Acencio Milena Marques Pagliarelli, Puka Juliana, Alvarenga Vanessa Adélia, Martins Vanessa, de Carvalho Mariana Lombardi Peres, Marchi Evaldo, Capelozzi Vera Luiza, Teixeira Lisete Ribeiro
Laboratorio de Pleura / LIM09 - Divisao de Pneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo SP, Brazil.
Departmento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo SP, Brazil.
Oncotarget. 2017 Sep 28;8(62):105093-105102. doi: 10.18632/oncotarget.21362. eCollection 2017 Dec 1.
Malignant pleural effusion has few options of treatment and drugs administrated by different routes can lead to a less permissive microenvironment for the development of malignant pleural disease.
To analyze therapies administered intrapleurally in malignant pleural disease and to study EGFR and KRAS mutations in adenocarcinoma.
Mice received LLC cells and were treated intrapleurally with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline. Animal survival, weight and mobility, volume, biochemistry and immunology of fluid, gene expression, KRAS and EGFR mutation were evaluated.
All animals developed malignant effusion and presented progressive weight loss without difference between groups; however, groups treated with anti-EGFR were more active. No difference in mortality was observed. Temporal increase of volume and inflammatory markers was observed mainly in the untreated group. Gene expression in tumors was overexpressed in VEGF, EGFR and KRAS compared with normal tissue. Mutation in exon 2 of the KRAS gene was observed.
Intrapleural Anti-VEGF and/or anti-EGFR reduced volume and inflammatory mediators in pleural fluid. Anti-EGFR and anti-VEGF+anti-EGFR decreased morbidity although without impact on survival. LLC tumors presented KRAS mutation, this could have influenced the action of these therapies.
恶性胸腔积液的治疗选择有限，不同给药途径的药物可能导致恶性胸膜疾病发展的微环境不那么宽松。
分析在恶性胸膜疾病中胸膜内给予的治疗方法，并研究腺癌中的表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变。
给小鼠接种 LLC 细胞，并胸膜内给予抗血管内皮生长因子（VEGF）、抗 EGFR、抗 VEGF + 抗 EGFR 或生理盐水。评估动物的存活率、体重、活动能力、胸腔积液体积、生物化学和免疫学指标、基因表达、KRAS 和 EGFR 突变情况。
所有动物均出现恶性胸腔积液，并呈现出体重逐渐减轻的情况，各实验组间无差异；然而，接受抗 EGFR 治疗的组活动能力更强。未观察到死亡率的差异。主要在未治疗组观察到胸腔积液体积和炎症标志物的暂时性增加。与正常组织相比，肿瘤中的 VEGF、EGFR 和 KRAS 基因表达上调。观察到 KRAS 基因第 2 外显子存在突变。
胸膜内给予抗 VEGF 和/或抗 EGFR 可减少胸腔积液的体积和炎症介质。抗 EGFR 和抗 VEGF + 抗 EGFR 可降低发病率，尽管对生存率无影响。LLC 肿瘤存在 KRAS 突变，这可能影响了这些治疗方法的效果。
