TRAIL在食道鳞癌及癌旁组织中的表达

目的 研究人肿瘤坏死因子相关凋亡诱导配体 (TNF relatedapoptosisinducingligand ,TRAIL)在食道鳞癌及癌旁组织中的表达及意义。方法 采用免疫组化S -P法 ,检测 42例食道鳞状细胞癌及其癌旁组织中TRAIL蛋白表达水平。结果 TRAIL在正常食道粘膜上皮、单纯增生、不典型增生、鳞癌组织中其阳性表达呈递减趋势 (P <0 .0 1) ;在Ⅰ、Ⅱ级鳞癌明显高于Ⅲ级和未分化鳞癌 (P <0 .0 1)。而在早期鳞癌和晚期鳞癌中的表达无差异 (P >0 .0 5 )。伴有淋巴结转移组和无转移组之间无差异 (P >0 .0 5 )。结论 TRAIL的表达可能与食道鳞癌的发生、发展密切相关 ;与食道鳞癌的分级呈负相关 ;与癌组织浸润深度和淋巴结转移无关。

环状RNAcirc-PDE3B对食道鳞癌细胞增殖和迁移的影响

目的:观察环状RNAcirc-PDE3B(circ-PDE3B)在食道鳞癌中的表达及对人食道鳞癌细胞株ECA109增殖、迁移的影响。方法:采用高通量测序方法检测食道鳞癌组织和癌旁组织中的环状RNA的表达; MTT法检测siRNA干扰circ-PDE3B表达后对食道鳞癌细胞增殖的影响;平板克隆实验、划痕实验检测siRNA干扰circ-PDE3B表达后对食道鳞癌细胞成瘤、细胞迁移的影响。结果:在食道鳞癌细胞中circ-PDE3B表达升高,siRNA干扰circ-PDE3B的表达可抑制食道鳞癌细胞ECA109的增殖和迁移。结论:在食道鳞癌中,干扰circ-PDE3B的表达可抑制肿瘤细胞的增殖和迁移。

食道鳞癌合并胃窦粘液腺癌1例

食道鳞癌合并胃窦粘液腺癌属多原发癌罕见．现报告1例如下：

热休克因子1调节PI3K/Akt通路对食道鳞癌细胞增殖的影响

研究热休克因子 1(HSF1),通过 PI3K/AKT 途径调节食道鳞癌细胞增殖的分子机制。方法 对35例食道鳞癌和癌旁组织中 HSF1 的表达水平进行了免疫组织化学检测。同时,研究HSF1 的表达水平与临床病理特征及预后的关联性,并针对食道鳞癌患者的临床病理数据展开进一步的研究。通过CCK8实验,对各组细胞的增殖能力进行检测;通过Westernblot实验,对PI3K/Akt通路相关分子的表达水平进行检测和评估,利用 HSF1SiRNA 转染食道鳞癌细胞系。结果 HSF1 在食道鳞癌组织和癌旁癌正常组织(P=0.038)的表达上存在差异,其癌变组织比正常癌旁癌组织更高;HSF1与患者性别、有无远处转移和肿瘤分期相关;Kaplan-Meier生存分析结果表明:HSF1 高表达的食道鳞癌患者的预后相对较差;将食道鳞癌细胞中HSF1 敲除后,明显抑制了食道鳞癌细胞的增殖;与正常食道鳞粘膜组织相比,食道鳞癌组织中HSF1、HSP90 和 P-AKT 的表达均显著升高。结论 食道鳞癌组织中HSF1的表达水平明显高于正常组织;HSF1的高表达与淋巴结转移和 TNM 分期存在正相关性,食道鳞癌患者中HSF1 表达水平高的患者,临床预后较差;通过激活 PI3K/AKT 通道,HSF1 可能会促进食道鳞癌细胞的增殖。

胃腺癌伴食道鳞癌1例报道

患者男性59岁,吞咽时噎感伴胸骨后隐痛二月余。上消化道钡餐：食道中段可见长约6cm管腔明显狭窄及不规则充盈缺损，粘膜破坏。胃体及胃窦部小弯侧可见向胃腔内生长的约4．5×3．5cm大小充盈缺损。缺损之阴影内可见不规则龛影。并可见“半月征”及“指压迹征”。X线印象：食道中上段癌。胃体、胃窦癌。纤维胃镜：距门齿33cm见粘膜增生性不规则息肉样改变并有菜花样改变。胃小弯胃体及胃窦部，可见较大范围菜花样改变，表面有坏死组织污秽分泌物,胃扩张度差、形态不规则。食管胃两处均取活检。病理诊断：胃腺癌、食管鳞癌。

食道鳞癌术后复发的临床病理特征与预后

目的研究食道鳞癌术后复发患者的临床及病理特征与总生存的关系。方法采用回顾性队列研究的方法,搜集53例食道鳞癌根治术后复发患者的15项临床及病理因素,应用Cox回归模型行生存分析,确定预后相关风险指标,构建预后评分。结果年龄>55岁、肿瘤长径>3 cm、淋巴结转移阳性、未行术后化疗、无病生存期<6个月以及复发时白蛋白<45 g/L为术后复发患者的预后不良指标,具备0-1个指标为低危组,2-3个为中危组,4个及以上为高危组,各个组别的总生存期差别有统计学意义(P<0.0001)。结论食道鳞癌根治术后复发患者的临床及病理特征可预测预后,指导患者的治疗随访。

食管鳞癌原位模型小鼠肠道菌群分析

背景随着肠道菌群高通量测序技术的应用与发展,越来越多的研究证实肠道菌群与多种肿瘤的发生、发展密切相关。食管鳞癌是威胁我国人民健康的常见肿瘤,其与肠道菌群的关系备受关注。目的分析比较食管鳞癌原位模型小鼠与正常小鼠肠道菌群的多样性,筛选出食管鳞癌特异性改变的菌属。方法2020年8月至2021年5月,将20只雌性SPF级C57BL/6小鼠适应性喂养1周后随机分为对照组(DZ组)和模型组(MX组),每组10只。DZ组小鼠常规喂养并给予普通饮用水32周,MX组小鼠按照造模方法常规喂养并给予含0.1 mg/ml诱癌剂4-硝基喹啉-1-氧化物(4NQO)的饮用水喂养16周,之后给予普通饮用水喂养至32周。收集两组小鼠粪便,提取DNA,应用聚合酶链式反应(PCR)扩增后进行高通量测序,获得的测序数据聚类成为基于序列间相似度的分类操作单元(OTU),并根据物种注释情况进一步分析Alpha多样性、Beta多样性、物种丰度。结果两组小鼠在实验过程中未出现死亡,MX组小鼠均造模成功。MX组与DZ组相比,拟杆菌门(Bacteroidota)及厚壁菌门(Firmicutes)比例升高,而疣微菌门(Verrucomicrobiota)及变形菌门(Proteobacteria)比例降低。Alpha多样性结果显示,MX组小鼠肠道菌群Shannon指数低于DZ组(P<0.05)。Beta多样性分析中PCoA图显示,MX组与DZ组样本分别聚集在不同的象限,相距较远,样本间多样性差异较大(t=22.444,P=0.004)。在门水平,MX组Unidentified_Bacteria、蓝细菌(Cyanobacteria)、易感微生物(Elusimicrobia)、弯曲杆菌(Campilobacterota)丰度高于DZ组(P<0.05)。在属水平,MX组普雷沃菌科_UCG-003(Prevotellaceae_UCG-003)、拟杆菌属(Bacteroides)、毛螺菌科NK4A136组(Lachnospiraceae_NK4A136_group)、瘤胃球菌属(Ruminococcus)、普雷沃菌科_UCG-001(Prevotellaceae_UCG-001)、普雷沃菌属(Prevotella)、大肠埃希菌(Colidextribacter)、毛螺菌科_UCG-006(Lachnospiraceae_UCG-006)丰度高于DZ组,罗姆布茨菌(Romboutsia)、土杆菌属(Turicibacter)丰度低于DZ组(P<0.05)。LEfSe分析结果显示,在属水平上,Prevotellaceae_UCG-003、埃希菌-志贺菌属(Escherichia-Shigella)、Bacteroides、Lachnospiraceae_NK4A136_group在MX组丰度增高(P<0.05);而Romboutsia丰度在DZ组增高(P<0.05)。结论食管鳞癌原位模型小鼠与正常小鼠相比肠道菌群物种多样性降低,存在特异性差异菌属,其中Prevotellaceae_UCG-003、Bacteroides、Lachnospiraceae_NK4A136_group和Romboutsia可作为食管鳞癌诊断的生物标志物。

周仲瑛治疗食道恶性肿瘤验案2则

南京中医药大学周仲瑛教授为全国首批国医大师，创复法大方治疗疑难杂症，屡起沉疴。笔者曾随侍左右，获益良多。现将周师治疗食道恶性肿瘤之验案2则介绍如下。 1 食道中下段鳞癌术后 案例1：患者，男，66岁，已婚，退休，2008年8月20日初诊。胸膈胀塞、吞咽困难半年。患者自2008年春节开始进食时吞咽困难，呈渐进性加重，经查诊为食道癌，2008年6月24日在某院行“食道中下段鳞癌根治术”，术中见胃左淋巴结转移2／2，因血小板低（30×10^9／L）而无法化疗。

MAD2基因沉默促进人食管鳞癌细胞系KYSE30细胞增殖和侵袭能力的实验研究

背景与目的:有丝分裂检测点缺陷可引起细胞染色体不稳定性而使细胞生物学行为改变,本实验探讨RNA干扰有丝分裂阻滞缺陷蛋白2(mitotic arrest deficient2,MAD2)基因表达对人食管鳞癌细胞系KYSE30细胞增殖和侵袭能力的影响。方法:利用脂质体转染的方法,将MAD2基因的siRNA转染食管鳞癌细胞KYSE30,并通过RT-PCR以及免疫印迹的方法进行siRNA效果鉴定。实验分为正常对照组、非特异干扰组、特异干扰组。MTT、克隆形成实验检测细胞增殖活性的变化,损伤刮擦实验和Transwell小室实验分别检测转染细胞株的迁移与侵袭能力。结果:siRNA作用48h组,MAD2蛋白的表达最低;相应地,迁移黏附能力增强,侵袭实验显示转染后细胞侵袭能力较转染前有显著加强。结论:MAD2基因沉默能够促进人食管鳞癌细胞系KYSE30的体外增殖和侵袭能力增强,并抑制凋亡,提示其变化对肿瘤的发生和转移发挥重要作用。

辅助放疗与单纯手术治疗pT_(2-3)N_(0)M_(0)期食管鳞癌临床价值的meta分析

目的比较根治性切除术后pT_(2-3)N_(0)M_(0)期的食管鳞癌患者辅助放疗对比单纯手术治疗的疗效与安全性。方法通过计算机全面检索Web of Science、Embase、PubMed、Cochrane Library、中国知网、维普网、中国生物医学文献数据库、万方等相关数据库,检索时限均从建库至2022年12月。根据纳入和排除标准进行文献筛选,采用RevMan 5.4软件进行meta分析。结果最终纳入8项包括2424例患者的临床对照研究资料。meta分析结果显示,术后辅助放疗与单纯手术相比,有较高的3、5年无瘤生存率(OR=2.33,95%CI为1.71~3.17,P<0.001;OR=2.38,95%CI为1.73~3.27,P<0.001)和3、5年总生存率(OR=1.89,95%CI为1.37~2.60,P<0.01;OR=1.94,95%CI为1.50~2.49,P<0.001),同时,术后辅助放疗组的局部复发率(OR=0.33,95%CI为0.21~0.50,P<0.001)及远处转移率(OR=0.62,95%CI为0.39~0.98,P=0.040)均低于单纯手术。术后放疗不良反应发生率报道了放射性食管炎发生率(1.4%~9.5%)、放射性肺炎发生率(2.1%)和吻合口狭窄发生率(5.3%)。结论对pT_(2-3)N_(0)M_(0)期食管鳞癌根治性切除术后患者,辅助放疗较单纯手术可提高3、5年无瘤生存率和3、5年总生存率,同时辅助放疗可降低局部复发率及远处转移率。因此,术后辅助放疗是pT_(2-3)N_(0)M_(0)期食管鳞癌可选的治疗方案。

食管肿瘤

9905865 在食管鳞状细胞癌中Bcl-2族:前凋亡成员Bar的表达/Sarbia M∥Int J Cancer.-1997,73(4).-508～513 津医情 9905866 超声内镜发现与食道或食道胃交界处肿瘤病人的后果间的关系/Hiele M∥Gastrointest Endosc.-1997,45(5).-381～386 湘医图 9905867 5种新建立的食管癌细胞株:表型和免疫学特性/Rockett J C∥Br J Cancer.-1997,75(2).-258～263

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls. METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPVA18 in the same samples using type-specific E6/E7 primers. RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P= 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P= 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P= 0.71). CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.

N-cadherin knock-down decreases invasiveness of esophageal squamous cell carcinoma in vitro

AIM： To examine the expressions of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithela, 31 adjacent atypical hyperplastic epithelia and 62 esophageal squamous cell carcinomas （ESCCs）, and to investigate the roles of N-cadherin in the invasiveness of ESCC cell line EC9706 transfected by N-cadherin shRNA.METHODS： PV immunohistochemistry was used to detect the expression pattern of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithelia, 31 adjacent atypical hyperplastic epithelia and 62 ESCCs. The invasiveness of ESCC line EC9706 was determined by transwell assay after EC9706 was transfected by N-cadherin shRNA.RESULTS： The positive rotes of N-cadherin decreased in the carcinoma, adjacent atypical hyperplastic and normal esophageal tissues （75.8%, 61.3% and 29.0%, P 〈 0.05）, respectively, while those of E-cadherin increased （40.3%, 71.0% and 95.2%, P 〈 0.05）. The increased expression of N-cadherin and decreased expression of E-cadherin were related to invasion, differentiation, and lymph node metastasis （P 〈 0.05）. The expression level of N-cadherin decreased in the N-cadherin knocked down cells, and the invasiveness of those cells decreased significantly as well. The number of cells which crossed the basement membrane filter decreased from 123.40 ± 8.23 to 49.60 ±6.80 （P 〈 0.05）.CONCLUSION： E-cadherin and N-cadherin expression is correlated with the invasion and aggravation of ESCC. The down-regulation of N-cadherin lowers the invasiveness of EC9706 cell line.

Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.

Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry(avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin(PRX)6 in 91 cases of esophageal cancer, tumoradjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo.RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend(P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age(P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues(P < 0.05).CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes(accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.

New magnifying endoscopic classification for superficial esophageal squamous cell carcinoma

To assess the accuracy of a new magnifying endoscopy (ME) classification for predicting depth of invasion of superficial esophageal squamous cell carcinoma (SESCC). METHODSThis study included a total of 70 lesions in 69 patients with SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of SESCC was analyzed by using a new ME classification proposed by the Japan Esophageal Society (JES), and interobserver agreement was assessed. RESULTSOverall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%. Sensitivity and specificity of type B1 for tumors limited to the epithelial layer (m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively. Sensitivity and specificity of type B2 for tumors invading into the muscularis mucosa (m3) or superficial submucosa (≤ 200 μm, sm1) were 94.4% and 73.1%, respectively, while those of type B3 for tumors invading into the deep submucosa (> 200 μm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was excellent (κ = 0.86, 95%CI: 0.76-0.95). CONCLUSIONThe recently developed JES ME classification is useful for predicting depth of invasion of SESCC, with reliable interobserver agreement.

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

AIM： To investigate the effect of endothelin-1 in the invasion of esophageal cancer and determine whethel cathepsin B plays a role in the course. METHODS： Western blotting was employed tc detect the expression of ET-1 protein in 75 sample., of esophageal squamous cell cancer and matched normal esophageal rnucosa. Bosentan, a dual ET （A/B）- receptor antagonist, was used to inhibit the binding of endothelin-1 and its receptors and cut down its biological role. In vitro matrigel invasion assays were made to show the invasive ability of esophageal cancer cells with and without bosentan. Subsequently, we evaluated cathepsin B activity and expression in EC9706 cell with and without bosentan. RESULTS： We found 74.7% （56/75） tumors had an overexpression of ET-1 protein by Western blotting. Bosentan significantly inhibited matrigel invasion of cancer cells in vitro. EC9706 cells have a positive expression of cathepsin B protein, and bosentan can down-regulate its expression and activity. CONCLUSION： Endothelin-1 may enhance the invasive ability of human esophageal cancer cells, and its role is correlated with cathepsin B.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.