肿瘤药物基因治疗

将基因治疗技术与肿瘤化疗药物结合起来，有选择性地杀伤肿瘤细胞，可增强化疗的效果。本文对肿瘤药物敏感基因治疗、肿瘤药物增敏基因治疗、肿瘤药物耐受基因治疗三个方面的研究进展进行了综述。     

肿瘤的精准化疗

根据化疗相关基因选择合适的化疗方案从而实现精准化疗是未来肿瘤化疗的方向.化疗相关基因包括DNA修复基因、药物代谢酶、药物转运蛋白、凋亡相关基因和肿瘤相关基因,这些基因可预测抗肿瘤药物的疗效和毒性,并能判定临床预后的情况.     

靶向时代肿瘤疗效评价标准的探索

肿瘤分子靶向药物具有与化疗药物不同的作用机理。目前对肿瘤的疗效评价标准主要是针对化疗药物疗效的评价,从最早的WHO标准发展到RECIST和RECIST1.1 标准,尽管在细节和标准化方面不断完善,但均以测量肿瘤的大小作为评价指标,其原理基于化疗药物直接杀死肿瘤细胞。但是,靶向治疗药物主要是抑制肿瘤细胞增殖,其对肿瘤的作用模式不同于化疗药物,因此近几年出现了对靶向药物疗效评价标准的探索,本文对以CT值作为功能学指标的肿瘤疗效评价标准-Choi标准及其后续的一系列mChoi、SACT、MASS的肿瘤疗效评价标准进行了详述。      

局部植入缓释化疗药物治疗腹部肿瘤的研究进展

随着新化合物的不断合成以及新剂型、新的给药方式在临床的广泛应用,化学药物治疗已成为目前最常见和有效的肿瘤治疗方式之一.为寻求对肿瘤患者提供更合理的方式给药,20世纪90年代初期,有学者提出"缓释化疗"的概念,即将化疗药制备成具有缓释作用的给药系统,经不同方式注入肿瘤组织、瘤周组织的间质或肿瘤切除后的瘤床,以达到局部持久化疗的目的.缓释药物化疗可保证肿瘤局部具有较高的药物浓度和较长的药物维持时间,是抗癌化学药物给药途径的一个新的研究方向.     

部分临床常用药物作为抗肿瘤增效药物的应用与机制

部分临床常用药物虽并不作为抗肿瘤药物应用,却可增进化疗药物和分子靶向药物的疗效,或逆转肿瘤对化疗药物和分子靶向药物的耐药性。对于晚期、多线治疗失败的难治性肿瘤,值得尝试单独应用或与化疗药物、分子靶向药物联用。这些药物包括pH值调节药物、血糖调节药物及心血管类药物等。     

化疗药物外渗的危险因素及预防

自美国发现氮芥,开创药物治疗肿瘤已50多年.化疗药物的使用挽救和延长了无数肿瘤患者的生命,但也带来了令人担忧的问题——化疗药物外渗.化疗药物外渗是指化疗药物输注过程中渗出或渗浸到皮下组织中[1].外周静脉化疗药物外渗的发生率国内报道0.1%～6.0%[2],国外报道5%[3].     

低剂量化学物质对肿瘤生长的抑制及其对正常组织的保护作用

化学治疗仍是肿瘤治疗的主要方法之一，但化疗的副作用往往会影响肿瘤的治疗效果。低剂量抗肿瘤化疗药物可使细胞对相继较大剂量的抗肿瘤药物诱发的损伤产生抗性；低剂量的生物反应调节剂也可通过生物调节作用来减轻抗肿瘤药物对机体正常组织的损伤。本文就低剂量化学物质对肿瘤生长的抑制及其化疗中保护正常组织的作用作一综述。     

肿瘤患者外周血淋巴细胞化疗药物敏感性检测的应用研究

目的：探讨肿瘤患者外周血淋巴细胞对临床常用化疗药物的敏感性,筛选个体敏感的化疗药物,指导临床用药。方法：采用MTT法检测154例肿瘤患者外周血淋巴细胞对常用15种化疗药物的敏感性。结果：本方法测定的结果与临床常规化疗的结果基本一致。结论：MTT法是一种简便、快速、可行的体外药敏实验方法,可为肿瘤患者化疗提供重要的实验依据。     

编者的话

在现代药物治疗方面,从第一个化疗药物氮芥的问世至今已有半个多世纪了,很多新的化疗药物,在肿瘤的治疗中取得了很好的疗效.然而化疗药物普遍具有针对性不强、不良反应较大的缺点.近年来,我们终于迎来了分子靶向药物的新时代.与以往的细胞毒药物相比,分子靶向药物针对性更强、毒性更低,疗效也更为突出,尤其在提高患者的生活质量方面独树一帜.大量临床研究证实,无论是单克隆抗体,还是小分子酪氨酸激酶抑制剂的应用,均显示出令人鼓舞的疗效.肿瘤的分子靶向治疗逐渐成为肿瘤治疗关注的焦点,针对新靶点所设计的靶向药物不断涌现,为肿瘤治疗带来了新的研究方向.     

MTT法应用于肝癌化学免疫治疗敏感性研究

目的 探讨MTT法应用于肝癌细胞化疗敏感性检测及化疗与免疫治疗的合理应用。方法 应用MTT法检测肝癌细胞的化疗敏感性和化疗对肿瘤浸润淋巴细胞（TIL）的毒性。结果 肝癌细胞和TIL细胞数增多与生成的甲Xun（formazan)的光密度（OD）值呈线性正相关。TIL在体外对自体肝癌细胞显示高活性的细胞毒作用。肝癌细胞对化疗药物的敏感性存在较大的个体差异。化疗药物对TIL的毒性作用大于对肝癌细胞的杀伤作用。结论 以MTT法作肝癌细胞化疗敏感性检测,既可指导临床选用肿瘤敏感性化疗药物,又可避免盲目选用肿瘤非敏感性化疗药物对机体抗肿瘤免疫的毒性;TIL过继免疫治疗与化疗不宜同时应用。     

Antiangiogenic Chemotherapeutic Agents

The mechanism of action of anticancer chemotherapeutic agents is mainly thought to be due to a direct inhibition of tumor cell proliferation. The enhanced endothelial cell proliferation rate in tumor specimens raised the question whether therapeutic effects of chemotherapeutic agents might be at least partially attributed to an inhibition of tumor angiogenesis. Meanwhile, numerous anticancer chemotherapeutic agents were tested for their antiangiogenic potential. A few agents seem to exert consistent inhibition of tumor angiogenesis even in drug-resistant tumors. Most recent investigations on the antiangiogenic efficacy of different application schedules suggested the use of a tightly spaced, continuous application of appropriate anticancer chemotherapeutic agents. These application schedules are able to exert a strong antiangiogenic effect as indicated by an increase of apoptosis of tumor endothelial cells. Future clinical trials have to determine the therapeutic benefit of novel combination chemotherapy and alternative application schedules.     

Potential Novel Drugs to Combine with Radiation in Rectal Cancer

The management of rectal cancer has seen significant advances in surgery, radiation therapy, and chemotherapy in recent years. These advances have translated into improved rates of local and distant disease control, survival, and quality of life for these patients. The recent implementation of novel chemotherapeutic and targeted agents in patients with advanced colorectal cancer has led to further improvements in disease-free and overall survival. These radiosensitizing agents are now being studied in combination with radiation therapy in the neoadjuvant therapy of rectal cancer.     

Management of recurrent testicular germ cell tumors

Although front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still important in a small but significant minority. Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients. New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, have added to the therapeutic armamentarium. Salvage surgical resection has an important role in selected patients. Cisplatin-refractory patients have a poor prognosis with current therapy, and novel chemotherapeutic and biologic agents need to be discovered for such patients.     

Cell cycle-mediated drug resistance: an emerging concept in cancer therapy.

The concept of combining chemotherapeutic agents to increase cytotoxic efficacy has evolved greatly over the past several years. The rationale for combination chemotherapy has centered, in the past, on attacking different biochemical targets, overcoming drug resistance in heterogeneous tumors, and by taking advantage of tumor growth kinetics with increasing the dose-density of combination chemotherapy. The overall goal was to improve clinical efficacy with acceptable clinical toxicity. With our increased understanding of the cell cycle and the impact chemotherapeutic agents have on the cell cycle, it is increasingly apparent that this physiology can create drug resistance, thereby reducing combination chemotherapeutic efficacy. This is particularly relevant with the advent of cell cycle-specific inhibitors but also has relevance for the action of standard chemotherapeutic agents currently in clinical practice. This cell cycle-mediated resistance may be overcome by a greater understanding of chemotherapeutic cell cycle effects and by appropriate sequencing and scheduling of agents in combination chemotherapy. In this review, we have elected to illustrate the evolving concept of cell cycle-mediated drug resistance with novel drug combinations that include the taxanes, camptothecins, and fluorouracil. This review indicates that as our understanding of the cell cycle grows, our ability to appropriately sequence chemotherapy to overcome cell cycle-mediated drug resistance can have a great impact on our therapeutic approach in the treatment of human cancers.     

Considerations with newer regimens for indolent non-Hodgkin lymphoma

Follicular lymphoma (FL) is considered incurable with current therapies and shows a pattern of multiple remissions and repeated relapses. After demonstrations of significant improvements in clinical outcomes with the addition of rituximab to chemotherapy regimens including alkylating agents and anthracyclines, rituximab-containing chemoimmunotherapy strategies have become central to the management of FL. More recently, novel cytotoxic agents such as bendamustine and pixantrone, that circumvent some of the limitations of conventional chemotherapeutic agents, have been developed and are being clinically investigated. These novel agents are showing promising clinical activity alone and in combination with rituximab in indolent lymphomas. In order to further improve the therapeutic index for patients with FL, rituximab is being combined with novel biologic agents such as immunomodulatory cytokines and monoclonal antibodies targeting CD80 and CD22. This article provides a review of newer chemoimmunotherapy strategies in the management of patients with FL.     

An overview of chemotherapy for mesothelioma

Mesothelioma is an extraordinarily challenging disease to treat. While numerous clinical trials testing various chemotherapeutic agents have been conducted over the last several decades, only recently have larger studies proven the efficacy of newer chemotherapy regimens. This article reviews the data regarding specific classes of chemotherapeutic agents. The role of treatment in various disease settings and the difficulty in assessing the benefit of that therapy is discussed. Finally, an update is provided on novel therapeutics being testing in mesothelioma.     

Triple-negative breast cancer: current management and future options

Triple-negative breast cancer is a particularly difficult to treat and biologically aggressive disease with limited treatment options. However, a subset of patients with triple-negative tumours may respond to chemotherapy. Therefore, optimisation of chemotherapy regimens may be key in treating triple-negative breast cancer. Emerging treatment approaches include novel chemotherapeutic agents such as the epothilones. The epothilones are a group of novel microtubule-stabilising agents with demonstrated activity in anthracycline-/taxane-resistant triple-negative breast cancer, and ongoing trials are evaluating the combination of epothilones with targeted agents or inclusion of epothilones in novel combination regimens. Other interesting new treatment options include the PARP inhibitors, which are currently in clinical trials for triple-negative breast cancer.     

Non-Size-Based Response Criteria to Preoperative Chemotherapy in Patients With Colorectal Liver Metastases: The Morphologic Response Criteria

Since the introduction of biological agents, accumulating results have suggested that conventional size-based RECIST criteria do not enable accurate assessment of response to therapy, and that non-size-based changes in tumor morphology can be a surrogate marker for assessment of chemotherapeutic effect. The morphological response criteria are recently introduced, non-size-based criteria for patients undergoing chemotherapy for colorectal liver metastases (CLM). These novel criteria predict pathologic response and long-term survival of patients treated with preoperative chemotherapy, with or without bevacizumab, irrespective of their RECIST response. They have been validated in patients with resectable and unresectable CLM. These criteria are difficult to apply for small metastases and can be used as an adjunct to RECIST in assessment of response to preoperative chemotherapy.     

肿瘤多药耐药机制及逆转耐药研究进展北大核心

癌症化学治疗被视为旨在最小化和延迟肿瘤的发生、发展或复发的策略,但是肿瘤多药耐药是肿瘤患者治疗失败和复发的主要原因,是实现肿瘤患者治愈的主要限制因素。如何逆转化疗药物的耐药及耐药机制的研究成为肿瘤研究的挑战。为了解决肿瘤多药耐药问题,本文对传统化疗药物发生肿瘤多药耐药的机制、靶向治疗发生多药耐药的机制以及免疫治疗发生多药耐药的机制进行阐述;确定了癌症耐药性的实验室方法,如MTT测试法、药物敏感性测试、多药耐药基因和途径检测、高通量筛选技术、基因芯片技术等,为多药耐药的研究提供实验方法;并对多药耐药抑制剂或逆转剂的研究进展进行简单的综述,旨在为进一步发明逆转肿瘤多药耐药的药物提供研究基础。     

Interstitial chemotherapy for brain tumors: review

An extensive effort to search for curative chemotherapeutic approaches has found no breakthrough in management of patients with malignant brain tumors. Despite the trials with new agents or protocols of multiple agents, systemic chemotherapy has failed to provide reliable clinical response. Interstitial chemotherapy has been practiced for malignant brain tumors with administering chemotherapeutic compounds directly into the tumor which provide increased and prolonged drug concentration in the tumor, reduction of systemic toxicity and bypassing the blood-brain barrier. These theoretical advantages encourage further pursuing interstitial chemotherapy for patients with malignant brain tumors who would otherwise be always fatal.In this review, the literature has been reviewed to identify methods toxicity and efficacy of interstitial chemotherapy. Clinical and experimental data indicate limited toxicity and promising efficacy. Various methods to administer the agents were utilized; intraoperative topical application, local injections through catheters or implantable controlled drug delivery system. Selection of ideal chemotherapeutic agents and development of drug delivery system need further investigations.