Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism

BACKGROUND It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2(ALDH2)is an important risk factor for the development of esophageal squamous cell carcinoma(ESCC).It remains controversial whether human papillomavirus(HPV)infection contributes to the occurrence/development of ESCC.There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B(ADH1B)and ALDH2 genotypes was evaluated.AIM To evaluate relationships between HPV infection and development of esophageal cancer,particularly early esophageal cancer,based on ADH1B/ALDH2 polymorphisms.METHODS We conducted an exploratory retrospective study using new specimens,and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital.Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2.We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.RESULTS HPV was detected in 15(10.3%)of the 145 patients with ESCC.HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1+*2/*2 were 10.8%and 9.8%,respectively(P=1.00).HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2+*2/*2 were 12.0%and 10.0%,respectively(P=0.72).HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1%and 8.7%,respectively(P=0.68).HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8%and 8.3%,respectively(P=0.59).The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPVnegative groups were 14.4%and 21.4%(P=0.22),respectively.CONCLUSION In the present situation,HPV status is considered to be less important than other risk factors,such as alcohol consumption,smoking habit,ADH1B/ALDH2 polymorphisms,and HPV status would therefore have no effect on ESCC risk management.

Molecular Mechanism of Induction on Apoptosis of Human Esophageal Cancer HCE-4 Cells by Active Components from Astragalus membranaceus

[Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measured by MTT assay. The induction of active components from A. membranaceus on apoptosis of HCE-4 cells was detected by Annexin V-FITC/PI double staining. The apoptotic-related protein expression levels were determined by Western blotting. [Results] Formononetin and astragaloside IV suppressed the proliferation of HCE-4 cells in a dose-dependent manner. The Annexin V-FITC/PI double staining results showed that formononetin and astragaloside IV could induce HCE-4 cells apoptosis in a time-dependent manner. The Western blotting results showed that formononetin and astragaloside IV could significantly down-regulate p-AKT,pro-caspase-3,and increase cle-caspase-3 protein expression in HCE-4 cells. [Conclusions]Active components from A. membranaceus such as formononetin and astragaloside IV significantly inhibited the proliferation of human esophageal cancer HCE-4 cells by inducing mitochondrial dependent apoptosis via AKT signaling pathway.

A STUDY OF THE CHARACTERISTICS OF γ-GLUTAMYLTRANSPEPTIDASE OF HUMAN ESOPHAGEAL CANCER

γ-Glutamyltranspeptidase (γ-GT) from human esophageal cancer, normal esophageal mucosa and normal kindney were partially purified and their biochemical and immunological properties were studied. (1) The γ-GT activity of esophageal cancer was higher than that of normal mucosa, yet still much lower than that of normal kidney. (2) The Michaelis constant and optimum pH of esophageal cancer γ-GT were the same as those of normal kidney tissue. (3) After staining of γ-GT activity, two molecular clusters, i.e. 100kD and 380kD γ-GT were shown in esophageal cancer by 4-20% linear gradient PAGE and the lOOkD γ-GT showed higher activity. (4) The γ-GT of esophageal cancer was immunologically identical with normal enzyme in double immunodif-fusion and immunoelectrophoresis. (5) In double lectin-diffusion, affinity column and crossed immuno-affino-electrophoresis, it was demonstrated that the carbohydrate components of γ-GT from esophageal cancer were heterogeneous and rich in D-Mannose, D-Glucose and N-Acetyl-Glucosamine. The relationship between the appearance of 100kD γ-GT cluster and the heterogeneous carbohydrate components will be further studied.

TRANSFORMING ACTIVITY OF DNA FROM HUMAN ESOPHAGEAL CANCER AND THE IDENTIFICATION OF THE TRANSFORMING GENE

Rat-1 cells were transfected with DNA from human esophageal cancer 2K, 4K, 6K, 7K. 8K. The transforming foci were obtained and the transforming cell lines were established. The cell lines can form larger colony in soft agar. Those nude mice injected subcutaneously with the cells suffered from larger fibrous sarcoma. This indicates that the cell lines have carcinogenicity. The experimental results suggest that human DNA sequence and human Ha-ras special 616Kb (BamHI) band are present in the DNA of the transforming cells. The over-expression of ras gene products P21 were found in the tissues of exophageal cancer, the tissues adjacent to tumor and the transforming cells.

HPV18 E6 and E7 Intratumour Heterogeneity in Esophageal Cancer

The development of esophageal cancer accompanied by the presence of human papillomavirus (HPV) DNA into the host genome. By evaluating the expression of this virus for tumor cell origin and also their cell grows and migrations, we examined esophageal cancer clonality in the context of intra-tumor heterogeneity. In this research, we have checked the expression of HPV18 E6 and E7 in different single cell clones by the manual cell picking method in the HPV positive esophageal cancer (EC109), EC109 cell line used as a negative control, and Hela cell line used as the positive control. Quantitative real-time PCR (QRT-PCR) was run to detect the expression levels of HPV E6 and E7, Cell Counting Kit-8 (CCK-8) assay was used to examine cell proliferation, invasion assays performed using Costar chambers and wounding assay to study cell migrations in vitro. We investigated the intra-tumor heterogeneity of HPV E6 and E7 in esophageal cancer and the evaluation of the growth and migrations at the clonal level, using 10 single cell clones. In particular clones, C7 & C10 displayed a highly variable expression in both HPV E6 and E7 and weak in four clones (C1, C3, C4, and C9) consequently, the cell invasion, proliferation, and migration increase with increasing the level of HPV expression and inverse. In conclusion, the resulting based on single cell cloning showed the relationship between HPV and cell growth and migration in esophageal cancer. Future study in HPV DNA integration needed to explore the mains specific integration site of HPV DNA in esophageal cancer and molecular monitoring of the HPV for future prevention researches and also effective therapeutic strategies.

Association of defective HLA-Ⅰ expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer

Background It has been confirmed that defective expression of human leukocyte antigen class Ⅰ （HLA-Ⅰ） molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class Ⅰ antigen and the antigen-processing machinery （APM） components in esophageal squamous cell carcinoma （ESCC） and their role in high risk human papillomavirus （HPV） infection, and to analyze their association with histopathological characteristics in the Kazak ethnic group.Methods A total of 50 formalin-fixed, paraffin-embedded ESCC lesions were collected from the First Affiliated Hospital of Xinjiang Medical University, China. The expression levels of HLA-Ⅰ antigen and APM components were determined by immunohistochemistry; the HPV DNA were detected using polymerase chain reaction （PCR）.Results A high frequency of down-regulation or loss of expression of HLA and APM components were found in esophageal cancer in Kazak people. HLA-Ⅰ, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%,44%, 48%, 40%, 52%, 32% and 20% of ESCC lesions then, respectively. The loss of expression of HLA-Ⅰ antigen was significantly correlated with part of the APM components and positively correlated with high risk HPV16 infection. TAP1,CNX, LMP7, Erp57 and Tapasin loss were significantly associated with tumor grading, lymph node metastasis and depth of invasion （P〈0.05）.Conclusion Our results suggest that APM component defects are a mechanism underlying HLA-Ⅰ antigen down-regulation in ESCC lesions, and indicate that the loss expression of HLA-Ⅰ and APM components will become an important marker of ESCC and analysis of HLA-Ⅰ and APM component expression can provide useful prognostic information for patients with ESCC from the Kazak ethnic group.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%).Accordingly,the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7(42.9%) vs 2 of 49(4.1%),P < 0.05].Of the pathological characteristics,only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27(74.1%) vs 8 of 29(27.6%) for ulcerative or protruding macroscopic type,P < 0.05].The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation,phases in depth of tumor infiltration,grades of nodal involvement and stages of tumor progression.CONCLUSION:Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex,progressive,multifactorial and multistep esophageal carcinogenesis.

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma.Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma.The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas.Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies.In human papillomavirus driven cancers,e.g.cervical,anogenital,head and neck cancers,associated lymph nodes with a high viral load suggest metastatic lymph node involvement.Thus,human papillomavirus could potentially be useful as a marker of micro-metastases.To date,there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma.This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.

Effect of recombinant human endostatin onradiotherapy for esophagus cancer

Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.

Human papillomavirus and gastrointestinal cancer: A review

Human papillomavirus(HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common,and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic,but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri,penis,vulva,vagina,anus and oropharynx,including the base of the tongue and the tonsils. However,studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal,colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile

AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS： We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5＋/GP6＋ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.RESULTS： HPV was detected in 21 ESCC specimens （29%）. Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases （13%） and in 5 Chilean cases （19%）. HPV-18 was detected in i0 cases （21%） in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 （without statistical significance）, but a significantly lower prevalence of HPV-18 than in Colombian cases （P = 0.011） even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION： HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil

AIM:To investigate the association between human papillomavirus(HPV)and esophageal squamous cell carcinoma(ESCC)in southern Brazil.METHODS:We studied 189 esophageal samples from125 patients from three different groups:(1)102 biopsies from 51 patients with ESCC,with one sample from the tumor and another from normal esophageal mucosa distant from the tumor;(2)50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma(HNSCC);and(3)37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients,not exposed to smoking or alcohol consumption.Nested-polymerase chain reaction(PCR)with the MY09/11 and GP5/6 L1primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks.All PCR reactions were performed with a positive control(cervicovaginal samples),with a negative control(Human Genomic DNA)and with a blank reaction containing all reagents except DNA.We took extreme care to prevent DNA contamination in sample collection,processing,and testing.RESULTS:The histological biopsies confirmed the diagnosis of ESCC in 52 samples(51 from ESCC group and 1 from the HNSCC group)and classified as well differentiated(12/52,23.1%),moderately differentiated(27/52,51.9%)or poorly differentiated(7/52,13.5%).One hundred twenty-eight esophageal biopsies were considered normal(51 from the ESCC group,42 from the HNSCC group and 35 from dyspeptic patients).Nine had esophagitis(7 from the HNSCC and 2 from dyspeptic patients).Of a total of 189 samples,only 6 samples had insufficient material for PCR analysis:1 from mucosa distant from the tumor in a patient with ESCC,3from patients with HNSCC and 2 from patients without cancer.In 183 samples(96.8%)GAPDH,G3PDH and/orβ-globin were amplified,thus indicating the adequacy of the DNA in those samples.HPV DNA was negative in all the 183 samples tested:52 with ESCC,9 with esophagitis and 122 with normal esophageal mucosa.CONCLUSION:There was no evidence of HPV infection in different ESCC from southern Brazil.

重组人血管内皮抑制素联合GP方案治疗对晚期食管癌患者肿瘤标志物和生存质量的影响

目的探讨重组人血管内皮抑制素联合GP方案治疗对晚期食管癌患者肿瘤标志物和生存质量的影响。方法选择该院2021年2月—2022年12月收治的90例晚期食管癌患者为研究对象,按随机数字表法将其分为对照组与观察组,各45例。对照组采用GP方案治疗,观察组在对照组基础上加用重组人血管内皮抑制素治疗,比较两组患者的临床疗效、生存质量、血清因子和肿瘤标志物。结果观察组治疗总有效率为88.89%,高于对照组的71.11%,差异有统计学意义(P<0.05)。治疗前,两组血管内皮生长因子(VEGF)、成纤维细胞生长因子受体-4(FGFR-4)、癌胚抗原(CEA)、脊椎蛋白-2(Spon-2)水平比较,组间差异无统计学意义(P>0.05);治疗后,观察组FGFR-4、VEGF、Spon-2和CEA水平分别为(125.97±5.20)pg/mL、(152.21±5.18)ng/L、(13.11±0.20)μg/L、(6.34±0.19)ng/mL,均低于对照组的(143.54±8.19)pg/mL、(174.97±6.34)ng/L、(15.96±0.23)μg/L、(8.21±0.09)ng/mL,组间差异有统计学意义(P<0.05)。治疗前,两组肿瘤卡氏(KPS)评分比较,差异无统计学意义(P>0.05);治疗后,观察组KPS评分为(84.92±2.99)分,高于对照组的(78.30±1.87)分,差异有统计学意义(P<0.05)。观察组1年存活率高于对照组,差异有统计学意义(P<0.05)。结论晚期食管癌患者采用重组人血管内皮抑制素联合GP方案治疗可有效改善患者短期存活率,降低其肿瘤标志物表达水平,实用性较高。

中国人群中HPV感染与食管癌发生关联的Meta分析

目的人乳头状瘤病毒(human papillomavirus,HPV)感染被认为是食管癌的重要易感因素之一,但在中国人群的流行病学关联研究结果中却有着不同的结论差异,因此本文对HPV感染与食管癌,尤其对HPV高危型别(16型与18型)感染与食管癌的发生关联做一全面的系统评价。方法计算机检索CNKI、Pubmed等数据库,同时利用文献追溯等途径收集国内外公开发表的关于中国HPV感染与食管癌的关联研究,收集了1982～2009年关于HPV感染与食管癌关联的病例-对照研究原始文献,并根据文献中的原始资料评价HPV感染与食管癌的易感关联,采用Revman5.0和Stata10.0软件对研究资料进行Meta分析,利用Egger's test评价发表偏倚。结果总计纳入文献19篇,计20项病例-对照研究,在19篇研究文献的Meta分析中,采用随机效应模型进行计算,结果显示中国人群中HPV感染对于食管癌的易感关联的综合OR值为3.30(95%CI:2.13-5.11),Egger's test显示无显著性发表偏倚(P=0.160);在关于食管癌的高低发区、HPV检测方法、对照组的不同设置等亚组分析中均显示了发病风险的存在(P<0.05)。结论尽管由于食管癌发病率存在地区性差异、各研究中正常对照组的设置有所不同、采用检测HPV方法不尽一致,但在中国人群中HPV高危型别(16与18型)的感染与食管癌的发生依然显示出明显的易感关联。

某食管癌高发区人群伏马菌素摄入量及尿二氢神经鞘氨醇/神经鞘氨醇比值的调查

为探讨伏马菌素与人类食管癌发生的关系 ,对食管癌高发区鹤壁市郊部分居民的伏马菌素摄入水平及尿二氢神经鞘氨醇 神经鞘氨醇 (Sa So)比值进行了调查。该地居民长期食用玉米 ,95 %的玉米样品检出了伏马菌素 ,其总伏马菌素含量 (伏马菌素B1、B2、B3之和 )为 7 2～ 72 6 8μg kg。估算受检者的伏马菌素摄入量为男性 0～ 4 84μg (kg·d) ,女性 0～ 4 0 4μg (kg·d)。检测他们的尿Sa So比值并与食管癌低发区睢县人群 (未接触伏马菌素 )比较 ,虽然两地女性尿Sa So比值间差异无显著性 ,但男性尿Sa So比值间差异存在显著性 ,食管癌高发区高于低发区。

食管癌与p53突变和人乳头状肉瘤病毒感染

目的探讨p53基因突变与人乳头状肉瘤病毒16(HPV16)感染在食管癌发病中的作用及相互关系。方法应用病例-病例研究方法进行分析,采用聚合酶链反应(PCR)、单链构像多态性(SSCP)、测序等分子生物学技术对110例食管癌组织标本中p53基因的突变与HPV16感染进行了检测。结果110例食管癌组织标本p53基因突变率为49.1%,其中外显exon5-6,exon7,exon8-9的突变率分别为19.1%,27.3%,17.2%。食管癌组织HPV16的检出率为49.1%。吸烟患者p53基因突变率(61.4%)明显高于非吸烟患者p53基因突变率(48.2%),差异有统计学意义;淋巴结转移患者p53基因突变率(65.2%)明显高于无淋巴结转移患者p53基因突变率(37.5%);HPV16阳性者中,p53突变率是40.7%,HPV16阴性者仅为57.1%,两者差异无统计学意义。结论HPV16感染可能是食管癌高发区的危险因素;p53基因突变与吸烟、淋巴结转移有明显相关性;HPV16感染和p53基因突变可能是2个独立的事件。

Marsdenia tenacissima extract induces G_0/G_1 cell cycle arrest in human esophageal carcinoma cells by inhibiting mitogen-activated protein kinase(MAPK) signaling pathway

Marsdenia tenacissima extract(MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal cancer and other cancers in the digestive tract. In the present study, the potential mechanism for MTE's activity in esophageal cancer was explored. The effects of MTE on the proliferation of human esophageal cancer cells(KYSE150 and Eca-109) were investigated by the MTT assay, the Brd U(bromodeoxyuridine) incorporation immunofluorescence assay, and flow cytometric analysis. MTE inhibited cell proliferation through inducing G0/G1 cell cycle arrest in KYSE150 and Eca-109. Western blot analysis was employed to determine protein levels in the MTE treated cells. Compared with the control cells, the expression levels of the cell cycle regulatory proteins cyclin D1/D2/D3, cyclin E1, CDK2/4/6(CDK: cyclin dependent kinase), and p-Rb were decreased significantly in the cells treated with MTE at 40 mg·m L-1. In addition, MTE had an inhibitory effect on the MAPK(mitogen-activated protein kinase) signal transduction pathway, including ERK(extracellular signal-regulated kinase), JNK(c-Jun N-terminal kinase), and p38 MAPK. Moreover, MTE showed little additional effects on the regulation of cyclin D1/D3, CDK4/6, and p-Rb when the ERK pathway was already inhibited by the specific ERK inhibitor U0126. In conclusion, these data suggest that MTE inhibits human esophageal cancer cell proliferation through regulation of cell cycle regulatory proteins and the MAPK signaling pathways, which is probably mediated by the inhibition of ERK activation.

人乳头状瘤病毒与食管癌的病因学关系

为探索人乳头状瘤病毒（ＨＰＶ）感染与四川盐亭地区食管癌高发的病因学关系，用生物素标记的ＨＰＶ１６ＤＮＡ探针对盐亭食管癌高发区食管癌、正常食管上皮及成都食管癌低发区正常食管上皮脱落细胞进行原位杂交，检测ＨＰＶ１６ＤＮＡ。结果：盐亭地区食管癌及正常食管上皮ＨＰＶ１６ＤＮＡ阳性率分别为５０．５％（２０／４０）和６２．１％（３６／５８），两者无显著性差异（Ｐ＞０．０５）；成都地区正常食管上皮ＨＰＶ１６ＤＮＡ阳性率为１５．４％（６／３９），低于盐亭地区正常食管上皮的阳性率，有显著性差异（Ｐ＜０．０１）。研究结果表明，ＨＰＶ感染与四川盐亭地区食管癌高发有关。

人乳头瘤病毒型别及其相关疾病

随着现代分子生物学技术的发展,科学家们发现越来越多的人乳头瘤病毒(HPV)亚型与多种不同疾病相关。高危型HPV16、18、31、33、45、52和61等是子宫颈、外阴、阴道、阴茎、肛门和口腔以及口咽癌的病因,低危型HPV6和11是生殖器疣的病因。HPV与喉癌有一定病因学联系,然而与食管癌和肺癌的关系尚不能确定。

姜黄素诱导人食管癌EC9706细胞凋亡过程中核磷蛋白的表达与定位变化

目的探讨核磷蛋白NPM在癌细胞诱导凋亡过程中在细胞内、细胞核基质上的定位与表达变化,以及NPM与凋亡调控相关蛋白的关系,探索其在凋亡调控中的作用。方法在姜黄素诱导人食管癌EC9706细胞凋亡的基础上,以亚细胞蛋白质组学方法分析NPM在核基质中的存在与变化,并以免疫印迹法杂交实验进行确证;激光扫描共焦显微镜观察NPM在EC9706细胞凋亡过程中的定位与变化,以及NPM与Bax、Bcl-2等基因产物的共定位关系。结果 NPM存在于EC9706细胞核基质蛋白组分中,并在姜黄素处理后表达下调。NPM在EC9706细胞凋亡过程中发生显著的胞质-核之间的穿梭定位变化,并与Bax、Bcl-2等蛋白具有共定位关系,且共定位区域发生了变化。结论 NPM是一种核基质结合蛋白,在EC9706细胞凋亡中的表达与定位变化,及其与凋亡调控蛋白的共定位关系提示,它在EC9706细胞凋亡调控中具有重要作用。