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題名 | Postoperative Administration of Interleukin-12 Significantly Enhances the Anti-tumor Immune Response of MBT-2 Bladder Cancer Bearing Mice=術後施打白血球間素-12能有效增強MBT-2膀胱癌老鼠體內特異性抗腫瘤免疫力 |
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作者姓名(中文) | 蔡宗欣; 蕭璦莉; 吳昭良; 蔡育賢; | 書刊名 | Proceedings of the National Science Council : Part B, Life Science |
卷期 | 24:2 2000.04[民89.04] |
頁次 | 頁56-62 |
分類號 | 415.138 |
關鍵詞 | 白血球間素-12; 膀胱癌; 特異性抗腫瘤免疫力; Interleukin-12; Bladder tumor; Immunomodulation; |
語文 | 英文(English) |
英文摘要 | This study, using the MBT-2 murine bladder tumor model, mainly investigated the role of interleukin-12 (IL-12) in the specific antitumor immune response of a tumor-bearing host when systemically administrated after surgery. Day 17 tumor-bearing mice (D17TBM) along with non-tumor bearing naive mice were treated with daily intraperitoneal (i.p.) injection of IL-12 (0.25 ug/mouse) from day 18 to day 24 for a total of 7 doses. Their splenocytes were obtained on Day 31 for natural killer cells (NK), lymphokine activated killer cells (LAK) and cytotoxic T lymphocyte (CTL) activity assay and lymphocyte subsets phenotypic analysis. The tumor suppression effect of systemic IL-12 administration was evaluated based on the tumor outgrowth of the higher number of tumor cells rechallenged 24 hours after resectioning of the primary tumor. After evaluation on Day 31, the result of in vitro cytotoxicity assay revealed that systemic administration of IL-12 mainly enhanced the splenic LAK and CTL activities in non-tumor-primed naive mice, and the NK activity in tumor-primed D17TBM, respectively. However, in vivo administration of IL-12 with or without IL-2 failed to upgrade the proportions of either CD4+CD44+ or CD8+CD44+ T cells subsets in the spleens and regional inguinal lymph nodes (LNs) of both the D17TBM and naive mice. However, the splenic CD8+CD44+ T-cell subset in the IL-12-treated D17TBM increased prominently after further culturing in the presence of IL-2 400 units/ml plus IL-12 25 ng/ml for 4 days. The fact that systemic administration of IL-12 significantly suppressed the outgrowth of Day-18 challenged tumor cells, especially in D17TBM, clearly indicates that the established specific antitumor immunity in tumor-primed D17TBM was efficiently augmented. From the results of this study, we conclude that, after surgical resection of a primary tumor, systemic administration of IL-12 can be an effective adjuvant therapy because it demonstrates a significant augmentation effect on the tumor-specific immune response in the tumor-primed host. |
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