非小细胞肺癌组织中DNA切除修复交叉互补基因1mRNA的表达及其对预后的影响

Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.     

非小细胞肺癌组织中DNA切除修复交叉互补基因1mRNA的表达及其对预后的影响

目的 探讨非小细胞肺癌(NSCLC)组织中DNA切除修复交叉互补基因1(ERCC1)的表达水平,及其对NSCLC患者预后的影响.方法 采用实时定量PCR技术检测60例NSCLC患者的癌组织及癌旁正常组织中ERCCI mRNA表达水平,采用Kaplan-Meier单因素与Cox多元回归进行生存分析.结果 NSCLC患者癌组织和癌旁相应正常组织中ERCCI mRNA的表达水平分别为-7.85 4±3.86和-11.194±5.03,差异有统计学意义(t=3.973,P=0.000).60例NSCLC中,ERCCI mRNA 高表达43例(71.6%),低表达17例(28.3%).Kaplan-Meier法生存分析显示,ERCCI mRNA高表达患者的生存率显著低于低表达患者(P=0.0003),淋巴结转移患者的生存率低于无淋巴结转移患者(P=0.026),有肿瘤家族史患者的生存率低于无肿瘤家族史患者(P=0.049),病理分级高的患者生存率低于病理分级低的患者(P=0.031).Cox回归分析结果显示,ERCCI mRNA表达水平、有无淋巴结转移、病理分级和是否吸烟是影响NSCLC患者术后生存的独立危险因素.结论 NSCLC组织中ERCCI高表达的患者术后生存时间较短.ERCCI mRNA表达水平、有无淋巴结转移、病理分级、肿瘤家族史和是否吸烟可作为评价NSCLC患者预后的参考指标.

Abstract：

Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.     

Expression of SKP2 protein in lung carcinoma

Objective： To study the expressive characteristics of SKP2 protein in lung carcinoma and its implication for prognosis. Methods： The expression of SKP2 protein was detected in 89 non small cell lung carcinoma, 13 small cell lung carcinoma, 10 lung benign lesion tissues by Tissue Chip and Immunohistochemistry technology. Results： The positive rate of SKP2 protein staining was （23.52±13.57）% in non small cell lung carcinoma and （53.85±12.26）% in small cell lung carcinoma, which were significantly higher than （2.91±1.27）% in lung benign lesion tissues. It was highest in small cell lung carcinoma and lowest in lung benign lesion tissues, with a significant difference between them （P=0.000）. The expressive level of SKP2 protein in lung carcinoma tissues was closely related to cell differentiation, lymph node metastasis and pathological types, but not to age, sex, smoking history, tumor site and size, and TNM staging. The survival analysis revealed that the 5-year survival rate of lung carcinoma patients was lower in SKP2 protein positive expression group than that in negative expression group （P1=0.003/0.002; r=-0.275, P2=0.005）. Conclusion. The positive expression of SKP2 protein is higher in lung carcinoma than in lung benign lesion tissues, in particular, much higher in small cell lung carcinoma. In lung carcinoma, its expressive level was closely related to cell differentiation, lymph node metastasis and pathological types. Moreover, it may be an independent factor to prognosis of patients with lung carcinoma.     

Clinical significance of the expression of inducible nitric oxide synthase in non-small cell lung cancer

Objective： To study the expressive characteristics of iNOS to the prognosis NSCLC patients. Methods： The expression in non-small cell lung carcinoma （NSCLC） and it＇s affection of iNOS was detected in 50 NSCLC tissues by Immunohistochemistry technology. Results： There was positive expression in NSCLC （positive rate 38.00%）. The expression of iNOS had a correlation with lymph node metastasis （P〈0.05）. There was no significant difference between positive expression of iNOS and lung cancer histological types, TNM stages, T stages （P〉0.05）. But the data suggested that there was a direct correlation between expression of iNOS and clinical prognosis （P〈0.05）. Conclusion： Positive expression of iNOS was observed in NSCLC, which correlated with postoperative survival time and lymph node metastasis. Although iNOS level had no significant relation with T stage, we find the positive rate in T2 stage was much higher than that in TI stage. The result suggested that positive expression of iNOS was related to bad clinical prognosis because of promoting tumor growth and metastasis.     

Expression of MMP-13 and its correlation with prognosis in non-small cell-lung cancer

Objective： To investigate the expression of MMP-13 in non-small cell lung cancer （NSCLC）, so as to analyze its correlation with prognosis of NSCLC. Methods： MMP-13 expression was detected in 99 NSCLC tissues and 32 normal lung tissues by immunohistochemical method. Results： （1） Expression of MMP-13 （51.5%, 51/99） in cancer tissues was significantly higher than that in normal tissues 0% （P 〈 0.05）. Expression level of MMP-13 was significantly related to lymph node metastasis and clinical stage （P 〈 0.01）. （2） Kaplan-Meier analysis showed that expression level of MMP-13 was closely cor- relate with the prognosis of NSCLC. Multivariate Cox model analysis suggested that the survival time was significantly related to clinical stage and the expression of MMP-13. Conclusion： MMP-13 is an independent factor that affect prognosis.     

DETECTING EXPRESSION OF MRP-1/CD9 mRNA IN LUNG CANCERS USING TISSUE MICROARRAYS AND FLUORESCENCE IN SITU HYBRIDIZATION METHODS

Objective： The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis and prognosis. Methods： To observe MRP-1/C9mRNA expression, tissue microarray （TMA） containing 54 lung cancers and 10 normal lung tissues was prepared and Fluorescence in situ hybridization was used. Results： The positive rate of MRP-1/CD9 expression was 48.1% in lung cancer, lower than that of normal lung tissues. The statistical difference was significant （P〈0.05）. Its protein expression had no relationship with the patients＇ ages, sex and the macroscopic type of tumor, but had relationships with the histological type, clinical stage, differentiated degree and metastasis. The expression in non-small cell lung cancer （NSCLC） was higher than that in small cell lung cancer （SCLC）; in well-moderately differentiated group was higher than that in poorly differentiated group; Earlier period group （I＋II） was higher than in later period group （Ⅲ＋Ⅳ）; and in group without lymphoid metastasis was higher than in patients with lymphoid metastasis. Conclusion： The progression of the lung cancer maybe related with the descended MRP-1/Cd9 expression, which may be useful in evaluating the prognosis of cancer patients.     

Elevated circulating levels of osteopontin are associated with metastasis in advanced non-small cell lung cancer

Objective:To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer(NSCLC).Methods:The expression of osteopontin mRNA were detected with RT-PCR technique.The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling.The tissues from fifteen patients with benign pulmonary diseases were studied as control group.Results:The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues(P<0.001).Over-expression of osteopontin mRNA was significantly associated with clinical stage(P=0.009).Advanced disease states had higher circulating level of osteopontin(stage I+II versus stage III+VI).In multivariate analysis,stage was the only independent factor influencing circulating levels of osteopontin.All patients were followed up for 12 months,2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis.There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.Conclusion:Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.     

Significance of the Expression of Rho-GDP Dissociation Inhibitorβ,γin Lung Squamous Cell Carcinoma and Adenocarcinoma

Objective:To study the expression of Rho-GDP dissociation inhibitor β,γ(Rho-GDIβ,Rho-GDIγ)in lung squamous cell carcinoma and adenocarcinoma and its relationship with the expression of RhoC(Ras homologus oncogenes C)and clinicopathologic parameters.Methods:Western blot assay was employed for Rho-GDIβ,Rho-GDIγ and RhoC in lung squamous cell carcinoma and adenocarcinoma and non-neoplastic lung tissues of 37 cases with fresh specimens.Results:The study showed that Rho-GDIβ,Rho-GDIγ and RhoC were expressed in lung cancer and non-neoplastic lung tissues,the level in lung cancer tissue was much higher than that in non-neoplastic tissues(P<0.001).In lung cancer,the expression of Rho-GDIβ was much higher in patients with lymph node metastasis(P=0.021),and the expression of Rho-GDIγ was much higher in poorly differentiated tumor than in well-differentiated and moderately differentiated tumor,but both of them were not correlated with other clinicopathologic parameters.The expressions of Rho-GDIβ and Rho-GDIγ were not correlated with the expression of RhoC.Conclusion:In lung cancer,Rho-GDIβ and Rho-GDIγ may play a role in the tumorigenesis,Rho-GDIβ may promote metastasis,and Rho-GDIγ may have some relationship with differentiation.     

Expression of heparanase and its clinical significance in human non-small cell lung cancer

Objective： To explore the expression and significance of heparanase in non-small cell lung cancer （NSCLC） regarding prognosis and clinicopathological parameters. Methods： The expression of heparanase was assessed using immunohistochemistry staining and Western blot in 122 paraffin-embedded specimens and 38 freshly taken tissues. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. Results： In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissue （78.7%, 96/122） while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissue （P=0.043）. Expression of heparanase significantly correlated with TNM stage （P=0.025）, lymphatic metastasis （P=0.002） and vascular invasion （P=0.0003）. The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression （P=0.0006）. In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion： Elevated level of heparanase in human non-small cell lung cancer tissues correlates with the TNM stage, invasion, metastasis and prognosis. However, heparanase expression is not an independent prognostic factor.     

EXPRESSION OF FRAGILE HISTIDINE TRIAD AND P53 IN NON-SMALL CELL LUNG CANCER

Objective： To investigate the expression offragile histidine triad （FHIT） and p53 protein in non-small cell lung cancer （NSCLC） and explore the relationship between their expressions and the clinicopathological features. Methods： FHIT protein and p53 protein were detected by immunohistochemistry in 76 cases of NSCLCs and matched normal lung tissues. Results： Fifty-one cases （67.1%） showed negative expression of FHIT （apparent reduction or loss） and thirty-seven cases （48.7%） showed p53 positive expression （overexpression）. The difference was significant （P=0.04）. However, there was no significant difference in FHIT expression between the p53-positive group and the p53-negative group （64.9% versus 69.2%, P=0.686）. The negative rate of FHIT protein expression was higher in squamous cell carcinoma than in adenocarcinoma, in moderately and poorly differentiated carcinoma than in well-differentiated carcinoma, and in cases with smoking history than in cases without smoking history （P〈0.05）. There was no relationship between FHIT expression and clinical stage or lymph node metastasis. The negative FHIT expression was not an independent predictor of overall survival （P=0.338）. Conclusion： The frequency of negative expression of FHIT protein is higher than that of positive expression of p53 in NSCLCs. The negative expression of FHIT is independent of the expression of p53. The change of expression of FHIT may play a role in the smoking related lung tumorigenesis while it may have no relationship with the progress of NSCLC or prognosis of the patients.     

食管平滑肌瘤10例临床治疗体会

我院１９７５年６月～１９９０年７月共收治食管平滑肌瘤１０例，占同期食管肿瘤总数的０．１９２％（１０／１０９２）。位于食管上段２例，中段５例，下段３例。Ｘ线食管钡餐造影是诊断本病的主要方法。行食管粘膜外肿瘤摘除９例，食管部分切除１例，效果良好。本文就其诊断与手术治疗进行了讨论。     

仙人掌原液毒性的初步研究

背景与目的： 研究仙人掌原液的毒性。 材料与方法： 小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验、大鼠30 d喂养试验。 结果： 仙人掌原液雌、雄小鼠LD50均大于20.0 g/kg,属无毒物质;Ames试验、微核试验和精子畸形试验结果均为阴性;大鼠30 d喂养试验结果显示该样品30 d喂养对大鼠各项观察指标未见毒性作用。结论： 在本次实验条件下,仙人掌原液为无毒物质,未显示有遗传毒性和亚急性毒性作用。     

Assessment of the degree of carcinogenicity of small doses of nitrites

Chronic experiments on CBA and C57B1 mice and acute experiments on CBA mice established: (a) carcinogenic effect of sodium nitrite given continuously with drinking water (0.1; 1.0 and 10.0 maximum allowable concentration) in combination with morpholine fed with bread, and (b) endogenous synthesis of nitrosomorpholine as a result of simultaneous intragastric administration of same doses of sodium nitrite and morpholine. Also, nitrosomorpholine and N-nitrosodimethylamine synthesis was observed in vitro following addition of low-dose sodium nitrite, morpholine and amidopyrine to human gastric juice. Carcinogenic hazard associated with low-dose nitrite consumption in humans is discussed.     

胰头癌手术切除可能性的术前评价

目的通过总结胰头癌病人的临床表现和影象学检查结果来评价手术切除的可能性。方法总结32例胰头癌病人的临床表现和CT、磁共振（MRI）检查结果,判断肿瘤是否已发生邻近浸润或远处转移,以此来评价其手术切除的可能性。结果在22例作CT检查的病例中,判断正确的为17例,准确率为77．3%。作MR检查9例,全部判断正确,准确率为100%。结论某些特殊的临床表现和CT、MR检查对判断肿瘤是否发生邻近浸润或转移有较大价值,为术前评价手术切除的可能性提供依据。     

仙人掌原毒性的初步研究

背景与目的:研究仙人掌原液的毒性。材料与方法:小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验、大鼠30 d喂养试验。结果:仙人掌原液雌、雄小鼠LD50均大于20.0 g／kg,属无毒物质;Ames试验、微核试验和精子畸形试验结果均为阴性;大鼠30 d喂养试验结果显示该样品30 d喂养对大鼠各项观察指标未见毒性作用。结论:在本次实验条件下,仙人掌原液为无毒物质,未显示有遗传毒性和亚急性毒性作用。     

Use of the data of quantitative analysis of organo-systemic distribution of tumors in the evaluation of real hazards of chemical carcinogens

The study was concerned with objective criteria for identification of actual carcinogenic hazards. It used quantitative analysis data on morphologic structures of tumors induced in 12565 albino noninbred rats in the course of carcinogenicity evaluation of 112 chemical agents. The totality of all the data were analyzed versus morphologic parameters of tumors and carcinogenicity of the agents. Spontaneous tumors turned to be the cause of death in animals treated with noncarcinogenic or slightly carcinogenic agents whereas a completely different spectrum of tumors were responsible for lethality in those receiving potent carcinogens. It was inferred that increased incidence of spontaneous tumors following treatment with maximum tolerable doses can not be used as a criterion of actual blastogenicity of an agent.