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通过用含有白血病细胞粗丁醇提取物的脂质体致敏小鼠并与细胞表面蛋白进行膜间转移来诱导体外和体内抗肿瘤反应。

Induction of in vitro and in vivo anti-tumor responses by sensitization of mice with liposomes containing a crude butanol extract of leukemia cells and transferred inter-membranously with cell-surface proteins.

作者信息

Shibata R, Noguchi T, Sato T, Akiyoshi K, Sunamoto J, Shiku H, Nakayama E

机构信息

Department of Oncology, Nagasaki University School of Medicine, Japan.

出版信息

Int J Cancer. 1991 May 30;48(3):434-42. doi: 10.1002/ijc.2910480322.

Abstract

Generation of cytotoxic T lymphocytes (CTL) in vitro and tumor-rejection responses by sensitization of semi-syngeneic mice with tumor-antigen-reconstituted liposomes were investigated. Liposomes were prepared from a crude butanol extract (CBE) of BALBRVD leukemia cells and egg phosphatidylcholine (PC): 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC) (3:2) or dimyristoylphosphatidylcholine (DMPC):DDPC (1:4). Inter-membrane protein transfer (IMPT) liposomes were prepared by incubating BALBRVD cells with DMPC:DDPC (1:4) liposomes. Sensitization of male CB6F1 mice with CBE or IMPT liposomes induced a level of cytotoxicity similar to that on sensitization with mitomycin-C(MMC)-treated BALBRVD against BALBRVD target cells after in vitro sensitization with the tumor cells. Sensitization with CBE alone resulted in only marginal cytotoxicity. The cytotoxic effector cells induced by either mode of sensitization were CD8+ T-cells whose recognition was Kd-restricted. No difference in specificity was observed with the different modes of sensitization. Two in vivo immunizations with CBE or with CBE liposomes at a dose of 25 micrograms of protein (equivalent to 2.5 x 10(7) cells) cause moderate inhibition of BALBRVD tumor growth in male CB6F1 mice and immunization with IMPT liposomes at a dose of 1 microgram of protein result in efficient protection.

摘要

研究了在体外产生细胞毒性T淋巴细胞(CTL)以及通过用肿瘤抗原重构脂质体致敏半同基因小鼠来诱导肿瘤排斥反应。脂质体由BALBRVD白血病细胞的粗丁醇提取物(CBE)与鸡蛋磷脂酰胆碱(PC):1,2 - 二肉豆蔻酰氨基 - 1,2 - 脱氧磷脂酰胆碱(DDPC)(3:2)或二肉豆蔻酰磷脂酰胆碱(DMPC):DDPC(1:4)制备而成。通过将BALBRVD细胞与DMPC:DDPC(1:4)脂质体孵育制备跨膜蛋白转移(IMPT)脂质体。用CBE或IMPT脂质体致敏雄性CB6F1小鼠后诱导的细胞毒性水平,与用丝裂霉素 - C(MMC)处理的BALBRVD细胞在体外致敏肿瘤细胞后再对BALBRVD靶细胞致敏所诱导的细胞毒性水平相似。单独用CBE致敏仅产生轻微的细胞毒性。两种致敏方式诱导的细胞毒性效应细胞均为CD8 + T细胞,其识别受Kd限制。不同致敏方式在特异性方面未观察到差异。以25微克蛋白质(相当于2.5×10⁷个细胞)的剂量用CBE或CBE脂质体进行两次体内免疫,可适度抑制雄性CB6F1小鼠体内BALBRVD肿瘤的生长,而以1微克蛋白质的剂量用IMPT脂质体进行免疫则可产生有效的保护作用。

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