热休克蛋白70在食道鳞状细胞癌中表达及其可能对凋亡的调控

目的 研究热休克蛋白 70 (HSP70 )在食道鳞状细胞癌中的表达与意义 .方法 采用鼠抗人 HSP70单克隆抗体及免疫组织化学 SABC法 .结果 在 60例食道鳞状细胞癌中 ,HSP70表达 46例 (76.7% ) .HSP70在食道鳞状细胞癌 级中表达强于在食道鳞状细胞癌 级中的表达 (P<0 .0 5) .结论 HSP70在大部分食道鳞状细胞癌中有不同程度表达 ,HSP70可能参与食道鳞状细胞癌的凋亡调变 ;

Hedgehog信号通路分子在食道鳞状细胞癌中的表达及临床意义

目的:探讨Hedgehog信号通路分子Gli1、Hip、PDGFRα、Smo和Su(Fu)基因在食道鳞状细胞癌组织中的表达及临床意义。方法:应用原位杂交方法检测内蒙古医科大学附属医院胸外科2013年3月-2014年5月经手术切除、病理科确诊的12例食道鳞状细胞癌组织及距肿瘤边缘2 cm处经病理证实为正常组织的12例食管黏膜(阳性对照)中Hedgehog信号通路分子Gli1、Hip、PDGFRα、Smo和Su(Fu)基因的表达。结果:12例癌组织中,10例癌组织中均检测到Hedgehog信号通路分子Gli1、Hip、PDGFRα、Smo基因的表达,8例癌组织中检测到Hedgehog信号通路分子Su(Fu)基因的表达,而其在对照组中均未表达,两组比较差异均有统计学意义(P<0.05)。Gli1、Hip、PDGFRα、Smo及Su(Fu)基因的表达与患者的年龄、性别、组织学分级、临床分期无关,差异无统计学意义(P>0.05)。结论:Hedgehog信号通路在食道鳞状细胞癌组织中存在高表达,其可能作为肿瘤治疗的新靶点。

食道鳞状细胞癌组织及癌旁组织中sonic hedgehog和patched1的表达

目的在食道鳞状细胞癌和配对癌旁组织中检测sonic hedgehog（SHH）和patched1（PTCH1）的表达。方法选取内蒙古医科大学附属医院胸外科2012~2014年经手术切除、病理科确诊为食道鳞状细胞癌的标本共30例及其癌旁组织,应用免疫组织化学染色方法检测SHH和patched1的表达。结果在30例食道鳞状细胞癌组织中10例（33.3%）PTCH1阳性表达,肿瘤组织中未检测到SHH蛋白的表达,癌旁组织中未见两种蛋白的表达。PTCH1的表达与患者吸烟、饮酒,食道鳞状细胞癌的肿瘤分化、分期,淋巴结转移无关（P〉0.05）。结论 SHH的表达不是激活hedgehog通路的原因。

肺和食道鳞状细胞癌中P27基因蛋白的表达

目的:探讨肺和食道鳞状细胞癌中P27基因蛋白的表达状况。方法:收集手术切除鳞癌标本63例,10％中性甲醛固定,石蜡切片,厚度5μm。超敏型S-P免疫组织化学染色。结果:P27在鳞状细胞癌中总阳性率39.68％,在肺和食道中阳性率分别为36.00％和42.15％。在高、中分化组阳性率为36.00％,低分化组阳性率为53.85％。结论:鳞癌组织中P27阳性表达与分化程度及是否转移的相关性有深入研究的必要。

右胸和左胸入路在食道鳞状细胞癌治疗中的效果比较

目的评价经右胸和左胸入路行食道癌切除并食道颈部吻合术手术治疗中段食道鳞癌的效果。方法选取收治的胸中段食道鳞状细胞癌患者97例,均为单纯手术患者,且术前与术后均经病理学证实为食道鳞状细胞癌,按手术入路方式分为观察组与对照组,其中对照组42例采用经左胸入路,观察组55例采用经右胸入路,均行食道大部切除后颈部吻合。对比2组淋巴结清扫个数、切缘癌残留情况、手术时间、术中失血量、术后首日胸腔引流量、胸腔总引流量、胸腔引流时间、术后住院时间、术后并发症发生情况及术后生存期。结果 97例患者中,观察组55例患者中,54例肿瘤完整性切除,肿瘤切除率98.2%,术后未见1例切缘阳性。对照组42例中,40例患者肿瘤完整切除,肿瘤切除率95.5%,术后未见1例切缘阳性。2组患者肿瘤切除率、切缘阳性发生率比较,差异均无统计学意义(P>0.05)。观察组清扫淋巴结总数990个,术后阳性淋巴结236个,转移率23.8%,对照组清扫淋巴结总量504个,术后阳性淋巴结63个,转移率12.5%,差异有统计学意义(P<0.05)。2组患者手术时间比较,观察组患者手术时间明显长于对照组,差异有统计学意义(P<0.05)。观察组术后失血量明显高于对照组,差异有统计学意义(P<0.05)。但2组患者术后住院时间、首日胸腔引流量、胸腔引流时间比较,差异无统计学意义(均P>0.05)。2组患者并发症比较,肺不张、心律失常差异有统计学意义(P<0.05)。其他差异均无统计学意义(P>0.05)。2组患者5年生存期比较,观察组5年生存率为45.5%高于对照组的21.4%,差异有统计学意义(P<0.05)。结论采用右胸入路行食道癌切除联合胃食道颈部吻合手术,治疗胸中段食道鳞癌,在手术视野及淋巴结清扫上可能优于经左胸入路手术方式,术后5年生存率高;但对于为减少术后并发症的患者,经左胸入路手术方式也可行。

经首次根治性手术治疗口腔鳞状细胞癌患者的生存相关影响因素分析

目的分析口腔鳞状细胞癌(OSCC)患者的总体生存率,以及影响生存率的临床病理因素。方法采集对首次接受根治性外科手术治疗的78例OSCC患者的临床病理及随访资料进行回顾性分析。对计数、计量资料进行描述性分析;采用Kaplan-Meier法绘制生存曲线;采用COX比例风险回归模型进行单因素和多因素分析,分析患者的生存率及预后相关影响因素。结果最终纳入生存分析的患者共计68例,中位随访时间为63(6~87)个月,5年总体存活率为55.9%,随访期间因OSCC死亡患者的中位生存时间为20.5(6~52)个月。单因素分析表明,临床分期、原发灶大小、淋巴结转移、病理分化及复发转移是影响生存时间的暴露因素(P<0.05);多因素分析表明,病理分化、复发转移是影响生存时间的独立危险因素(P<0.05)。78例OSCC患者中合并发生食道鳞状细胞癌(ESCC)者有4例(5.1%)。结论根据肿瘤的临床分期(TNM分期)、原发灶大小、淋巴结转移、病理分化及复发转移可对患者的生存预后作出一定的预测,其中病理分化及复发转移是影响生存预后的独立危险因素。有吸烟饮酒史的OSCC患者应常规进行ESCC临床筛查。

食管下段鳞癌与胃底恶性间质细胞瘤并存1例

食管鳞状细胞癌与胃间质细胞瘤并存在临床少见,我科曾收治1例患者,术后病理诊断为:食管下段溃疡型中分化鳞状细胞癌;胃肠道恶性间质细胞瘤。经术后化疗并中药治疗,疗效评价达完全缓解,现报道如下。

p53在食道癌中的表达及与淋巴结转移的关系

目的：探讨p53在食道癌中的表达及与淋巴结转移的关系。方法收集2011年1月～2013年12月经病理检查确诊的食道鳞状细胞癌根治标本154例，其中高分化鳞癌39例、中分化鳞癌56例、低分化鳞癌59例，经常规取材、脱水、透明、浸蜡、包埋、切片、HE染色后镜下观察淋巴结转移情况；并选取癌组织行免疫组化（ S-P法）检测p53。结果154例病例中，高分化鳞癌p53阳性率41％，中分化鳞癌p53阳性率54.2％，低分化鳞癌p53阳性率67.8％；p53阳性而有淋巴结转移者58例、p53阴性而有淋巴结转移者29例。各组间经χ2检验，高分化与中分化及中分化与低分化比较，χ2值分别为2.4及1.38、P＞0.1，无统计学意义；但高分化与低分化比较，χ2值6.89、P＜0.01，具有统计学意义；p53阳性伴淋巴结转移率明显高于p53阴性病例，经检验，χ2值为7.44，P＜0.01，亦具有统计学意义。结论 p53可作为食道鳞状细胞癌重要的预后参考指标。

缺锌增加食道癌发病危险

人体组织中锌水平降低会增加食道鳞状细胞癌发病危险。

我院在Nature子刊报道食道癌研究新进展

2014-02-28的Nature属下权威医学生命科学期刊《Cell Death and Disease》在线发表的一项研究中,汕头大学医学院张灏教授带领的课题组报道了抗糖尿病药物二甲双胍对人类食道癌的作用机制和临床前研究。食道鳞状细胞癌（ESCC）是第三大最常见的消化道恶性肿瘤,是全世界第六大癌症致死原因。潮汕地区是食管癌高发区。目前,这种致命的疾病还没有有效的预防和治疗策略。

食道鳞状上皮细胞癌转移体外细胞模型的建立

目的建立一个适宜的食道鳞状上皮细胞癌(ESCC)体外转移研究模型。方法将ESCC细胞系HK2置于未处理细胞培养皿中培养、传代,筛选出具有非锚定依赖生长能力的细胞株。以体外侵袭实验,软琼脂克隆形成实验比较、验证筛选细胞系与母代细胞的侵袭能力和非锚定依赖生长能力。利用比较蛋白质学的方法分析筛选细胞与母代细胞间的蛋白表达图谱差异。结果成功筛选出具有较高转移能力并可传代培养的HK2-AD细胞株。HK2和HK2-AD细胞侵袭至小室膜反侧的细胞数分别为(16.7±2.5)和(28.7±7.4),软琼脂集落生成实验表明,HK2和HK2-AD细胞形成的集落数分别为(16.8±3.2)和(25±5.1),差异均有统计学意义(P<0.05)。HK2-AD细胞中一些与细胞运动、细胞无氧代谢及抑制凋亡相关的蛋白质分子表达明显上调。结论利用肿瘤细胞的非锚定依赖生长特性建立了一个高转移能力、呈三维生长的HK2-AD细胞株,为ESCC肿瘤转移机制研究和药物筛选提供了一个有价值且易于操作的食道癌转移体外细胞模型。

Expression of MUC1 in esophageal squamous-cell carcinoma and its relationship with prognosis of patients from Linzhou city, a high incidence area of northern China

AIM: To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved.METHODS: 114 specimens of ESC were collected from Linzhou city, and all patients were followed up for more than 5 years after resection. Histopathological analysis and immunohistochemical staining (ABC) were employed to detect the alteration of MUC1.RESULTS: The positive immunostaining rate for MUC1 was 79 % (90/114), and the high-expression rate was 63 %(72/114). The mean survival periods (months) of those with high- and low-expression rates of MUC1 were 41 (95 % CI:35, 47) and 52 (95 % CI: 45, 59), respectively. Patients in the low-expression group obviously survived longer than those in high-expression group, and the difference was significant (P＜0.05). The expression of MUC1 protein in the esophageal carcinoma specimens with metastasis was stronger than those without metastasis, the difference was also significant (P＜0.05). The stepwise multivariate analysis showed that 'differentiation', 'expression of MUC1' and 'TNM staging' were the most important factors affecting the prognosis of esophageal carcinoma patients (P＜0.05).CONCLUSION: A good correlation between the alteration of MUC1 and the regional lymph node metastasis was observed. Furthermore, high-expression of MUC1 was associated with poor prognosis for esophageal cancer patients. These results indicated that MUC1 is a promising biomarker for predicting lymph node metastasis and prognosis in esophageal cancer.

Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province

AIM: To characterize the protein files in blood from same patients with esophageal squamous cell carcinoma (ESCC) before and after operation at Me high-incidence area for ESCC in Henan Province, China. METHODS: Two-dimensional electrophoresis, silver staining and ImageMaster 2-DE analysis software were applied to the determination of protein files in the blood obtained from normal controls and ESCC patients before and after operation. RESULTS: A total of 655, 662 and 677 protein spots were identified, respectively, from the normal controls and ESCC patients before and after operation. No significant difference in the number of protein spots was observed between Me normal group and ESCC patients. A total of seven protein spots were identified wi~ a dramatic difference among the samples before and after operation. Six protein spots were up-regulated and one protein spot was down-regulated in the group after operation compared with those in normal and before operation. Three protein spots were further characterized by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The proteins from these three spots were identified as serum amyloid A (SAA), amyloid related serum protein and haptoglobin. CONCLUSION: Serum amyloid A, amyloid related serum protein and haptoglobin may be related with ESCC and/or surgery. The significance of ~ese proteins needs to be further characterized. The present study provides informative data for Me establishment of serum protein profiles related with ESCC.

Expression properties of recombinant pEgr-P16 plasmid in esophageal squamous cell carcinoma induced by ionizing irradiation

AIM: To construct the recombinant pEgr-P16 plasmid for the investigation of its expression properties in esophageal squamous cell carcinoma induced by ionizing irradiation and the feasibility of gene-radiotherapy for esophageal carcinoma.METHODS: The recombinant pEgr-P16 plasmid was constructed and transfected into EC9706 cells with lipofectamine. Western blot, quantitative RT-PCR and flow cytometry were performed to study the expression of pEgr-P16 in EC9706 cells and the biological characteristics of EC9706 cell line after transfection induced by ionizing irradiation.RESULTS: The eukaryotic expression vector pEgr-P16 was successfully constructed and transfected into EC9706 cells.The expression of P16 was significantly increased in the transfected cells after irradiation while the transfected cells were not induced by ionizing irradiation. The induction of apoptosis in transfection plus irradiation group was higher than that in plasmid alone or irradiation alone.CONCLUSION: The combination of pEgr-P16 and irradiation could significantly enhance the P16 expression property and markedly induce apoptosis in EC9706 cells. These results may lay an important experimental basis for gene radiotherapy for esophageal carcinoma.

Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma

AIM: To investigate telomerase activity and hTERT, TP-1 expression and their relationships in esophageal squamouscell carcinoma (ESCC).METHODS: Telomerase activity was measured in 60 ESCCtissues using telomeric repeat amplification protocol (TRAP)assay by silver staining. In situ hybridization was used for detecting hTERT and TP-lmRNA.RESULTS: The telomerase activity was detected in 83.3 % of ESCC tissues. The difference of telomerase activity was significant between well and poorly cancer differentiated lesions (P<0.05). The positive rate of telomerase activity was higher in patients with lymphatic metastasis than in patients without lymphatic metastasis. In cancer tissues hTERT mRNA expression was 75 % and TP-1 mRNA expression was 71.7 %. The expression of hTERT, TP-1 mRNA in well and poorly differentiated carcinoma was not significant. The expression of hTERT mRNA was correlated with telomerase activity, but TP-1 mRNA expression was not correlated with it.CONCLUSION: Telomerase activity and hTERT, TP-1 mRNA expression are up-regulated in ESCC. Telomerase activity in ESCC is correlated with lymphatic metastasis and cancer differentiation. Telomerase activity may be used as a prognostic marker in ESCC. hTERT mRNA expression is correlated with telomerase activity. Enhanced hTERT mRNA expression may initially comprehend the telomerase activity level, but it is less sensitive than TRAP assay.

Epoxide hydrolase Tyr113 His polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma in population of North China

AIM: To investigate the possible association of microsomal epoxide hydrolase ( mEH) Tyr113 His polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a population of North China.METHODS: The mEH-Tyr113 His genotypes were determined by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 257 patients with esophageal squamous cell carcinoma (ESCC) and 252 healthy subjects as a control group.RESULTS: The frequencies for Tyr and His alleles were 44.2 %, 55.8 % in ESCC patients, and 44.0 % and 56.0 %in healthy subjects, respectively. No statistic difference in allele distribution was observed between ESCC patients and controls (x2=0.008, P=0.929). The overall genotype distribution difference was not observed between cancer cases and controls (x2=2.116, P=-0.347). Compared with Tyr/Tyr genotype, neither His/His genotype nor in combination with Tyr/His genotype significantly modified the risk of the development of ESCC, the adjusted odds ratio was 1.076 (95 % CI=0.850-1.361) and 0.756 (95 % CI=0.493-1.157),respectively. When stratified for sex, age, smoking status and family history of upper gastrointestinal cancer, His/His genotype alone or in combination with Tyr/His genotype also did not show any significant influence on the risk of developing ESCC.CONCLUSION: MEH Tyr113His polymorphism may not be used as a stratification marker in screening individuals at a high risk of ESCC.

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.

Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma

AIM： To investigate the role of cytochrome P450 （CYP） in the carcinogenesis of squamous-cell carcinoma （SCC） in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS： mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC （/7 = 21） and in controls （n = 10）. Protein levels of CYP2E1, CYP2CS, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS： Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue （-39% and -74%, respectively, P 〈 0.05） than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients （4.8-, 2.9-, and 1.9-fold elevation, P 〈 0.05） than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients （＋46%, P 〈 0.05）. CONCLUSION： Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue （e.g. CYP2CB, CYP3A4, CYP3A5, and CYP2E1） between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.

Regulation of apoptosis by the papillomavirus E6 oncogene

Infection with human papillomaviruses is strongly associated with the development of multiple cancers including esophageal squarnous cell carcinoma. The HPV E6 gene is essential for the oncogenic potential of HPV. The regulation of apoptosis by oncogene has been related to carcinogenesis closely; therefore, the modulation of E6 on cellular apoptosis has become a hot research topic recently. Inactivation of the pro-apoptotic tumor suppressor p53 by E6 is an important mechanism by which E6 promotes cell growth; it is expected that inactivation of p53 by E6 should lead to a reduction in cellular apoptosis, numerous studies showed that E6 could in fact sensitize cells to apoptosis. The molecular basis for apoptosis modulation by E6 is poorly understood. In this article, we will present an overview of observations and current understanding of molecular basis for E6-induced apoptosis.