食管鳞癌基因多态性表达与生存分析

目的:探讨食管鳞癌肿瘤组织中ERCC1、TYMS、TUBB3基因表达与预后生存的关系。方法:选择2012年9月至2016年5月我科收治的68例食管鳞癌患者,术后病理分期IIa-IIIa期;检测肿瘤组织ERCC1、TYMS、TUBB3 mRNA表达水平。术后患者分为个体化化疗组和标准化疗组,个体化组患者根据基因检测结果选择敏感药物化疗方案（CF/DCF/TC方案）进行化疗,标准组应用CF方案化疗,所有患者长期随访,统计化疗不良反应及生存数据。结果:肿瘤组织中ERCC1、TYMS、TUBB3阳性表达率分别为43%、47%、51%,无统计学差异（P＞0.05）。所有患者总一年生存率、两年生存率及三年生存率为分别为90.57%,72.45%和59.77%。生存曲线分析提示:0项基因阳性组预后最佳（P＜0.05）,而1项、2项和3项基因阳性组间无统计学差异（P＞0.05）。个体化化疗组的III/IV级化疗不良反应发生率明显低于标准化疗组（P＜0.05）。结论:食管鳞癌患者中ERCC1、TYMS、TUBB3表达具有特定的临床特征,其高表达患者预后欠佳。根据基因检测结果进行个体化化疗可以获得更好的疗效和耐受性,不良反应更轻。     

ERCC1、RRM1和p53表达与Ⅰ-Ⅱ期肺癌术后预后相关性分析

背景与目的 顺铂是肺癌化疗的基础药物,而EBCC1、RRM1、p53表达水平与铂类耐药和预后有关,本研究分析Ⅰ-Ⅱ期NSCLC的ERCC1、RRM1、p53表达与术后生存期的关系,探讨它们与患者预后及与顺铂耐药的相关性.方法 收集1992年2月-1994年1月有随访的75例Ⅰ-Ⅱ期NSCLC术后患者,Ⅰ期术后随机分成不化疗组和化疗组,Ⅱ期术后均作化疗,化疗采用以DDP为基础的方案.免疫组化法检测手术标本的ERCC1、RRM1、p53表达,并进行统计分析.结果 Ⅰ期ERCC1高表达患者预后明显好于ERCC1低表达,1、3、5年生存率分别为100.00%、91.30%、86.74%和96.43%、60.71%、57.14%(P=0.0058).Ⅰ期不化疔组ERCC1高表达者生存情况优于ERCC1低表达,中位生存期(MST)分别为72.00+个月和64.67个月(P=-0.0327).Ⅱ期与Ⅰ期相反,ERCC1低表达者预后好,ERCC1低表达者的MST为60.00+个月,而高表达者仅为25.50+月(P=0.0442).RRM1、p53表达与术后生存率无关.结论 ERCC1高表达是Ⅰ期NSCLC术后预后良好的独立指标;含DDP化疗延长了Ⅱ期ERCC1低表达患者的生存,术后可根据ERCC1的水平决定是否选用含DDP化疗;ERCC1表达对NSCLC术后生存期的影响在I期和Ⅱ期DDP化疗患者中可能不尽相同,ERCC1高表达在Ⅰ期NSCLC术后展现的是其保护的一面,而Ⅱ期以化疗抵抗为主.     

上皮性卵巢癌组织中TUBB3和ERCC1的表达

目的通过检测TUBB3和ERCC1在上皮性卵巢癌组织中的表达情况,探讨两者与上皮性卵巢癌化疗疗效及预后的关系。方法采用免疫组化技术检测25例正常卵巢组织和50例上皮性卵巢癌组织中TUBB3和ERCC1蛋白的表达情况。结果 TUBB3和ERCC1在上皮性卵巢癌组织中的阳性率明显高于正常卵巢组织（P〈0.05）,两者的阳性表达率与上皮性卵巢癌的分化程度及临床分期有关。上皮性卵巢癌组织中TUBB3和ERCC1蛋白表达呈正相关关系（r=0.332,P〈0.05）。TUBB3、ERCC1阳性表达患者化疗有效率分别为34.6%和31.4%,均明显低于阴性患者的91.7%和93.3%（P〈0.05）。结论上皮性卵巢癌组织中TUBB3、ERCC1的表达可能影响化疗疗效及其预后存,两者阳性表达可能提示上皮性卵巢癌化疗耐药,可作为上皮性卵巢癌化疗耐药和预后检测的重要指标。     

非小细胞肺癌中ERCC1的表达与新辅助化疗疗效之间的关系

背景与目的已有研究表明:肿瘤组织中核苷酸切除修复交叉互补组1(ERCC1)的阳性表达与铂类耐药密切相关,本研究探讨ERCC1在NSCLC中的表达及其与新辅助化疗疗效之间的关系。方法采用免疫组化法检测手术切除的73例NSCLC患者肿瘤组织中ERCC1的表达水平,其中33例接受含铂方案的新辅助化疗。采用χ2检验、Logrank分析和COX风险模型等分析ERCC1在NSCLC中的表达及其对新辅助化疗疗效的影响。结果ERCC1在NSCLC中的阳性表达率为34.25%。ERCC1的阳性率在新辅助化疗组(48.48%,16/33)要高于对照组(20.45%,9/40)(χ2=6.008,P=0.025)。ERCC1阳性组新辅助化疗客观缓解率31.3%,阴性组为58.8%(χ2=2.528,P=0.112);MST分别为36月和54月(P=0.118);3年生存率分别为43.8%和47.1%(χ2=0.029,P=0.866);5年生存率分别为18.8%和23.5%(χ2=0.414,P=0.520)。COX多因素回归分析结果显示:肿瘤组织中ERCC1表达水平、TNM分期和新辅助化疗与否是影响患者的预后因素。结论新辅助化疗可诱导NSCLC表达ERCC1,ERCC1高表达患者新辅助化疗客观缓解率低,ERCC1是影响该组患者预后的独立因素。     

ERCC1表达与Ⅲ期胃癌术后预后的关系

目的 探讨切除修复交叉互补基因(ERCC1)蛋白在Ⅲ期胃癌中表达及其与预后的关系.方法 采用免疫组化En Vision二步法检测477例Ⅲ期胃癌组织中ERCC1蛋白的表达情况,并分析其与预后的关系.结果 胃癌组织中ERCC1蛋白阳性表达率为67.1％(320/477).ERCC1阳性表达的320例患者中,化疗组中位生存期(MST)为30.9个月,5年生存率为30％;未化疗组MST为26.3个月,5年生存率为25％,差异无统计学意义(P=0.184).ERCC1阴性表达的157例患者中,化疗组MST为33.0个月,5年生存率30％;未化疗组MST为18.5个月,5年生存率为9％,差异有统计学意义(P=0.000).未行术后辅助化疗的131例患者中,ERCC1阳性表达者生存时间长于阴性者(P=0.034).Cox多因素分析显示,肿块大小、浸润深度、有无脉管神经受侵、淋巴结转移、化疗与否为胃癌的独立预后因素.结论 胃癌根治术后患者ERCC1阴性表达者可从含铂方案辅助化疗中获益;ERCC1阳性可能是预后良好的指标,但应用含铂药物化疗后患者似乎未能显著延长生存.     

Survivin、BRCA1及class Ⅲ β-tubulin在非小细胞肺癌组织中的表达及与紫杉醇耐药的关系

[目的]探讨Survivin、BRCA1及class Ⅲ β-tubulin蛋白在非小细胞肺癌(NSCLC)中的表达及与紫杉醇耐药的关系.[方法]应用免疫组织化学法检测64例NSCLC患者Survivin、BRCA1及class Ⅲ β-tubulin蛋白的表达;给予紫杉醇为基础的化疗方案,分析上述蛋白表达与紫杉醇化疗敏感性的关系.[结果]Survivin阳性与class Ⅲβ-tubulin阳性患者对紫杉醇方案治疗的有效率(RR)分别低于Survivin阴性患者(27.8％vs 71.4％,P＜0.05)与class Ⅲ β-tubulin阴性患者(23.5％ vs 73.3％,P＜O.01);而BRCA1阳性患者对紫杉醇方案治疗的RR高于BRCA1阴性患者(60.0％ vs 31.0％,P＜O.05).多因素分析表明class Ⅲ β-tubulin是NSCLC紫杉醇治疗无进展生存期(PFS)的独立影响因素(x2=4.852,P=0.027),分期是与总生存期(OS)相关的独立影响因素(x2=4.105,P=0.035).[结论]NSCLC患者Survivin、class Ⅲ β-tubulin蛋白表达阳性及BRCA1蛋白表达阴性预示对紫杉醇治疗相对不敏感.     

非小细胞肺癌EGFR、KRAS基因突变与RRM1、TUBB3 mRNA表达水平的相关性

目的:探讨非小细胞肺癌（NSCLC）EGFR、KRAS基因突变与核苷酸还原酶亚基M1（RRM1）、Ⅲ型β微管蛋白（TUBB3）mRNA表达水平的相关性及其临床意义。方法:69例NSCLC组织标本来自解放军空军总医院胸外科2010年6月至2014年10月手术中从肿瘤中心切取。使用xTAG-液相芯片法检测EGFR、KRAS基因突变,分支DNA-液相芯片法检测RRM1、TUBB3 mRNA表达水平。结果:在69例NSCLC组织样本中,28例为EGFR基因突变（40.6%,28/69）,13例为KRAS基因突变（18.8%,13/69）,EGFR基因突变与性别（P=0.005）、病理类型（P=0.036）、吸烟史（P=0.029）相关。KRAS基因突变与性别相关（P=0.007）。TUBB3 mRNA的表达水平与病理类型相关（P=0.008）,RRM1 mRNA的表达水平与患者各临床病理特征无关（P＞0.05）。EGFR基因突变与RRM1、TUBB3 mRNA表达水平无关（P＞0.05）,KRAS基因突变与RRM1 mRNA表达水平无关（P＞0.05）,KRAS突变型患者TUBB3 mRNA表达水平比KRAS野生型患者高（P＜0.05）。结论:在NSCLC患者中,EGFR及KRAS基因的突变状态对评估患者使用吉西他滨及抗微管类药物的疗效有重要意义,尤其在KRAS突变型NSCLC患者中,抗微管类化疗药物的疗效可能不佳,这有利于指导化疗药物方案的制定,促进NSCLC的个体化治疗。     

非小细胞肺癌组织ERCC1和RRM1基因表达及其对预后影响探讨

目的比较非小细胞肺癌（non-small cell lung cancer,NSCLC）患者原发灶与转移淋巴结中切除修复交叉互补基因1（excision repair cross-complementation group1,ERCC1）和核糖核苷酸还原酶M1亚基（ribonucleotidereductase subunit M1,RRM1）表达情况,探讨ERCC1和RRM1表达状态与NSCLC患者治疗效果及预后的关系,为NSCLC患者的合理治疗提供依据。方法选取山东省肿瘤医院外科六病区2008-08-01-2012-08-31行手术切除且术后病理确诊为NSCLCⅡA-ⅢA期的患者106例,所有患者术前均未接受任何针对肿瘤的治疗措施,均釆用免疫组化技术测定组织中ERCC1和RRM1表达状况,术后均采用长春瑞滨联合顺铂（NP方案）进行辅助化疗,并进行临床随访。结果 NSCLC癌组织及转移淋巴结中RRM1阴性表达患者中位无疾病进展时间分别为23.1和24.7个月,显著优于RRM1阳性表达患者的16.4和19.1个月,两组比较差异有统计学意义,P值分别为0.007和0.026;而ERCC1阴性表达患者中位无疾病生存期为17.5个月,与ERCC1阳性表达患者的19.4个月比较,差异无统计学意义,P=0.59。原发灶和淋巴结转移灶中ERCC1和RRM1的表达水平差异无统计学意义,P〉0.05。不同性别、分期及病理类型的NSCLC患者ERCC1及RRM1表达水平差异均无统计学意义,P〉0.05。结论 NSCLC患者癌组织及转移淋巴结中,RRM1基因表达情况可作为NP方案术后辅助化疗预后的重要指标。     

ERCC1和BRCA1与非小细胞肺癌完全切除术后铂类化疗及预后的临床研究

目的:探讨ERCC1和BRCA1在ⅢA-N2期非小细胞肺癌(NSCLC)中的表达及其与铂类药物辅助化疗的相关性,为NSCLC个体化辅助化疗提供依据.方法:免疫组化方法检测ERCC1、BRCA1在89例手术完全切除并行含铂辅助化疗的ⅢA-N2期NSCLC中的表达.应用统计学软件SPSS 16.0行数据处理,回顾性分析ERCC1和BRCA1的表达与临床、病理各因素及患者预后的关系.结果:ⅢA-N2期NSCLC中ERCC1和BRCA1阳性表达率分别为46.1%和59.6%.ERCC1和BRCA1的表达与铂类化疗明显相关,表达阴性者在含铂化疗组有更长的无瘤生存期(P=0.000,P=0.022)和总生存期(P=0.000,P=0.009).ERCC1和BRCA1表达均阴性者在含铂化疗组有更长的无瘤生存期(P=0.000)和总生存期(P=0.000).结论:ERCC1表达阳性、组织病理分化低、全肺切除是影响ⅢA-N2期NSCLC预后的危险因子.ERCC1和BRCA1的表达与铂类化疗相关,表达均阴性者预后较好.     

晚期非小细胞肺癌组织中切除修复交叉互补基因1和核糖核苷酸还原酶亚单位1表达与吉西他滨联合顺铂治疗的相关性研究

目的探讨核苷酸切除修复交叉互补基因1(ERCC1)和核糖核苷酸还原酶(RR)亚单位M1(RRM1)在Ⅳ期非小细胞肺癌(NSCLC))组织中的表达水平,分析其与吉西他滨联合顺铂(GP)方案化疗疗效的关系。方法采用液相芯片技术检测148例经过4个周期以上GP方案化疗的Ⅳ期NSCLC组织中RRM1和ERCC1的表达情况。结果Ⅳ期NSCLC组织中ERCC1的阳性率为47.3%,RRM1的阳性率为35.1%,与患者的性别、年龄及是否吸烟无关。ERCC1和RRM1低表达者接受GP方案化疗的效果均优于高表达者,两者差异有统计学意义(P<0.05)。此外,RRM1低表达的患者生存时间明显长于高表达者(P=0.004)。结论晚期NSCLC患者组织中ERCC1和RRM1mRNA的表达与GP方案化疗疗效及预后密切相关。     

GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population

Tobacco smoking and occupation are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Glutathione S-transferase (GST) M1, T1 and P1 are involved in the detoxification of PAH reactive metabolites. Two N-acetyltransferase isozymes, NAT2 and NAT1, have major roles in catalyzing the N-acetylation and O-acetylation of aromatic amines. Cytochrome p450 1B1 (CYP1B1) and sulfotransferase 1A1 (SULT1A1) are also involved in the metabolism of PAHs and aromatic amines. It is hypothesized that the genetic polymorphisms of these metabolic enzymes have an effect on the individual susceptibility to bladder cancer in particular by interacting with relevant environmental exposures. A hospital-based case-control study among men in Brescia, Northern Italy recruited 201 incidence cases and 214 controls from 1997-2000. Occupational exposures were blindly coded by occupational physicians. Genotyping of polymorphisms were carried out with PCR-RFLP method. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk. Effect modifications by age of onset, smoking and occupational exposures to PAHs and aromatic amines were evaluated. We also conducted an analysis of interaction between genetic factors. GSTM1 and GSTT1 null genotype were associated with an increased risk of bladder cancer with an odds ratio (OR) of 1.69 (95% confidence interval [CI] = 1.11-2.56) and 1.74 (95% CI = 1.02-2.95), respectively. The effect of GSTM1 null was seen particularly in heavy smokers, and there was a combined effect with occupational exposure of aromatic amines (OR = 2.77, 95% CI = 1.08-7.10). We observed a trend (p-value < 0.01) of increasing cancer risk comparing subjects with normal GSTM1 and T1 activity to subjects with one (OR = 1.82, 95% CI = 1.16-2.85) or both null genotypes (OR = 2.58, 95% CI = 1.27-5.23). NAT2 slow acetylator was associated with marginally increased risk of bladder cancer (OR = 1.50, 95% CI = 0.99-2.27), and the OR for the joint effect with occupational exposure of aromatic amines was 3.26 (95% CI = 1.06-9.95). SULT1A1 Arg213His polymorphism showed a marginal protective effect. These findings suggest that individual susceptibility to bladder cancer may be modulated by GSTM1, GSTT1 and NAT2 polymorphisms.     

Multiplex PCR with Confronting Two-pair Primers for CYP1A1 Ile462Val,GSTM1, GSTT1, and NQO1 C609T

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an effective genotyping method ‍for single nucleotide polymorphisms (SNPs) in aspects of reducing time and costs for analysis. So far we have ‍established PCR-CTPP conditions for tens of SNPs, including a triplex genotyping (Kawase et al., 2003). In the ‍present study we report a quadruplex PCR-CTPP to genotype simultaneously four functional polymorphisms of ‍carcinogen-metabolizing enzymes, CYP1A1 Ile462Val, GSTM1 null, GSTT1 null and NQO1 C609T, which were ‍reported that they have significant associations with smoking-related cancers. We applied this method for 475 health ‍check-up examinees to demonstrate the performance. Among the subjects, the genotype frequency of CYP1A1 ‍Ile462Val was 56.8% for Ile/Ile, 38.1% for Ile/Val and 5.1% for Val/Val. The null type frequencies of GSTM1 and ‍GSTT1 were 52.8% and 49.9%, respectively. And the genotype frequency of NQO1 C609T was 41.9% for C/C, ‍41.3% for C/T and 16.8% for T/T. Their distributions were similar to those reported for Japanese by other studies. ‍To the best of our awareness, this is the first paper that reports the success in quadruplex PCR-CTPP. The applied ‍polymorphisms are useful ones, which would be adopted not only for research purposes, but also for risk assessment ‍of individuals exposed to carcinogenic substances. This convenient genotyping would be applied for cancer prevention ‍especially in Asian Pacific regions, where expensive genotyping methods are hardly available.     

DNA切除修复交叉互补基因1、乳腺癌易感基因、核苷酸还原酶1与非小细胞肺癌

 阐述了近年来非小细胞肺癌（NSCLC）化疗敏感性与DNA 切除修复交叉互补基因1 （ERCC1）、乳腺癌易感基因（BRCA1）、核苷酸还原酶1（RRM1）基因表达关系的研究进展，分析3个基因对NSCLC个体化化疗潜在的指导意义     

CARMA1-BCL10-MALT1,NF-κB信号传导通路与淋巴瘤

CARMA1、BCL10和MALT1是NF-κB信号传导通路中重要的3种信号蛋白分子,也是淋巴细胞特异性的传导分子。这些信号分子的异常与多种淋巴瘤的发生有重要联系。本文综述了这些信号分子的生理和各种病理异常与不同类型淋巴瘤的发生机制的联系,以及目前对淋巴瘤靶向治疗的思路。     

Expression and prognostic role of pan-Ras, Raf-1, pMEK1 and pERK1/2 in patients with hepatocellular carcinoma

Aims

Ras/Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling cascades play important roles in the transmission of signals involved in apoptosis. Importantly, components of these pathways are aberrantly expressed in human cancer. However, there is limited data linking clinical outcomes with the aberrant expression of this pathway. The present study analyzed the prognostic values of pan-Ras, Raf-1, phosphorylated MEK1 (pMEK1) and phosphorylated ERK1/2 (pERK1/2) in hepatocellular carcinoma (HCC).

Methods

Expression of pan-Ras, Raf-1, pMEK1 and pERK1/2 in 81 HCC patients who underwent curative resection was examined by immunohistochemical staining. Long-term survival after resection of patients according to the expression of pan-Ras, Raf-1, pMEK1 and pERK1/2 was assessed using univariate analysis and multiple Cox proportional hazards model.

Results

In univariate analysis, patients with Raf-1 or pMEK1 overexpression had shorter disease-free survival (DFS) (P＜ 0.05) and poorer overall survival (OS) (P＜ 0.05) than groups with weak-expression of Raf-1 or pMEK1, respectively. Patients with pan-Ras overexpression had poorer overall survival (OS) (P＜ 0.05) than the group with weak-expression of pan-Ras. Importantly, Raf-1 overexpression was a promising prognostic marker for poor survival according to multivariate Cox regression analysis (DFS, Hazard Ratio 1.807, P = 0.035; OS, Hazard Ratio 1.959, P = 0.044).

Conclusions

Raf-1 overexpression could be considered as an independent prognostic biomarker in HCC and may predict early tumor recurrence and death for HCC patients. It can be used to stratify patients at higher risk for poor prognosis and help to select the appropriate therapeutic regime of HCC.     

Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.     

Methylation Profiles of BRCA1, RASSF1A and GSTP1 in Vietnamese Women with Breast Cancer

Objective: This study investigated the DNA promoter methylation profiles of BRCA1, RASSF1A and GSTP1 genes,both individually and in an integrative manner in order to clarify their correlation with clinicopathological parameters ofbreast cancer from Vietnamese patients, and establish new potential integrative methylation biomarkers for breast cancerdetection. Material and methods: The methylation frequencies of BRCA1, RASSF1A and GSTP1 were analyzed bymethylation specific polymerase chain reaction (MSP) in 70 specimens of breast carcinomas and 79 pairs of tumor andmatched adjacent normal tissues from breast cancer patients. Results: All the three analyzed genes showed a concordanceconcerning their promoter methylation in tumor and adjacent normal tissue. The methylation of BRCA1, RASSF1Aand GSTP1 was found in 58.23 %, 74.68 % and 59.49 % of tumor tissues and 51.90 %, 63.29 % and 35.44 % ofcorresponding adjacent tissues, respectively. When each gene was assessed individually, only the methylation ofGSTP1 was significantly associated with tumor tissues (p=0.003). However, the methylation frequency of at least one ofthe three genes and the methylation frequency of all the three genes both showed significant association with tumor(p=0.008 and p=0.04, respectively). The methylation of BRCA1 was found to be significantly associated with tumorgrade (p=0.01). Conclusion: This study emphasized that the panel of the three genes BRCA1, RASSF1A and GSTP1can be further developed as potential biomarkers in diagnosis and classification of breast cancer in Vietnamese women.     

Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy

Background

The aim of this study was to investigate prognostic value of excision repair cross-complementing 1 (ERCC1), BCL2-associated athanogene (BAG-1), the breast and ovarian cancer susceptibility gene 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3) in patients with non-small cell lung cancer (NSCLC) who received platinum- based adjuvant chemotherapy.

Methods

Messenger RNA expressions of these genes were examined in 85 tumor tissues and 34 adjacent tissue samples using semi-quantitative RT-PCR. The expressions of these five genes were analyzed in relation to chemotherapy and progression-free survival (PFS) and overall survival (OS). Seventy-four patients were enrolled into chemotherapy.

Results

Patients with ERCC1 or BAG-1 negative expression had a significantly longer PFS (P = 0.001 and P = 0.001) and OS (P = 0.001 and P = 0.001) than those with positive expression. Patients with negative ERCC1 and BAG-1 expression benefited more from platinum regimen (P = 0.001 and P = 0.002). Patients with BRCA1 negative expression might have a longer OS (P = 0.052), but not PFS (P = 0.088) than those with BRCA1 positive expression. A significant relationship was observed between the mRNA expression of ERCC1 and BAG-1 (P = 0.042). In multivariate analysis, ERCC1 and BAG-1 were significantly favorable factors for PFS (P = 0.018 and P = 0.017) and OS (P = 0.027 and P = 0.022).

Conclusions

ERCC1 and BAG-1 are determinants of survival after surgical treatment of NSCLC, and its mRNA expression in tumor tissues could be used to predict the prognosis of NSCLC treated by platinum.     

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphicgenes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which areinvolved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation inlung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northernIndian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lungcancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in thispopulation when compared with other populations (OR=1.87, 95%CI: 1.25-2.80–0.73, P=0.002). However, GSTM1null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Ourstudy showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1null polymorphism to have a link with non-smoking related lung cancer.     

大鼠放射性肺损伤进程中PAI-1、P21WAF1/CIP1、α-SMA和PCNA表达的变化及意义

目的探讨I型组织纤溶酶原激活物抑制剂(PAI-1)、P21WAF1/CIP1、α-平滑肌肌动蛋白(α-SMA)及细胞增殖核抗原(PCNA)在大鼠放射性肺损伤中表达的变化及意义。方法采用25Gy60Coγ射线全胸照射二级雄性Wistar大鼠60只,复制大鼠放射性肺损伤动物模型,分别于照射后1d,1w,1m和3m活杀取材,采用免疫组化SP法检测PAI-1、P21WAF1/CIP1、α-SMA和PCNA在该病进展过程中表达的变化并对前三者的积分光密度和PCNA胞核阳性细胞数定量分析。结果 PAI-1表达于支气管上皮细胞和平滑肌细胞、血管壁平滑肌细胞、成纤维/纤维细胞等间质细胞胞浆,照射后1m和3m表达显著增强,除上述部位外,还见于渗出区巨噬细胞胞浆。P21WAF1/CIP1表达于支气管上皮细胞和平滑肌细胞、血管平滑肌细胞、成纤维/纤维细胞等间质细胞、巨噬细胞胞浆,照射后1w、1m和3m阳性细胞减少,表达减弱。正常肺组织中α-SMA表达于支气管壁和血管壁平滑肌细胞胞浆,照射后1w和3m,除上述表达部位外,肺间隔内可见大量强阳性细胞。PCNA阳性细胞数(主要为成纤维细胞、巨噬细胞等)于照射后1m显著增加,照后3m增加至正常的6倍。结论 PAI-1、PCNA和α-SMA的表达随着放射性肺损伤病变进展而增强,表明成纤维细胞等细胞成分的增殖和活化在放射性肺损伤过程中发挥重要作用,提示上述指标有可能作为放射性肺损伤进程的标志物。