超抗原葡萄球菌肠毒素在肿瘤治疗中的应用

葡萄球菌肠毒素(SE)可通过细胞毒作用、细胞因子分泌和黏附因子的表达等发挥抗癌作用,在肿瘤治疗中有较好的应用前景.作为天然的细菌外毒素,SE有着潜在的不良反应.目前研究主要集中在靶向治疗、肿瘤疫苗、使用策略等方面,以提高其临床疗效,降低不良反应.     

脂质体介导的人α-干扰素基因转移的肿瘤细胞克隆株的建立及其生物学活性的观察

肿瘤的基因疗法近年来有了飞速的发展，其中被认为很有希望在肿瘤基因治疗领域有所突破的途径之一就是肿瘤细胞靶向的细胞因子基因疗法。(Tumor cells-targeted cytokine gene thempy)α-干扰素(IFN-α)是一种经大量临床应用证实了的具有显著免疫调节作用和抗肿瘤、抗病毒作用的细胞因子：因此，     

细胞因子与肿瘤临床表现及转归的关系

肿瘤组织中含有多种免疫细胞、致炎细胞因子和抗炎细胞因子,其相互作用可影响肿瘤的发生和发展,并且细胞因子可以预测肿瘤的预后.致炎细胞因子与疲劳、抑郁、认知障碍、厌食、恶液质、疼痛以及治疗引起的不良反应和耐药性有关,影响肿瘤患者的生活质量.     

细胞因子与肿瘤临床表现及转归的关系

肿瘤组织中含有多种免疫细胞、致炎细胞因子和抗炎细胞因子,其相互作用可影响肿瘤的发生和发展,并且细胞因子可以预测肿瘤的预后.致炎细胞因子与疲劳、抑郁、认知障碍、厌食、恶液质、疼痛以及治疗引起的不良反应和耐药性有关,影响肿瘤患者的生活质量.     

细胞因子与肿瘤临床表现及转归的关系

肿瘤组织中含有多种免疫细胞、致炎细胞因子和抗炎细胞因子,其相互作用可影响肿瘤的发生和发展,并且细胞因子可以预测肿瘤的预后.致炎细胞因子与疲劳、抑郁、认知障碍、厌食、恶液质、疼痛以及治疗引起的不良反应和耐药性有关,影响肿瘤患者的生活质量.     

B7-H1与头颈部鳞状细胞癌免疫治疗

B7-H1(又称programmed death receptor ligand 1,PD-L1)是一种细胞表面糖蛋白,属于共刺激分子B7家族。研究证明B7-H1大量表达于肺癌、卵巢癌、结肠癌、黑素瘤、头颈肿瘤和乳腺肿瘤等少数肿瘤细胞系,存在于肿瘤内皮细胞及上皮细胞中,且与肿瘤免疫逃避有关。近年来发现大多数头颈部鳞状细胞癌(SCCHN)新鲜标本可见B7-H1在细胞膜或细胞质内表达,并且阻断其共刺激通路可增强肿瘤免疫疗法的疗效。本文通过综述B7-H1在各种肿瘤治疗方法,如细胞因子疗法、抗体及其偶联物疗法、免疫活性细胞过继疗法、肿瘤疫苗疗法等方法中的应用前景,来探讨B7-H1研究在头颈部鳞状细胞癌免疫治疗研究中的突破性作用。     

《嵌合抗原受体T细胞疗法的免疫相关不良事件管理:ASCO指南》解读

免疫疗法革新了多种癌症的治疗现状.嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)疗法在血液肿瘤包括白血病、淋巴瘤和多发性骨髓瘤等疾病的治疗中取得巨大成功.与传统化疗不同的是,CAR-T疗法有独特的不良反应包括细胞因子释放综合征和中枢神经毒性等.自2021年6月以来我国...     

白细胞介素-15与肿瘤的相关性

白细胞介素-15 (IL-15)是一种多功能的细胞因子,是T细胞、B细胞、自然杀伤(NK)细胞、淋巴因子激活杀伤(LAK)细胞等细胞活化因子及诱导分泌细胞因子,有刺激造血干细胞增殖分化、增强免疫和抗肿瘤等作用.IL-15具有与白细胞介素-2(IL-2)类似的结构和功能,但许多活性作用强于IL-2,其与肿瘤的发生发展密切...     

以IL—2在体内激活LAK细胞：联合疗法展望

体外或体内给予白细胞介素-2(IL-2)能激活多种涉及 T 淋巴细胞和自然杀伤细胞(NK)的免疫效应功能。这些免疫细胞及其分泌的细胞因子在宿主抗肿瘤反应中起着重要作用。单独使用较低剂量 IL-2疗法已使一小部分病人肿瘤明显缩小。临床前研究表明,IL-2与其他疗法联用可增强体内淋巴因子激活性杀伤细胞(LAK)效能;与其他细胞因子及单克隆抗体联用显示很有希望。嵌合抗体及双特异性杂交抗体的应用可能使 IL-2与抗体联合疗法更加有效。通过进一步研究,IL-2可能成为更为有效的抗癌治疗方案的组成部分。     

生物反应调节剂的不良反应及其处理

1 概述 一个世纪以前,美国学者Coley观察到病人在急性感染后肿瘤自发消退的现象.其后,企图利用各种细菌提取物和BCG的尝试几十年来均未得到实质性进展.肿瘤的主要治疗手段仍然是手术、放疗和(或)化疗.随着对免疫学和分子生物学的深入认识和现代科学技术的不断进展,使得大规模制造生产和临床应用生物反应调节剂(BRMs)成为可能.而生物治疗(biotherapy)也已经成为攻克肿瘤的第四手段.目前临床使用的生物治疗主要包括以下几方面:(1)主动性非特异性免疫治疗如干扰素和白介素等细胞因子.(2)被动性免疫治疗如以单克隆抗体为基础的治疗.(3)过继性免疫治疗如以癌为目标的各类细胞的治疗.(4)主动特异性免疫治疗如肿瘤疫苗.本文仅就以上范围内临床应用最多的BRMs的不良反应及其处理作一概要介绍,供临床医师参考.     

Clinical phase I and pharmacokinetic study of S 16020, a new olivacine derivative: report on three infusion schedules.

S 16020, a new 9-OH olivacine derivative, is a novel topoisomerase II inhibitor with activity in cell lines presenting the classical multidrug resistance phenotype. This report summarizes, in addition to pharmacokinetic data, the whole phase I clinical experience of S 16020 using three different infusion schedules. Asthenia and skin toxicity were the main side effects. In an attempt to understand the skin toxicity mechanism, experiments in animals were performed, the results of which are reported. S 16020 showed rapid tumor necrotizing activity in some patients, with soft tissue metastases of epidermo?d tumors and pain at the tumor site. To document the side effects of S 16020 and tumor site reactions (pain, edema, inflammatory signs), inflammatory parameters and some cytokines were measured. In our patients there was no hemolysis and no detection of anti-S 16020 antibodies, confirming the absence of immunogenicity of the compound. Based on the overall data of the three infusion schedules of S 16020, the dose of 100 mg/m(2) over 3 h every 3 weeks was selected for phase II studies.     

CD4＋CD25＋Foxp3＋Treg细胞调控肿瘤免疫抑制微环境的研究进展

目的： CD4＋CD25＋Foxp3＋调节性T细胞（ Treg ）是肿瘤免疫抑制微环境的主要组成部分,其在肿瘤的免疫抑制微环境中分泌IL－10、IL－35、TGF－β1和FGL2等细胞因子发挥免疫抑制作用。Treg细胞抑制CD4＋T、CD8＋T淋巴细胞和NK细胞,进而抑制特异性抗肿瘤免疫反应使肿瘤细胞更容易逃避免疫监视。进一步研究Treg细胞在肿瘤免疫中的作用机制,对深入了解恶性肿瘤的发病机制及免疫治疗具有重要的理论意义。此外,Treg细胞及其分泌的细胞因子在肿瘤治疗和预后评估等方面也具有广阔的临床应用前景。     

Secretion of sHLA-G molecules in malignancies

Our clinical studies revealed significantly increased soluble HLA-G (sHLA-G) plasma levels in patients suffering from malignant melanoma, glioma, breast and ovarian cancer. Specific ELISpot assays demonstrate that sHLA-G molecules expressing intron-4 sequences are preferentially secreted by peripheral blood monocytes. In vitro, the sHLA-G secretion of monocytes and tumor cells was strongly enhanced by TH1 cytokines like IFN-alpha, -beta, -gamma whereas TH2 cytokines (e.g. IL-4, -10) had minor effects. As sHLA-G can inhibit the functions of T and NK cells high concentration of these molecules should systemically or at the tumor side reduce the immune surveillance and thus favour the progression of cancer.     

生物标志物对抗血管生成药物疗效预测作用的进展

血管生成与肿瘤的生长、浸润和转移过程密切相关,针对恶性肿瘤血管生成的治疗已经逐渐成为肿瘤治疗的重要方式。抗血管生成药物在临床上的广泛应用,给患者带来获益的同时也带来了毒副反应以及经济负担,因此有关预测抗血管生成药物疗效的标志物的研究也越来越多。有部分研究发现,血管内皮生长因子（VEGF）／血管内皮生长因子受体（VEGFR）通路相关因子、血管内皮破坏相关的循环内皮细胞、CXC趋化因子家族的细胞因子及其他血管生成调控因子可以预测抗血管生成药物的疗效,但是不同的研究得出的结论并不完全相同,相关预测因子的研究并没有获得大范围的认可。本文就生物标志物在抗血管生成药物的疗效预测作用方面做一综述。     

树突状细胞调节细胞因子诱导杀伤细胞疗法配合中药治疗化疗无效晚期恶性肿瘤的临床疗效

目的探讨树突状细胞调节细胞因子诱导杀伤细胞（DC—CIK）配合中药治疗化疗无效晚期恶性肿瘤的临床疗效。方法选取2012年2月至2013年2月间采用DC-CIK配合中药治疗化疗无效的晚期恶性肿瘤患者120例,观察评价其近期疗效,生活质量改善情况及不良作用。结果120例患者中,临床有效率为12．5％,疾病控制率为69．2％。治疗后,患者生活质量明显改善,治疗过程中未发生明显不良反应。结论DC—CIK细胞因子配合中药治疗化疗无效的晚期恶性肿瘤是一种有效的姑息治疗方法,有必要进行深入的临床研究。     

Immunotherapy with cytokine gene-transduced tumor cells: the next wave in gene therapy for cancer.

Recently, new tumor vaccine approaches were developed in animal systems that modify tumor cells genetically to secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigens or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. The development of high efficiency gene transfer technologies such as defective retroviral vectors allows for the translation of these preclinical studies to clinical trials. However, before large investments are made in this area of gene therapy, it will be important to demonstrate that the actual gene transfer component of the strategy significantly enhances antitumor immune responses relative to alternative nongenetic approaches.     

人参皂甙Rg1协同诱生LAK细胞的抗瘤活性

淋巴因子激活性杀伤细胞(LAK细胞)过继输入疗法已经被证明是一种有效的抗肿瘤免疫治疗措施,但此疗法的临床应用却受到LSK细胞抗瘤活性尚低问题的困扰.我们曾经证明人参总皂甙能够增强LAK细胞杀伤新鲜急性白血病细胞的活性,本文进一步检测了人参总皂甙的单体之一人参皂甙Rg_1(Ginsenoside Rg_1)对LAK细胞抗瘤活性的影响,报告如下.     

参芪扶正注射液辅助治疗晚期肺癌的疗效及对相关细胞因子的影响

目的:探讨参芪扶正注射液辅助治疗非小细胞肺癌患者的疗效及对相关细胞因子的影响。方法:选取2017年9月至2018年12月本院收治的126例非小细胞肺癌患者作为研究对象，按照随机数字表将其分为研究组（n=63）及对照组（n=63）。对照组:采用培美曲塞钠联合顺铂化疗方案，研究组:在对照组的基础上联合应用参芪扶正注射液进行治疗。治疗过程中检测记录两组患者近期临床化疗毒副作用；酶联吸附法检测两组患者血清中干扰素（interferon，IFN-γ）、血管内皮生长因子（vascular endothelial growth factor，VEGF）、白细胞介素2（interleukin 2，IL-2）、可溶性白介素-2受体（soluble interleukin-2 receptor，SIL-2R）表达水平变化。结果:两组患者客观有效率比较，差异无统计学意义（P>0.05）；与对照组相比，研究组患者的化疗毒副作用和肿瘤促进细胞因子均有所下降，而肿瘤抑制细胞因子上升并且延长患者生存期。结论:参芪扶正注射液可通过联合用药降低患者化疗毒副作用和肿瘤相关细胞因子表达，其可作为一种辅助性治疗手段在非小细胞肺癌患者治疗过程中推广应用。     

Potential antitumor effects of statins (Review)

Statins, which have been introduced to the clinic for the treatment of hypercholesterolemia, are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid (MA). MA is the precursor in the biosynthesis of isoprenoid compounds including cholesterol, dolichol and ubiquinone. Furthermore, mevalonate-derived prenyl groups enable precise cellular localization and function of many proteins such as Ras and Rho proteins. Therefore, besides lowering cholesterol level, statins exert pleiotropic effects on many essential cellular functions including cell proliferation, differentiation, and survival but also participate in the regulation of cell shape and motility. Statins have been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells. They have also been found to display antitumor effects against melanoma, mammary carcinoma, pancreatic adenocarcinoma, fibrosarcoma, glioma, neuroblastoma, and lymphoma in animal tumor models resulting in retardation of tumor growth, and/or inhibition of the metastatic process. In preclinical studies statins have also been demonstrated to potentiate the antitumor effects of some cytokines and chemotherapeutics. The molecular mechanisms underlying antitumor activity of statins have not been fully elucidated but interference with the function of Ras and Rho family GTPases, inhibition of the activity of certain cyclin-dependent kinases (CDK), and activation of CDK inhibitors, all seem to participate in this activity. The results of several clinical studies of statins in cancer patients including phase I, phase I/II, and phase II trials have been published. Although evaluation of the therapeutic efficacy is not the purpose of early clinical trials and all conclusions might be premature at this stage, some preliminary conclusions have already been drawn. The results of these studies do not show any significant therapeutic effects of statins in cancer patients. However, the results of one of these studies suggest that statins could effectively strengthen the therapeutic activity of some chemotherapeutics. This observation seems to agree with the results of preclinical studies. However, as toxic side effects of statins have been particularly evident in their combination with some other drugs great caution should be advised while planning clinical trials based on combination therapy including statins in cancer patients.