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11.
肿瘤浸润性淋巴细胞(TIL)经白细胞介素2(IL-2)体外培养后具有很强的体内外抗肿瘤作用,且有一定的靶细胞特异性,其抗肿瘤效果强于淋巴因子激活的杀伤细胞即LAK细胞(P<0.01)。从瘤体中新鲜分离到的TIL对自体肿瘤细胞的杀伤活性极低,经IL-2体外培养后,其杀伤活性逐渐增高,以培养至7~25d的杀伤活性最强,这与IL-2使TIL分泌3种抗癌淋巴因子包括IL-2、IFN-γ、淋巴毒素(LT)增加有关。体外培养25d后,TIL的抗肿瘤活性下降,实验表明这与培养过程中TIL的Lyt-2~+细胞(Tc)减少而L3T4~+细胞(T_H)增多有关。TIL经冻存复苏和IL-2体外培养后仍保持很强的抗肿瘤活性,冻存前后比较未见显著差异(P>0.05),这为间断地运用TIL治疗复发性、晚期肿瘤提供了一条可行的途径。 相似文献
12.
Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells 总被引:5,自引:0,他引:5
Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC50 values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier. 相似文献
13.
IL-2诱导外周血单个核细胞对肿瘤细胞的杀伤效应 总被引:2,自引:2,他引:0
目的 了解白细胞介素 2 (IL 2 )诱导外周血单个核细胞 (PBMC)对肿瘤细胞的杀伤效应 ,探讨其作用机制。方法 IL 2 ( 10 5IU/L)体外诱导PBMC 5d ,并与Raji细胞株共同培养 ,采用MTT法测定不同时间诱导后的PBMC对Raji细胞的杀伤效应 ;采用BAS ELISA法检测杀伤活性最大时的IFN γ、TNF α、sFasL的表达 ,采用流式细胞仪检测诱导后PBMC的FasL、穿孔素、颗粒酶B的表达。结果 IL 2 ( 10 5IU/L)体外诱导PBMC 5d时 ,都能明显增强对Raji细胞的杀伤活性 ,而且在培养的第 4天杀伤活性最高 (P <0 0 5 ) ,诱导PBMC 4d后 ,FasL、穿孔素、颗粒酶B的表达与B组相比 ,明显增加 ,差异有显著性 (P <0 0 5 )。结论 IL 2 ( 10 5IU/L)体外诱导PBMC能明显增强对Raji细胞的杀伤活性 ,主要是通过诱导PBMC表达IFN γ、穿孔素、颗粒酶B和FasL的表达而发挥抗肿瘤细胞的作用 相似文献
14.
用微量细胞法观察了肝癌细胞SMMC-7721,成纤维细胞L929。肺癌细胞A549及中国地鼠卵巢细胞CHOk1等4株传代细胞对绿脓杆菌外毒素A细胞毒作用的敏感性,结果SMMC-7721最敏感,L929次之,A549次于前两者,CHOk1最次,用ELISA法显示各细胞株表面绿脓杆菌外毒素A受体,且用图像分析比较受体密度,结果与细胞毒作用一致,以SMMC-7721为最高,显示了细胞毒敏感程度与受体量呈正相关。 相似文献
15.
Michael Irwin 《Stress and health》1988,4(2):95-103
Clinical studies have demonstrated that measures of cell-mediated immune function are altered in bereaved persons and depressed patients. This review article focuses on our recent observations of changes in T cell subpopulations and natural killer cytotoxicity in women undergoing adverse life events including conjugal bereavement. A reduction in natural cytotoxicity has also been found in depressed patients. The mechanism by which psychologic states might influence immune function is discussed. 相似文献
16.
甘草甜素和甘草酸单铵促进IL-2增强NK活性的研究 总被引:1,自引:0,他引:1
本实验采用乳酸脱氢酶释放法研究甘草甜素和甘草酸单铵对人外周血NK细胞活性的影响。结果表明,甘草甜素和甘草酸单铵本身无增强NK细胞活性的作用,但可明显促进IL-2增强NK活性,这种增强作用与甘草甜素和甘草酸单铵的浓度有关。 相似文献
17.
本文着重检测了不同免疫缺陷的纯合子615-nu、615-bg、615-nu/bg、Ba1b/c-nu和表现型正常的杂合子615/PBI小鼠的巨噬细胞细胞毒活性、吞噬功能,并与它们的NK细胞活性和T、B细胞功能进行了对比分析。实验结果表明:这些不同免疫缺陷的615小鼠其相应的免疫缺陷的性质是确定的。615-nu、615-nu/bg、Ba1b/c-nu的巨噬细胞毒活性与615/PBI无明显差别,但吞噬指数较正常升高,而615-bg的巨噬细胞细胞毒活性和吞噬功能则都显著低于615/PBI的。 相似文献
18.
N. ASKAR T. CIRPAN E. TOPRAK B. KARABULUT† N. SELVI‡ M.C. TEREK R. USLU† U.A. SANLI† & E. GOKER† 《International journal of gynecological cancer》2006,16(4):1552-1556
The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3). 相似文献
19.
本文采用离体细胞培养法,以细胞存活率、乳酸脱氢酶活性和酸性磷酸酶活性为指标,研究了几种α-Keggin结构的杂多阴离子对石英粉尘细胞毒性的影响。结果表明,与对照组比较,所用杂多阴离子无细胞毒性(P>0.05),石英尘经杂多阴离子作用后,细胞毒性显著降低,与石英尘组比较,上述三项指标差异均有显著意义(P<0.01),由此表明杂多阴离子对石英的细胞毒性有明显的拮抗作用。 相似文献
20.
C. Moyer D. Allen A. Basabe R.R. Maronpot A. Nyska 《Experimental and toxicologic pathology》2004,55(6):455-465
Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (Nyska etal. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma. 相似文献