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在荷瘤小鼠中,聚肌苷酸-聚胞苷酸与聚-L-赖氨酸混合并用羧甲基纤维素增溶后的治疗作用与毒性作用的解离

Dissociation of therapeutic and toxic effects of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose in tumor-bearing mice.

作者信息

Hartmann D, Adams J S, Meeker A K, Schneider M A, Lenz B F, Talmadge J E

出版信息

Cancer Res. 1986 Mar;46(3):1331-8.

PMID:3484679
Abstract

In this paper, we describe a study of the therapeutic parameters (dose and schedule) and immunomodulatory activity (macrophage, natural killer cell, and T-cell number and function) of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose [poly(I,C)-LC] in the treatment of MBL-2 tumor ascites. Tumor-bearing mice received an optimal therapeutic protocol [100 micrograms poly(I,C)-LC administered twice a wk], a maximum tolerated dose [50 micrograms poly(I,C)-LC administered daily], or the optimal immunomodulatory protocol for normal mice [10 micrograms poly(I,C)-LC administered daily]. The percentage of tumor-associated macrophages and their cytotoxic activity correlated with host survival. In addition, splenic T-cell activity correlated with host survival, and splenic natural killer cell function had a near significant correlation with host survival. These results indicate that the optimal dose and schedule of poly(I,C)-LC for immunomodulation in tumor-bearing animals are also the optimal therapeutic protocol but have less toxicity than the maximum tolerated dose.

摘要

在本文中,我们描述了一项关于聚肌苷酸-聚胞苷酸与聚-L-赖氨酸混合并用羧甲基纤维素增溶[聚(I,C)-LC]治疗MBL-2肿瘤腹水的治疗参数(剂量和给药方案)及免疫调节活性(巨噬细胞、自然杀伤细胞以及T细胞数量和功能)的研究。荷瘤小鼠接受了最佳治疗方案[每周两次给予100微克聚(I,C)-LC]、最大耐受剂量[每日给予50微克聚(I,C)-LC]或正常小鼠的最佳免疫调节方案[每日给予10微克聚(I,C)-LC]。肿瘤相关巨噬细胞的百分比及其细胞毒性活性与宿主存活率相关。此外,脾脏T细胞活性与宿主存活率相关,脾脏自然杀伤细胞功能与宿主存活率有近乎显著的相关性。这些结果表明,聚(I,C)-LC在荷瘤动物中进行免疫调节的最佳剂量和给药方案也是最佳治疗方案,但毒性低于最大耐受剂量。

相似文献

1
Dissociation of therapeutic and toxic effects of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose in tumor-bearing mice.在荷瘤小鼠中,聚肌苷酸-聚胞苷酸与聚-L-赖氨酸混合并用羧甲基纤维素增溶后的治疗作用与毒性作用的解离
Cancer Res. 1986 Mar;46(3):1331-8.
2
Toxicity of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethylcellulose in mice.聚肌苷酸-聚胞苷酸与聚-L-赖氨酸混合并用羧甲基纤维素增溶后在小鼠体内的毒性
Pathol Immunopathol Res. 1987;6(1):37-50. doi: 10.1159/000157040.
3
Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC].肿瘤负荷和给药途径对羧甲基纤维素中用聚-L-赖氨酸稳定的聚肌苷酸-聚胞苷酸[聚(I,C)-LC]免疫治疗特性的影响。
Int J Immunopharmacol. 1992 Nov;14(8):1341-53. doi: 10.1016/0192-0561(92)90005-6.
4
Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose.羧甲基纤维素溶解的聚肌苷酸-聚胞苷酸和聚-L-赖氨酸在小鼠肿瘤模型中的免疫治疗潜力。
Cancer Res. 1985 Mar;45(3):1066-72.
5
Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.
Cancer Res. 1985 Mar;45(3):1058-65.
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Pharmacokinetic and therapeutic activity of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethylcellulose [poly(I,C)-LC].
J Biol Response Mod. 1985 Dec;4(6):621-7.
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Optimization of an immunotherapeutic protocol with poly(I,C)-LC.聚肌胞苷酸-LC免疫治疗方案的优化
J Biol Response Mod. 1985 Oct;4(5):484-9.
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Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly-ICLC].聚肌苷酸:聚胞苷酸与聚-L-赖氨酸在羧甲基纤维素中稳定化后的产物[聚肌胞苷酸]在小鼠体内的免疫反应调节活性。
Int J Immunopharmacol. 1981;3(4):329-37. doi: 10.1016/0192-0561(81)90028-x.
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Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.用聚赖氨酸和羧甲基纤维素稳定的聚肌苷酸-聚胞苷酸肌肉注射长期治疗恶性胶质瘤:一项开放性初步研究。
Neurosurgery. 1996 Jun;38(6):1096-103; discussion 1103-4.
10
Phase I trials of poly(I,C) complexes in advanced cancer.
J Biol Response Mod. 1985 Dec;4(6):640-9.

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