摘要
原发性支气管肺癌(primary bronchogenic carcinoma)简称肺癌(lung cancer),是当前世界各地最常见的恶性肿瘤之一,严重威胁人民健康,由于耐药常导致化疗失败,近年来关于化疗耐药与促/抗凋亡基因表达失衡关系的研究倍受关注,已成为发展迅速的基因靶点治疗基础研究中的热点,随着肿瘤耐药细胞株的建立以及分子生物学的发展,大量研究表明耐药肿瘤的遗传与生化特性发生了复杂的变化,众多机制参与肿瘤细胞耐药与恶性表型的形成。
在本课题的第一部分,我们主要应用Oligo GE Array细胞凋亡基因芯片检测人肺腺癌亲代与耐顺铂细胞(A549和A549DDP)凋亡相关基因谱的表达情况并分析其意义。结果显示A549DDP细胞表达BAD、BAG3(BCL-2凋亡调节基因家族中的促凋亡基因)、CARD8 (Caspase相关的招募域家族)、CASP6(Caspase家族)、TNFRSF14(肿瘤坏死因子受体超家族成员)、TRAF1、TRAF3(肿瘤坏死因子受体相关因子)、GADD45(修复蛋白)、CD70(TNF家族)、TRADD(凋亡因子)、BFAR(凋亡双向调节剂)较亲代A549细胞显著增高,二者比值上调2倍以上;A549DDP细胞表达BAG1、BAX、BCL2L2(BCL-2凋亡调节基因家族中的促凋亡基因)、XIAP(凋亡抑制蛋白)、CARD14、CARD6(Caspase相关的招募域家族)、CASP1、CASP4、CASP9(Caspase家族成员)、TNFRSF1B(肿瘤坏死因子受体超家族成员)、TRAF5(肿瘤坏死因子受体相关因子)、NOD2、NOD1(核苷酸结合寡聚化结构域)、DFFB(兔抗人DNA断裂因子)、BIRC8(凋亡抑制基因家族)、BNIP2 (BCL2/腺病毒E1B 19kd相互作用蛋白家族)、CIDEB(细胞死亡引导DFFA样效应因子)、CRADD (CASP2/RIPK1结构域死亡功能区)、TP53BP2(肿瘤蛋白P53结合蛋白2)、HRK基因较亲代A549细胞显著降低,二者比值下调2倍以上,说明这些基因参与肺腺癌细胞的凋亡抑制和细胞耐药的发生。
在本课题的第二部分,系统的回顾分析了我院呼吸科收治的肺及胸膜肿瘤所致的恶性胸腔积液病例的诊断和治疗特点。我们认为胸水细胞学检查简单易行,多次送检胸水可提高诊断率。对于胸水细胞学检查无法确诊的病例,可考虑应用胸腔镜手术获得诊断。中心静脉导管代替反复胸腔穿刺治疗恶性胸水,具有操作简单,损伤小,术后并发症少,导管护理及携带方便,患者耐受更持久等特点,且有利于反复留取标本和胸膜腔内给药,可提高疗效,缩短病程,在临床上应大力推广。高聚金葡素治疗恶性胸水有效率高,副作用小,可作为恶性胸腔积液治疗的理想药物。
Part I Expression and significance of apoptosis-related genes in parental and drug-resistant lung adenocarcinoma cell line
Objective To study the expression of drug resistance and apoptosis-related genes in A549DDP and the parental A549 cell line Method Expression of apoptosis- related genes was examined by Oligo GE Array Assay. Result The expression of BAD、BAG3、BFAR、CARD8、CASP6、GADD45、TNFRSF14、CD70、TRADD、TRAF1 and TRAF3genes were increased in A549DDP cells compared to A549 cells, but the expression of BAG1、BAX、BCL2L2、XIAP、BIRC8、BNIP2、CARD14、NOD2、NOD1、CARD6、CASP1、CASP4、CASP9、CIDEB、CRADD、DFFB、HRK、TNFRSF1B、TP53BP2 and TRAF5 genes were decreased in A549DDP cells compared to A549 cells. Conclusion This result suggests that the altered genes may play roles in anti-apoptosis and drug resistance in A549DDP cells
Part II Clinical Study of Malignant Pleural Effusion
Objective To summarize the clinical diagnosis and treatment of malignant pleural effusion in our hospital. Method To analyze retrospectively clinical data of 114 cases of lung cancer complicated with malignant pleural effusion in our hospital from 2006 to 2008, and evaluate the diagnosis and treatment. Result Pleural effusions from all patients were collected for detection of hydrothorax exfoliated cells. 110 cases have been confirmed, including 38 cases of pleural effusion that is the first inspection to find cancer cells, and the rest has been diagnosed through several times examination; 4 cases of pleural effusion has been confirmed through check-assisted thoracoscopic pleural biopsy.After exclusion of pleural effusion, pleural adhesion agent were injected into into the pleural space in 76 patients. 46 cases were injected with Highly Agglutinative Staphylococcin, total effectively rate for this group was 85.37%. Adverse event consisted of fever, which had been happened in 15 cases accounting for 32.6%), and chest pain, which had been happened in 10 cases accounting for 21.74%. 15 cases were injected with Corynebacterium parvum, total effective rate for it was 61.54%. Adverse reactions were fever, which was seen in 8 cases (53.33%), chest pain in 10 cases (66.67%), abnormal liver and kidney functions in 2 cases (13.33% ); 10 cases were injected with cisplatin, total effective rate was 50%, of which two cases had high fever (20%), eight cases had gastrointestinal reactions (80%), five cases had neutropenia (50%); In addition, 5 cases were injected with talc, during this group, total effective rate was 100%, all of the cases had high fever, severe chest pain. Conclusion According to the above clinical data and literature review, we conclude that the pleural fluid cytology is simple, many submitted to improve the diagnosis rate of pleural effusion. The case who can not be confirmed by Pleural fluid cytology could consider the application of video-assisted thoracoscopic surgery to diagnose. The closed drainage of pleural cavity with central venous catheter is easy to manipulate, with minor trauma, less post-operative complications, convenience in patients with activity and more durable. It is conducive to collecting specimens and repeated administration of pleural cavity, and can increase efficacy, shorten the course, should be used extensively in clinic. Highly Agglutinative Staphylococcin has better efficacy and less side effects in malignant pleural effusion, and can be used as an ideal treatment drug of malignant pleural effusion.
引文
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