Lewis X抗原表达与支架治疗的晚期直肠癌患者预后的相关性研究

目的 研究细胞粘附分子Lewis X抗原在金属支架治疗的晚期直肠癌患者癌组织中的表达状况及其与肿瘤侵袭、转移及患者预后的关系。方法 应用免疫组织化学催化信号放大法(CSA)和计算机图像分析技术,对30例支架治疗的晚期直肠癌患者活检标本进行Lewis X抗原表达和反应强度定量检测。结果 30例支架治疗的晚期直肠癌患者癌组织中共27例呈Lewis X抗原阳性表达,阳性率高达90.0％。阳性物质主要分布于癌组织腺管细胞膜、细胞浆和黏液腺癌的黏液糊内。图像分析,LewisX抗原阳性细胞平均积分光密度值在低分化腺癌中显著高于高、中分化腺癌和黏液腺癌(P<0.01),有淋巴结转移者显著高于无淋巴结转移者(P<O.01),1年内死亡病例显著高于生存病例(P<O.01)。结论 Lewis X抗原表达阳性率和反应强度与晚期直肠癌侵袭程度、淋巴结转移状况和患者生存期密切相关,对于判断其恶性程度、预测生物学行为和评估支架置入后患者的预后具有一定意义。

食管鳞癌选择素P及其配体sialyl lewis A、sialyl lewis X的表达

目的:了解P-选择素及其配体sLeA、sLeX在食管癌组织及区域淋巴结中的表达,探讨其与食管癌侵袭转移的关系。方法:应用组织芯片技术结合免疫组化检测食管鳞癌86例及其淋巴结P-选择素和sialy lewis A(sLeA)、sialylewis X(sLe X)的表达情况,并与16例正常食管鳞状上皮对照。结果:P-选择素在食管癌组织、正常食管鳞状上皮表达率分别为59.3%、12.5%(P<0.05),在转移淋巴结、非转移淋巴结中表达率分别为92.9%、31.3%(P<0.05)。sLeA在食管癌组织,正常食管组织中表达率分别为77.9%、6.25%(P<0.05),在转移淋巴结和非转移淋巴结中表达率分别为97.6%、20.3%(P<0.05)。sLe X食管癌组织、正常食管组织中表达率分别为15.1%、6.25%(P>0.05)。P-选择素和配体sLeA过度表达与食管鳞癌病理分级,TNM分期及淋巴结转移成显著相关性;而配体sLeX在食管癌组织中无过度表达。结论:P-选择素和配体sLeA在食管鳞癌组织、转移淋巴结中表达率明显升高,其与食管癌的侵袭转移有一定关系;配体sLeX与食管癌侵袭转移无关。

大肠癌唾液酸化Lewis X表达的临床意义

目的 :探讨大肠癌组织中细胞粘附分子唾液酸化LewisX表达状况与肿瘤发生、分化、转移及预后的关系。方法 :应用免疫组织化学催化信号放大法 (catalyzedsignalamplification ,CSA)和计算机图像分析技术 ,对 90例大肠癌原发癌灶、距肿瘤边缘 2cm的癌旁粘膜组织、远离癌组织 10cm以上的非癌大肠粘膜以及 5 1例转移淋巴结进行唾液酸化LewisX表达和反应强度进行比较 ,并对其中 5 3例患者进行随访。结果 :唾液酸化LewisX阳性物质在远离癌组织的非癌大肠粘膜中阳性率为 16 .7% (15 / 90 ) ,主要位于腺腔缘游离面 ;癌旁粘膜组织阳性率为 83.3% (75 / 90 ) ,主要位于细胞浆和 /或腺腔缘游离面 ;大肠癌组织中唾液酸化LewisX阳性表达率为 94 .4 % (85 / 90 ) ,主要分布于癌组织腺管细胞膜、细胞浆以及粘液腺癌的粘液湖内。转移淋巴结中唾液酸化LewisX阳性率为 96 .1% (49/ 5 1)。图像分析 :唾液酸化LewisX阳性细胞平均积分光密度值在低分化腺癌中显著高于高、中分化腺癌和粘液癌 (P <0 .0 1) ;有淋巴结转移者显著高于无淋巴结转移者 (P <0 .0 1) ;5年内死亡病例显著高于生存病例 (P <0 .0 1)。结论 :唾液酸化LewisX表达阳性率和反应强度对反映大肠癌组织发生发展、判断恶性程度、预测转移和评估患者预后具有重要意?

乳腺癌Lewis X和唾液酸化Lewis X表达研究

目的:研究Lewis X(LeX)和唾液酸化 Lewis X(sLeX)在乳腺癌组织中表达状况及其与肿瘤发生、分化、转移及预后的关系。方法:应用催化信号放大法(CSA)检测120例乳腺癌、71例转移淋巴结和30例远离癌组织的正常乳腺组织上皮细胞LeX和sLeX的表达状况。结果:LeX和sLeX阳性物质在远离癌组织的正常乳腺组织上皮细胞中阳性率分别为 70 .0%(21 /30)和 20 .0%(6 /30),而在乳腺癌组织中阳性率分别为81. 7%(98 /120)和86. 7%(104 /120),转移淋巴结标本中阳性率分别为66 .2%(47 /71)和88. 7%(63 /71)。结论:癌细胞膜Lewis糖抗原异常糖基的形成及其唾液酸化,可能与肿瘤转移行为有关。sLeX可以作为预测乳腺癌侵袭、转移的肿瘤相关抗原,对评估患者预后较 LeX具有更重要的临床意义。

唾液酸化Lewis X和p53在大肠癌中的表达及其与浸润转移的关系

目的 研究唾液酸化LewisX和 p5 3在大肠癌中的表达及其与肿瘤发生发展、浸润转移及预后的关系。方法 应用免疫组化微波 LSAB法检测 90例大肠癌中唾液酸化LewisX和 p5 3蛋白的表达状况。 结果 大肠癌组织中唾液酸化LewisX和p5 3表达阳性率分别为 92 .2 %和 5 7.8% ,唾液酸化LewisX与大肠癌的浸润和转移有关。结论 在大肠癌的发展及浸润、转移过程中唾液酸化LewisX和 p5 3表达具有相关性。对两者联合检测更有助于判断大肠癌发生、分化、浸润、转移和预后。

唾液酸化Lewis X和半乳糖凝集素-3表达与甲状腺乳头状癌浸润转移的关系

目的:探讨唾液酸化Lewis X (SLeX)和半乳糖凝集素-3 (Galectin-3)在甲状腺乳头状癌中的表达及其与癌组织浸润转移的关系。方法:应用免疫组化染色EliVisionTM plus两步法检测164例甲状腺乳头状癌组织和30例癌旁甲状腺组织中SLeX和Galectin-3的表达状况。结果:癌组织SLeX和Galectin-3总体阳性表达率分别为70.7%和92.1%,癌旁甲状腺组织SLeX和Galectin-3总体阳性表达率分别为6.7%和20.0%,两者在癌组织总体阳性表达率显著高于癌旁甲状腺组织(P <0.05)。有浸润患者SLeX和Galectin-3总体阳性表达率分别为84.8%和98.0%,无浸润患者分别为49.2%和83.1%,两者在有浸润患者中的总体阳性表达率均显著高于无浸润患者(P <0.05)。有淋巴结转移患者SLeX和Galectin-3总体阳性表达率分别为89.2%和96.8%,无淋巴结转移患者分别为46.5%和85.9%,两者在有淋巴结转移患者中的总体阳性表达率均显著高于无淋巴结转移患者(P <0.05)。癌组织SLeX与Galectin-3表达具有一定正相关性(r = 0.41)。结论:SLeX和Galectin-3在甲状腺乳头状癌组织中多数呈强阳性表达,两者与癌组织浸润转移密切相关。

Inhibition of Adhesion and Metastasis of HepG2 Hepatocellular Carcinoma Cells In Vitro by DNA Aptamer against Sialyl Lewis X

The sialyl Lewis X（SLe;） antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin（E-selectin）. The combination of SLe;antigen and E-selectin represents an important way for malignant tumor metastasis. In the present study, the effect of the SLe;-binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated. Reverse transcription-polymerase chain reaction（RT-PCR） and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels. The SLe;expression in HepG2 cells treated with different concentrations of SLe;-binding DNA aptamer was detected by flow cytometry. Besides, the adhesion, migration, and invasion of HepG2 cells were measured by cell adhesion assay, and the Transwell migration and invasion assay. The results showed that the FUT7 expression was up-regulated at both mR NA and protein levels in HepG2 cells. SLe;-binding DNA aptamer could significantly decrease the expression of SLe;in HepG2 cells. The cell adhesion assay revealed that the SLe;-binding DNA aptamer could effectively inhibit the interactions between E-selectin and SLe;in the HepG2 cells. Additionally, SLe;-binding DNA aptamers at 20 nmol/L were found to have the similar effect to the monoclonal antibody CSLEX-1. The Transwell migration and invasion assay revealed that the number of penetrating cells on the down-side of Transwell membrane was significantly less in cells treated with 5, 10, 20 nmol/L SLe;-binding DNA aptamer than those in the negative control group（P<0.01）. Our study demonstrated that the SLe;-binding DNA aptamer could significantly inhibit the in vitro adhesion, migration, and invasion of HepG2 cells, suggesting that the SLe;-binding DNA aptamer may be used as a potential molecular targeted drug against metastatic hepatocellular carcinoma.

大肠癌组织黏蛋白MUC2和sialyl lewis X联合表达的临床意义

目的探讨大肠腺癌组织粘蛋白MUC2和sialyl lewis X(sLex)的分型与临床各个病理参数之间的关系。方法应用免疫组织化学双染法对34例远切端大肠黏膜、18例大肠腺瘤及55例大肠腺癌组织进行粘蛋白MUC2、sLex检测。结果远切端大肠黏膜、大肠腺瘤及大肠腺癌中,黏蛋白MUC2阳性表达率分别为100%、94.4%和58.2%(P<0.01);sLex阳性表达率分别为5.9%、50.0%和80.0%(P<0.05)。根据MUC2和sLex在大肠腺癌中的表达把大肠腺癌分为四型:MUC2+/sLex+、MUC2+/sLex-、MUC2-/sLex+、MUC2-/sLex-。MUC2+/sLex+型与患者的性别具有相关性;MUC2+/sLex-型与淋巴结转移、Duke’s分期具有相关性;MUC2-/sLex+型与发生部位、分化程度具有相关性;MUC2-/sLex-型与大肠腺癌临床病理参数均不具有相关性。结论 MUC2的下调表达或sLex的上调表达可能参与了大肠肿瘤的发生及恶性转化,各型大肠腺癌不同程度与其分化、生物学行为相关,对临床上判断预后具有较大的意义。

膀胱移行细胞癌中血型抗原Lewis A和Lewis X表达

目的 探讨血型抗原LewisA和LewisX在膀胱移行细胞癌中的表达及其诊断应用价值。方法 采用免疫组织化学EnVision方法 ,测定血型抗原LewisA和LewisX在 83例膀胱移行细胞癌和 6 8例非肿瘤性移行上皮黏膜中的表达 ,并收集10例膀胱癌及 10例正常人的尿脱落细胞标本进行LewisX免疫染色。结果 LewisA和LewisX在膀胱癌中的表达阳性率分别为 81 9% (6 8/ 83)和 83 1% (6 9/ 83) ,非肿瘤黏膜中的表达阳性率分别为 5 2 9% (36 / 6 8)和 11 8% (8/ 6 8)。LewisA和LewisX的表达强度与膀胱癌的病理分级和临床分期无关 (P >0 0 5 ) ,但膀胱癌的LewisA和LewisX表达强度高于非肿瘤黏膜 (P <0 0 5 )。 2 0例尿脱落细胞标本中 ,8例膀胱癌LewisX表达阳性 ,正常人组全部阴性。结论 LewisA和LewisX可成为诊断膀胱移行细胞癌的参考指标 ,特别是LewisX 。

流式细胞术分析膀胱移行细胞癌中血型抗原Lewis X的表达

目的探讨血型抗原LewisX在膀胱移行细胞癌中的表达及其意义。方法应用流式细胞技术(FCM)对膀胱移行细胞癌组织和非肿瘤膀胱黏膜组织标本进行LewisX抗原的测定,结果用阳性细胞百分率表示,并结合临床资料分析LewisX抗原在膀胱移行细胞癌中的作用。结果LewisX抗原在膀胱移行细胞癌中的阳性表达为(52.58±22.69)%,在非肿瘤膀胱组织中的阳性表达为(24.38±4.97)%,两者间有显著性差异(P<0.01);LewisX的阳性表达在膀胱移行细胞癌的临床分期,病理分级中差异无统计学意义(P>0.05)。结论LewisX在膀胱癌中高表达对膀胱癌的诊断有一定的帮助,FCM可作为检测LewisX的一种快捷方法。

血型抗原Lewis A和Lewis X在膀胱移行细胞癌中的表达及其诊断价值

目的探讨血型抗原Lewis A和Lewis X在膀胱移行细胞癌中的表达及其诊断应用价值。方法病理标本取1981-2001年间复旦大学附属金山医院病理科的膀胱移行细胞癌标本,具有完整临床病理资料共83例及非肿瘤移行上皮标本68例。试剂选用Lewis A、Lewis X单克隆抗体,应用免疫组化Envision二步法进行染色。并收集10例膀胱移行细胞癌及10例正常人的尿脱落细胞标本进行Lewis X免疫染色。结果Lewis A和Lewis X在膀胱移行细胞癌中的表达阳性率分别为81.9%(68/83)和83.1%(69/83),非肿瘤黏膜中的阳性表达率分别为52.9%(36/68)和11.8%(8/68)。Lewis A和Lewis X的表达强度与膀胱移行细胞癌的病理分级和临床分期无关(P>0.05),但膀胱移行细胞癌的Lewis A和Lewis X表达强度显著高于非肿瘤黏膜(P<0.05)。20例尿脱落细胞标本中,8例膀胱移行细胞癌Lewis X表达阳性,10例正常对照全部阴性。结论Lewis X免疫标记应用到膀胱移行细胞癌的尿脱落细胞学诊断上,为膀胱移行细胞癌早期诊断及随访提供一种可能的方法。Lewis A抗原对膀胱移行细胞癌诊断价值低于Lewis X。

血型抗原Lewis A和Lewis X在甲状腺乳头状癌中的表达

目的 :探讨血型抗原LewisA和LewisX在甲状腺乳头状癌中表达的意义。方法 :采用免疫组织化学EnVision方法 ,测定血型抗原LewisA和LewisX在 70例甲状腺乳头状癌和 70例癌旁正常甲状腺滤泡上皮 ,以及 16例甲状腺滤泡性腺瘤、17例结节性甲状腺肿和 14例桥本氏甲状腺炎中的表达。结果 :LewisA和LewisX在甲状腺乳头状癌中的表达阳性率分别为 94 3% ( 66/ 70 )和 85 7% ( 60 / 70 ) ,癌旁正常甲状腺滤泡上皮中的表达阳性率分别为 2 9% ( 2 / 70 )和 5 7% ( 4 / 70 )。肿瘤直径≥ 1cm组LewisX的表达强度较肿瘤直径 <1cm组明显增高 ,P <0 0 1。淋巴结转移组LewisX的表达强度较非转移组显著增高 ,P <0 0 1。结论 :LewisA和LewisX可作为诊断甲状腺乳头状癌的参考指标。

Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression:A Hypothesis

Cancer testis antigens（CTAs） are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation（XCR）,a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

IMMUNOHISTOCHEMICAL STUDY ON X ANTIGEN OF HBV (HBxAg) IN PRIMARY HEPATIC CARCINOMA

The specimens were from 110 patients with primary hepatic carcinoma. The formalin- fixed and paraffin-embedded sections were stained for HBxAg by ABC method and for HBsAg and HBcAg by PAP method. Of the 110 cases, 64 (58. 2%) showed HBxAg-positive reaction in tumor tissue, and 63 (78. 8%) of 80 cases displayed positive HBxAg in surrounding non-cancerous hepatic tissue. Among the 64 cases with positive HBxAg in tumor tissue, 15 (23. 4%) were associated with HBsAg and/or HBcAg, while in the 63 cases with positive HBxAg in non-tumor tissue, 45(71. 4%) were accompanied with HBsAg and/or HBcAg. These findings suggest a dose relationship between prlmay hepatic carcinoma and HBV infection. The high detection rate of HBxAg Indicates a very active expression of the Integrated HBV- DNA genome in the host cells. However, the action of HBxAg in pathogenesis of hepatocellular carcinoma remains to be further investigated.

唾液酸化Lewis X和选择素P对支架治疗晚期直肠癌的预后意义

目的 研究金属支架治疗晚期直肠癌组织中细胞粘附分子唾液酸化Lewis X和选择素P的表达与肿瘤转移及患者预后的关系。方法 应用催化信号放大法（CSA），对30例支架治疗的晚期直肠癌患者活检组织标本中唾液酸化Lewis X和选择素P表达进行免疫组织化学检测。结果 30例支架治疗的晚期直肠癌组织中唾液酸化Lewis X和选择素P的阳性表达率分别为93．3％和86．7％，并且具有较高的一致性。结论 联合检测唾液酸化Lewis X和选择素P，可以作为预测支架治疗后晚期直肠癌肿瘤转移及患者预后的一种有用指标。

Single-Chain Expression and Crystallization of an Antigenic C-Terminus in Complex with the Regulatory Domain of ER Aminopeptidase 1

Human endoplasmic reticulum aminopeptidase 1 (ERAP1) is one of two ER luminal aminopeptidases that participate in the final processing of peptide precursors and generates the N-termini of the MHC class I-restricted epitopes. In order to investigate the interactions of its binding site with substrate peptides, X-ray crystallographic analyses have been carried out to study structures of ERAP1 regulatory (ERAP1_R) domain in complex with antigenic peptides. Single-chain bimodular constructs with various antigenic peptides linked to the C-terminal end of ERAP1_R domain are designed to facilitate crystallization process of these complexes. These recombinant proteins have been purified and crystalized, and x-ray diffraction data of one crystal have been processed to a resolution of 2.8 . The crystal belongs to the space group P21, with unit cell parameters a =64.2, b = 66.8, c = 66.3 , β = 110.2°. A Refmac-refined omit map reveals a clear density for the antigenic peptide’s carboxylate-end that is in contact with the ERAP1 regulatory domain of neighboring molecule. Thus the single-chain bimodular constructs have provided an expedited approach to study sequence-specific interactions between the ERAP1 regulatory domain and antigen peptide’s C-terminal ends.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a leading cause of death from cancer worldwide.Tumor markers like carbohydrate antigen 19-9(CA 19-9)have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy.AIM To delineate the phenotype of normal CA 19-9 PDAC according to clinical features,disease staging and prognosis as compared with high CA 19-9 PDAC cases.METHODS We performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition.Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL.We performed a comparison between the two groups with regard to demographic and clinical data,biomarkers,tumor staging and 6-mo survival.RESULTS Altogether 111 patients were recruited with 29 having documented normal CA 19-9(<37 U/mL).In the CA 19-9 negative group of patients,20.68%had elevated levels of both CEA and CA 125,13.79%for CA 125 only whilst 17.24%for CEA only.The two groups had similar demographic characteristics.Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases(76.83%vs 55.17%),while smoking was slightly more prevalent in the latter group(28.04%vs 31.03%).Tumors over 2 cm were more frequently seen in the positive CA 19-9 group,reflecting a higher proportion of locally advanced and metastatic neoplasia(87.7%vs 79.3%).Sixmonth survival was higher for the negative CA 19-9 group(58.62%vs 47.56%).CONCLUSION Elevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology,high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases.CEA and CA 125 can be adjunctive useful markers for PDAC,especially in CA 19-9 negative cases.

prognostic significance of pretreatment serum carcinoembryonic antigen levels in gastric cancer with pathological lymph node-negative: A large sample singlecenter retrospective study

AIM To assess whether elevated serum carcinoembryonic antigen(CEA) is in the inferior prognosis for pathological lymph node-negative(p N_0) gastric cancer(GC) patients who underwent D_2 gastrectomy.METHODS About 469 p N0 GC patients,who received D^2 radical gastrectomy were retrospectively analyzed. The X-tile plots cut-off point for CEA were 30.02 ng/m L using minimum P-value from log-rank χ~2 statistics,and p N_0 GC patients were assigned to two groups: those more than 30.02 ng/m L(n = 48;CEA-high group) and those less than 30.02 ng/m L(n = 421;CEA-low group). Clinicopathologic characteristics were compared usingPearson's χ2 or Fisher's exact tests,and survival curves were so manufactured using the Kaplan-Meier method. Univariate and multivariate analysis were carried out using the logistic regression method.RESULTS The percentage of vessel carcinoma embolus(31.35% vs 17.1%) and advanced GC(T_(2-4b))(81.25% vs 65.32%) were higher in CEA-high group than CEA-low group. The CEA-positive patients had a significantly poorer prognosis than the CEA-nagetive patients in terms of overall survival(57.74% vs 90.69%,P < 0.05),and no different was found between subgroup of T category,differentiation,nerve invasion,and vessel carcinoma embolus(all P > 0.05). Multivariate survival analysis showed that CEA(OR = 4.924),and T category(OR = 2.214) were significant prognostic factors for stage p N0 GC(all P < 0.05). Besides,only T category(OR = 1.962) was an independent hazard factor in the CEA-high group(P < 0.05).CONCLUSION Those pretreatment serum CEA levels over 30.02 ng/m L on behalf of worse characteristics and unfavourable tumor behavior,and a poor prognosis for a nearly doubled risk of mortality in GC patients.

Hepatitis B virus markers in hepatitis B surface antigen negative patients with pancreatic cancer:Two case reports

BACKGROUND Hepatitis B virus(HBV)is a known carcinogen that may be involved in pancreatic cancer development.Detection of HBV biomarkers[especially expression of HBV regulatory X protein(HBx)]within the tumor tissue may provide direct support for this.However,there is still a lack of such reports,particularly in non-endemic regions for HBV infection.Here we present two cases of patients with pancreatic ductal adenocarcinoma,without a history of viral hepatitis,in whom the markers of HBV infection were detected in blood and in the resected pancreatic tissue.CASE SUMMARY The results of examination of two patients with pancreatic cancer,who gave informed consent for participation and publication,were the source for this study.Besides standards of care,special examination to reveal occult HBV infection was performed.This included blood tests for HBsAg,anti-HBc,anti-HBs,HBV DNA,and pancreatic tissue examinations with polymerase chain reaction for HBV DNA,pregenomic HBV RNA(pgRNA HBV),and covalently closed circular DNA HBV(cccDNA)and immunohistochemistry staining for HBxAg and Ki-67.Both subjects were operated on due to pancreatic ductal adenocarcinoma and serum HBsAg was not detected.However,in both of them anti-HBc antibodies were detected in blood,although HBV DNA was not found.Examination of the resected pancreatic tissue gave positive results for HBV DNA,expression of HBx,and active cellular proliferation by Ki-67 index in both cases.However,HBV pgRNA and cccDNA were detected only in case 1.CONCLUSION These cases may reflect potential involvement of HBV infection in the development of pancreatic cancer.