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Immunostimulatory and anti-neoplasm effects of anovel palindrome CpG oligodeoxynucleotide in mice
  • ISSN号:1671-4083
  • 期刊名称:《中国药理学报:英文版》
  • 时间:0
  • 分类:Q939.139[生物学—微生物学] S852.4[农业科学—基础兽医学;农业科学—兽医学;农业科学—畜牧兽医]
  • 作者机构:[1]Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China, [2]Drug Clinical Trial Insti-tution, Beijing Anzhen Hospital of Capital Medical University, Beijing 100029, China, [3]Department of Cardiovascular Surgery, XijingHospital, Fourth Military Medical University, Xi'an 710032, China
  • 相关基金:This work was supported by the National Natural Sci- ence Foundation of China (grant number 30572197) and the National High Biotechnology Development Program of China (grant number 2003AA2Z347B). We gratefully acknowledge Prof Wen TAN (Cancer Insti-tute & Hospital, Chinese Academy of Medical Sciences) for her excellent technical assistance.
中文摘要:

目的: 包含 unmethylated CpG 主题的 DNA 能刺激天生、适应的免疫。这研究的目的是调查新奇 CpG oligodeoxynucleotide 的 immunostimulatory 和反瘤效果, ODN10,在忍受肿瘤的老鼠。

英文摘要:

Aim: DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODNIO, in tumor-bearing mice. Methods: B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODNIO or conventional CpG 0DN1826 on the indi- cated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lym-phocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were deter- mined using [3H]-thymidine incorporation assay, 4-h^51Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4, and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry. Results: ODNIO (1, 5, and 25 mg/kg) significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with 0DN1826. The immune status was suppressed in tumor-bearing mice. Both ODNIO and 0DN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lym-phocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting 11-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODNIO presented more potent activity, and displayed the most prominent immunostimulatory potential. Conclusion: ODNIO produces prominent immunomodutatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Thl-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.

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期刊信息
  • 《中国药理学报:英文版》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中科院上海药物研究所
  • 主编:丁光生
  • 地址:上海市太原路294号31号楼
  • 邮编:200031
  • 邮箱:
  • 电话:021-54922821 54922822
  • 国际标准刊号:ISSN:1671-4083
  • 国内统一刊号:ISSN:31-1347/R
  • 邮发代号:4-295
  • 获奖情况:
  • 1992、1996年两届全国优秀科技期刊一等奖,1992、1996、1997年中国科协、中科院以及上海市优...,首届国家期刊奖、2000年中科院优秀期刊评比特别奖
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  • 被引量:1239