Forest V, Campos L, Péoc'h M, Guyotat D, Vergnon J-M
Faculté de médecine Jacques-Lisfranc, UPRES-EA 3063, Saint-Etienne, France.
Pathol Biol (Paris). 2005 May;53(4):199-203. doi: 10.1016/j.patbio.2004.08.002.
Adenocarcinomas are today the most frequent lung cancers. They are mainly treated by surgery or by chemotherapy, but for the most advanced stages a local cryotherapy can be proposed as a palliative option for bronchial desobstruction.
The aim of this work was to establish an experimental model to study in vivo the biological effects of this technique to propose it as a neoadjuvant treatment.
A xenograft system was used: cells from the A549 cell line were injected subcutaneously into SCID mice. Tumour nodes could be treated after seven weeks. The histological study showed that these tumours faithfully reproduced the morphological features of adenocarcinoma, and developed an intratumoral neovascularization. Two protocols of cryotherapy (1 vs 3 cycles of freezing) were performed and the induction of apoptosis was analyzed by immunohistochemical staining of cleaved caspase-3.
The basal expression of cleaved caspase-3 in untreated tumours (23%) increased after cryotherapy. The increase was maximal eight hours after treatment (up to 47% of positive cells) and was less important with the first protocol, suggesting a lesser efficiency in the induction of apoptosis.
The establishment of this model, which is faithful to physiological features, allowed us to demonstrate in vivo time and dose-dependent effects of cryotherapy.
腺癌是目前最常见的肺癌类型。其主要治疗方式为手术或化疗，但对于最晚期病例，可采用局部冷冻疗法作为缓解支气管阻塞的姑息治疗选择。
本研究旨在建立一个实验模型，以在体内研究该技术的生物学效应，从而将其作为新辅助治疗方法。
采用异种移植系统：将A549细胞系的细胞皮下注射到SCID小鼠体内。七周后可对肿瘤结节进行治疗。组织学研究表明，这些肿瘤忠实地再现了腺癌的形态特征，并形成了肿瘤内新血管生成。实施了两种冷冻疗法方案（1个与3个冷冻周期），并通过对裂解的半胱天冬酶-3进行免疫组织化学染色来分析细胞凋亡的诱导情况。
冷冻疗法后，未治疗肿瘤中裂解的半胱天冬酶-3的基础表达（23%）有所增加。治疗后8小时增加最为显著（阳性细胞高达47%），且第一种方案的增加幅度较小，表明诱导细胞凋亡的效率较低。
建立的这个忠实反映生理特征的模型，使我们能够在体内证明冷冻疗法的时间和剂量依赖性效应。
