循环肿瘤细胞数目与血清中Cyfra21-1、CEA、Fg表达水平的关系

目的:探讨肿瘤患者外周血循环肿瘤细胞(CTCs)与常用的肿瘤指标细胞角质素19可溶片段（Cyfra21-1）、癌胚抗原（CEA）及凝血功能指标纤维蛋白原（Fg）表达水平的关系,比较CTCs阳性组和阴性组转移灶数目差异。方法:采集66例进展期晚期肺癌住院患者治疗前7.5ml外周血,保存于4℃冰箱中,24小时内由益善生物技术公司使用“免疫去除结合纳米过滤法”行CTCs检测。同时检测血清中Cyfra21-1、CEA、Fg水平,收集并分析CTCs数目与转移灶数目、临床T分期、转移淋巴结的关系。结果:纳入患者中CTCs检出率为86.4%。CTCs数目与Cyfra21-1水平有相关关系,相关系数为0.365（P=0.003）;CTCs数目与Fg水平相关,相关系数为0.330（P=0.007）;CEA与CTCs两变量无明显相关性。两组患者的肿瘤转移器官数目大于3个的比例有显著差异。结论:两组患者Cyfra21-1异常增高率有显著差异,且CTCs数目与Cyfra21-1表达水平正相关,可由Cyfra21-1初步估计CTCs水平。而外周血中Fg异常增高率无显著差异,但二者表达水平呈明显正相关,因此分析CTCs数目需要考虑Fg表达水平的影响。     

血清人附睾蛋白4检测在非小细胞肺癌诊断中的临床意义

目的探讨血清人附睾蛋白4(HE4)对非小细胞肺癌(NSCLC)的诊断意义。方法选择2013年1月至2015年1月徐州医学院附属连云港医院进行手术治疗的96例NSCLC患者为观察组,另选同期96例健康体检者为对照组,检测两组血清HE4水平,比较手术前不同临床病理特征NSCLC患者血清HE4水平差异。以病理诊断为金标准,绘制血清HE4、血清癌胚抗原(CEA)、细胞角蛋白21-1(CYFRA21-1)对NSCLC诊断的ROC曲线。结果观察组患者手术前血清HE4水平显著高于对照组,差异有统计学意义(P<0.05),且显著高于手术后水平,差异有统计学意义(P<0.05)。手术前不同TNM分期的血清HE4表达水平差异有统计学意义(P<0.05),其中Ⅲ期患者HE4水平显著高于Ⅰ期和Ⅱ期患者,差异有统计学意义(P<0.05)。当血清中HE4、CEA和CYFRA21-1浓度分别为67.75 pmol/L和2.49 ng/ml,2.53 ng/ml时,对NSCLC有最大诊断价值,曲线下面积(AUC)分别为0.887,0.840和0.711。HE4检测灵敏度显著高于CEA和CYFRA21-1,差异有统计学意义(P<0.05)。结论与CEA和CYFRA21-1比较,血清HE4对NSCLC的诊断有较高的敏感性,对NSCLC早期诊断、疗效评估和病情监测具有重要价值。     

血清肿瘤标志物测定在肺癌诊断中的意义

目的分析血清肿瘤标志物测定在肺癌诊断中的意义。方法选取2011年2月至2013年6月间80例肺癌患者为研究组,80例肺部良性疾病患者为良性对照组,40例健康人群为健康对照组。比较血清肿瘤标志物CYFRA21-1、NSE、CA125和CEA检测结果。结果研究组CYFRA21-1、NSE、CA125和CEA水平显著高于良性组和健康组,差异有统计学意义(P<0.05)。其中CYFRA21-1、NSE、CEA分别在肺鳞癌、小细胞肺癌、肺腺癌中表达水平最高(P<0.05),CA125表达差异无统计学意义(P>0.05)。CYFRA21-1、NSE、CA125和CEA联合检测的灵敏度显著高于单项检测,差异有统计学意义(P<0.05)。结论血清肿瘤标志物CYFRA21-1、NSE、CA125和CEA的测定在肺癌诊断中具有重要价值,联合检测的灵敏度较高,辅助价值大。     

肺癌血清肿瘤标志物对肺癌早期诊断和治疗的临床意义

目的检测神经元特异性烯醇化酶(NSE)、血清癌胚抗原(CEA)、细胞角蛋白19片段抗原(cytokeratin 19 fragment antigen,CYFRA21-l)、糖类抗原-125(CA125)和糖类抗原-153(CA153)水平,探讨其在肺癌早期诊断和治疗中的临床意义。方法检测87例肺癌患者、50例肺部良性疾病患者和30例健康人血清中NSE、CEA、CA125、CYFRA21-1和CA153的水平。结果肺癌组血清中NSE、CEA、CYFRA21-1、CA125、CA153水平明显高于良性肺部疾病组和健康对照组,差异有统计学意义(P<0.01),而肺良性病变组和健康对照组血清中NSE、CEA、CYFRA21-1、CA125、CA153水平差异无统计学意义(P>0.05);复发组患者血清中NSE、CEA、CYFRA21-1、CA125、CA153水平明显高于未复发组,差异有统计学意义(P<0.01)。5项指标联合检测能明显提高肺癌诊断的敏感性,与单独各项指标敏感性比较差异具有统计学意义(P<0.01)。结论肺癌血清肿瘤标志物在肺癌早期诊断和治疗中具重要的临床价值,并且肿瘤标志物联合检测可以提高肺癌诊断的敏感性。     

肺癌患者化疗前后外周血肿瘤标志物水平变化的临床价值

目的 对肺癌患者化疗前后外周血内肿瘤标志物水平改变进行分析.方法 随机选取50例肺癌患者,给予紫杉醇类或联合顺铂方案化疗2个周期,采用放射免疫技术对不同病理类型组化疗前后外周血内肿瘤标志物CEA、NSE、CYFRA 21-1水平进行监测,并结合化疗前后肺部CT影像学变化分析化疗前各病理类型血清肿瘤外周血内肿瘤标志物水平.结果 50例患者经2个周期化疗后,行CT影像学检测评估,肿块PR+ CR者38例,NC+ PD者12例.化疗前,腺癌组血清CEA水平显著高于鳞癌组和小细胞肺癌组;鳞癌组CYFRA 21-1水平显著高于腺癌组和小细胞肺癌;小细胞肺癌组NSE水平显著高于腺癌组和鳞癌组,数据对比差异均具有统计学意义(P＜0.05).腺癌组(CR+ PR)化疗后CEA水平显著低于化疗前;鳞癌组(CR+ PR)化疗后CYFRA 21-1水平显著低于化疗前;小细胞肺癌组(CR+ PR)化疗后NSE水平显著低于化疗前,数据对比差异均具有统计学意义(P＜0.05).结论 通过检测外周血内肿瘤标志物CEA、NSE、CYFRA 21-1水平改变可用于化疗疗效判定,具有简便、经济的特点.     

肿瘤标志物与非小细胞肺癌病理分期的相关性

目的探讨肿瘤标志物与非小细胞肺癌病理分期的相关性。方法选取2013年2月至2014年12月间收治的150例非小细胞肺癌患者,其中T分期:T_1期79例,T_2期52例,T_3期16例,T_4期3例;N0期92例,N1期30例,N2期28例。对比在非小细胞肺癌N分期中淋巴结单组转移和多组转移情况,及T分期中肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段抗原(CYFRA21-1)和神经元特异性烯醇化酶(NSE)水平。结果血清CEA、CYFRA21-1水平随着病理N分期递增而提高,组间差异有统计学意义(P<0.05)。血清NSE浓度水平随着病理N分期递增变化不明显,组间差异无统计学意义(P>0.05)。血清CEA、CYFRA21-1水平随着病理N分期递增和淋巴结转移组增加而提高,组间差异有统计学意义(P<0.05)。血清NSE水平随着病理N分期递增和淋巴结转移组增加变化不明显,组间差异有统计学意义(P>0.05)。血清CEA、CYFRA21-1和NSE水平均随着病理T分期递增而提高,组间差异有统计学意义(P<0.05)。结论在非小细胞肺癌不同病理分期中,血清肿瘤标志物CEA、CYFRA21-1和NSE的水平存在较大差异,这对于非小细胞肺癌病理分期的准确判定具有重要的辅助诊断意义,值得在临床中推广肿瘤标志物CEA、CYFRA21-1和NSE的监测。     

硫氧还蛋白还原酶在肺癌治疗中的研究

目的探讨硫氧还蛋白还原酶(TrxR)在肺癌治疗中的表达及诊断价值。方法选取2013年1月至2015年12月青岛市胶州中心医院放疗科收治的80例肺癌患者为观察组,另选取医院同期健康查体者80名为对照组。检测比较两组空腹血清TrxR活性表达水平,分析TrxR在肺癌中的表达。结果肺癌患者血清中TrxR活性表达水平明显高于对照组,差异有统计学意义(P<0.05)。肺癌3种不同组织类型中,而鳞癌及腺癌者之间相比,差异无统计学意义(P>0.05),而小细胞肺癌与鳞癌、腺癌血清中TrxR活性表达水平比较,差异有统计学意义(P<0.05)。Ⅲ~Ⅳ期肺癌血清TrxR活性表达水平显著高于Ⅰ~Ⅱ期肺癌,肺癌伴有淋巴结及远处转移者TrxR活性表达水平明显高于无淋巴结及远处转移者。结论 TrxR活性水平与肺癌的发生、临床分期、转移等密切相关,充分地监测肺癌患者不同时期的血浆TrxR值,对临床诊疗有指导意义。     

血清癌胚抗原鳞状细胞癌抗原神经特异型烯醇化酶糖类抗原125与肺癌病理分型及临床特征的关系

目的探讨血清癌胚抗原(CEA)、鳞状细胞癌抗原(s SCC-Ag)、神经特异型烯醇化酶(NSE)、糖类抗原(CA125)水平与肺癌病理分型和临床特征的关系。方法采用罗氏E-70型电化学发光及免疫分析仪检测107例肺癌患者血清中CEA、SCC-Ag、NSE和CA125的水平,并探讨其与肺癌患者临床特征及肿瘤-淋巴结-转移(TNM)分期的关系。结果腺癌患者中血清CEA水平显著高于鳞癌及小细胞癌(P<0.05),鳞癌患者血清SCC-Ag水平显著高于腺癌及小细胞癌(P<0.05),小细胞癌患者血清NSE水平显著高于腺癌及鳞癌,血清CEA在腺癌患者中的表达水平与是否有远处转移、转移部位数量、TNM分期有关(P<0.05),SCC-Ag与转移部位数量有关(P<0.05),CA125与是否有远处转移有关(P<0.05);血清SCC-Ag在鳞癌患者中的表达水平与TNM分期有关(P<0.05);血清NSE在小细胞肺癌中的表达与是否有远处转移及TNM分期有关(P<0.05),CA125仅与是否有远处转移有关(P<0.05)。血清CEA与腺癌患者远处转移、转移部位数量及TNM分期呈正相关(P<0.05),SCC-Ag与腺癌患者的转移部位数量及鳞癌患者的TNM分期呈正相关(P<0.05),NSE与小细胞癌患者的远处转移及TNM分期呈正相关(P<0.05),CA125与腺癌及小细胞肺癌患者的远处转移呈正相关(P<0.05)。结论血清CEA、SCC-Ag、NSE、CA125水平与肺癌的临床特征及病理分型有关,4种肿瘤标志物联合检测有利于更加全面地评价肺癌患者的病情,值得临床重视。     

非小细胞肺癌患者化疗前后血清癌胚抗原细胞角蛋白19片段和糖类抗原125的变化

目的探讨晚期非小细胞肺癌(NSCLC)患者化疗前后血清癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和糖类抗原(CA125)的变化。方法选取2013年8月至2015年8月间辽宁省本溪市本钢总医院经病理以及细胞学诊断证实的NSCLC患者42例为研究组,化疗前采用酶联免疫法测定患者血清CEA、CYFRA21-1和CA125表达水平,化疗治疗结束3周后再次测定患者血清中CEA、CYFRA21-1和CA125表达水平变化,并行胸部CT检查,根据结果分为化疗有效者(完全缓解+部分缓解)和无效者(病情稳定+疾病进展)。选取同期来院体检的42例健康者为对照组,均排除肺部疾病,与研究组患者血清中CEA、CYFRA21-1和CA125水平变化进行比较。结果研究组患者化疗前血清CEA、CYFRA21-1和CA125水平分别为(38.78±10.37)ng/ml、(3.51±1.37)ng/ml和(37.22±15.39)U/ml,对照组患者分别为(1.86±0.47)ng/ml、(2.0±0.11)ng/ml和(20.1±15.7)U/ml,两组比较差异有统计学意义(P<0.05)。研究组患者化疗前血清CEA、CYFRA21-1和CA125在化疗有效组和无效组中无显著统计学意义(P<0.05)。化疗后血清CEA、CYFRA21-1和CA125在治疗有效组明显低于化疗前,有显著统计学意义(P<0.05);在无效组化疗后血清CEA、CYFRA21-1和CA125表达水平与化疗前相比差异不大,无统计学意义(P>0.05)。结论对临床NSCLC患者进行血清CEA、CYFRA21-1和CA125检测,可有效评估患者临床疗效及预后,为临床NSCLC化疗疗效提供标准依据。     

血清CEA、CYFRA21-1及TSGF在肺癌化疗前后的表达变化及意义

目的 探讨血清癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和肿瘤特异性生长因子(TSGF)在肺癌化疗前后的水平变化及疗效评估价值.方法 选取80例接受紫杉醇联合吉西他滨化疗的肺癌患者,应用电化学发光免疫分析技术和生化比色法,检测化疗前及化疗21天后患者血清中CEA、CYFRA 21-1和TSGF水平变化.结果 患者血清中CEA、CYFRA 21-1和TSGF的水平在紫杉醇联合吉西他滨化疗后显著降低,差异具有统计学意义(P<0.05).且患者血清中CEA、CYFRA 21-1和TSGF水平变化与紫杉醇联合吉西他滨的化疗疗效具有明显的统计相关性.结论 肺癌患者应用紫杉醇联合吉西他滨化疗可明显降低血清CEA、CYFRA 21-1和TSGF水平,说明CEA、CYFRA 21-1和TSGF在临床肺癌治疗效果的评估中具有重要的意义.     

Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo

Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade from low pH through changes in gene expression to functional properties of tumors in vitro and in vivo.Methods: In two experimental tumor lines the expression of 13 genes was tested under acidic conditions in combination with overexpression or downregulation of 4 pH-sensitive miRNAs (miR-7, 183, 203, 215). Additionally, the impact on proliferation, cell cycle distribution, apoptosis, necrosis, migration and cell adhesion were measured.Results: Most of the genes showed a pH-dependent expression, but only a few of them were additionally regulated by miRNAs in vitro (Brip1, Clspn, Rif1) or in vivo (Fstl, Tlr5, Txnip). Especially miR-215 overexpression was able to counteract the acidosis effect in some genes. The impact on proliferation was cell line-dependent and most pronounced with overexpression of miR-183 and miR-203, whereas apoptosis and necrosis were pH-dependent but not influenced by miRNAs. The tumor growth was markedly regulated by miR-183 and miR-7. In addition, acidosis had a strong effect on cell adhesion, which could be modulated by miR-7, miR-203 and miR-215.Conclusions: The results indicate that the acidosis effect on gene expression and functional properties of tumor cells could be mediated by pH-dependent miRNAs. Many effects were cell line dependent and therefore do not reflect universal intracellular signaling cascades. However, the role of miRNAs in the adaptation to an acidic environment may open new therapeutic strategies.     

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains

Summary A total of 22 surgical specimens, 16 astrocytomas with various malignancy, 3 brains adjacent to tumor and 3 brains with non-neoplastic lesion, was investigated immunohistochemically for the expression of thrombomodulin (TM). This membrane protein is localized on the vascular endothelium of nearly every human tissue and plays a crucial role in the maintenance of antithrombotic property of the endothelial cells. Although the normal cerebral vessels were negative for TM, the tumor vessels were positive for TM. The increased expression of TM was, however, demonstrated not only in glioblastomas but also in low-grade astrocytomas. Furthermore, the vessels in the brains adjacent to tumor and gliotic brains were also positive for TM. Those observations suggested that the tendency of intratumoral bleeding, which is rather characteristic of glioblastomas, is not simply explained by the altered expression of vascular endothelial TM. In two cases of glioblastoma, not only the blood vessels but also the tumor cells were positive. Considering the mitogenic activity of thrombin, a ligand for TM, the increased expression of TM might be related to the tumor neovascularization and also the tumor growth.     

The role of alcohol in oral and pharyngeal cancer in non-smokers, and of tobacco in non-drinkers

Data from a hospital-based case-control study of oral and pharyngeal cancer conducted in Northern Italy were used to analyse the risk associated with alcohol in non-smokers and with tobacco in non-drinkers. Out of a total of 336 cases (291 males and 45 females) and 1,652 controls (1,272 males and 380 females) 27 cases and 572 controls described themselves as lifelong non-smokers. Odds ratios (ORs) were 1.5 for 14-55 vs. 0-13 alcoholic drinks per week and 2.2 for 56 or over; the trend in risk was statistically significant. Among 19 cases and 213 controls who described themselves as non-drinkers, the ORs were 3.8 and 12.9 for smokers of less than 15 and greater than or equal to 15 cigarettes per day, with a highly significant trend. This study therefore confirms that tobacco has an independent role in the aetiology of oral and pharyngeal cancer, and suggests that alcohol may have an independent role as well, even where, as in Northern Italy, wine is its predominant source. Indeed, ORs were similar to those for tobacco and alcohol individually, each adjusted for the other factor, in the overall data-set.     

Nitrate and nitrite in saliva and urine of inhabitants of areas of low and high incidence of cholangiocarcinoma in Thailand

Cholangiocarcinoma is one of the main liver diseases in northeast Thailand. Associations with exposure to liver fluke and N-nitrosodimethylamine in formation of the tumour have been demonstrated in animals. This study was carried out to compare possible endogenous formation of N-nitroso compounds in inhabitants of areas with low and high incidences of cholangiocarcinoma by examining the levels of nitrate and nitrite in their saliva and urine. Thirty-two subjects (16 males and 16 females) living in the north-east (high incidence) and 12 volunteers (6 males and 6 females) in Bangkok (low incidence) were allowed to take regular meals, and their saliva and urine were collected before, and 30, 60 and 120 min after each meal. Nitrate and nitrite concentrations in saliva of the group in the high-incidence area were significantly higher than those of the group in Bangkok: salivary nitrate was 2-2.8 times higher and nitrite 2-5.6 times higher in the north-eastern group when compared with levels at each corresponding time interval in the low-incidence group. Nitrate levels in urine were also significantly higher in the north-eastern group at some time intervals, but urinary nitrite levels were similar and very low in both groups throughout the day. This finding may indicate a greater possibility of in-vivo formation of N-nitroso compounds in the north-east area than in Bangkok and might be associated with the occurrence of cholangiocarcinoma in north-east Thailand.     

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Background:

The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious.

Methods:

We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats.

Results:

The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented.

Conclusion:

The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.