The diagnostic value of multiple tumor markers in malignantovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

Study on combined assay for serum tumor markers in patients,with hepatic carcinoma

INTRODUCTIONSince the hepatic solid-occupying lesion (HSOL) wasfound by both ultrasonoscopy (US) and computed tomography(CT).If the customary alpha-fetoprotin (AFP) standard fordiagnosis primary hepatic carcinoma is used,those cancerswith lower AFP concentration may miss the diagnosis.Onthe other hand,the use of the standard:AFP-positive(≥20μg/L)+HSOL=primary hepatocellular carcinoma(PHCC),may yield false positive results.In order to ele-vate both the preoperative and differential diagnosis levels forhepatic carcinoma,we assayed combindedly the preoperativelevels of serum AFP,carbohydrate antibody (CA) 19-9 andcarcinoembryonic antigen (CEA) in the patients with HSOL.

Multiple biomarkers of colorectal tumor in a differential diagnosis model:A quantitative study

AIM:To evaluate the multiple biomarkers of colorectal tumor and their potential usage in early diagnosis of colorectal cancers. METHODS:Multiple biomarkers (DNA contents,AgNOR, PCNA,p53,c-erbB-2) in 10 normal colorectal mucosae,37 colorectal adenomas and 55 colorectal cancers were analyzed quantitatively in the computed processing imaging system. Discrimination patterns were employed to evaluate the significance of single and multiple indices in diagnosis of colorectal cancers. RESULTS:The mean values of the analyzed parameters increased in order of the normal mucosa,adenoma and adenocarcinoma,and this tendency reflected the progression of colorectal malignancy.The parameters including DNA index,positive rates,densities of AgNOR,c-erbB-2,and p53, shape and density of nucleus were relatively valuable for diagnoses.Then a diagnostic discrimination model was established.The samples were confirmed with the model, the sensitivity rates in cancer group and adenoma group were 96.36% and 89.19%,respectively.The value of proliferating cell nuclear antigen (PCNA) in early diagnosis of colorectal cancers was uncertain. CONCLUSION:The quantitative evaluation of some parameters for colorectal tumor can provide reproducible data for differential diagnosis.The established diagnostic discrimination model may be of clinicopathological value, and can make the early diagnosis of colorectal cancer possible.

Combined measurement of serum tumor markers in patients with hepatocellular carcinoma

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The prognostic molecular markers in hepatocellular carcinoma

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma(ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450 K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1,CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

miR-93-5p/FOXJ2轴介导胃癌细胞的生物学功能

目的:评估miR-93-5p对胃癌细胞的调节和功能。方法:采用qPCR检测miR-93-5p在胃癌组织、胃癌细胞系中表达,MTT、克隆形成、Transwell实验检测miR-93-5p对胃癌细胞增殖、侵袭的影响,双荧光素酶报告基因实验检测miR-93-5p与FOXJ2的靶向关系。结果:miR-93-5p在胃癌细胞系和胃癌组织中表达升高,抑制miR-93-5p表达后胃癌细胞增殖和侵袭能力受抑。双荧光素酶报告基因检测显示,miR-93-5p mimic显著降低MKN28和MKN45细胞Wt-FOXJ2相对荧光素酶活性,FOXJ2为胃癌细胞中miR-93-5p的直接靶基因。结论:miR-93-5p靶向FOXJ2促进胃癌细胞的增殖和侵袭,miR-93-5p/FOXJ2轴可能是判断胃癌预后的生物标志物和治疗靶点。

术前测定血清CA125、CA199、CA724、CEA和GM-CSF在鉴别附件包块性质中的作用

探讨术前测定患者血清CA12 5、CA19 9、CA72 4、CEA和GM -CSF水平在鉴别附件包块良恶性质中的作用。方法 :74例附件包块患者术前 1周内采外周血 ,用固相免疫放射法测定各种肿瘤标志物浓度 ,并与术后组织学诊断比较。计算各标志物单独和联合应用诊断卵巢癌的相应诊断参数。结果 :( 1)CA12 5(临界值 70U/ml)鉴别卵巢肿瘤性质的敏感性和特异性分别为 85 71%和 82 61% ,CA19 9(临界值 30U/ml)分别为 4 2 86%和 73 33% ,CA72 4 (临界值 3 8U/ml)分别为 53 57%和 90 90 % ,CEA(临界值 5ng/ml)分别为 4 6 4 3%和 4 8 89% ;( 2 )联合应用肿瘤标志物 :CA12 5联合CA19 9的敏感性和特异性分别为 89 2 9%和 73 33% ;CA12 5联合CA72 4的敏感性和特异性分别为 89 2 9%和 75 56% ;CA12 5联合CEA的敏感性和特异性分别为 92 86%和 4 0 0 0 % ;( 3)如果去除 9例子宫内膜异位症 ,CA12 5、CA19 9、CA72 4和CEA的特异性分别增至 89 19% ,80 55% ,94 2 9%和4 7 2 2 %。结论 :此项研究应用的肿瘤标志物中以CA12 5最为敏感。将CA12 5临界值定为 70U/ml时诊断效果最佳。CA72 4的特异性最高 ,但诊断卵巢癌的敏感性低。CEA的诊断价值有限 ,GM -CSF则无价值。CA12 5与其他肿瘤标志物联合检测时诊断的特异性会部分丧失。?

P53 immunohistochemical scoring:an independent prognostic marker for patients after hepatocellular carcinoma resection

AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (【10% -, 10-30% +, 31-50% ++, 】50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P【0.05) and capsule (P【0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P【0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P【0.01), vascular invasion (RI 0.5271, P【0.01) and capsule (RI-0.8691, P【0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P【0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.

DNA ploidy and c-Kitmutation in gastrointestinal stromal tumors

AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.

不同病理分级腹膜假黏液瘤:^(18)F-FDG PET/CT双时相显像表现及血清肿瘤标志物水平

目的对比不同病理分级腹膜假黏液瘤(PMP)^(18)F-FDG PET/CT双时相显像表现及血清肿瘤标志物水平。方法回顾性分析31例经病理确诊阑尾来源PMP患者,根据病理结果分为低级别、高级别及高级别伴印戒细胞PMP。对比不同级别PMP^(18)F-FDG PET/CT常规和延迟显像表现,以及PET/CT检查前1个月内血清癌胚抗原(CEA)、糖类抗原(CA)125及CA 19-9水平。结果31例PMP包括14例低级别、12例高级别及5例高级别伴印戒细胞PMP。^(18)F-FDG PET/CT延迟显像中,低、高级别PMP病灶最大标准摄取值(SUV_(max))、病灶SUV_(max)与肝脏平均标准摄取值之比(SUV_(max)/SUV_(livermean))及PET-腹膜癌指数(PCI)均高于常规^(18)F-FDG PET/CT显像(P均<0.05);延迟显像中,高级别伴印戒细胞PMP病灶SUV_(max)、SUV_(max)/SUV_(livermean)和PET-PCI均与常规显像差异均无统计学意义(P均>0.05)。不同病理分级PMP患者之间,CEA、CA 125及CA 19-9水平差异均无统计学意义(P均>0.05)。结论不同病理分级PMP的^(18)F-FDG PET/CT双时相显像表现具有一定特征性,血清肿瘤标志物水平与PMP病理分级无明显相关。

Circulating tumor cell isolation:the assets of filtration methods with polycarbonate track-etched filters

Circulating tumor cells （CTCs） arise from primary or secondary tumors and enter the bloodstream by active or passive intravasation. Given the low number of CTCs, enrichment is necessary for detection. Filtration methods are based on selection of CTCs by size using a filter with 6.5 to 8 pm pores. After coloration, collected CTCs are evaluated according to morphological criteria. Immunophenotyping and fluorescence in situ hybridization techniques may be used. Selected CTCs can also be cultivated in vitro to provide more material. Analysis of genomic mutations is difficult because it requires adapted techniques due to limited DNA materials. Filtration-selected CTCs have shown prognostic value in many studies but multicentric validating trials are mandatory to strengthen this assessment. Other clinical applications are promising such as follow-up, therapy response prediction and diagnosis. Microfluidic emerging systems could optimize filtration-selected CTCs by increasing selection accuracy.

Research progress on circulating tumor cell detection in brain gliomas

Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.

CD5L在多种疾病中生物学功能的研究进展

CD5L主要由巨噬细胞分泌和表达,是一种重要的免疫效应蛋白,其主要的细胞表面受体CD36存在于多种细胞中(包括巨噬细胞、树突状细胞、内皮细胞、脂肪细胞、肝细胞、心肌细胞和上皮细胞等),CD5L可作用于多种类型的细胞和组织。目前国内外的研究发现,CD5L不仅可作为抗凋亡蛋白,还广泛参与了多种疾病的发生、发展、预后及治疗。因此,该研究对CD5L与各个疾病的关系进行了综述。

卵巢交界性肿瘤及Ⅰ期上皮性卵巢癌143例临床分析

目的:比较卵巢交界性肿瘤及Ⅰ期上皮性卵巢癌的临床病理特征,探讨鉴别于交界性肿瘤的早期上皮性卵巢癌的高危因素。方法:回顾性分析2002年11月至2010年5月于北京大学人民医院妇科诊治的143例卵巢交界性肿瘤(91例,borderline ovarian tumor,BOT组)和Ⅰ期上皮性卵巢癌患者(52例,epithelial ovarian carcinoma,EOC组),比较两组患者的临床病理特征。结果:BOT组患者发病年龄显著低于Ⅰ期卵巢癌患者[(41.16±14.95)岁vs.(50.90±14.37)岁,P<0.01],Ⅰ期卵巢癌患者中绝经患者占42.3%(22/52),有恶性肿瘤家族史患者占26.9%(14/52),均显著高于BOT组患者的23.1%(21/91,P=0.016)和13.2%(12/91,P=0.04)。术前阴道彩色超声检查提示两组间肿物大小差异无统计学意义,但卵巢癌组患者肿物实性部分明显大于BOT组(P<0.01)。两组间血清学肿瘤标记物(CA125,CA199,CP2,CEA)阳性率差异无统计学意义,但在CP2升高的患者中,Ⅰ期卵巢癌患者CP2值升高幅度显著高于BOT组(256.99 kU/Lvs.116.59 kU/L,P=0.028)。两组间肿物组织病理类型有显著不同,交界性肿瘤中以浆液性和黏液性肿瘤为主(90.1%,82/91),而Ⅰ期卵巢癌患者中浆液性和黏液性肿瘤仅占44.2%(23/52),但其他病理类型(如子宫内膜样癌、透明细胞癌和混合性上皮癌)比例明显增高(P<0.01)。结论:早期上皮性卵巢癌与卵巢交界性肿瘤虽临床表现相似,但早期卵巢癌患者的发病年龄、绝经与否、恶性肿瘤家族史、超声检查提示的卵巢肿物实性部分大小、血清学肿瘤标记物的升高幅度(特别是CP2的升高程度)以及组织病理类型均有别于交界性肿瘤,这些临床病理特征可能有助于临床医师在术前对两种疾病进行鉴别诊断。

TCF-4在肺癌中高表达并与肺癌的进展有关

背景与目的T细胞因子4(Tcellfactor4,TCF-4)是Wnt信号传导通路的重要分子,但其mRNA及蛋白在肺癌组织及细胞系中的表达情况和意义的相关研究较少。本研究的目的是检测TCF-4在肺癌组织和细胞系中的表达情况,并探讨其与肺癌的临床病理因素和生物学行为的关系。方法采用免疫组织化学(S-P法)检测120例肺鳞癌和肺腺癌患者及10例癌旁正常肺组织中TCF-4的表达;应用免疫荧光法检测肺癌细胞系及HBE(人正常支气管上皮)细胞系中TCF-4的表达水平及亚细胞定位;应用RT-PCR方法检测九种肺癌细胞系中TCF-4mRNA的表达水平。结果在120例肺鳞癌和肺腺癌组织标本中,96例为TCF-4高表达(80.0%),其中包括37例同时有细胞浆和核表达(30.8%)。TCF-4的高表达水平与患者的TNM分期正相关(P=0.022),10例癌旁正常肺组织无TCF-4表达。免疫荧光显示TCF-4蛋白在正常支气管上皮细胞系中表达极弱,而在肺癌细胞系中则出现明显的表达,主要定位于细胞核。TCF-4的mRNA在不同组织学类型的肺癌细胞系中的表达并不一致,巨细胞癌细胞系中相对较高,而腺癌细胞系中表达较低。结论TCF-4的高表达与肺癌的进展密切相关,有效抑制TCF-4在肺癌中的高表达可能成为肺癌治疗的新途径。

子宫颈癌干细胞的分离培养及生物学特性鉴定

目的:分离、培养子宫颈癌干细胞,并鉴定其生物学特性。方法:收集19例不同临床分期(ⅠA～ⅡB期)子宫颈癌患者的肿瘤组织,通过机械剪切、酶消化等方法处理后分离获得单个细胞,采用肿瘤细胞球培养液(tumor sphere medium,TSM)培养获得悬浮细胞球。收集悬浮细胞球形成细胞,通过有限稀释法观察该细胞的克隆形成能力,MTT法检测紫杉醇(paclitaxel)和多柔比星(adriamycin)对细胞的抑制率,荧光活性细胞分类仪(fluorescence activated cell sorter,FACS)检测细胞表面标志物,RT-PCR和Western印迹法检测干细胞、耐药基因及相关癌基因表达。裸鼠皮下接种分离获得的干细胞,观察其成瘤能力,并进行病理类型分析。结果:19例原代细胞经过10～15d培养,其中8例有悬浮细胞球形成,形成比例随肿瘤临床分期的提高而增加。细胞球形成细胞具有克隆形成能力。紫杉醇(100nmol/L)和多柔比星(100nmol/L)对其细胞的平均抑制率分别为(77.65±6.46)%和(48.00±7.15)%,差异有统计学意义(P<0.01)。FACS检测结果提示,细胞表面标志为CD34-CD105-CD44+CK17+;RT-PCR检测结果提示,细胞球表达干细胞标志Oct4和Piwil2,耐药基因ABCG2及相关癌基因c-myc、stat3和sox-2也有mRNA水平的表达;Western印迹法检测结果进一步提示,肿瘤细胞球表达干细胞标志Oct4和Piwil2蛋白。裸鼠皮下接种细胞12周后全部成瘤,且病理类型与来源标本一致。结论:成功分离获得子宫颈癌干细胞,为将来研究子宫颈癌个性化治疗及疗效评价提供了很好的研究模型。

大鼠肝癌诱导过程中肝癌干细胞标志及炎症因子的动态变化

背景:近年来已有研究者从肝癌组织和细胞系中发现了CD133、乙醛脱氢酶(ALDH)、CD90、CD44、Epc AM、CD13、OV6、K19、c-kit、ABCG2等多种肝癌干细胞的标志物,其中CD家族的CD133、CD90、CD44等被认为与肝癌的复发和转移密切相关。目的:探讨大鼠肝癌诱导过程中肝癌干细胞标志及炎症因子的动态变化及两者相关性。方法:应用二乙基亚硝胺(DEN)溶液饲养SD大鼠24周诱导大鼠肝癌模型,并设立普通水喂养的健康对照组。结果与结论:免疫组织化学检测显示,模型组肝癌诱导过程中Kupffer细胞相关ED2表达呈现出逐渐增多的情况,与健康对照组比较,模型组ED2在诱癌第12,16,20,24周的表达均显著升(P<0.05)。定量PCR检测显示,肝癌诱导过程中CD90呈逐渐上升趋势(P<0.05),较之健康肝脏组织,肝癌组织中CD90上升更明显(P<0.05);CD133呈现出一定升高趋势,但经单因素方差分析无统计学意义(P>0.05);在诱癌过程中其他肝癌干细胞标志物未出现明显改变(P>0.05)。肝癌诱导过程中,肿瘤坏死因子α、转化生长因子β、MCP-1及白细胞介素6均明显上升(P<0.05),较之健康肝脏组织,肝癌组织中转化生长因子β、MCP-1、白细胞介素6表达显著偏高(P<0.05),其余炎症因子在诱癌过程中则未出现明显改变(P>0.05)。经Pearson相关性分析,MCP-1、转化生长因子β、白细胞介素6与CD90的表达之间呈显著正相关(P<0.05)。表明Kupffer细胞所释放的部分炎症因子与肝癌干细胞标志之间存在一定的相关性,Kupffer细胞可促进肝癌的发生。

四项肿瘤标记物在肺癌中的表达及其相关因素分析

目的通过检测肿瘤标志物癌胚抗原(CEA)、细胞角蛋白l9片段21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)和血清铁蛋白(SF)在肺癌患者血清中的表达及其相关因素分析探讨CEA、CYFRA21-1、NSE、SF的临床应用价值。方法采用电化学发光免疫技术分别对39例体检健康人员和196例肺癌患者的血清标本进行CEA、CYFRA21-1、NSE、SF的含量检测。结果肺癌组血清与对照组相比均明显升高,差异有统计学意义(P<0.01);诊断效能ROC分析显示,CEA、CYFRA21-1、NSE和SF曲线下面积分别为0.824、0.734、0.809和0.787,对肺癌具有诊断意义(P<0.01);血清CEA、CYFRA21-1、NSE和SF四项联合检测阳性率81.6%,其中对肺腺癌为74.6%,肺鳞癌为91.3%,小细胞肺癌为75.5%,均高于单项检测及前三项联合检测。四项肿瘤标记物的表达与肺腺癌、肺鳞癌、小细胞肺癌、肝转移、骨转移等因素之间有不同的直线相关关系。结论四项肿瘤标志物联合检测有助于肺癌的诊断及病理类型鉴别,对其病程推断、脏器转移监测、预后等具有一定的临床价值。