p73、p63和p53基因在人非小细胞肺癌组织中的表达

目的：探讨p73、p63和p53在非小细胞肺癌（NSCLC）的表达及与预后的关系。方法：免疫组化法测定93例NSCLCp73、p63和p53的表达并对其与年龄、性别、吸烟、病理类型、组织分化等因素进行统计学分析。结果：p53、p63和p73在正常肺组织表达阳性率分别为25％、25％和12．5％，在NSCLC的表达阳性率分别为65．6％、54．8％和71％，差异有显著性（P〈0．05）。p53表达阳性率与淋巴结转移相关（P〈0．05）；p63表达阳性率与肺癌的组织类型和淋巴结转移有关（P〈0．05）；肺鳞癌组织p63随分化程度降低表达增强（P〈0．05）。结论：p53、p63和p73均参与了NSCLC的发展、浸润和转移，可作为了解NSCLC的生物学行为和判断预后的指标。     

非小细胞肺癌Bcl-2、PCNA表达的临床研究

目的：探讨Bcl-2(B细胞淋巴瘤／白血病－2）和PCNA（增殖细胞抗核抗原）在非小细胞肺癌中发生、发展中的作用以及Bcl-2表达＋PCNA过表达与淋巴结转移的关系。方法：应用免疫组化方法检测40例非小细胞肺癌Bcl-2和PCNA的表达，并研究该表达和肿瘤组织学类型、分化程度、TNM分期、既往慢性支气管、肺病病史等病理学特征之间的关系，以及Bcl-2表达＋PCNA过表达复合出现与淋巴结转移的相关性。结果：①Bcl-2和PCNA在非小细胞肺癌中的阳性表达率分别为35％（14／40）和755（30／40），其阳性率因TNM分期和组织分化程度的不同而不同；②Bcl-2和PCNA表达与鳞癌TNM分期显著相关（P＜0.05)；③PCNA表达与组织学类型，既往病史（慢性支气管、肺病病史）相关（P＜0.05)。④中分化－高分化肿瘤与低分化肿瘤的Bcl-2与PCNA的阳性表达率差异无显著性。⑤Bcl-2表达＋PCNA过表达复合出现，与淋巴结转移无关。结论：评估非小细胞肺癌Bcl-2、PCNA的表达情况有助于判断病人的预后，为进一步研究该类肿瘤的发生和发展，提供必要的理论依据。     

三维适形放疗联合深部热疗对局部晚期非小细胞肺癌的疗效研究

目的：探讨三维适形放疗联合深部热疗对局部晚期非小细胞肺癌的疗效及预后影响。方法选取2012年6月—2014年6月该院收治的111例局部晚期NSCLC患者为研究对象,采用随机抽样法分成联合组（A 组,n=56）和对照组（B 组,n=55）两组。 B 组给予单纯三维适形放疗方案,A 组则在上述基础上联合深部热疗方案进行治疗。比对近期治疗效果及不良反应发生情况,行为期一年随访,记录患者KPS 评分结果差异。结果①治疗后A组近期治疗有效率为62.5%,随访期内生存45例,死亡11例,生存率为80.4%,B 组近期治疗总有效率为38.2%,随访期生存率为54.6%,两组就近期疗效及随访生存率对比而言差异有统计学意义（P＜0.05）;②治疗后,A组KPS评分增高45例,稳定8例,降低3例,生存质量改善率为80.4%,明显高于B组的54.6%,差异有统计学意义（P＜0.05）;③治疗后,A组白细胞降低率为37.5%,放射性肺炎发生率为30.4%,放射性食管炎发生率为17.9%,皮肤反应发生率为16.1%,均同B组对比差异无统计学意义（P>0.05）。结论对局部晚期NSCLC 患者予以三维适形放疗联合深部热疗方案,临床疗效显著,可有效改善患者生活质量,值得推广使用。     

以奈达铂为主联合方案治疗非小细胞肺癌的临床观察

目的:观察3种含奈达铂联合化疗方案治疗中晚期非小细胞肺癌(NSCLC)的短期疗效及毒副反应.方法:应用含奈达铂联合化疗方案治疗20例非小细胞肺癌.化疗2周期后按WHO标准进行评价.结果: 入组20例均可以进行疗效评价, 其中完全缓解2例,部分缓解7例,稳定12例,进展1例.总有效率45.0%.毒副作用以骨髓抑制为主,但Ⅰ～Ⅱ度占多数,其中白细胞下降发生率85.0%,Ⅲ～Ⅳ度为35.0%;血小板下降为40.0%,Ⅲ～Ⅳ度为25.0%,经相应处理均可恢复,并不影响下一周期的化疗.未出现严重的肝肾功能损害的现象.胃肠道反应均为Ⅰ～Ⅱ度.结论:以奈达铂为主的3组联合化疗方案经临床初步观察有一定疗效且毒性患者可耐受,但应进一步观察研究奈达铂联合方案对NSCLC的生存率的影响.     

紫杉醇联合顺铂双周和周疗法治疗晚期非小细胞肺癌的疗效比较

目的:比较和评价紫杉醇联合顺铂双周和周疗法治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒副反应.方法:经病理和细胞学证实的60例Ⅲ、Ⅳ期NSCLC患者随机分为两组.双周疗法组30例:紫杉醇 80 mg/m2 ,顺铂 40 mg/m2, iv gtt d1、d8,第21天重复;周疗法组30例:紫杉醇 40 mg/m2,顺铂 30 mg/m2 iv gtt d1、d8、d15,第28天重复.测定给药后 3 h、12 h、24 h 的血药浓度,并评价经化疗2周期后的疗效和毒副反应.结果:双周疗法和周疗法的有效率分别为40.0%和36.7%,无统计学上的差异,但双周疗法的毒副反应发生率较低.结论:紫杉醇联合顺铂双周方案治疗晚期NSCLC较周疗法更为经济安全有效.拟增加病例数做进一步深入研究.     

Prognostic value of thoracic tumor staging and volume parameters in non-small cell lung cancer patients with synchronous solitary bone metastasis

BackgroundNon-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis are a heterogeneous population. The analysis and evaluation of NSCLC patients with synchronous solitary bone metastases by cTN stage (thoracic tumor staging) and volume parameters have not yet been studied. The purpose of this study is to estimate the prognostic value of cTN stage and volume parameters obtained by fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC patients with synchronous solitary bone metastasis.MethodsA total of 157 NSCLC patients with synchronous solitary bone metastasis were retrospectively analyzed. Patients’ cTN stage, metabolic tumor volume (MTV) parameters, and clinical data were collected. Kaplan-Meier survival analysis and a Cox regression model were performed to determine the association between each factor and overall survival (OS). Finally, time-dependent receiver operating characteristic (TDROC) curve analysis was used to assess the predictive capacity of the independent prognostic factors.ResultsKaplan-Meier survival analysis showed significant differences between subgroups in terms of cTN stage. The median OS of group I was 44 months, and the 5-year survival rate was 39.6%. In the multivariate Cox regression analysis, cTN stage, MTV of the whole body (MTVwb), and MTV of thorax (MTVtho) were significantly associated with patient OS, even after adjusting for other clinical factors. However, MTV of bone (MTVbon) was not found to be an independent prognostic factor. TDROC curve analysis showed that cTN stage, MTVwb, and MTVtho had good predictive capacity for NSCLC patients with synchronous solitary bone metastasis. Compared with cTN stage and MTVtho, MTVwb had obviously better predictive specificity and sensitivity for the 5-year survival rate [5-year area under the curve (AUC) of MTVwb =0.844 vs. cTN stage (P=0.035) vs. MTVtho (P=0.052)]. The best cutoff value of MTVwb was 33.05.ConclusionsThe results of this study confirmed that cTN stage, MTVwb, and MTVtho were independent prognostic factors of NSCLC patients with synchronous solitary bone metastases. These factors can be used for risk stratification of these patients. TDROC curve analysis indicated that cTN stage, MTVtho, and MTVwb had good performance for survival prediction.     

CD163、E-Cadherin在非小细胞肺癌肿瘤芽殖中的表达及意义

目的 探讨血红蛋白清道夫受体(CD163)、E钙粘附蛋白(E-Cadherin,E-Cad)在非小细胞肺癌(non-small cell lung cancer,NSCLC)肿瘤芽殖(Tumor Budding)中的表达情况及对预后的影响.方法 收集海口市人民医院手术切除经病理证实的NSCLC组织标本60例(其中鳞状细胞癌30例,肺腺癌30例),采用免疫组化法检测CD163、E-Cad在实体瘤、肿瘤芽殖(Tumor budding)及周围正常肺组织中的表达情况.结果 NSCLC肿瘤芽殖中CD163阳性率为55.0％(33/60)显著高于实体瘤的31.7％(19/60)和正常肺组织的0％(0/60),肿瘤芽殖中CD163阳性率与病理分级、淋巴结转移有关(P＜0.05).E-Cad在肿瘤芽殖中的阳性率33.3％ (20/60),明显低于实体瘤的51.7％(31/60)和正常肺组织的100％ (60/60).肿瘤芽殖中E-Cad与病理分级、淋巴结转移有关(P＜0.05).结论 NSCLC肿瘤芽殖中的CD163高表达、E-Cad低表达与临床预后有一定关系.     

CA-IX E-cadherin在非小细胞肺癌中的表达及临床意义

目的:探讨碳酸酐酶-IX( carbonic anhydrase-IX ,CA-IX)、上皮型钙粘蛋白( epithelial cadherin ,E-cad)在非小细胞肺癌( non-small cell lung cancer ,NSCLC)中的表达及其与临床病理特征的关系,并研究CA-IX与E-cad表达的相关性. 方法:采用免疫组化SP 法检测78例NSCLC组织和20例正常肺组织中CA-IX、E-cad的蛋白表达情况. 结果:78例NSCLC组织中CA-IX和 E-cad 的阳性率分别为61.5%(48/78)和 26.9%(21/78),而正常肺组织中分别为0.0%(0/20)和 100%(20/20),差异均有统计学意义( P<0.05);NSCLC 组织中CA-IX和 E-cad 的表达与组织分化程度、TNM 分期和淋巴结转移显著相关(P<0.05);NSCLC中CA-IX与E-cad表达呈负相关(r=-0.352,P<0.05). 结论:CA-IX和E-cad在NSCLC的发展中扮演着重要角色,同时检测NSCLC患者癌组织中CA-IX和E-cad的表达可为临床早期判断侵袭和转移提供有力证据.     

ER-β在骨转移为首发的非小细胞肺癌中的表达

目的：检测分析骨转移为首发的非小细胞肺癌中ER-β的表达,分析其与临床预后相关性。方法应用免疫组织化学方法检测经病理证实骨转移为首发的非小细胞肺癌肿瘤组织标本中ER-β的表达,利用χ2检验检测组间表达差异,生存率单因素采用Kaplan-Meier法及Log-rank方法分析,多因素采用COX回归模型进行分析。结果46例骨转移为首发的非小细胞肺癌中ER-β总阳性78.3%,χ2检验未见性别、年龄、病理类型、骨转移灶数目、有无骨外其他部位转移、ALK及CEA影响ER-β表达,各组阳性率差异无统计学意义。多因素分析显示ER-β为影响该类患者预后的独立影响因素(P=0．035),单因素分析可见ER-β阳性表达组的生存时间明显长于阴性表达组,差异有统计学意义(P<0．05)。另外ER-β阳性表达时腺癌、单发骨转移患者能获得较长的生存时间,差异有统计学意义( P<0．05)。结论骨转移为首发的非小细胞肺癌 ER-β表达阳性率高, ER-β阳性表达的患者预后明显好于阴性患者,且其可能为影响患者预后的独立影响因素,ER-β的阳性表达可能与腺癌及单发骨转移患者的预后相关。     

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.