抗肿瘤药物心脏毒性的中医药防治进展

<正>美国癌症研究学会(American Association for Cancer Research,AACR) 2012年发布研究结果显示,肿瘤患者中51%死于肿瘤本身,49%死于非肿瘤疾病;在诸多非肿瘤死亡原因中,心血管疾病首当其冲~([1]),抗肿瘤药物导致的心脏毒性成为肿瘤幸存者继肿瘤复发转移之外的第二大死因~([2])。     

抗肿瘤药物致心脏损伤的药物防治进展

随着恶性肿瘤治疗手段的改进，抗肿瘤药物如化疗、靶向治疗、内分泌治疗及生物免疫制剂等相关心脏损伤已经成为肿瘤患者长期生存的难题，严重影响患者生活质量。在某些肿瘤人群中，心血管死亡的长期风险已经超过了癌症死亡的风险。为了降低心血管疾病的风险，人们对在抗肿瘤治疗开始时使用心脏保护策略越来越重视。相关研究表明右丙亚胺、神经激素拮抗剂、腺苷酸活化蛋白激酶(AMPK)激活剂等可干预抗肿瘤治疗相关心脏损伤，现对最近完成的以及正在进行的抗肿瘤药物致心脏损伤药物防治的临床试验的证据进行评价并作一综述。     

抗肿瘤药物的肝脏毒副作用及治疗策略

近年来恶性肿瘤的发病率逐年增加,死亡率已高居总体死亡原因的第一位。在恶性肿瘤的治疗中化疗占有重要地位,随着抗肿瘤药物的不断研发,恶性肿瘤的预后有了明显提高,但抗肿瘤药物引起的不良反应为肿瘤治疗带来新的问题。药物性肝损害是肿瘤治疗过程中常见的不良反应,特别是在肝炎发病率较高的中国,肝脏毒副作用及具有肝脏基础病的肿瘤患者的治疗策略值得关注。     

从肿瘤心脏病学探讨恶性肿瘤与心血管疾病及药物干预相关性研究进展

恶性肿瘤与心血管疾病具有多项共同危险因素，许多抗肿瘤治疗方案具有潜在心血管毒性，日益成为影响这类疾病预后的关键因素。目前，国际上对于肿瘤心脏病学的研究主要围绕恶性肿瘤和心血管疾病的共同危险因素，抗肿瘤治疗与心血管毒性相关性研究，以及肿瘤心脏病的干预和治疗。然而，肿瘤心脏病学的研究在国内尚处于萌芽阶段，很多的临床研究领域仍处于空白。本文从抗肿瘤治疗与心血管毒性，肿瘤和心血管疾病的共同危险因素，肿瘤心脏病的干预和治疗3个方面予以综述，旨在为国内肿瘤心脏病学的发展提出建议和展望。      

细胞骨架在肿瘤侵袭转移中的研究进展*

肿瘤转移是肿瘤导致死亡最主要的原因之一,细胞骨架与肿瘤的侵袭转移密切相关,但细胞骨架各组分在肿瘤侵袭转移中作用的研究均较独立、分散,且随着细胞骨架相关研究的不断深入,微管在肿瘤转移中的重要性开始凸显,微管关键相互作用蛋白和微丝细胞骨架间的交互作用也越来越受到关注,这可能给转移性肿瘤的治疗带来新的思路。本文就细胞骨架的结构功能、重要信号通路、新进展及相关抗肿瘤药物研究进行综述,并探讨细胞骨架蛋白相互间的联系以及细胞骨架相关的潜在抗肿瘤药物新思路。      

肿瘤恶病质治疗潜在分子靶点的研究进展

摘 要：肿瘤恶病质是各种恶性肿瘤患者的主要并发症,常出现于肿瘤晚期,主要表现为患者体重丢失、贫血、代谢失衡及全身性器官衰竭,导致癌症患者生活质量下降,肿瘤化疗治疗效果被严重削弱,是众多癌症患者死亡的主要原因。目前,肿瘤恶病质治疗尚缺乏有效的特异针对性药物,但随着对肿瘤恶病质发生分子机制的深入研究,多个新的恶病质治疗潜在分子靶点被提出,为开发新的靶向治疗药物提供了可能。全文综述了抗肿瘤恶病质导致的肌肉减少以及脂肪降解的新分子靶点,并分类阐述其分子机制以及相关体内外实验研究成果,收集针对这些靶点的药物研究的现状,希望能为肿瘤恶病质新药开发及治疗提供研究思路和方向。     

营养不良肿瘤患者抗肿瘤药物治疗临床建议路径

摘 要：恶性肿瘤住院患者营养不良发生率高且重度营养不良多见。肿瘤患者发生营养不良严重影响患者生活质量,降低抗肿瘤治疗耐受性。抗肿瘤药物治疗是最重要的打击肿瘤病灶的方法之一。为保证实施营养不良肿瘤患者抗肿瘤药物治疗有效性与安全性,建立本临床诊疗路径,从而为临床医师提供营养不良患者抗肿瘤药物治疗的可行性和规范性流程。     

抗肿瘤药物对肾上腺机制影响的研究进展

多种抗肿瘤药物如激素类、化疗、靶向药物和免疫检查点抑制剂在发挥抗癌作用的同时对内分泌腺具有毒性作用,其中对肾上腺的影响逐渐受到临床重视。药物治疗相关的肾上腺功能不全若无法及时诊治,可导致肾上腺危象的发生甚至危及生命。本文将就抗肿瘤药物对肾上腺机制影响进行综述,为临床防治肿瘤患者的肾上腺功能异常提供指导。      

抗肿瘤靶向药物研究进展

 【摘要】　靶向药物是目前治疗肿瘤疾病的研究热点。文章系统地介绍了靶向药物的分类、特性、作用原理及临床应用，并对近年抗肿瘤靶向药物的研究现状进行了综述，展望了其发展前景。     

抗肿瘤转移的新药研究

抗肿瘤转移的新药研究仲维学胥彬主题词肿瘤转移／药物疗法抗肿瘤药物／药理学细胞粘附细胞运动血管生成中图号Ｒ７３０．５３约有５０％以上的肿瘤患者在临床诊断时，已发生了局部或远处的转移。局部性的治疗方法（手术，放疗）只能将原位肿瘤切除或杀灭，可导致肿瘤的复...     

Non-steroidal anti-inflammatory drugs and cancer, with an especial focus on esophageal cancer

Non-steroidal anti-inflammatory drugs (NSAIDs) have been extensively used for relief of pain and fever, and prevention of cardiovascular and cerebrovascular diseases for several decades. Recently, the use of these compounds has been reported to be associated with reduction in occurrence of a variety of cancers. In this paper, we reviewed anti-cancer mechanisms of NSAIDs and their potential preventive and even therapeutic effects on cancer, focusing on esophageal cancer in particular.     

Anti-Diabetic Drugs: Cure or Risk Factors for Cancer?

Anti-diabetic drugs are an important group of therapeutics used worldwide. Different anti-diabetic drugs lower blood glucose level by different mechanisms. In recent years, numerous investigations have been performed based on both comparative and cohort studies, in order to establish the relationship between anti-diabetic pharmacotherapy and cancer incidence as well as mortality due to cancer. Some anti-diabetic drugs have been found to exhibit anti-cancer activity while others might increase the risk for cancer. The underlying cause for this disparity is likely to be the varying mechanisms of action of these drugs in controlling blood glucose level. This review discusses the various carcinogenic and/or anti-cancer effects of commonly used anti-diabetic drugs. The information is vital in view of the fact that diabetes mellitus is a commonly occurring disease with a rising incidence rate.     

Gastrointestinal malignancies and cardiovascular diseases

Nowadays, antiplatelet and anticoagulant drugs has been applied to a variety of cardiovascular diseases, such as atrial fibrillation and coronary artery disease. Several clinical studies show that there is a higher prevalence of gastrointestinal cancers in patients with cardiovascular disease. In addition, in patients taking antithrombotic drugs, positive fecal occult blood test (FOBT) improves the sensitivity for early detection of colorectal malignancies. This suggests that antithrombotic drugs may facilitate the detection of unrecognized cancers in patients with cardiovascular disease. However, there is no established evidence concerning whether more aggressive gastrointestinal tract screening will reduce the mortality of cancer in cardiology patients. But in an era of multiple antithrombotic drug usage, when patients appear unexplained anemia, gastrointestinal symptoms or positive FOBT, timely gastrointestinal tract screening is helpful to find concomitanted malignancies in these patients.     

Statin drugs to reduce breast cancer recurrence and mortality

Epidemiologic studies have, variably, shown the concomitant use of statin drugs to be beneficial to cancer outcomes. Statin drugs have been FDA approved for three decades for the treatment of high cholesterol and atherosclerotic coronary artery disease and are widely used. This has engendered studies as to their influence on concomitant diseases, including cancers. In this context, statin use has been correlated, variably, with a decrease in deaths from breast cancer. However, there is no extant model for this effect, and the extent of efficacy is open to question.The overarching goal of this article is to communicate to the reader of the potential of statins to reduce breast cancer progression and mortality. This is the use as a secondary prevention measure, and not as a therapy to directly counter active cancer. First, salient aspects of statin pharmacology, as relates to cardiovascular disease, will be discussed. Second, the basic and clinical research studies that investigate statin usage in breast cancer will be presented. Additionally, statin effects in other cancer types will be included for context. Finally, proposals for future basic and clinical research studies to determine the role of statins in breast cancer management will be presented.     

Casting light on molecular events underlying anti-cancer drug treatment: What can be seen from the proteomics point of view?

Regardless of continuous advances in technology and expansion of the knowledge in the field of genomic information, cancer still remains one of the leading causes of death in developed countries for many reasons, including non-selectiveness of commonly used anti-cancer drugs that often influence non-specific rather than tumour-specific targets. As cancer cells are characterized by the ability to divide and multiply in an uncontrolled manner whereby a set of specific proteins modulate cell division processes, proteomics seems to be a suitable tool for seeking out molecular mediators of anti-cancer drugs action and resistance, thus improving chemotherapy outcome. This review will focus on the recent knowledge of the molecular mechanisms involved in the anti-cancer drugs response revealed by the proteomics tools. In addition, we will touch upon the effects of "gene drugs" with p53 and p21(waf1/cip1) genes on the protein complement of tumour cells assessed by the two-dimensional gel electrophoresis combined with mass spectrometry. Such studies could substantially contribute to further drug optimization prior to its clinical use and represent an important but still small step in the long way of drug discovery. However, fluctuations in protein expression, distribution, posttranslational modifications, interactions, functions and compartmentalization make it difficult to use exclusively expression proteomics data without putting it in broader biological context. Thus, the challenge today is to shift from the identification of drug response and disease biomarkers to more time-consuming process of revealing the biochemical mechanism that connects a specific protein with a disease or cellular response to a drug.     

Amplifying tumour-specific replication lesions by DNA repair inhibitors - a new era in targeted cancer therapy

Many anti-cancer drugs used in the clinic today damage DNA, resulting in cell death either directly or following DNA replication. Many anti-cancer drugs are exclusively toxic to replicating cells and toxic lesions are formed when a replication fork encounters a damaged DNA template. Recent work shows that replication lesions, similar to those produced during anti-cancer therapy, are commonly associated with cancer aetiology. DNA replication lesions are present in cancer cells owing to oncogene expression, hypoxia or defects in the DNA damage response or DNA repair. Here, I review how novel therapies can exploit endogenous replication lesions in cancer cells and convert them to toxic lesions. The aim of these therapies is to produce similar lesions to those produced by DNA damaging anti-cancer drugs. The difference is that the lesions will be cancer-specific and produce milder side-effects in non-cancerous cells.     

Recent development of oral anti-cancer drugs for breast cancer

Oral anti-cancer drugs play an important role in the treatment of breast cancer. Because these hormonal agents are related to mammary carcinogenesis and tumor growth, they are used not only for therapy but also to prevent the onset of the disease. Tamoxifen, toremifene, fadrozole and other aromatase inhibitors, goserelin, leuprolin and MPA are used widely in Japan as hormonal anti-cancer drugs. In addition oral anti-cancer chemotherapeutic agents, such as cyclophosphamide, 5-FU, 5'-DFUR, FT and UFT are used for breast cancer. The combination of these hormonal and chemotherapeutic agents produces good clinical results in curing the disease. Oral drugs are superior to injected drugs with regard to the QOL of patients.     

Cost of cancer in France: pharmaceutical expenditure as part of global patients' care

The INCa, as well as the French National Health Insurance recently published, and for the first time, important reports making it possible to take stock of the cost of care for the patients treated for a cancer or a malignant hemopathy, and in particular on the pharmaceutical expenditure related to cancer. The number of people with full medical coverage ("ALD") for cancer increased by 62% in 10 years, and exceeds 1.25 million people today. The corresponding expenditure is close to 14 billions euros for public health insurance systems, appreciably lower than that related to the cardiovascular diseases. The annual expenditure by patient treated for cancer is much lower than that related on the chronic renal failure, transplantations or the VIH-AIDS. The share of the expenditure related to the medical drugs and other goods (devices) is estimated by the INCa at 13% of the total expenditure related to the care. The anti-cancer drugs count for 20% of the pharmaceutical expenditure of the hospitals, of which the half related to specialities reimbursed in addition to the "T2A" fixed rates. Due primarily to the new anti-cancer drugs, the expenditure for this class increased by more than 6 fold in 10 years, responsible for 37% of the total increase in hospital health care expenditure. However, the share of the expenditure related to the drugs is lower for the patients treated in "ALD" for cancer than that of the whole of the ALD (19.5 vs 20%). For the Health insurance, the cost for anticancer drugs, all classes and indications included, accounts for 2.1% of the expenses, i.e. 1.5% of the national current health expenditure. The innovating anti-cancer drugs count for less than 4% of the expenditure related to cancer, i.e. less than 0.45% of the total expenditure. It is necessary to consider these data, correlatively to the clinical and social benefit gained, in the strategies of care.     

ATP-MgCl2联合介入化疗晚期癌疗效观察

目的 :探讨ATP MgCl2 加常规抗癌药物局部动脉灌注对晚期恶性肿瘤疗效的影响。方法 :将对象分为A(化疗药 ATP MgCl2 )和B (单纯化疗药 ) 2组 ,进行动脉灌注治疗 ,并对比 2组临床疗效及其副反应。结果 :A组 4 0例 ,CR 5例 ,PR 8例 ,MR 5例 ,SD 17例 ,PD 5例 ,有效率为 32 5 %。B组 39例 ,CR 1例 ,PR 7例 ,MR 11例 ,SD 14例 ,PD 6例 ,有效率为 2 0 5 %。 2组间未见明显毒副反应差异。结论 :ATP MgCl2 可提高抗癌药物的抗癌作用 ,对一些中、晚期恶性肿瘤具有较好的疗效 ,无明显的毒副反应 ,是一种安全、有效的抗肿瘤药物     

Investigational agents for epithelial ovarian cancer

Ovarian cancer is the leading cause of gynecologic cancer deaths and accounts for 4% of women’s cancer diagnoses and 5% of all cancer mortalities. Despite the ability of current chemotherapy and cytoreductive surgery to put patients in remission, most patients with advanced cancer will eventually relapse. Many advances in the treatment of ovarian cancer have been reported in the past several years and a historical background is provided. Attention will then turn to analogs of current chemotherapeutic agents, new cytotoxic drugs, targeted molecular therapy, intraperitoneal therapy and immunotherapy. This review will give a perspective on current drugs, potential agents and upcoming clinical trials.