NKT细胞的生物特性及其在抗肿瘤免疫中的作用

[摘要] NKT细胞是一类特殊的T 淋巴细胞亚群,既表达NK 细胞受体,也表达T 细胞的相关受体。NKT细胞在多种免疫应答的调节中发挥重要作用,包括感染、自身免疫性疾病、代谢性疾病和癌症,其通过连接固有免疫系统和适应性免疫系统显示出强大的抗肿瘤活性。NKT细胞不仅能杀伤肿瘤细胞,也可激活其他抗肿瘤免疫细胞间接地发挥抗肿瘤作用,还能在肿瘤微环境中激活衰竭的免疫细胞,在抗肿瘤免疫中发挥重要的作用。本文就NKT细胞的生物学特性及其在抗肿瘤免疫中的作用作一综述。     

PHA,抗CD3单抗,IL—2诱导脾细胞增殖及其抗肿瘤效应的实验研究

本文应用PHA、抗CD_3单抗、IL-2体外诱导正常人脾细胞增殖,并探讨了在不同条件的诱导下脾细胞体外增殖能力和抗肿瘤效应,以及细胞表面标志的表达特征.结果显示,抗CD_3单抗、PHA不仅可增强IL-2诱导脾细胞的增殖作用,且两者合用有协同增强效应.PHA、抗CD_3单抗还可增强体外扩增细胞CD_4和Tas受体的表达.LAK细胞抗肿瘤活性测定结果提示,PHA有直接和间接增强LAK细胞抗肿瘤效应的作用,抗CD_3单抗则可通过增加细胞增殖作用,间接地增强LAK细胞的抗肿瘤活性.     

中药抗肿瘤作用分子机制研究进展

从天然物质中寻找毒副作用小、安全有效的抗肿瘤药物为近年的研究热点。中药及其有效成分抗肿瘤作用的分子机制研究取得较大进展 ,可通过诱导细胞凋亡、细胞毒性作用、调节细胞信号转导、诱导细胞分化、逆转多药耐药、抑制端粒酶活性等机制发挥抗肿瘤作用     

中药抗肿瘤作用分子机制研究进展

从天然物质中寻找毒副作用小、安全有效的抗肿瘤药物为近年的研究热点.中药及其有效成分抗肿瘤作用的分子机制研究取得较大进展,可通过诱导细胞凋亡、细胞毒性作用、调节细胞信号转导、诱导细胞分化、逆转多药耐药、抑制端粒酶活性等机制发挥抗肿瘤作用.     

细胞穿透肽修饰脂质体的抗肿瘤靶向给药研究进展

细胞穿透肽是一类对细胞膜具有强力穿透作用的短肽,可促进细胞摄取,经细胞穿透肽修饰的脂质体可提高脂质体的入胞率,是目前靶向给药载体研究的新方向。作者查阅了近年来国内外的相关文献,就细胞穿透肽的种类、穿膜机制和细胞穿透肽与多肽、叶酸等大分子组成共修饰脂质体及保护性细胞穿透肽提高对肿瘤细胞的穿透稳定性等在抗肿瘤领域的应用展开综述,以期为脂质体的抗肿瘤靶向给药研究提供参考。     

树突状细胞与卵巢癌的免疫治疗

树突状细胞(DC)是目前发现的体内功能最强的专职抗原提呈细胞,可在体内外激活初始T细胞,并有效诱发细胞毒性T淋巴细胞反应,在抗肿瘤免疫中发挥重要作用.近年来采用DC疫苗进行抗肿瘤治疗已成为肿瘤生物治疗领域的热点之一.DC抗肿瘤机制及DC疫苗在卵巢癌治疗中的应用等研究也取得了很大进展.     

Th9细胞抗肿瘤免疫作用及机制研究进展

Th9细胞作为新命名的辅助T细胞亚群,在抗肿瘤免疫治疗中起着重要作用,由转化生长因子-β（transforming growth factor-β,TGF-β）和白细胞介素-4（interleukin,IL-4）共同诱导初始CD4+T细胞分化而来,也可在特定的条件下由其他T细胞转化而来,表现出一定的可塑性。动物实验表明Th9可以抑制肿瘤生长,主要通过分泌IL-9等细胞因子以及其他方式发挥抗肿瘤免疫作用,细胞因子等分子可通过不同的信号途径调控Th9细胞分化、发育。本文旨在对Th9细胞的来源、抗肿瘤免疫作用及机制、相关信号通路等进行阐述,为抗肿瘤治疗提供新的视野和思路。      

细胞因子诱导杀伤细胞的抗肿瘤机制及其应用研究

 细胞因子诱导杀伤细胞（CIK）为自然杀伤（NK）细胞活性的T淋巴细胞,具有抗肿瘤活性。研究发现,CIK细胞通过分泌细胞毒颗粒及细胞因子、活化NKG2D受体、调节癌基因表达等发挥抗肿瘤作用。CIK不仅杀伤肿瘤细胞,而且可提高肿瘤患者的免疫力,改善生活质量。国内外研究显示CIK治疗无明显不良反应,是肿瘤治疗的一种全新模式,因此,可广泛应用于临床。     

G蛋白调节信号5在肿瘤中的作用

G蛋白调节信号5(RGS5)是G蛋白信号调节蛋白(RGS)家族中的一员,负性调节该信号通路的传导.RGS5主要表达在血管周细胞,与血管的发生、发展及成熟密切相关.RGS5基因缺失可引起周细胞成熟和肿瘤血管正常化,此期间联合化疗或免疫治疗可提高疗效,提示RGS5可能成为抗肿瘤治疗的新靶点.RGS5还与肿瘤转移、细胞凋亡有关,可通过诱导细胞凋亡来增加抗肿瘤治疗的效果.     

趋化因子和B7分子联合应用抗肿瘤的研究进展

恶性肿瘤的发生常常是多个基因改变的结果,单一基因治疗的抗肿瘤效应往往十分有限,联合应用不同特性的细胞因子或趋化因子抗肿瘤是近年来的研究热点。本文着重综述趋化因子和B7分子在肿瘤基因治疗中的联合应用。B7分子是重要的共刺激分子,可为T细胞激活提供第二信号;趋化因子可通过趋化免疫活性细胞,部分趋化因子还可抑制肿瘤血管生成,从而产生抗肿瘤效应。共转染趋化因子和B7分子除通过“招引-活化”的机制外,还可抑制CD4 CD25 调节性T细胞亚型向肿瘤局部浸润,进而改善肿瘤局部免疫抑制状态;同时可抑制肿瘤血管生成,从而通过多个不同的途径,产生更强的抗肿瘤效应。但趋化因子具有抗肿瘤和促肿瘤双向性,因此选择合适的趋化因子与B7分子联合应用是至关重要的。     

磁场抗肿瘤生物效应机制

磁场抑制肿瘤机制较为复杂,并且有众多的影响因素制约着磁场作用效果。磁场可以抑制肿瘤细胞分裂,并可作用于肿瘤细胞的细胞器、细胞膜,以及非肿瘤组织,从而间接起到抑制肿瘤的作用。其可能机制为磁场能选择性破坏肿瘤细胞的DNA,抑制肿瘤细胞的恶性增殖;激活自由基间接损伤DNA;调控肿瘤细胞的增殖分裂周期;作用于肿瘤细胞质内线粒体、蛋白酶等生命物质以及肿瘤细胞的细胞膜,从而破坏肿瘤细胞功能,减少肿瘤细胞的养分而抑制或杀死肿瘤细胞等。     

磁场抗肿瘤生物效应机制

磁场抑制肿瘤机制较为复杂,并且有众多的影响因素制约着磁场作用效果.磁场可以抑制肿瘤细胞分裂,并可作用于肿瘤细胞的细胞器、细胞膜,以及非肿瘤组织,从而间接起到抑制肿瘤的作用.其可能机制为磁场能选择性破坏肿瘤细胞的DNA,抑制肿瘤细胞的恶性增殖;激活自由基间接损伤DNA;调控肿瘤细胞的增殖分裂周期;作用于肿瘤细胞质内线粒体、蛋白酶等生命物质以及肿瘤细胞的细胞膜,从而破坏肿瘤细胞功能,减少肿瘤细胞的养分而抑制或杀死肿瘤细胞等.     

冻融肿瘤细胞和肿瘤细胞培养上清对淋巴细胞活化能力的影响

 目的　比较冻融肿瘤细胞和肿瘤细胞培养上清对淋巴细胞活化能力影响的差异。方法　常规冻融法制备恶性黑色素瘤B16细胞全肿瘤细胞抗原,收集培养不同时间的肿瘤细胞培养上清;利用Transwell法检测冻融肿瘤细胞以及肿瘤细胞培养上清对淋巴细胞的趋化能力;用CCK-8法检测各组趋化淋巴细胞的肿瘤杀伤活性。结果　冻融肿瘤细胞及培养2 h以上的肿瘤上清液对淋巴细胞均有趋化作用;培养4 h以上的肿瘤上清液的趋化能力明显强于冻融瘤细胞。各组趋化的淋巴细胞均具有肿瘤杀伤活性;培养4 h以上的肿瘤上清液组淋巴细胞的杀伤能力明显强于冻融肿瘤细胞组。在一定范围内,培养上清对淋巴细胞的趋化和活化能力随时间延长而增强。结论　培养一定时间的肿瘤上清液对淋巴细胞的趋化和活化能力均强于冻融肿瘤细胞,用培养上清液代替冻融肿瘤细胞抗原作为抗原活化淋巴细胞可获得更好的免疫效果。     

Interaction of rat ascites hepatoma cells with cultured mesothelial cell layers: a model for tumor invasion

Interactions of rat ascites hepatoma cells with primary cultured layers of rat mesentery-derived cells were studied. The mesentery-derived cells were isolated from rat mesentery and cultured in Eagle's minimum essential medium with a 2-fold concentration of amino acids and vitamins supplemented with 10% calf serum. The primary cultured cells, consisting mainly of mesothelial cells in polygonal shape, forms a "paving stone" sheet. Upon seeding the tumor cells on the mesentery-derived cell layers, three different types of tumor cell growth were observed. Type 1 was the formation of piled-up tumor cell nests on mesothelial cell layers. Type 2 was the formation of flattened tumor cell islands underneath mesothelial cell layers. This island formation was clearly observed under a phase contrast microscope 2 days after the tumor cell seeding. Protrusion of cellular processes of the tumor cells beneath mesothelial cells was occasionally seen. Type 3 was the growth of tumor cells in suspension. These types of tumor cell growth closely resemble those in the peritoneal cavity observed after i.p. implantation of the tumor cells. When the tumor cells recovered from the blood of tumor-bearing rats were seeded, flattened tumor cell islands were formed 15 times more frequently than when the tumor cells isolated from host peritoneal cavity were seeded. Shortly after the appearance of small flattened tumor cell islands, a distinct morphological change of mesothelial cells from polygonal to spindle shape was seen preferentially at the marginal area of the cell layers (a partial retraction of cell edges). The retraction of mesothelial cells was induced not only by seeding the tumor cells but by adding the tumor ascites fluid or the medium conditioned by the tumor cell culture. The morphological change was reversed by changing the culture medium to remove the effectors. These results indicate that the system described in this study can provide a useful model to study tumor cell invasion.     

骨巨细胞瘤中单核基质细胞的分离培养及其性质研究

目的对骨巨细胞瘤中单核基质细胞的性质和来源进行探讨。方法体外分离培养8例骨巨细胞瘤的单核基质细胞，用胶原酶分离方法和差速贴壁法分离纯化细胞，将分离培养的骨巨细胞瘤单核基质细胞与狗股骨薄磨片共培养，观察骨巨细胞瘤单核基质细胞的噬骨能力、TRAP染色和RT—PCR检测降钙素受体（CTR）和细胞核因子KB受体活化因子（RANK）。结果利用酶消化的方法可以获得较高纯度的单核基质细胞；TRAP染色阳性；体外培养具有噬骨能力；采用RT—PCR方法可检测到降钙素受体和细胞核因子KB受体活化因子。结论利用胶原酶-Ⅱ消化的方法结合差速贴壁方法可以获得较纯的单核基质细胞，可用于生化和分子生物学研究，是进行骨巨细胞瘤细胞学研究的细胞来源。     

Reduction of tumorigenicity by placental extracts

The influence of adult stem cells on tumor growth is paradoxical. On one hand, angiogenic factors secreted by stem cells are known to be essential for tumor vascularization. On the other hand, stem cell-derived factors can reportedly induce tumor differentiation or direct death of tumor cells. Both the placenta and umbilical cord are rich sources of stem cells with immune modulatory and tissue-healing properties; however, the effects of placental components on cancer cells have not been fully defined. Here we demonstrate that extracts of placental lysates reduce the malignancy of a variety of human tumor cell lines in a species-unrestricted manner. Using a standard model of leukemia cell differentiation, we demonstrated that addition of placental extracts to tumor cells, or co-culture of tumor cells with the CD34(+) cells from umbilical cord blood, induced tumor cell differentiation. Inhibition of tumor growth and metastasis in vivo was also observed following administration of placental extracts. These data support the concept of non-toxic biological therapy of cancer using stem cell derivatives, possibly through the induction of tumor cell differentiation.     

In vitro Invasion of Endothelial Cell Monolayer by Rat Ascites Hepatoma Cells

To study the tissue preference of invasion, we developed an assay system for the invasion of endothelial cells as a modification of the previously established assay of tumor cell invasion of meso-thelial cells. Rat ascites hepatoma cells (AH 130) that had been seeded on a monolayer of cultured endothelial cells penetrated and formed tumor cell colonies under the monolayer. The penetration was time-dependent and the number of penetrated tumor cells and colonies was proportional to the number of tumor cells seeded. Comparison of the in vitro tumor cell invasion of endothelial cell monolayer with that of cultured mesothelial cell layer showed that a clone from the tumor cells (CI-30) which was highly penetrative into the mesothelial cell layer had only a limited ability to penetrate the endothelial cell layer.     

肿瘤干细胞相关研究进展

干细胞具有自我更新和多向分化的特征.随着对干细胞进一步了解及肿瘤基础研究的不断深入,越来越多证据表明肿瘤中极少数细胞具有干细胞特征,肿瘤干细胞概念随之产生,且已从血液肿瘤、乳腺癌及神经系统肿瘤中分离出肿瘤干细胞.这些细胞具有治疗抵抗特性,能够耐受传统的细胞毒化疗和放射治疗.肿瘤生长正是这些具有特殊表型细胞分化增殖的结果.许多学者认为,肿瘤复发、转移以及耐药等均与肿瘤干细胞相关,肿瘤治疗关键应该针对肿瘤干细胞.这一全新的治疗概念给肿瘤治疗带来希望,同时对传统肿瘤治疗模式提出了巨大挑战.肿瘤干细胞的发现、自身特点以及对肿瘤治疗可能影响的研究具有重要意义.     

In vitro invasion of endothelial cell monolayer by rat ascites hepatoma cells

To study the tissue preference of invasion, we developed an assay system for the invasion of endothelial cells as a modification of the previously established assay of tumor cell invasion of mesothelial cells. Rat ascites hepatoma cells (AH 130) that had been seeded on a monolayer of cultured endothelial cells penetrated and formed tumor cell colonies under the monolayer. The penetration was time-dependent and the number of penetrated tumor cells and colonies was proportional to the number of tumor cells seeded. Comparison of the in vitro tumor cell invasion of endothelial cell monolayer with that of cultured mesothelial cell layer showed that a clone from the tumor cells (Cl-30) which was highly penetrative into the mesothelial cell layer had only limited ability to penetrate the endothelial cell layer.     

A human xenograft model for testing early events of epithelial neoplastic invasion

We report on a model of human prostate tumor cell invasion using the SCID (severe combined immunodeficient) mouse diaphragm. Tumor cells were injected into SCID mice intraperitoneally and the diaphragms harvested three to five weeks later. Electron microscopy showed tumor cell penetration of the mesothelial cell layer and adhesion to the underlying basement membrane on the inferior surface of the mouse diaphragm, where colonies developed. Immunohistochemistry showed invasion by tumor cells through the basement membrane into the muscle of the diaphragm, presence of human tumor cells among the muscle cells and the presence of selected proteins on the invasion front of the tumor cells. Digital image analysis enabled quantitative comparison of events in the metastatic cascade by variants of the tumor cell line and evaluation of the effectiveness of a putative tumor inhibitor. Results suggest that the SCID mouse diaphragm model is a convenient, effective, easily oriented and reproducible in vivo model of the early events associated with human prostate tumor cell invasion.