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使用中断RAS/RAF相互作用的肽在侵袭性淋巴瘤中诱导凋亡的新形式。

New forms of induction of apoptosis in aggressive lymphoma using peptides that interrupt the RAS / RAF interaction.

作者信息

Bergna C, Marin G H, Maiz M, Bruzzoni Giovanelli H, Ponzinibbio C, Schinella G, Errecalde J, Rebollo A

机构信息

Faculty of Medical Science, National University of La Plata, Argentina.

出版信息

Ceylon Med J. 2019 Jun 30;64(2):46-51. doi: 10.4038/cmj.v64i2.8890.

DOI:10.4038/cmj.v64i2.8890
PMID:31455066
Abstract

INTERPRETATION

RAS-RAF-MEK-ERK is a key pathway for apoptosis regulation in cancer cells. B-Raf-inhibitors such as PLX4032 peptide was developed by Institute Curie-Université Pierre et Marie Curie in order to induce apoptosis in cancer cells.

OBJECTIVES

To demonstrate pro-apoptotic properties and survival outcome of EP2014/064243 peptide in murine aggressive lymphoma.

MATERIAL AND METHODOLOGY

BALBc mice with T-lymphoma were randomized assigned either in Group A (peptide+cyclophosphamide-CFM); Group B (peptides), Group C (CFM-control) or Control D (Cl-Na 0.9%-SF control group). Survival probability was calculated by Kaplan-Meier analysis. Apoptosis was detected using TUNEL technique. The protocol was approved by the Institutional Committee for Animal Care (CICUAL: T04-01-2015)

RESULTS

The median survival was 24 days (21.6-26.4) for placebo, 33 days (28.0-35.4) for the CFM monotherapy group, 33 (27.1-35.8) for the peptide group and 34 days (24,4-40) for CFM-peptide combined treatment (p<0.05). In lymph node tissue the mean TUNEL positive cells per field for each treatment group was 2, 12 and 13 and 35 for SF, CFM, peptide and combined therapy (p<0.05).

CONCLUSION

These findings suggest that in murine aggressive lymphoma treated by an experimental peptide in addition with CFM, had an exponentially pro-apoptotic effect than CFM alone, suggesting that the peptide potentiated the anti-tumoural effect of CFM.

摘要

解读

RAS-RAF-MEK-ERK是癌细胞凋亡调控的关键通路。居里研究所-皮埃尔和玛丽·居里大学研发了诸如PLX4032肽等B-Raf抑制剂,以诱导癌细胞凋亡。

目的

证明EP2014/064243肽在小鼠侵袭性淋巴瘤中的促凋亡特性和生存结果。

材料与方法

将患有T淋巴瘤的BALBc小鼠随机分为A组(肽+环磷酰胺-CFM);B组(肽),C组(CFM-对照组)或D组(0.9%氯化钠溶液-生理盐水对照组)。通过Kaplan-Meier分析计算生存概率。使用TUNEL技术检测细胞凋亡。该方案已获得动物护理机构委员会(CICUAL:T04-01-2015)的批准。

结果

安慰剂组的中位生存期为24天(21.6-26.4),CFM单药治疗组为33天(28.0-35.4),肽组为33天(27.1-35.8),CFM-肽联合治疗组为34天(24.4-40)(p<0.05)。在淋巴结组织中,每个治疗组每视野TUNEL阳性细胞的平均数,生理盐水组、CFM组、肽组和联合治疗组分别为2、12、13和35(p<0.05)。

结论

这些发现表明,在小鼠侵袭性淋巴瘤中,实验性肽联合CFM治疗比单独使用CFM具有更强的促凋亡作用,提示该肽增强了CFM的抗肿瘤作用。

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