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合成寄生虫衍生肽 GK1 可提高临床前小鼠黑色素瘤模型的存活率。

The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

机构信息

1 Department of Cell and Tissue Biology, Facultad de Medicina, Universidad Nacional Autónoma de México , Distrito Federal, Mexico City, México .

出版信息

Cancer Biother Radiopharm. 2013 Nov;28(9):682-90. doi: 10.1089/cbr.2012.1438. Epub 2013 Jul 10.

Abstract

PURPOSE

The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal.

EXPERIMENTAL DESIGN

C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C).

RESULTS

The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (p<0.05) in the treated mice. The overall survival rates obtained with surgical treatment at 6 months were 83.33% for group A, 40% for group B, and 0% for group C, with significant differences (p<0.05) among the groups.

CONCLUSIONS

The GK1 peptide demonstrated therapeutic properties in a mouse melanoma model, as treatment resulted in a significant increase in the mean survival time of the treated animals (42.58%). The potential for GK1 to be used as a primary or adjuvant component of chemotherapeutic cocktails for the treatment of experimental and human cancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

摘要

目的

评估一种合成寄生虫衍生肽 GK1(一种免疫反应增强剂)在小鼠黑色素瘤模型中的治疗效果。该黑色素瘤模型与人 IIb 期黑色素瘤相关,后者采用广泛的手术切除治疗;同时进行了一项平行的手术治疗研究,作为一个有指导意义的目标。

实验设计

C57BL/6 小鼠在侧腹皮下注射 2×10(5) B16-F10 小鼠黑色素瘤细胞。当肿瘤达到 20mm3 时,将小鼠分为两组;GK1 组每周通过肿瘤周围注射 GK1(10μg/100μL 无菌生理盐水)进行治疗,对照组每周通过肿瘤周围注射 100μL 无菌生理盐水进行治疗,无进一步干预。所有小鼠每天监测临床外观、肿瘤大小和存活情况。当肿瘤大小为 20mm3(A 组)、500mm3(B 组)和>500mm3(C 组)时,同时进行手术治疗。

结果

GK1 肽可有效将平均存活时间延长 9.05 天,对应增加 42.58%,并显著延迟治疗第 3 天至 12 天的肿瘤生长。此外,治疗小鼠的肿瘤坏死明显增加(p<0.05)。6 个月时手术治疗的总生存率分别为 A 组 83.33%、B 组 40%和 C 组 0%,各组间差异有统计学意义(p<0.05)。

结论

GK1 肽在小鼠黑色素瘤模型中具有治疗特性,治疗可显著增加治疗动物的平均存活时间(42.58%)。GK1 作为实验和人类癌症化疗鸡尾酒的主要或辅助成分的潜力有待确定,而手术切除仍然是任何新的实验性黑色素瘤治疗方法在小鼠模型中的挑战。

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