肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛

2006年8月12～15日,上海会议通知(第一轮)“肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛”将于2006年8月12日至15日在中国上海举行。此次盛会由国际肿瘤靶向治疗学会、中国生物医学工程学会肿瘤靶向治疗技术分会、上海市抗癌协会、同济大学附属东方医院、上海《肿瘤》杂志社、和佳肿瘤医院联合举办。本次大会的宗旨是推动现代肿瘤基础研究和临床治疗的发展,促进肿瘤的个体化、靶向治疗、综合治疗理念与临床的紧密结合;介绍国内外肿瘤治疗最新技术及研究成果。因此论坛将围绕“肿瘤多学科综合治疗及靶向治疗的最新研究进展和发展趋势…     

肿瘤药物靶向治疗的最新进展

肿瘤药物的靶向治疗是以已知肿瘤发生中涉及的异常分子和基因为靶点而设计和研制的药物。实践证明,肿瘤靶向药物治疗为乳腺癌、肠癌、肺癌等多种恶性肿瘤的治疗提供了新的有效方法。肿瘤靶向药物分为肿瘤细胞单克隆抗体和抑制肿瘤细胞增殖的靶向药物,其中前者又包括抗肿瘤单抗药物和抗肿瘤单抗偶联物。本文对肿瘤抗体介导的靶向治疗药物的应用现状作一阐述。     

多靶向嵌合抗原受体T细胞在恶性肿瘤中的研究进展

中国恶性肿瘤发病率和死亡率居全球第一,降低肿瘤复发率和死亡率的研究进展迫在眉睫。其中发展较快,治疗效果较好的方式是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞治疗,但是单靶向CAR-T细胞治疗恶性肿瘤存在抗原丢失、肿瘤复发等局限性,目前国内外通过构建多靶向CAR-T治疗肿瘤可以同时识别和靶向两个及两个以上肿瘤相关抗原,从而有效避免抗原逃逸和防止肿瘤复发。本文重点综述目前正在开发和测试的多靶向CAR-T细胞治疗恶性肿瘤的研究进展,以及多靶向CAR-T细胞治疗的优势和克服单靶向CAR-T细胞治疗后肿瘤复发的局限性,并探讨多靶向CAR-T联合其他方式的治疗效果。多靶向CAR-T细胞治疗有望成为提高抗癌疗效和缓解癌症进展的方法之一。     

肿瘤靶向切除治疗的现状

肿瘤靶向治疗是肿瘤治疗领域中一门新兴学科，它将引领21世纪肿瘤发展的方向。国际生物治疗学会2002年10月在北京举办了肿瘤靶向治疗国际论坛，主要内容是基因与生物、药物靶向治疗和包括氩氦、超声、射频、放射、电化学等肿瘤靶向切除治疗或称肿瘤靶向消融治疗(tumor targeted ablate therapy,TTAT)的研究现状及临床应用。前者是微观的细胞分子水平的研究，后者(TTAT)则是利用理化原理对主体肿瘤靶区进行微创或无创治疗，     

肿瘤综合治疗暨首届肿瘤靶向治疗东方国际论坛

为推动现代肿瘤基础研究和临床治疗的发展,深入宣传肿瘤的个体化、靶向治疗、综合治疗理念,肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛将于2006年8月12~15日在上海举行,此次盛会由同济大学附属东方医院、《肿瘤》杂志社、上海市抗癌协会、国际肿瘤靶向治疗学会、中国生物医学工程学会肿瘤靶向治疗技术分会、东方和佳医院联合举办。届时将邀请美国M.D.Anderson癌症中心、美国国立癌症研究所(NCI)的多名专家和国内专家、学者呈献精彩的讲演,介绍目前国内外肿瘤多学科综合治疗及靶向治疗的最新研究进展和发展趋势,并为参与本次大会…     

肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛

由国际肿瘤靶向治疗学会、中国生物医学工程学会肿瘤靶向治疗技术分会、同济大学附属东方医院等联合举办的”肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛”将于2006年8月12日至15日在中国上海举行。     

肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛征文

肿瘤多学科综合治疗暨首届肿瘤靶向治疗东方国际论坛会将于2006年8月12日至15日在中国上海举行。此次盛会由国际肿瘤靶向治疗学会、中国生物医学工程学会肿瘤靶向治疗技术分会、上海市抗癌协会、同济大学附属东方医院、上海《肿瘤》杂志社、和佳肿瘤医院联合举办。     

表皮生长因子受体与放射敏感性关系的研究进展

近年来,随着对肿瘤形成机制的进一步了解以及分子生物学的进展,针对肿瘤形成发展过程中异常生物学途径的靶向治疗日益发展起来,研究表明靶向药物能够抑制肿瘤生长的活性,而且与放疗或化疗具有协同作用.但放化综合治疗会产生较大的毒副反应,从而限制了其在肿瘤治疗中的应用.靶向治疗的出现,使得放射治疗和靶向治疗联合应用于恶性肿瘤的新策略成为可能.表皮生长因子受体(Epidermal growth factor receptor,EGFR)是目前研究最多、应用最广的靶向药物治疗靶点,本文就目前肿瘤治疗中针对EGFR的靶向药物与放射治疗联合应用的机制、其与放射敏感性的关系做一综述.     

靶向治疗在胃肠道间质瘤中的应用

肿瘤的分子靶向治疗逐渐成为肿瘤治疗的关注焦点,分子靶向药物的出现为肿瘤的治疗带来了新的方向.伊马替尼的应用极大地提高了胃肠道间质瘤的生存率,然而其疗效评价的方法、服药的时间、是否可以中断治疗、耐药后的治疗及靶向治疗与外科治疗的结合仍是目前研究的热点.     

免疫脂质体在肿瘤治疗中的应用

免疫脂质体具有主动靶向性、降低肿瘤药物的治疗毒性、提高药物治疗指数等特点,在肿瘤治疗研究中被广泛使用作为肿瘤化疗和放疗药物、基因治疗和肿瘤影像学诊断治疗的载体。作为常见肿瘤药物治疗靶向载体,免疫脂质体可提高药物疗效,降低毒性;作为肿瘤基因治疗载体,免疫脂质体可提高siRNA的稳定性与靶向性;作为放射治疗的载体,免疫脂质体可在细胞或者亚细胞水平对肿瘤组织进行靶向显影,具有影像监测和放射性治疗的双重潜能。随着功能结构复合化、靶标优化筛选等方面的进展,免疫脂质体在肿瘤治疗领域将有更广阔的应用前景。     

新型线粒体靶向铂类配合物Mor-platin抑制肝癌细胞HepG2增殖和抑制细胞球侵袭的研究

  目的  探讨新型线粒体靶向性铂类配合物Mor-platin对人肝癌细胞HepG2的细胞增殖和细胞球侵袭的影响。  方法  运用细胞毒性实验CCK-8法,比较新型线粒体靶向性铂类配合物Mor-platin和经典铂类抗癌药顺铂(cisplatin)对人肝癌细胞HepG2的细胞增殖抑制作用;利用激光共聚焦显微镜观察Mor-platin是否靶向于线粒体;利用透射电子显微镜观察Mor-platin对细胞线粒体形态的影响;流式细胞仪检测Mor-platin作用细胞后细胞凋亡的改变;建立三维肿瘤细胞球模型,探讨Mor-platin对细胞球侵袭的影响。  结果  Mor-platin能够抑制HepG2细胞增殖,半数抑制浓度(IC₅₀)少于cisplatin;Mor-platin能够靶向到线粒体;加Mor-platin后,细胞线粒体膜结构不完整,嵴不清晰或消失以及线粒体中有大片空白区域;Mor-platin引起的细胞凋亡具有剂量依赖性;三维肿瘤细胞球模型显示,Mor-platin处理的细胞球面积小于对照组。  结论  新型线粒体靶向性铂配合物Mor-platin能够靶向于细胞的线粒体,引起线粒体形态变化,抑制细胞增殖,最终导致细胞凋亡,Mor-platin还能抑制三维肿瘤细胞球侵袭,比cisplatin具有更好的抗癌效果。上述研究结果提示Mor-platin具有成为新抗肿瘤药物的潜质。      

Positive and negative regulation of Natural Killer cells: therapeutic implications

Natural Killer (NK) cells can mediate numerous anti-tumor and anti-viral effector functions as well as play important immunoregulatory roles in various disease states. Promoting the ability of NK cells to respond in an immunotherapeutic setting has often been sought by the addition of NK cell-stimulating factors. However, such therapies are often found to be insufficient, which may in part be due to the presence of inhibitory influences on the NK cell. NK cells can respond to a plethora of cytokines which are generated by numerous cell types and these interactions can markedly affect NK cell survival and activity. NK cells also possess multiple activating and inhibiting receptors which can alter their function. Whether the NK cell will become activated or not can depend on a complex balance of activating and inhibitory signals received by the cell and modulation of these signals may shift the balance on NK activation. This review discusses the various activating and inhibitory stimuli which can act on NK cells, and suggests that future NK cell-based therapies consider not only activating stimuli but also removal of possible inhibitory elements which could prevent optimal NK cell function and/or survival.     

Mig-6基因表达对肝癌细胞增殖和凋亡的影响

目的:研究Mig-6对肝癌细胞增殖和凋亡的影响,以探讨Mig-6在肝癌中的作用机制。方法:采用Mig-6过表达质粒和siRNA转染肝癌细胞,使用Real-time PCR和Western Blot法检测转染后的过表达或沉默效果;CCK-8实验检测细胞增殖水平的变化;流式细胞仪检测细胞凋亡百分比的变化;蛋白免疫印迹检测相关蛋白的表达变化。结果:转染Mig-6能抑制肝癌细胞的增殖,促进肝癌细胞的凋亡;干扰Mig-6能促进肝癌细胞的增殖,抑制肝癌细胞的凋亡。上调Mig-6能增加肝癌细胞Caspase-3 的活性,抑制P-ERK的磷酸化;干扰下调Mig-6能抑制肝癌细胞Caspase-3 的活性,增加P-ERK的磷酸化。结论:在肝癌细胞中,Mig-6表现出抑制细胞增殖及促进细胞凋亡的作用,该作用可能与Mig-6能增加Caspase-3 的活性,同时抑制P-ERK的表达有关。     

p42/44MAPK抑制剂U0126对人胃癌SGC-7901细胞增殖和凋亡的影响

目的 研究U0126对人胃癌SGC-7901细胞生物学特性的影响。方法 用MTT法测定U0126对SGC-7901细胞增殖的影响,流式细胞仪检测U0126对SGC-7901细胞周期和细胞凋亡的影响,用Western blot分析p42/44和p38以及其磷酸化水平的变化。结果 10、15、20μM U0126均能够抑制胃癌SGC-7901细胞的增殖;可使S和G2/M期肿瘤细胞比例减少,G₀/G₁期肿瘤细胞比例增加,其中20μM浓度的U0126作用最强(P<0.01);U0126诱导肿瘤细胞凋亡,其中20μM浓度的U0126凋亡作用最强(P<0.01);U0126使p-p42/44下调而使p-p38上调。结论 U0126诱导肿瘤细胞凋亡,抑制肿瘤细胞的增殖,其机制可能是抑制p-p42/44表达,并使p-p38表达增强。     

B7—1单抗和CsA联用诱导人T细胞无能及其特性探讨

目的:在体外探讨T细胞无能诱导的条件及其生物学特性.方法:将B7-1单抗和CsA联用在体外诱致了抗原特异性T细胞无能,采用RT-PCR法检测了无能T细胞细胞因子基因的表达.结果:T细胞无能为抗原特异性的,多克隆激活剂PHA、CD3单抗和PMA A23187可以恢复无能T细胞的活性 ; IL-2可以阻止T细胞无能的形成,但不能逆转其耐受状态;无能T细胞IL2和IFNmRNA是关闭的,而IL-4和IL-10RNA则是开放的.结论对细胞无能在体外可以诱导的,无能T细胞细胞因子基因格局向Th2样偏离.     

紫杉醇诱导胆管癌QBC939细胞凋亡的初步研究

目的：探讨紫杉醇对胆管癌QBC939细胞作用的敏感性并研究紫杉醇对胆管癌细胞周期及细胞凋亡率的影响,并初步探讨紫杉醇诱导胆管癌细胞发生凋亡的机制,为胆管癌的临床治疗寻找新的治疗药物。方法：体外培养胆管癌细胞QBC939,采用不同浓度紫杉醇予以干预,通过细胞形态观察和Mrrr实验,初步研究紫杉醇对人胆管癌细胞QBC939的敏感性;应用流式细胞仪检测紫杉醇诱导胆管癌细胞凋亡,同时对细胞周期的变化和动力学予以检测。结果：各浓度紫杉醇对人胆管癌细胞QBC939生长均有明显抑制作用;胆管癌细胞被紫杉醇明显阻滞在S期及G2／M期,且抑制作用呈剂量和时间依赖效应。结论：紫杉醇对人胆管癌细胞QBC939增殖的抑制作用呈剂量和时间依赖效应;紫杉醇能诱导人胆管癌QBC939细胞发生凋亡。     

Pharmacologic manipulations of mitochondrial membrane potential (ΔΨm) selectively in glioma cells

Metabolic control theory applies principles of bioenergetics for the control or management of complex diseases. Since metabolism is a general process underlying all biologic phenotypes, changes in metabolism can potentially modify phenotype. Therefore, it is reasonable to assume that experimental modulation of the availability of cellular energy can potentially alter cell phenotypes and cell functions critical to tumor progression including cell division. The purpose of this study was to determine if OMX-2, a methylquinone system designed to shuttle electrons from mitochondrial complexes, was able to target mitochondria in cancer cells and trigger cell death. Using flow cytometry, cell viability assays, and ATP measurements, we found that OMX-2 differentially decreased ΔΨm without triggering cell death. In contrast, known blockers of the Electron Transport Chain (ETC) decreased ΔΨm and triggered cell death. When normal cells were treated with OMX-2, neither ΔΨm or cell death was triggered. Furthermore, OMX-2 modulated intracellular ATP and decreased cell numbers of glioma cells. Cell cycle analysis indicated that OMX-2 induced a reversible cell cycle arrest in G1/S. Finally, impairment of glycolysis by 2-Deoxyglucose (2-DOG) acted synergistically with OMX-2 to trigger cell death. Overall, these results indicate that it is possible to selectively target cancer cells by decreasing ΔΨm and induced cell cycle arrest without triggering cell death. Moreover, pharmacological approaches designed to act on both glycolysis and oxidative phosphorylation can be considered as a new approach to selectively kill cancer cells. In Memory of R. Griguer. This OMX-2 can be provided through the corresponding author.     

The cellular basis of long-term marrow injury after irradiation

Haemopoietic recovery from radiation injury can appear complete when measured by blood cell counts, but this can hide deficiencies in the precursor cell populations because of compensatory mechanisms of increased numbers of divisions in the maturing cell populations and increased cycling of the stem cells. These mechanisms can operate for quite long but finite periods, before they fail which then leads to hypoplasia. Also, while these mechanisms are operating, small further injuries could precipitate marrow failure. Persistent injury in the stem cell population can be induced by quite small doses, and in mice the threshold total dose is probably in the region of 1.5 Gy using fractionated whole-body irradiations. The sensitivity of the environment varies enormously, depending largely on the proliferative stress applied to the cell populations involved in the particular assay technique used. When similar tests of reproductive integrity are applied, stromal progenitor cells are more radioresistant than haemopoietic stem cells. The contribution of environmental injuries to haemopoietic defects is uncertain and difficult to assess.     

Tissue factor as a tumor procoagulant

Summary Tissue factor is a cell surface glycoprotein responsible for initiating the extrinsic pathway of coagulation. Many tumor cell homogenates and intact tumor cells have been shown to contain tissue factor activity. Immunohistochemical studies show that many tumors associated with Trousseau's syndrome express tissue factor on their cell surfaces. Tumor cells shed membrane fragments which carry tissue factor that can account for the activation of the clotting system. Tumor cells also produce soluble substances that can induce tissue factor expression on host cells, such as endothelium and monocytes, at sites distant from the tumor. Although, all the functional TF molecules are localized on the outer cell membrane in many tumor cells, the procoagulant activity on the intact cell surface is largely dormant and can be greatly enhanced upon cell injury or damage. Tissue factor procoagulant activity on the cell surface can be modulated by alterations in the plasma membrane without loss of cell viability. Tissue factor activity on cell surfaces is largely regulated by a plasma inhibitor, tissue factor pathway inhibitor. This inhibitor binds to both functional and non-functional tissue factor/VIIa complexes on the cell surface and prevents non-functional tissue factor/VIIa complexes from becoming functional after cell injury or lysis. Heparin, but not warfarin, therapy is effective in preventing the occurrence of devasting thrombotic events in patients with Trousseau's syndrome and the reason(s) for this are still unknown.Abbreviations TF tissue factor - DIC disseminated intravascular coagulation - TFPI tissue factor pathway inhibitor - FPA fibrinopeptide A     

TGFα反义寡聚核苷酸抑制大肠癌细胞株的增殖

研究ＴＧＦａ反义家聚核苷酸抑制大肠癌ＨＲ８３４８细胞株恶性增殖的作用。方法采用２３个碱基组成的ＴＧＦα反义寡聚核苷酸和２１个碱基组成的对照寡聚核苷酸作用于人大肠癌ＨＲ８３４８细胞,通过细胞生长抑制实验、Ｈ－ＴｄＲ掺入、ｍＲＮＡ斑点杂交及细胞周期分析以确定其对大肠癌细胞的增殖抑制作用和作用环节。结果ＴＧＦα反义寡聚核苷酸均能抑制ＨＲ８３４８细胞的增殖、ＤＮＡ合成和ＴＧＦαｍＲＮＡ的表达,并能有效地延缓ＨＲ８３４８细胞由Ｇ０／Ｇ１期向Ｓ期的转化,延缓了细胞的分裂增殖。结论ＴＧＦα反义寡聚核苷酸能有效地抑制ＨＲ８３４８细胞的恶性增殖。