺癌相关心脏毒性研究现状的回顾与评述

近些年,随着乳腺癌患者的5年生存率不断提高,抗肿瘤治疗相关的心血管疾病已成为乳腺癌患者最常见的非肿瘤死亡因素。早期识别抗肿瘤治疗相关的心脏毒性对提高患者生存质量和改善预后有重要意义。本文就乳腺癌治疗相关的心血管不良事件研究现状作一简要回顾和评述,旨在加强肿瘤科医师和心血管科医师的共同关注与协同合作,让更多的肿瘤患者获益。     

阿拓莫兰为主治疗化疗所致药物性肝损害20例报告

化疗为治疗恶性肿瘤的主要手段之一,由于化疗药物的毒副反应,如肝脏毒性,肾脏毒性,心脏毒性,心脏毒性,骨髓抑制等严重影响了化疗的正常进行,使患者生存质量下降,其中化疗所致的药物性肝损害在临床上较为多见,近一年来,我们选用注射用还原型谷胱甘肽阿拓莫兰配合中药治疗化疗所致药物肝损害20例,疗效尚满意。现报告如下。     

PD-1/PD-L1免疫检查点抑制剂致心脏毒性的研究进展

心脏毒性是抗肿瘤药物的严重不良反应,随着抗肿瘤药物的不断发展,免疫检查点抑制剂已被应用于多种癌症的治疗,特别是程序性死亡受体1（PD-1）或程序性死亡配体1（PD-L1）免疫检查点抑制剂近年来受到广泛关注,本文将从PD-1及PD-1/PD-L1免疫检查点抑制剂概述、PD-1/PD-L1免疫检查点抑制剂致心脏毒性的表现及可能机制的探索、心脏毒性的检测方法和PD-1/PD-L1所致心脏毒性的治疗等方面进行综述。     

The role of antioxidants in the era of cardio-oncology

Although most chemotherapeutic drugs have the potential to exert cardiotoxicity, these drugs have been chosen for use in cancer treatment because survival and curability benefits outweigh the risk of these complications. Anthracyclines, for example, are a powerful class of chemotherapeutic agents; however, their use is restricted by dose-related cardiotoxicity. Experimental evidence strongly supports the role of reactive oxygen species in this process, suggesting that antioxidants may be effective in protecting the heart from toxicity. Clinical use of antioxidants to protect the heart during anthracycline chemotherapy has been controversial due to the potential for reduced cytotoxic efficacy toward cancer cells. Results from randomized clinical trials addressing whether antioxidants either reduce the incidence of clinical heart failure among patients undergoing anthracycline-based chemotherapy or reduce the response rates to anthracycline-based chemotherapy have been unclear. While anthracyclines are by far the most well-studied antitumor agents with cardiotoxic properties, evidence now shows that reactive oxygen species may play roles in cardiotoxicity induced by other chemotherapeutic agents such as cyclophosphamide, cisplatin, 5-fluorouracil, and trastuzumab. Thus, in the new era of combination therapy and long-term survival of cancer patients, the use of antioxidants to support cancer therapy should be revisited.     

化疗药物体外诱导白血病细胞凋亡与临床疗效的关系

目的 :探索急性淋巴细胞白血病 (AL L)患者体外化疗药物诱导白血病细胞凋亡在化疗疗效预测中的价值。方法 :应用 Td T介导的脱氧核苷酸切口和末端标记法 (Tunel)、单克隆抗体免疫组化检测等方法研究 2 8例初治 AL L 患者体外化疗药物诱导白血病细胞凋亡、bcl- 2表达与临床化疗疗效的关系。结果 :2 8例 AL L 患者中 ,2 0例获完全缓解 (CR)者 ,bcl- 2表达显著低于 8例未缓解(NR)者 (P<0 .0 5 ) ;CR患者长春新碱 (VCR)、柔红霉素 (DNR)和地塞米松 (DXM)体外诱导白血病细胞凋亡率均高于 NR患者 ,差异有显著性 (P均 <0 .0 5 ) ;体外 VCR、DNR和 DXM3种药诱导白血病细胞的总凋亡率 ,可以作为临床预测 AL L 患者 VDCP方案疗效的定量指标。结论 :体外化疗药物能否有效地诱导白血病细胞凋亡是判断 AL L 患者化疗敏感性的重要指标     

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.     

蒽环类药物心脏毒性防治药物研究进展

蒽环类药物包括阿霉素、表阿霉素、柔红霉素和阿克拉霉素等,广泛地用于治疗血液系统恶性肿瘤和实体肿瘤,如急性白血病、淋巴瘤、乳腺癌、胃癌、软组织肉瘤和卵巢癌等。蒽环类药物可以与其他化疗药物及分子靶向药物联合应用,以蒽环类药物为基础的联合治疗通常是一线治疗的标准方案。蒽环类药物的抗瘤谱广,抗瘤作用强,疗效确切,但是可以引起脱发、骨髓抑制和心脏毒性等毒副反应。针对骨髓抑制可采用造血刺激因子(G-CSF、EPO、TPO等)进行防治,而心脏毒性是蒽环类药物最严重的毒副反应。临床研究和实践观察均显示蒽环类药物导致的心脏毒性呈进展性和不可逆性,特别是初次使用蒽环类药物就可能造成心脏损伤,因此早期监测和积极预防蒽环类药物引起的心脏毒性显得尤为重要,已经引起临床上的高度重视,制定了蒽环类药物心脏毒性防治指南。本研究对目前蒽环类药物心脏毒性的防治药物进行综述。      

The combined effects of multiple chemotherapeutic agents for malignant glioma cells

The prognosis of malignant gliomas remains poor, despite the progress of surgery and radiotherapy. Chemotherapy has been shown to prolong an overall survival, but the benefits are still small. To overcome this situation, the optimal regimen of antineoplastic agents is required. In the present study, we investigated the effect of the association of five chemotherapeutic drugs, including ACNU, CBDCA, CDDP, VCR, and VP-16, on cell survival of U87, YKG1, A172, and U251 human glioma cell lines, using median-effect analysis. A synergistic effect was obtained by treatment involving the association of VP-16 with ACNU or CDDP among the combinations of two drugs, and the association of ACNU, CBDCA, and VP-16 in the combination of three drugs. This preclinical screening using median-effect analysis supports the design of clinical trials by indicating more effective combinations of antineoplastic agents for malignant gliomas.     

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。     

Epilepsy in the cancer patient

Purpose

Epileptic seizures in patients with malignancies usually occur as a consequence of brain metastases from systemic cancer or the presence of a primary brain tumor. Other less-frequent causes include metabolic disorders such as electrolyte abnormalities, hypoglycemia, hypoxia and liver failure, paraneoplastic encephalitis, leptomeningeal carcinomatosis, side effects of certain chemotherapeutic agents, central nervous system infections, and pre-existing epilepsy.

Methods

We reviewed all published literature in the English language regarding the use of antiepileptic drugs in patients with cancer.

Results

In patients with brain metastases or primary brain tumors that had never experienced seizures, prophylactic anticonvulsant treatment is justified only for a period up to 6?months postoperatively after surgical excision of a cerebral tumor, since approximately half of the patients will never develop seizures and the anti-epileptic drugs may cause toxicity and interactions with antineoplastic therapies. For brief prophylaxis, newer antiepileptic drugs such as levetiracetam and oxcarbazepine are superior to older agents like phenytoin. In patients with a malignancy and seizures, certain antiepileptic drugs that express tumor inhibitory properties should be used such as valproic acid and levetiracetam, followed by oxcarbazepine and topiramate that exhibit good tolerance, efficient seizure control and absence of significant interactions with the chemotherapy.

Conclusions

Future clinical trials in patients with cancer and epilepsy should focus on combinations of chemotherapeutic interventions with antiepileptic drugs that demonstrate antineoplastic activities.     

Prevention and management of cardiotoxicity from antineoplastic therapy

Cardiotoxicity is a major side effect of various antineoplastic agents, particularly the anthracyclines. Recently, some of the newer drugs and biologic agents that have been introduced into cancer therapeutics also have been shown to have potential cardiotoxic effects. The spectrum of cardiac side effects varies with the antineoplastic agent, dose, and schedule used. Important risk factors associated with cardiotoxicity are cumulative dose, infusion schedule, and pre-existing cardiac disease. This review focuses on the various adverse cardiovascular events associated with antineoplastic agents, what to anticipate, how to recognize the toxicity, how to prevent and minimize the cardiac side effects, and how to manage the full-blown toxicity if and when it occurs.     

Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes

Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration.