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Sample records for advanced esophageal carcinoma

  1. A STUDY OF ENDOSCOPIC TREATMENT OF ADVANCED ESOPHAGEAL AND GASTRIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Zhang Jichang; Zhang Lijian; Wang Yanmeng; Li Wei

    1998-01-01

    Objective: To investigate the effect of endoscopic treatment on advanced esophageal and gastric carcinoma.Methods: Twenty advanced gastric cancer patients and 25advanced esophageal cancer patients, who had recurrence after operation and radiotherapy were managed by endoscopic treatment. Results: 10 cases were treated to stop bleeding only, 35 cases were treated by microwave,dilation and local chemotherapy. The successful rate of hemostasis was about 67%, the remission rate of digestive obstruction was about 100% after dilation, 83% of the recurrence lesions were relieved by endoscopic chemotherapy. Conclusion: Endoscope treatment has certain therapeutic efficiency for the recurrence of advanced esophageal and gastric cancer.

  2. Epidemiological investigation of esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Shao-Hua Chen; You-Ming Li

    2004-01-01

    AIM: To review the characteristics of esophageal carcinoma in recent 30 years in the epidemiological investigation.METHODS: A total of 1 520 cases of esophageal carcinoma in the First Affiliated Hospital of Zhejiang University Medical College admitted from 1970 until now were reviewed. Their age, gender, position of carcinoma and histological type were analyzed.RESULTS: The morbidity of esophageal carcinoma was increasing during the observation period. Compared with the 1970s (9.5%), the ratio of adenocarcinoma significantly increased after the 1980s (19.1%). The difference was significant (P≤0.05).CONCLUSION: The morbidity of esophageal adenocarcinoma was increasing and advanced clinical study should be strengthened.

  3. Combination of radiotherapy with chemotherapy using cisplatin of advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Of 38 patients with esophageal carcinoma who were treated at the Department of Radiology, Tokushima University Hospital between 1983 and 1987, 13 (34 %) received a combination of radiation and chemotherapy of cisplatin-based combination regimens. Twelve patients with squamous cell carcinoma and one with adenocarcinoma were treated by a 6 MV linear accelerater. They received a cummulative dose ranging from 18 to 68 Gy (average dose : 50.5 Gy), in 2 Gy fractions. The response rate was 62 % (CR 1, PR 7). Two of the six patients with Stage III survived more than three years. Median survival time was 11.4 months for patients with Stage III and 4.7 months for Stage IV. Chemotherapy improved median survival duration for patients with advanced esophageal carcinoma but did not produce a significant improvement in survival, as reported in other recent series. (author)

  4. EFFECT OF PREOPERATIVE CHEMOTHERAPY ON METASTASIZED LYMPH NODES IN PATIENTS WITH ADVANCED ESOPHAGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the effect and clinical value of preoperative chemotherapy on the treatment of metastasized lymph nodes in patients with advanced esophageal carcinoma. Methods We studied the pathological results of primary lesions and lymph nodes of 97 patients with advanced esophageal cancer between 1996 and 1999,62patients were treated by preoperative chemotherapy and 35 patients were treated by surgery only. Results The metastasized rate and degree of mediastinum in preoperative group were 16. 1% and 4.7% ,whereas 65.7% and 34.2% in the surgery only group (P<0. 05);That of abdomen in preoperative group were 25.8% and 6.6% ,whereas 48. 6%and 12.0% in the surgery only group (P<0.05). Conclusion Preparative chemotherapy is effective not only against the primary lesions but also the metastasized lymph nodes. The lower complete response rate of the metastasized lymph may account for the unsatisfied long-term results. Whole resection of primary lesions and lymph nodes are still very important for a better prognosis even for patients who have a good response for the preoperative chemotherapy.

  5. Protocol and result of neoadjuvant chemotherapy for locally advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    The protocol and result were described of chemotherapy and radiotherapy for locally advanced esophageal carcinoma, especially for A3 stage one with metastasis at neighboring tissues such as aorta, trachea and bronchia. Chemotherapy was done with 5-FU and CDDP and radiotherapy, with 30 Gy/15 fx/3 wk. Double contrast roentgenography, dynamic CT and MRI were performed to follow the process. The efficacy rate was 55.0% with 4 CR and 7 PR in 20 cases. Three CR patients survived at present. Major adverse effects were leukopenia and thrombocytopenia, of which grade 4 were found in 14 and 12% cases, respectively. Low-dose FP therapy might be useful for lowering the adverse effects and for elevating the efficacy rates. (K.H.)

  6. [Esophageal intubation for palliative treatment in advanced carcinoma of the esophagus and cardia].

    Science.gov (United States)

    Domene, C E; Cecconello, I; Volpe, P; Zilberstein, B; Sakai, P; Ishioka, S; Pinotti, H W

    1998-01-01

    This is a report of 121 cases of advanced esophageal and cardia cancer managed by endoscopic and surgical esophageal intubation. They were submitted to surgical intubation 69 (53%) patients, and 52 (47%) to endoscopic intubation. There were 32.5% of technical complications in endoscopic intubation and 26.5% in surgical intubation. Perfuration was more frequent (11.5%) in endoscopic intubation than surgical group. Mortality rate was 17.3% for endoscopic and 5.8% for surgical intubation. Perfuration was the main cause of death in endoscopic intubation. Survival rate was 3.5 months for endoscopic and 4.7 months for surgical intubation. The majority of patients died of cancer evolution--caquexia (55.5%), carcinomatosis (4.5%) and brain methastasis (1.1%). The results of endoscopic and surgical intubation in this group of patients recommend its use in patients with advanced esophageal and cardic cancer. PMID:9699358

  7. Clinico-pathological studies on the effects of preoperative hyperthermo-chemo-radiotherapy for advanced esophageal carcinoma

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    Nakamura, Tsutomu; Ide, Hiroko; Eguchi, Reiki (Tokyo Women' s Medical Coll. (Japan)) (and others)

    1991-12-01

    We report clinico-pathological studies on the effect of preoperative hyperthermia and chemotherapy combined with radiotherapy (HCR) for progress of the local curability of advanced esophageal carcinoma. The subjects of these studies were 17 patients who underwent subtotal esophagectomy after preoperative irradiation of 40 Gy from 1980 to 1989, of which 8 patients had HCR, 6 patients irradiation only (R), 3 patients both irradiation and chemotherapy (CR). The clinical response rate of the patients with R or CR was 33% (PR 3, MR 3, NC 3), and the histological effective (Ef{sub 3} or Ef{sub 2}) rate was 56% (Ef{sub 3} 1, Ef{sub 2} 4, Ef{sub 1} 4). The clinical response rate of the patients with HCR was 88% (PR 7, MR 1), and the histological effective rate was 100% (Ef{sub 3} 1, Ef{sub 2} 7). HCR was more effective than R or CR for the local lesion of esophageal carcinoma histopathologically (p<0.05). However, the survival rate of patients with HCR was similar to R and CR, respectively. These results suggest that further improvement of the heating methods and the methods of combining hyperthermia with irradiation and chemotherapy is needed. (author).

  8. Combined radiotherapy and preradiation chemotherapy with Cisplatin and 5-Fluorouracil for advanced esophageal carcinoma, 1

    International Nuclear Information System (INIS)

    Eight patients with untreated squamous cell carcinoma of the esophagus accompanying distant metastases who were treated by one to five cycles of chemotherapy consisting of Cisplatin and 120 hour infusion of 5-Fluorouracil were reported. Two patients showed complete response (CR), four partial response (PR), one minor response, and one no response. High response rate of 75% (6 of 8) was obtained. Radiation therapy was then administered to six of the patients. After definitive treatment, CR was obtained in four, and PR in two of the cases. However, relapses were noted in all four of the CR cases, with four at distant sites, and one locally. Five of the eight patients (62.5%) survived one year and two survived three years (25%). Two patients could not receive radiotherapy because of uncontrollable lung metastases or death from duodenal ulcer. Although the follow-up period is still short, the combined treatment of radiation and preradiation chemotherapy appears to be an effective treatment, and has made a major impact upon survival time in cases of disseminated esophageal carcinoma. (author)

  9. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

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    Du, Zhongli [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Wencheng [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xiao, Zefen, E-mail: xiaozefen@sina.com [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tan, Wen, E-mail: tanwen@cicams.ac.cn [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  10. Qualitative and Quantitative Studies of Polygene Proteins Expression in Esophageal Precancerous Lesions and Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Chao-xia; WU Ming-yao; KUANG Li-ping

    2007-01-01

    Objective: To examine the expressions of MDM2, P53 and P27 proteins in chronic esophagitis, para-cancer mucosa and esophageal carcinoma. Methods: Immunohistochemistry was used to detect the expressions of MDM2, P53 and P27 proteins in forty-seven patients suffering from chronic esophagitis and eighty-five cases of esophageal carcinoma and corresponding para-cancer mucosa. Flow cytometry((FCM) was applied to detect the quantities of these proteins expressed in fresh tissues of 48 cases of esophageal cancer and their para-cancer tissues and 24 cases of relative normal mucosa at the surface of cutting edge. Results: Immunohistochemistry results showed that the expressions of the three studied proteins were very similar in the epithelia of chronic esophagitis and para-cancer mucosa (P>0.05). Both the qualitative and quantitative studies displayed that the P53 protein had no expression and its accumulations would appear only in the early stages of esophagus canceration while the MDM2 and P27 proteins had different degrees of expressions in cases of normal esophageal mucosa. MDM2 protein markedly increased in the advanced stages of esophageal canceration. A quantitative study showed that the expression of P27 protein had a linearity of decreasing tendency (F=9.132,P=0.002) in the course of esophageal canceration. Conclusion: Chronic esophagitis may be a precancerous lesion. Owing to the changes of the P53 and P27 proteins, we can also conclude that these occur in the early stages of esophagus oncogenesis, however the changes of MDM2 expression may occur in the advanced stage of esophageal canceration.

  11. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma

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    Dong Jun

    2010-09-01

    Full Text Available Abstract Background The oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CDC25B-Abs in patients with ESCC. Methods CDC25B autoantibodies were measured in sera from both 134 patients with primary ESCC and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (ELISA in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca-109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (CEA, squamous cell carcinoma antigen (SCC-Ag and cytokeratin 19 fragment antigen 21-1(CYFRA21-1. Results Higher levels of CDC25B autoantibodies were present in sera from patients with ESCC (A450 = 0.917, SD = 0.473 than in sera from healthy control subjects (A450 = 0.378, SD = 0.262, P 450 greater than the cut-off value of 0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag and CYFRA21-1 (13.4%, 17.2%, and 32.1%, respectively. A significantly higher number of patients with ESCC tested positive for a combination of CEA, SCC, CYFRA21-1 and CDC25B-Abs (64.2% than for a combination of CEA, SCC-Ag and CYFRA21-1 (41.0%, P P P = 0.001, log-rank. In the N1 subgroup, the cumulative five-year survival rate of CDC25B-seropositive patients was 13.6%, while that of CDC25B-seronegative patients was 54.5% (P = 0.040, log-rank. Conclusions Detection of serum CDC25B-Abs is superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for diagnosis of ESCC, and CDC25B-Abs are a potential prognostic

  12. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma

    OpenAIRE

    Dong Jun; Zeng Bo-hang; Xu Li-hua; Wang Jun-ye; Li Man-Zhi; Zeng Mu-sheng; Liu Wan-li

    2010-01-01

    Abstract Background The oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC) have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CD...

  13. BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy.

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    Yong Gao

    Full Text Available BACKGROUND: The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1 expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qPCR was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments. RESULTS: Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively and median overall survival (mOS; P = 0.002 and P<0.001, respectively in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively and mOS (both P<0.001 in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007 or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001 group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001 or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001 group. CONCLUSIONS: BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.

  14. Aspirin and esophageal squamous cell carcinoma: bedside to bench

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Cheng Rui; Zhang Shutian

    2014-01-01

    Objective To review the advances of studies on clinical results of aspirin's chemopreventive effect against esophageal squamous cell carcinoma (ESCC) and evidences for mechanisms of the antitumoural effects of aspirin in experimental research.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as aspirin and esophageal cancer.Study selection Articles associated with aspirin and esophageal cancer are analyzed.Results This review focuses on the current evidence for use of aspirin as a chemopreventive agent in ESCC.Aspirin is the most widely used among all nonsteroidal anti-inflammatory drugs (NSAIDs),which is cheap and acceptable to patients.Several observational results provide the further investigation of prevention and therapy of aspirin or similar drugs in esophageal cancer.Data from case control studies,cohort studies and randomized controlled trials (RCTs) also give some support of a beneficial role of aspirin on ESCC.Experimental data suggest that aspirin may prevent carcinogenesis of ESCC by favorably affecting proliferation,apoptosis,or other as yet unidentified growth-regulating processes.But the mechanism by which aspirin influence on esophageal squamous cell carcinoma needs further investigation.Conclusion A wealth of evidences ranging from clinical data to experimental results are building to suggest that aspirin has significant effects in reducing both the incidence and mortality of ESCC.

  15. Study on establishment of esophageal carcinoma animal models

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    Zhao, Qiang; WEN Danyi; Sun, Jianhe

    2013-01-01

    Esophageal cancer is one of the common human gastrointestinal malignancies.In recent years,the global incidence of esophageal cancer and its mortality rise.China is the high incidence area of esophageal cancer with the highest morbidity and mortality in the world.However,the exact pathogeny of esophageal cancer has not been fully clarified yet.Thus,it is of significant importance to establish ideal and stable esophageal carcinoma animal models with similar biological characteristics to clinic...

  16. Avanços na abordagem do carcinoma precoce de esôfago Advances in the management of early esophageal carcinoma

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    Vitor Arantes

    2012-12-01

    Full Text Available Nos países ocidentais, o carcinoma de células escamosas de esôfago (CCE geralmente é detectado em estágio avançado, quando as possibilidades de cura são remotas e o prognóstico reservado. Entretanto, nos anos recentes, ocorreu uma série de avanços na abordagem do CCE de esôfago, tais como a identificação dos grupos de risco para o surgimento desta neoplasia; o uso da endoscopia de alta resolução e cromoendoscopia com lugol favorecendo o diagnóstico do CCE em estágios iniciais; e o desenvolvimento de técnicas endoscópicas de ressecção tumoral endoluminal em monobloco denominada dissecção endoscópica de submucosa. Este progresso tem possibilitado a aplicação do tratamento endoscópico minimamente invasivo com potencial curativo em pacientes selecionados com CCE superficial de esôfago. O presente artigo de revisão, elaborado por um grupo multicêntrico internacional, tem como objetivo primário contribuir para o entendimento dos principais avanços recentes ocorridos no manejo do CCE precoce de esôfago. Como objetivo secundário, pretende propiciar uma revisão detalhada e minuciosa da estratégia técnica de DES desenvolvida pelos experts japoneses, de forma a colaborar para a difusão deste conceito e a incorporação destas tecnologias na Medicina Brasileira e Latino-americana.Esophageal squamous cell cancer (ESCC has a dismal prognosis mainly because its recognition in Western countries usually occurs in late stages, when the possibilities of cure are minimal. However, in recent years, several advances have been observed in the management of ESSC, such as the identification of high-risk patients, the use of high-resolution endoscopy and lugol chromoscopy favoring the diagnosis of early stage ESCC, and the development of endoluminal techniques of en-block tumor resection, namely endoscopic submucosal dissection (ESD. These factors have enabled the application of endoscopic minimally invasive curative interventions in

  17. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

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    Hu GF

    2016-07-01

    Full Text Available Guofang Hu,1 Zhehai Wang,2 Yuan Wang,1 Qingqing Zhang,1 Ning Tang,1 Jun Guo,2 Liyan Liu,2 Xiao Han2 1School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, 2Department of Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, People’s Republic of China Background: To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC who received nonsurgical treatment. Methods: This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy. The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS and overall survival (OS by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological, and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results: Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively. The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate

  18. Surgical Treatment of Perforation Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Depu Duan; Jihua Zou; Zhigang Cai; Shengyong Wu; Haibo Xiao; Yiyong Zhou; Xiang Liang; Dekui Sun; Songchang Wu

    2006-01-01

    OBJECTIVE To determine the ideal method of surgical preoperative treatment for perforation with esophageal carcinoma.METHODS 36 cases of perforation with esophageal carcinoma were treated surgically in this series.Perforations occurred into the right lung in14 cases ,the mediastinum in 17 cases and trachea in 5 cases.Open thoracic surgery was performed in 34 cases,in which the right thoracic approach using a 3-incision method was applied in 16 cases,and operation by stages in 15 cases.Of the 34 cases,retrosternal substitution of the esophagus with stomach or colon was performed in 26 cases.RESULTS Surgery was successful in 31 cases and operative death occurred in 3 cases.The postoperative follow up study was from 3~72months.Of these cases 15 wree alive at 7~12 months, 2 at 24 months,and 1 at 72 months. The results can be considered satisfactory.CONCLUSION The therapeutic results of surgical treatment of perforation with esophageal carcinoma were markedly superior to that of conventional conservative treatment. The authors suggest that surgical intervention without delay should be undertaken for patients having a perforation with carcinoma of the esophagus. A right thoracic approach with a 3-incision method (retrosternal replacement of esophagus with stomach or colon) or operation by stages is preferable.

  19. Delayed transverse radiation myelitis in esophageal carcinoma

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    Objective: To investigate the prevention and treatment of delayed transverse myelitis caused by radiotherapy in patients with thoracic esophageal carcinoma. Methods: Radical radiotherapy had been given to five patients (female 3, male 2) with thoracic esophageal carcinoma with delayed transverse myelitis developed 7 to 30 months after radiotherapy without any local recurrence. The study was done in an attempt to describe the clinical symptoms and signs. Analysis of causes was done to seek possible means of treatment and prevention. Results: Once delayed transverse myelitis had happened, it was not possible to cure. In this group, four patients died 1-2 years after myelopathy had occurred, and one was alive with functional neurological loss. Conclusions: Delayed transverse myelitis is an uncommon and serious complication induced by irradiation. It is very difficult to manage and indicates a very poor prognosis. The authors recommend precise radiation design and prudent performance for prevention

  20. Experimental studies of metastases of esophageal carcinoma to lymph nodes

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    Marked progress has been made in surgery for esophageal carcinoma, however, when compared to results of surgery for other carcinomas of the digestive tract, much research remains to be done. The author transplanted VX2 carcinoma, a transplantable tumor of the rabbit, to the esophagus in attempt to determine the mode of metastases of esophageal carcinoma to lymph nodes and also to observe the effect of chemotherapy (Bleomycin) and radiotherapy (Betatron). Carcinoma of the cervical esophagus metastasized to the cervical lymph nodes and then to the paratracheal lymph nodes. Carcinoma of the upper thoracic esophagus metastasized to the paratracheal lymph nodes and then to the cervical lymph nodes. Carcinoma of the mid-thoracic esophagus metastasized to the intrathoracic lymph nodes and then to the intraperitoneal lymph nodes. Carcinoma of the abdominal esophagus metastasized to the intraperitoneal lymph nodes and then to the intrathoracic lymph nodes. Skipping metastasis was rarely observed. Carcinoma of the thoracic esophagus with metastases of lymph nodes in the cervical or abdominal portion was considerably advanced, therefore it is considered that cleaning of the intrathoracic lymph nodes and simultaneous chemotherapy are required when such cases are encountered clinically. Irradiation resulted in regression in the size of the tumor and metastases to lymph nodes and there was a decrease in metastases to the distant lymph nodes. Effects of irradiation were similar on tumors and lymph nodes with positive metastases located within the field of irradiation. Bleomycin medication resulted in regression in the size of tumor and metastases to lymph nodes. Effects of Bleomycin medication were similar on tumors and lymph nodes with positive metastases. (auth.)

  1. Second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma

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    Song ZB

    2014-10-01

    Full Text Available Zhengbo Song, Yiping Zhang Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Purpose: This retrospective analysis evaluates the clinical efficacy and toxicity of second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma (ESCC. Methods: We retrospectively reviewed patients who had received second-line docetaxel-based chemotherapy for advanced ESCC in Zhejiang Cancer Hospital between January 2008 and December 2011. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis. Results: Eighty-five patients received docetaxel-based second-line chemotherapy after the failure of first-line fluorouracil-based treatment. Forty-four patients received docetaxel-platinum chemotherapy, and 41 received docetaxel single-agent treatment. The progression-free survival (PFS and overall survival (OS were 3.5 and 5.5 months in all of the patients, respectively. There were no statistically significant differences in PFS and OS between docetaxel-platinum and docetaxel single-agent chemotherapy groups (P-value 0.38 and 0.64, respectively. Response to first-line chemotherapy was a favorable prognostic factor for PFS in uni- and multivariate analyses (P-value 0.005 and 0.028, respectively. Conclusion: Patients with docetaxel-based second-line treatment obtained a moderate PFS advantage in advanced ESCC. Response to first-line chemotherapy was a favorable prognostic factor for PFS of second-line chemotherapy in advanced ESCC. Keywords: ESCC, efficacy, toxicity

  2. A Case of Esophageal Squamous Cell Carcinoma with Pancreatic Metastasis

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    Park, Choulki; Jang, Jae Young; Kim, Youn Hwa; Hwang, Eun Jung; Na, Ki Yong; Kim, Kyung-Yup; Park, Jae Hyun; Chang, Young Woon

    2013-01-01

    Solitary pancreatic metastasis of esophageal cancer is extremely rare. We report the case of a 58-year-old male admitted with esophageal cancer. Additional asymptomatic solitary hepatic and pancreatic masses were observed in the staging work-up for esophageal cancer. The hepatic mass was confirmed as a primary hepatocellular carcinoma with an ultrasound-guided needle biopsy. An esophagectomy with a distal pancreatectomy and radiofrequency ablation for hepatocellular carcinoma were performed. ...

  3. Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk. Planning study in esophageal carcinoma

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    Fakhrian, K. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Dept. of Radiation Oncology; Marienhospital Herne (Germany). Dept. of Radiation Oncology; Bochum Univ., Herne (Germany). Universitaetsklinikum; Oechsner, M.; Kampfer, S.; Molls, M.; Geinitz, H. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Dept. of Radiation Oncology; Schuster, T. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Inst. of Medical Statistics and Epidemiology

    2013-04-15

    The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive {>=} 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced

  4. Radiological Imaging in Patients with Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    BarbaraKrug; ClaudiaMorgenroth

    2004-01-01

    Diagnostic imaging is carried out in patients with esophageal carcinoma in order to decide on the therapeutical procedure, to control therapy, to document complications and to assess concomitant diseases.Chest X-rays and esophagograms give a 2-dimensional view of the X-ray absorption ill 3-dimensional examination volumes, the diagnostic accuracy thus being limited by overshadowing. Because of the robust examination technique, the broad availability and the low costs chest X-rays are usually used for short-term controls under therapy and follow-up. Esophagography is carried out in order to asses the exact location and length of a known esophageal carcinoma prior to therapy and in order to assess peristaltic disturbances and fistulas. CT and MRI provide tomographic images with a spatial resolution of up to 1mm3 allowing the reconstruction of high-resolution images not only in the transversal but also in any other plain. The diagnostic accuracy of esophagography is comparatively high in T1 T3 stages (80%-90%). T1 and T2 tumors cannot be diagnosed by CT and MRI, because both methods do not visualize the mucosa(unlike esophagography and endoscopy) and the esophageal wall layers (unlike EUS). Infiltration depth tends to be overestimated in T1 and T2 carcinomas and to be underestimated in T3 and T4 cancers. CT and MRI cannot detect metastases in normally sized lymph nodes and cannot accurately differelltiate between benign and malignant lymphadenopathy in enlarged nodes with a reported sensitivities and spccifities of 60% and 74%, respectively. However, further prospective studies using up to date CT and NIR technology are needed to assess the present diagnostic situation. CT and MRI do not only visualize the inediastinum,but also the lungs, the pleura and the skeleton as well as the neck and the abdomen thus providing a comprehensive overview of the TNM stage in 3 body regions.

  5. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    Science.gov (United States)

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    Background To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT) with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received nonsurgical treatment. Methods This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy). The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS) and overall survival (OS) by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological), and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively). The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  6. Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jian-Gang Jiang; Dao-Wen Wang; Jiang-Bo Tang; Chun-Lian Chen; Bao-Xing Liu; Xiang-Ning Fu; Zhi-Hui Zhu; Wei Qu; Katherine Cianflone; Michael P. Waalkes

    2004-01-01

    AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human esophageal squamous cell carcinoma.METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, immunohistochemistry and immunofluorescence were used to assess the expression level of COX-2 in esophageal tissue.RESULTS: COX-2 mRNA levels were increased by >80-fold in esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue. COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was performed to directly show expression of COX-2 in tumor tissue.CONCLUSION: These results suggest that COX-2 may be an important factor for esophageal cancer and inhibition of COX-2 may be helpful for prevention and possibly treatment of this cancer.

  7. A comparative analysis by SAGE of gene expression profiles of esophageal adenocarcinoma and esophageal squamous cell carcinoma

    NARCIS (Netherlands)

    van Baal, Jantine W. P. M.; Milana, Francesco; Rygiel, Agnieszka M.; Sondermeijer, Carine M. T.; Spek, C. Arnold; Bergman, Jacques J. G. H. M.; Peppelenbosch, Maikel P.; Krishnadath, Kausilia K.

    2008-01-01

    Esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett's esophag

  8. A second primary esophageal cancer developing 7 years after chemoradiotherapy for advanced esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Suto, Ryuichiro; Enjoji, Akihito; Okudaira, Sadayuki; Furui, Junichiro; Kanematsu, Takashi [Nagasaki Univ. (Japan). School of Medicine; Matsuo, Takeshi

    2001-07-01

    We report a rare case of advanced carcinoma and a second primary carcinoma of the esophagus, both of which were successfully cured by chemotherapy and operation at different times. In 1991, a 38-year-old Japanese man was diagnosed with advanced esophageal cancer, which was unresectable because of the bronchial invasion of the tumor. He was given chemotherapy with cisplatin (CDDP), combined with radiotherapy. During a 4-year follow-up, neither regrowth of the primary tumor nor distant metastasis occurred. In 1995, esophagoscopy demonstrated a lugol-unstained region located 3 cm distal from the area of radiation to the primary lesion shown by esophagography. Histological examination of a biopsy specimen showed the mucosa to be normal. Nevertheless, yearly surveillance by endoscopy and histological examinations showed that the mucosa of the esophagus gradually began to demonstrate mild dysplasia, followed by severe dysplasia; in 1998, a diagnosis of squamous cell carcinoma was made. Esophagectomy with lymph node dissection was performed. Microscopic examination revealed that there had been pathologic complete response for the original advanced esophageal cancer. (author)

  9. Clinical significance of expression of Klotho and β-Catenin in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    汤小伟

    2013-01-01

    Objective To investigate the clinical significance of expression of Klotho and β-Catenin in esophageal carcinoma. Methods Tissue microarray technique and immunohistochemistry were used to examine Klotho and β-Catenin expression in 75 esophageal carcinoma tissue

  10. Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

    International Nuclear Information System (INIS)

    Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression. Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays. The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels. The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer

  11. MicroRNA and esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiaoting He; Xiufeng Cao

    2007-01-01

    Objective:An abundant class of non-coding small RNA molecules, 21-25 nucleotide in length, are widely found in animals and plants and named microRNA(miRNA)[1-2]. MiRNAs are highly evolutionarily conserved, expressing in specific tissue and timing[2], and negatively regulate the gene expressions at the posttranscriptional level[3], and subsequently control crucial physiological processes such as metabolism, amplification, differentiation, development and apoptosis[4-7]. Therefore, miRNAs could provide an access to many human diseases in theory. Recent evidence demonstrates that miRNAs play an important role in the initiation and progression of human cancer, mainly by interrupting the cell cycle at the cellular level and by interacting with signaling [7-11] The expression profiling of miRNAs can be used as a tool of diagnosis, staging, prognosis and biotherapy of some tumors, as has already been proven to have superiority to mRNA, in the categorization of tumors. This review focuses on the genesis, mechanism of action of miRNA and its relationship to tumors, detection methods and its potential effect on the diagnosis, staging, and biotherapy in esophageal carcinoma.

  12. Esophageal carcinoma originating in a duplication cyst: case report

    Directory of Open Access Journals (Sweden)

    Pimenta Amadeu P. A.

    1997-01-01

    Full Text Available The authors present the case report of a 61-year-old man, admitted with middle third squamous cell esophageal carcinoma. He was submitted to a curative gastroesophageal resection via a medium laparotomy and a right thoracotomy. An intrathoracic esophagogastric anastomosis was performed. The pathological analysis of the surgical specimen revealed a squamous cell carcinoma clearly originating from the epithelial lining of an esophageal duplication cyst. Immunohistochemitry showed p 53 staining of the tumor cells. The patient at 11 month follow up was asymptomatic.

  13. Peptidergic innervation of human esophageal and cardiac carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shuang-Hong Lü; Yan Zhou; Hai-Ping Que; Shao-Jun Liu

    2003-01-01

    AIM: To investigate the distribution of neuropeptideimmunoreactive nerve fibers in esophageal and cardiac carcinoma as well as their relationship with tumor cells so as to explore if there is nerve innervation in esophageal and cardiac carcinoma.METHODS: Esophageal and cardiac carcinoma specimens were collected from surgical operation. One part of them were fixed immediately with 4 % paraformaldehyde and then cut with a cryostat into 40-pm-thick sections to perform immunohistochemical analysis. Antibodies of ten kinds of neuropeptide including calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP), etc. were used for immunostaining of nerve fibers. The other part of the tumor specimens were cut into little blocks (1 mm3) and cocultured with chick embryo dorsal root ganglia (DRG) to investigate if the tumor blocks could induce the neurons of DRG to extend processes, so as to probe into the possiblereasons for the nerve fibers growing into tumors. RESULTS: Substantial amounts of neuropeptide including GAL-, NPY-, SP-immunoreactive nerve bundles and scattered nerve fibers were distributed in esophageal and cardiac carcinomas. The scattered nerve fibers waved their way among tumor cells and contacted with tumor cells closely. Some of them even encircled tumor cells. There were many varicosities aligned on the nerve fibers like beads. They were also closely related to tumor cells. In the co-culture group, about 63 %and 67 % of DRG co-cultured with esophageal and cardiac tumor blocks respectively extended enormous processes,especially on the side adjacent to the tumor, whereas in the control group (without tumor blocks), no processes grew out.CONCLUSION: Esophageal and cardiac carcinomas may be innervated by peptidergic nerve fibers, and they can induce neurons of DRG to extend processes in vitro.

  14. Clinical value of hematologic test in predicting tumor response to neoadjuvant chemotherapy with esophageal squamous cell carcinoma

    OpenAIRE

    Liu, Yinan; Chen, Jinfeng; Shao, Ningsheng; Feng, Yuan; Wang, Yuzhao; Zhang, Lijian

    2014-01-01

    Background To investigate the relationship between hematologic test results and the predictive effect of regression of esophageal cancer after neoadjuvant chemotherapy (NACT), we analyzed pre-NACT hematologic data and their relationship to tumor regression. Methods Thirty-eight consecutive patients with locally advanced squamous cell esophageal carcinoma who had undergone two cycles of paclitaxel/carboplatin NACT were enrolled. On the day prior to the first cycle of chemotherapy, hematologic ...

  15. Technological advances in radiotherapy for esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Milan; Vosmik; Jiri; Petera; Igor; Sirak; Miroslav; Hodek; Petr; Paluska; Jiri; Dolezal; Marcela; Kopacova

    2010-01-01

    Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer.The goal of modern radiotherapy approaches,based on recent technological advances,is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning),reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy),and by better dose delivery to the precisely defined planning ...

  16. Computerized tomographic evaluation of upper mediastinal lymph node metastasis from esophageal carcinoma. For decision of therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, Toshiki; Kinoshita, Iwao; Nakagawa, Ken; Ohashi, Ichiro; Hori, Masaharu; Kajiya, Tamaki; Kaneda, Koichi; Kato, Hiroshi

    1985-01-01

    Computed tomography (CT) was performed in patients with esophageal carcinoma including 76 preoperative patients, 11 with upper mediastinal lymph node metastasis after radical surgery, and 10 with unresectable advanced tumors of the lymph nodes. CT was useful in diagnosing metastasis of the most upper part of the right mediastinal lymph nodes and the left paratracheal lymph nodes. During preoperative irradiation, enlargement of paratracheal lymph node metastasis was seen outside the irradiated field on CT images. An enlarged pretracheal lymph node was not seen on CT images even in cases of far advanced carcinoma. Nodal failures frequently occurred at the upper part of the right mediastinal lymph nodes, the left paratracheal lymph nodes and the left tracheobronchial lymph nodes in the 11 patients with upper mediastinal recurrence. CT seems to be of great value in the decision of therapeutics for esophageal carcinioma.

  17. Incidence of brain metastasis in patients with esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ron S Smith; Robert C Miller

    2011-01-01

    AIM: To determine the incidence of brain metastasis in a contemporary group of patients with carcinoma of the esophagus. METHODS: Retrospective analysis of 53 patients with esophageal carcinoma who received radiotherapy as a component of treatment between 1998 and 2007, including patient and tumor characteristics, and subsequent diagnosis of brain metastasis. The association between the histological type of esophageal cancer and the incidence of brain metastasis was assessed using Fisher's exact test. RESULTS: Forty-four of the fifty-three patients in this study had adenocarcinoma and nine had squamous cell carcinoma, ranging from stage ⅡA-ⅣB. Primary treatment was surgery with neoadjuvant chemoradiotherapy (trimodality therapy) in 19% of patients; chemoradiotherapy in 42%; and surgery and adjuvant radiotherapy in 7%. Twenty-five percent of patients in this study received palliative radiotherapy. The overall incidence of brain metastasis in this cohort was 13%. Adenocarcinoma was the primary tumor histology in all of the patients who developed brain metastasis, representing an incidence of 16% in this subgroup. No patients with squamous cell carcinoma received trimodality therapy. The association between histology and brain metastasis was not statistically significant. CONCLUSION: The incidence of brain metastasis in this contemporary cohort of patients with esophageal carcinoma is higher than previously reported and was confined to those with adenocarcinoma.

  18. Personalized Management of Anastomotic Leak after Surgery for Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong-yu Ye; Wei-zhao Huang; Yin-meng Wu; Yi Liang; Jun-meng Zheng; Hai-ming Jiang

    2012-01-01

    To summarize the management of anastomotic leak following surgery for esophageal carcinoma.Methods The medical records of the patients developing digestive tract leak after surgery for esophageal carcinoma in our hospital from January 2003 to March 2011 were retrospectively analyzed.Results A total of 36 patients were included,in whom 13 developed cervical anastomotic leak,18 had intra-thoracic anastomotic leak,and 5 had intra-thoracic gastric necrosis.Of these patients,7 were treated with resurgery,6 with esophageal stent implantation,and 23 with conservative treatment.Treatment lasted for 5 to 181 days,averagely 47.0±31.9 days.After management,9 patients died (25.0%).Among seven patients with resurgery,four had deceased,two were cured,and one developed leak again and was switched to conservative treatment until discharged.All the 6 patients treated with stent implantation were cured.Of the 24 patients receiving conservative treatment (including one switched from resurgery),18 (75.0%) were cured and 1 was not cured but survived.Conclusions Anastomotic leak following surgery for esophageal carcinoma should be treated individually based on the onset time,location,size,and extent of the leakage.Conservative treatment is still a safe and effective method.The efficacy of stent implantation needs further investigation to confirm.

  19. Weekly nanoparticle albumin bound-paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-09-01

    Full Text Available Hai-ying Wang, Zhi-hua Yao, Hong Tang, Yan Zhao, Xiao-san Zhang, Shu-na Yao, Shu-jun Yang, Yan-yan Liu Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China Objective: More effective regimens for advanced esophageal squamous cell carcinoma (ESCC are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP versus solvent-based paclitaxel plus cisplatin (sb-TP as a first-line therapy was conducted in Chinese patients with advanced ESCC.Methods: From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2 on the first and eighth days (30 minutes infusion and cisplatin (75 mg/m2 on the second day every 21 days (nab-TP arm. Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2 intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm. The two groups were compared in terms of objective response rate (ORR, disease control rate, progression-free survival (PFS, overall survival (OS, and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes.Results: Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082 and disease control rate (81% vs 65%; P=0.124 than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269. However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9] than sb-TP (5.0 months [95% confidence interval: 4.4–5.6] (P=0.029. The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy

  20. Coexistence of esophageal blue nevus, hair follicles and basaloid sqamous carcinoma: A case report

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    We present the case of a 57-year-old man who underwent esophagectomy for esophageal carcinoma found at barium meal and gastroscopic examination. He was diagnosed as esophageal basaloid squamous carcinoma (BSC) and gastric stromal tumor, which were associated with focal proliferation of melanocytes/ pigmentophages and hair follicles in esophageal mucosa. Melanocytic hyperplasia (melanocytosis) has previously been recognized as an occasional reactive lesion, which can accompany esophageal inflammation and invasive squamous carcinoma. The present case is unusual because of its hyperplasia of not only melanocytes but also hair follicles. To our knowledge, this is the first report of esophageal blue nevus and hair follicle coexisting with BSC.

  1. Evidence of human papilloma virus infection and its epidemiology in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Pin-Fang Yao; Ju-Wei Sha; Guang-Can Li; Jin Li; He-Shun Xia; Xiao-Ling Yang; Huan-Yuan Huang; You-Gao Fu; Rui-Qin Wang; Xi-Yin Wang

    2006-01-01

    AIM: To look for the evidence of human papilloma virus (HPV) infection in esophageal squamous cell carcinomas (ESCC) and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants.METHODS: Papilloma virus (PV) and HPV were determined by UltrasensiveTM S-P immunohistochemistry (IHC)and in situ hybridization (ISH) in esophageal carcinoma tissues (82.cases) and the normal mucosa (40 cases).RESULTS: IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%, 36.36%, 37.5%,respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV (16/18) DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens (P< 0.05). The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens (P>0.05).CONCLUSION: HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squamous cell carcinoma. HPV infection may play an important role in esophageal squamous cell carcinoma.

  2. Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction

    Institute of Scientific and Technical Information of China (English)

    Masaya; Uesato; Tuguaki; Kono; Tooru; Shiratori; Yasunori; Akutsu; Isamu; Hoshino; Kentarou; Murakami; Daisuke; Horibe; Tetsurou; Maruyama; Yoshihide; Semba; Ryuma; Urahama; Yukiko; Ogura; Takashi; Oide; Toru; Tanizawa; Hisahiro; Matsubara

    2014-01-01

    Esophageal lymphoepithelioma-like carcinoma(LELC) is extremely rare. We report the first case of esopha-geal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed aroundthe carcinoma cells. Therefore, this lesion was consid-ered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagec-tomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1 b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.

  3. Low-dose rate telecobalt therapy as a boost against esophageal carcinomas

    International Nuclear Information System (INIS)

    The results of treatment of 54 esophageal carcinomas managed with low-dose-rate telecobalt therapy (LDRT) as a boost were compared with those of 89 esophageal carcinomas treated with conventionally fractionated irradiation alone (CFI). The LDRT (1 Gy/hr, 5-7 Gy/day, to a total dose of 14-20 Gy) was boosted about 10 days after the CFI dose of 60 Gy. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rate of the LDRT group, especially those with tumorous X-P and serrated types, were better than those of the CFI group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose in the LDRT group was brought under 80 Gy. (author)

  4. Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Si; Tang, Wenqing; Weng, Shuqiang; Liu, Xijun; Rao, Benqiang; Gu, Jianxin; Chen, She; Wang, Qun; Shen, Xizhong; Xue, Ruyi; Dong, Ling

    2014-08-30

    Patients with esophageal squamous cell carcinoma (ESCC) are often diagnosed with advanced diseases that respond poorly to chemotherapy. Here we reported that Apollon, a membrane-associated inhibitor of apoptosis protein, was overexpressed in ESCC cell lines and clinical ESCC tissues, and Apollon overexpression clinically correlated with poor response to chemotherapy (P = 0.001), and short overall survival (P = 0.021). Apollon knockdown increased cisplatin/docetaxel-induced apoptosis, mitochondrial dysfunction and cytochrome c release in two ESCC cell lines. Apollon knockdown potentiated cisplatin/docetaxel-induced long-term cell growth inhibition, and enhanced chemosensitivity of ESCC cells to cisplatin/docetaxel in xenograft tumor models. Apollon knockdown also enhanced cisplatin/docetaxel-induced activation of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) in ESCC cells and xenograft tumor models. Mechanism studies revealed that the effect of Apollon on chemosensitivity is mainly mediated by Smac. Apollon expression strongly and negatively correlated with Smac expression in clinical ESCC tissues (P = 0.001). Apollon targeted Smac for degradation in ESCC cells. The effect of Apollon on chemosensitivity was reversed by Smac knockdown in ESCC cells. Taken together, our data show association of Apollon expression with chemotherapeutic response in ESCC, and provide a strong rationale for combining Apollon antagonism with chemotherapy to treat ESCC.

  5. Advances in rodent models of human esophageal squamous cell carcinoma%食管鳞癌动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄裔腾; 殷秀凯; 钟雪云; 张灏

    2011-01-01

    建立和应用真实模拟人类疾病的动物模型,从整体水平动态地揭示肿瘤发生机制,从而寻找防治对策和开发治疗新药,是成功开展转化医学研究的关键.食管癌是最高发的恶性肿瘤之一.由于相关活体动物模型研究和开发的相对滞后,对于食管鳞癌的病因、发病机制和相关分子通路缺乏全面系统深入的认识,直接导致无法有针对性地进行早期分子诊断标志物和有效药物靶点的开发和转化,严重影响早期诊断和治疗预后.合适的动物模型是改变这一现状的关键.本文就食管鳞癌动物模型的种类、构建和应用方面作一综述,并着重介绍了4-硝基喹啉-氧化物(4NQO)化学致癌结合基因工程的小鼠模型.%Esophageal squamous cell carcinoma (ESCC) is a common form of malignant disease. Appropriate animal models recapitulating human cancers, which are powerful not only for the elucidation of in vivo process and relevantmechanisms of the diseases but also for the evaluation of efficacy and safety of new drugs and management concepts, are critical for the success of translational research. In this context, compared with other malignancies, the present situation for human ESCC that novel discoveries for either diagnostic markers or therapeutic targets as well as the clinical application are out of step (laggard) is largely attributed to the lack of suitable in vivo animal model for this human disease. This article provides an overview of the currently available animal models established for human ESCC, encompassing chemically induced and genetically engineered rodents. Genetically engineered mice coupling induction with 4-nitroquinoline-l-oxide (4NQO) are discussed in more detail.

  6. Radiotherapy for postoperative regional recurrence in esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the significance of radical radiotherapy for regional recurrence in esophageal carcinoma at different sites after radical surgery and its prognostic factors. Methods: 110 patients who developed regional recurrence in esophageal carcinoma after radical resection were analyzed retrospectively. The sites of recurrence were: supraclavicular lymph node 17, mediastinal lymph node 72, abdominal lymph node 5 and anastomotic stoma 16. Radiotherapy was given by 60Co unit or 6 MV X-ray with a median dose of 62 Gy (50-76 Gy). Results: The overall 1-, 2-, 3-, and 4-year survival rates were 55.4%, 30.4%, 21.8% and 14.5%, with a median of 14 months. Site of recurrence, T stage, total radiotherapy dose, symptom amelioration level and total treatment response were related with prognosis, but only TNM stage and symptom amelioration level after radiotherapy were independent prognostic factors. Conclusions: Radiotherapy may improve the survival in patients with postoperative recurrence in esophageal carcinoma. Patients with early lesion found at surgery and complete response of symptom after radiotherapy have better prognosis. (authors)

  7. Esophageal combined carcinomas: Immunohoistochemical and molecular genetic studies

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada; Hirotoshi Maruo

    2012-01-01

    Primary esophageal combined carcinoma is very rare.The authors herein report 2 cases.Case 1 was a combined squamous cell carcinoma and small cell carcinoma,and case 2 was a combined squamous cell carcinoma,adenocarcinoma,and small cell carcinoma.Case 1 was a 67-year-old man with complaints of dysphagia.Endoscopic examination revealed an ulcerated tumor in the middle esophagus,and 6 biopsies were obtained.All 6 biopsies revealed a mixture of squamous cell carcinoma and small cell carcinoma.Both elements were positive for cytokeratin,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The small cell carcinoma element was positive for synaptophysin,CD56,KIT,and platelet-derived growth factor-α (PDG-FRA),while the squamous cell carcinoma element was not.Genetically,no mutations of KIT and PDGFRA were recognized.The patient died of systemic carcinomatosis 15 mo after presentation.Case 2 was a 74-year-old man presenting with dysplasia.Endoscopy revealed a polypoid tumor in the distal esophagus.Seven biopsies were taken,and 6 showed a mixture of squamous cell carcinoma,small cell carcinoma,and adenocarcinoma.The 3 elements were positive for cytokeratins,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The adenocarcinoma element was positive for mucins.The small cell carcinoma element was positive for CD56,synaptophysin,KIT,and PDGFRA,but the other elements were not.Mutations of KIT and PDGFRA were not recognized.The patient died of systemic carcinomatosis 7 mo after presentation.These combined carcinomas may arise from enterochromaffin cells or totipotential stem cell in the esophagus or transdifferentiation of one element to another.A review of the literature was performed.

  8. Simultaneous resection of left atrial myxoma and esophageal carcinoma via right thoraco-abdominal approach.

    Science.gov (United States)

    Ni, Buqing; Lu, Xiaohu; Gong, Qixing; Shao, Yongfeng

    2016-07-01

    Concomitant occurrence of atrial myxoma and esophageal carcinoma is an extremely rare entity. Here we present two cases of synchronously suffered left atrial myxoma and esophageal carcinoma. Both patients underwent simultaneous resection of two tumors via the right thoraco-abdominal approach and recovered well.

  9. Surgical Treatment of Primary Esophageal Small-cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the clinical biocharacteristics of primary esophageal small-cell carcinoma (PESC) and factors influencing prognosis and to find rational indications for combination therapy. Methods: To analyze the clinical materials of 47 patients who had undergone an operation with PESC and to compare it with those patients with esophageal squamous-cell carcinoma (ESCC) or primary esophageal adenocarcinoma (PEAC). Results: The overall resectability, morbidity and 30-day mortality rates of PESC were 93.6%, 17.0%and 2.1% respectively, similar to those of ESCC or PEAC. TNM staging and lymph node metastasis were the major determinants influencing long-term survival. Tumor length, depth of tumor invasion and type of operation had little influence on long-term prognosis. The 5-year survival rate of PESC was 7.5%, which was much lower than that of ESCC and PEAC (P<0.01). Among the 42 deceased patents, one died of anastomotic leakage and the others died of remote metastasis and recurrence. Adjuvant chemotherapy did not help improve the patients' long-term survival. Conclusions: Compared with ESCC and PEAC, PESC is the most malignant type with early lymphatic and hematogenous metastases and poor prognosis. Lymph node metastasis is the major factor influencing the prognosis. Patients in stage 0, I and II a of PESC are indicated for surgical resection, while those in stage II b, III or IV should be managed with non-surgical combined therapy.

  10. Esophageal Squamous Cell Carcinoma With Pancreatic Metastasis: A Case Report

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    Abbas Alibakhshi

    2011-11-01

    Full Text Available Malignant tumors of pancreas are usually primary neoplasms and pancreatic metastases are rare findings. We are reporting a case of squamous cell carcinoma (SCC of the esophagus with pancreatic metastasis. A 59-year old woman was admitted with chief complaint of abdominal pain and mass. She was a known case of esophageal SCC since 4 years before when she had undergone transthoracic esophagectomy and cervical esophago-gastrostomy. In order to evaluate recent abdominal mass, CT scan was done which revealed septated cystic lesion in the body and the tail of the pancreas. Palliative resection of the tumor was performed and its histological study showed SCC compatible with her previously diagnosed esophageal cancer.

  11. Surgical treatment of hepatocellular carcinoma with cirrhotic esophageal varices and hypersplenism:a 184 case report

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    JIANG Bin; CHEN Xiaoping; HUANG Zhiyong; ZHANG Zhiwei; HE Songqing; WANG Shaofa; WU Zaide; QIU Fazu

    2007-01-01

    In treating hepatocellular carcinoma (HCC)patients with advanced cirrhosis,one of the most difficult problems is concomitant esophageal varices and hypersplenism.Whether these conditions should be treated surgically in association with HCC resection is still in debate.To elucidate whether esophageal devascularization or splenectomy is beneficial when simultaneously performed with liver resection in HCC patients with both varices and hypersplenism,HCC patients (n = 184) with esophageal varices and hypersplenism received one of the three treatments:simultaneous liver resection and esophageal devascularization (Group Ⅰ,n=41);simultaneous liver resection and splenectomy (Group Ⅱ,n = 61);liver resection only (Group Ⅲ,n = 82).The incidences of postoperative complications of the three groups were 31.7%,29.5% and 24.4%,respectively,with no significant difference among them.The 5-year tumor-free survival rates for the group Ⅰ,group Ⅱ and group Ⅲ were 34.1%,36.1% and 37.8%,respectively.Variceal bleeding caused death by only 4.2% in group Ⅰ,but by 14.3% in group Ⅱ and 23.2% in group Ⅲ.The survival rates in the group Ⅰ and the group Ⅱ were comparable to those in the group Ⅲ,however,the recurrences of postoperative fatal variceal bleeding in group Ⅰ and group Ⅱ were significantly lower than those in group Ⅲ.The results suggest that HCC patients with esophageal varices and hypersplenism should undergo hepatic resection plus esophageal devascularization or splenectomy if radical resection of HCC can be expected.

  12. Metastases of esophageal carcinoma to skeletal muscle:Single center experience

    Institute of Scientific and Technical Information of China (English)

    Jan Cincibuch; Miroslav Myslive(c)ek; Bohuslav Melichar; (C)estmír Neoral; Iva Metelková; Michaela Zezulová; Hana Procházková-(S)tudentová

    2012-01-01

    Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT).A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases.Four patients had skeletal muscle metastases of esophageal carcinoma,including two patients with squamous cell carcinoma.In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases,muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma.In all cases,skeletal muscle metastases were the first manifestation of systemic disease.In three patients palliation was obtained with the combination of external beam radiation therapy,systemic chemotherapy or surgical resection.Skeletal muscle metastases are a rare complication of esophageal carcinoma.

  13. Overexpression of Periostin and Lumican in Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared to the adjacent normal epithelium. In the current study, we performed immunohistochemical analyses of protein products for two candidates genes identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM), using tissue microarrays. Increased expression of both periostin and lumican was observed in 100% of 137 different ESCC samples arrayed on tissue microarrays. Increased expression of periostin and lumican was observed in carcinoma as well as in stromal cell in the large majority of cases. These findings suggest that these candidates can be investigated in the sera of ESCC patients using ELISA or multiple reaction monitoring (MRM) type assays to further explore their utility as biomarkers

  14. Concurrent Chemoradiotherapy in Locally Advanced Esophageal Cancer

    International Nuclear Information System (INIS)

    This study was designed to evaluate the results of local control, survival rate, prognostic factors, and failure pattern in locally advanced esophageal cancer. We retrospectively studied 50 patients with locally advanced esophageal cancer treated with concurrent chemoradiotherapy at Keimyung University Dongsan Medical Center from June of 1999 to August of 2008. Seven patients with inappropriate data were excluded, and 43 patients were analyzed. There were 39 males and four female patients ranging in age from 43 to 78 years (median, 63 years). There were seven patients with stage IIA and 36 with stage III. Irradiation from 46 Gy to 63 Gy (median, 54 Gy) was carried out 5 days per week, 1.8 Gy once a day. There were eight patients with neo-adjuvant chemotherapy, and we mostly used 5-fluorouracil, cisplatin with 3 cycles for concurrent chemotherapy. The range of follow up periods was from 2 to 82 months (median, 15.5). There were nine patients that exhibited a complete response, 23 that exhibited a partial response, 9 that exhibited no response, and 2 that exhibited disease progression. The median survival time was 15 months. Two-year and 5-year survival rates were 36.5% and 17.3%, respectively. Two-year and 5-year disease-free survival rates were 32.4% and 16%, respectively. Treatment failure occurred in 22 patients (51.2%). Patterns of failure were categorized as local failure in 18 patients and distant metastasis in four patients. In a univariate analysis for prognostic factors related to overall survival and disease-free survival, the hemoglobin levels during chemoradiotherapy (≥12 vs. <12, p=0.02/p=0.1) and the response to the treatments (CR/PR vs. NR/PD, p=0.002/p <0.0001) were statistically significant. In a multivariate analysis, only response to the treatments was revealed to be statistically significant. There was no statistical significance associated with patient age, gender, disease stage, T-stage, smoking history, tumor location, or neo

  15. Airway and esophageal stenting in patients with advanced esophageal cancer and pulmonary involvement.

    Directory of Open Access Journals (Sweden)

    Fabrice Paganin

    Full Text Available BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\\-8 years of age with esophageal stenting indication were investigated. Seven patients (group 1 were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression. Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2: stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication. Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks than in group 2 (28+/-11 weeks, p<0.001. Scheduled double stenting significantly improved symptoms (95% at day 7 with a low complication rate (13%, and achieved a specific cancer treatment (84% in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased

  16. Treatment of medium and late stage esophageal carcinoma with combined endoscopic metal stenting and radiotherapy

    Institute of Scientific and Technical Information of China (English)

    钟捷; 吴云林; 许帧; 刘晓天; 许斌; 翟祖康

    2003-01-01

    Objective To evaluate clinical feasibility and efficacy of endoscopic metal stenting combined with radiotherapy for treatment of medium and late stages of esophageal carcinoma. Methods Thirty-four patients of late stage esophageal carcinoma were treated with endoscopic stent implantation in combination with radiotherapy. Evaluations of CES stainless steel metal stent on the effect of radiation, clinical symptom alleviation and complication and survival rates in both groups were made. Conclusion Endoscopic metal stenting in combination with radiotherapy was a feasible and practical management in treating medium and late stages esophageal carcinoma and was superior to simple metal stent implantation.

  17. 139例晚期食管鳞状细胞癌的一线化疗及生存分析%First-line chemotherapy of patients with advanced esophageal squamous cell carcinoma:A survival analysis of 139 cases

    Institute of Scientific and Technical Information of China (English)

    闫晓杰; 夏学明; 刘钦兰; 白莉

    2015-01-01

    目的:研究晚期食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)一线化疗情况及影响预后的相关因素。方法回顾性分析2009年1月-2014年8月在我院初治Ⅳ期行一线化疗的139例ESCC患者的临床资料,其中男性124例,女性15例,年龄39~78岁,中位年龄为58岁。采用Kaplan-Meier法分析总生存时间(overall survival,OS),单因素和Cox回归多因素分析影响生存及预后的相关因素。结果139例患者化疗总有效率为46.8%,1年、3年、5年生存率分别为55.4%、15.8%、4.5%。一线化疗的中位OS为13.9个月,单因素及多因素分析显示,肝转移(P=0.028)、一线化疗疗效(P=0.001)、是否胸部放疗(P=0.000)与OS有关。结论有无肝转移、化疗是否有效、是否接受放疗对患者预后有重要影响,无肝转移患者的预后好,化疗评价有效、接受放疗有益于生存。%Objective To study the survival of patients with advanced esophageal squamous cell carcinoma (ESCC) in first-line chemotherapy and the factors related to the prognosis. Methods Clinical data about 139 advanced ESCC patients with 124 males and 15 females who received first-line chemotherapy in our hospital from January 2009 to August 2014 were retrospectively analyzed. The distribution of age range was 39 to 78 years old with median age of 58 years old. Kaplan-Meier method was used to calculate the overall survival (OS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival and prognosis. Results The response rate of 139 patients with chemotherapy was 46.8%with 1-year, 3-year, 5-year survival rates of 55.4%, 15.8%, 4.5%, respectively. The median OS of patients with advanced ESCC in first-line chemotherapy was 13.9 months. According to the results of univariate and COX multivariate analysis, OS of patients with advanced ESCC was closely associated with liver metastasis (P=0.028), curative effect of first

  18. Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    Science.gov (United States)

    Wang, Hai-ying; Yao, Zhi-hua; Tang, Hong; Zhao, Yan; Zhang, Xiao-san; Yao, Shu-na; Yang, Shu-jun; Liu, Yan-yan

    2016-01-01

    Objective More effective regimens for advanced esophageal squamous cell carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line therapy was conducted in Chinese patients with advanced ESCC. Methods From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the second day every 21 days (nab-TP arm). Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms of objective response rate (ORR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes. Results Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9]) than sb-TP (5.0 months [95% confidence interval: 4.4–5.6]) (P=0.029). The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy, arthralgia, and myalgia occurred in the nab-TP arm (all Pline therapy were similar between the two regimens. There were no treatment-related deaths in either group. Conclusion Nab-paclitaxel plus cisplatin is found to be an effective and tolerable option for advanced

  19. Surgical resection for esophageal carcinoma: Speaking the language

    Institute of Scientific and Technical Information of China (English)

    Robert J. Korst

    2005-01-01

    The terminology used to describe esophagectomy for carcinoma can be confusing, even for specialists in gastrointestinal disease. As a result, specific terms are often used out of their intended context. To simplify the nomenclature, two points regarding procedures for surgical resection of the esophagus are critical: the extent of resection (radical vs standard) and the operative approach (choice of incisions). It is important to understand that the radicality of the resection may have little to do with the operative approach, with the exception of esophagectomy without thoracotomy (transhiatal esophagectomy), which mandates the performance of a standard or non-radical resection. Esophagectomy has emerged as the standard curative treatment option for patients with esophageal carcinoma; however, unlike the surgical resection of other types of solid tumors, many different surgical options and/or approaches exist for these patients. This heterogeneity of care may result from the fact that the esophagus is accessible through more than one body cavity (left hemithorax, right hemithorax, abdomen).In addition, and partially as a result of its accessibility,different types of surgical specialists harbor this operation in their armamentarium, including general surgeons,thoracic surgeons, and surgical oncologists. Despite this enthusiasm amongst surgeons, little consensus exists as to which option is most oncologically sound. Further, the details of the various surgical approaches and procedures for resection of the esophagus are often difficult to comprehend, even for specialists in gastrointestinal disease, with much of the relevant terminology used out of its intended context. To facilitate the understanding of the surgical options for esophageal carcinoma, it is useful to view the operation from two angles: the extent of resection (Aradical@ vs Astandard@) and the operative approach (choice of incisions).

  20. UPPER ESOPHAGEAL STRICTURE POST CHEMOIRRADIATION IN PATIENTS WITH CARCINOMA HYPOPHARYNX

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    Nikhila Radhakrisha

    2014-11-01

    Full Text Available BACKGROUND: Concurrent chemo irradiation is the standard treatment for patients with head & neck cancer (HNC. Dysphagia is a common late toxicity of treatment. 7-21% of these patients have treatment induced stricture of the upper esophagus causing dysphagia, with a high incidence of the same in cases of carcinoma hypopharynx. The objective of the present study was to identify the incidence of treatment related stricture of the upper esophagus in patients with hypopharyngeal cancer in our institution. METHODS: A retrospective analysis on patients treated for carcinoma hypopharynx, in the department of Radiotherapy at our Institute, between 2008-12 was conducted. All patients who had received chemo irradiation were included Patients who had developed upper esophageal stricture post treatment diagnosed by upper GI endoscopy and required periodic dilatation were analyzed using Fisher’s exact test. RESULTS: 377 patients of H&N cancers were evaluated, out of which 15.38 % (58/377 had a hypopharyngeal primary. 51 patients were evaluable for the current analysis (15 females, 36 males; mean age 57yrs; out of which 10 patients developed treatment related stricture in the proximal esophagus (20% (4 females, 6 males. Post cricoid primary had a higher incidence of stricture (7/10 (p=0.0012** two-tailed, followed by primary of the pyriform sinus (3/10. Posterior pharyngeal wall malignancies did not have treatment induced strictures. The mean interval between completion of treatment and endoscopic diagnosis of stricture was 4 months. 5 out of 10 patients underwent periodic dilatations up to an average of 13mm. CONCLUSIONS: Upper esophageal stricture is an important late effect of chemo irradiation in patients with carcinoma hypopharynx. Post cricoid cancers have a higher incidence of treatment induced strictures.

  1. Macroscopic extent of gastric mucosal atrophy: increased risk factor for esophageal squamous cell carcinoma in Japan

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    Kobayashi Noritoshi

    2009-05-01

    Full Text Available Abstract Background We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection. Methods Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. Results Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma. Conclusion Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

  2. Difference of gene expression profiles between esophageal carcinoma and its pericancerous epithelium by gene chip

    Institute of Scientific and Technical Information of China (English)

    Shen-Hua Xu; Li-Juan Qian; Han-Zhou Mou; Chi-Hong Zhu; Xing-Ming Zhou; Xiang-Lin Liu; Yong Chen; Wen-Yu Bao

    2003-01-01

    AIM: To study the difference of gene expression between esophageal carcinoma and its pericancerous epithelium and to screen novel associated genes in the early stage of esophageal carcinogenesis by cDNA microarray.METHODS: Total RNA was extracted with the original single step way from esophageal carcinoma, its pericancerous epithelial tissue and normal esophageal epithelium far from the tumor. The cDNA retro-transcribed from equal quantity of mRNA was labeled with Cy5 and Cy3 fluorescence functioning as probes. The mixed probes were hybridized with two pieces of BioDoor 4 096 double dot human whole gene chip. Fluorescence signals were scanned by ScanArray 3 000 laser scanner and farther analyzed by ImaGene 3.0software with the digital computer.RESULTS: (1) A total of 135 genes were screened out, in which 85 and 50 genes whose the gene expression levels (fluorescence intensity) in esophageal carcinoma were more than 2 times and less than 0.5 times respectively compared with the normal esophageal epithelium. (2) There were also total 31 genes, among then 27 and 4 whose expressions in pericancerous tissue were 2-fold up-regulated and 0.5-fold down-regulated respectively compared with normal esophageal epithelium. (3) There were 13 genes appeared simultaneously in both pericancerous epithelium and esophageal carcinoma, while another 18 genes existed in pericancerous epithelium only.CONCLUSION: With the parallel comparison among these three gene profiles, it was shown that (1). A total of 135genes, Whose expression difference manifested as fluorescence intensity were more than 2 times between esophageal carcinoma and normal esophageal epithelium,were probably related to the occurrence and development of the esophageal carcinoma. (2). The 31 genes showing expression difference more than 2 times between pericancerous and normal esophageal epithelium might be relate to the promotion of esophageal pericancerosis and its progress. The present study illustrated that by using

  3. Tumour length is an independent prognostic factor of esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    WU Ning; PANG Lie-wen; CHEN Zhi-ming; MA Qin-yun; CHEN Gang

    2012-01-01

    Background The latest version of the American Joint Committee on Cancer (AJCC) TNM staging system has not comprehensively evaluated the impact of tumour length on survival in patients with esophageal squamous cell carcinoma.Our study explored the relationship between tumour length and clinicopathological characteristics as well as long-term survival.Methods All 202 cases of esophageal resections done from January 1,2004 to December 31,2008 in Huashan Hospital,Fudan University were reviewed and followed up.Results Patients with tumour length >3 cm were related to more advanced tumour stage (X2=55.9,P <0.001),more metastatic lymph nodes (X2=14.6,P <0.001),increased metastatic lymph node ratio (x2=16.1,P <0.001) and worse overall TNM stage (X2=48.1,P <0.001).Univariate and multivariate analyses indicated that tumour length was a significant prognostic risk factor (95% CI 0.235-0.947,P=0.035).Subgroup analyses disclosed that tumour length was a valuable prognostic predictor in patients with lower T stage,absence of metastatic lymph nodes and lower TNM stage.Conclusions Esophageal tumour length is a predictive factor for long-term survival especially for lower tumour stage,absence of metastatic lymph nodes and lower TNM stage patients.Tumour length should be incorporated in the staging system as an important grouping factor for better prognostic evaluation.

  4. Inhibitory Role of Pentraxin-3 in Esophageal Squamous Cell Carcinoma

    Science.gov (United States)

    Ma, Dan; Zong, Ye; Zhu, Sheng-Tao; Wang, Yong-Jun; Li, Peng; Zhang, Shu-Tian

    2016-01-01

    Background: Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Pentraxin-3 (PTX3) is a member of the PTX superfamily. Here, we investigated the role of PTX3 in esophageal squamous cell carcinoma (ESCC). Methods: The effect of PTX3 on ESCC cell proliferation, colony formation, apoptosis, migration, and invasion was investigated using cell viability assays, colony formation assays, flow cytometry, and migration and invasion assays. The effect of PTX3 on the tumorigenicity of ESCC in vivo was investigated with xenograft studies in nude mice. Results: PTX3 overexpression in ESCC cells reduced cellular proliferation and colony formation (P apoptosis (P < 0.05). PTX3 expression had no significant effect on the migratory or invasive potential of ESCC cells. In our mouse model of human ESCC, we achieved 100% successful tumor establishment. Compared with the control and empty vector-expressing groups, the PTX3-expressing group formed significantly smaller tumors (P < 0.05). Conclusions: This study indicates that PTX3 might play an inhibitory role in ESCC. PMID:27625097

  5. Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Yong-Dong Wu; Peng Li; Jun Tu; Ying-Lin Niu; Cai-Min Xu; Shu-Tian Zhang

    2011-01-01

    AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells.METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis.RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group.CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC.

  6. Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

    Science.gov (United States)

    Mai, Shi-Juan; Wang, Meng-He; Zhang, Mei-Yin; Zheng, X.F. Steven; Wang, Hui-Yun

    2016-01-01

    Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/α-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy. PMID:27295551

  7. Expressions of p16 and FHIT Proteins During Esophageal Carcinomatous Development in High Incidence Area of Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-wei; YU Wei-fang; WEN Deng-gui; MENG Xia; WANG Xiao-ling; XU Zhi-bin; WANG Ding-xin; WANG Shi-jie

    2007-01-01

    Objective: To detect the changes of p16 and FHIT and investigate their relationship in esophageal squamous cell carcinoma development by measuring their expression levels in normal squamous epithelium tissue, mild, moderate, severe dysplasia lesions, carcinoma in situ and invasive squamous cell carcinomas. Methods: Expressions of p16 protein and FHIT protein were detected and analyzed in 17 cases of normal squamous epithelium, 16 cases of mild dysplasia, 16 cases of moderate dysplasia, 17 cases of severe dysplasia, 10 cases of carcinoma in situ, and 18 cases of esophageal squamous cell carcinoma by immunohistochemical method. Results: With increasing histopathologic grades, the expressions of p16 and FHIT became gradually lower. There was no remarkable difference of p16 and FHIT expressions between the normal and mild dysplasia group (P>0.05), but the differences between the normal and other groups were all significant (P<0.05). There was no remarkable difference among the squamous cell carcinoma group, the moderate and severe dysplasia groups, and the carcinoma in situ group (P>0.05), but significant differences existed in the expressions of p16 and FHIT proteins between the squamous cell carcinoma and the normal groups, and between the squamous cell carcinoma and the mild dysplasia groups (P<0.05). There was an association of descending trend between p16 and FHIT protein expressions. Conclusion: Reduced expressions of p16 and/or FHIT proteins possible play an important role in the early occurrence of esophageal cancer. There was a positive correlation between the expressions of p16 and FHIT proteins.

  8. Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

    Science.gov (United States)

    Kijima, H; Oshiba, G; Kenmochi, T; Kise, Y; Tanaka, H; Chino, O; Shimada, H; Ueyama, Y; Tanaka, M; Makuuchi, H

    2000-04-01

    Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (pCEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

  9. Multimodality approach for locally advanced esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Khaldoun Almhanna; Jonathan R Strosberg

    2012-01-01

    Carcinoma of the esophagus is an aggressive and lethal malignancy with an increasing incidence world-wide.Incidence rates vary internationally,with the highest rates found in Southern and Eastern Africa and Eastern Asia,and the lowest in Western and Middle Africa and Central America.Patients with locally advanced disease face a poor prognosis,with 5-year survival rates ranging from 15%-34%.Recent clinical trials have evaluated different strategies for management of locoregional cancer; however,because of stage migration and changes in disease epidemiology,applying these trials to clinical practice has become a daunting task.We searched Medline and conference abstracts for randomized studies published in the last 3 decades.We restricted our search to articles published in English.Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States.Esophagectomy remains an essential component of treatment and can lead to improved overall survival,especially when performed at high volume institutions.The role of adjuvant chemotherapy following curative resection is still unclear.External beam radiation therapy alone is considered palliative and is typically reserved for patients with a poor performance status.

  10. Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jón O Kristinsson; Paul van Westerveld; Rene HM te Morsche; Hennie MJ Roelofs; T Wobbes; Ben JM Witteman; Adriaan CITL Tan; Martijn GH van Oijen; Jan BMJ Jansen; Wilbert HM Peters

    2009-01-01

    AIM: To determine whether - 1195 A→ G and/or - 765 G→ C polymorphisms in Cyclooxygenase-2 ( COX-2) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS: Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: The dist r ibut ion of the - 1195 A→ G polymorphism was significantly different in esophageal cancer patients compared to controls. The - 1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma (OR = 3.85, 95% CI: 1.45-10.3) compared with the - 1195 AA genotype as a reference. The - 765 G→ C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls (OR = 3.45, 95% CI: 1.24-9.58; with AG/AG as a reference). The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION: Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.

  11. [Peptide vaccine therapy with TLR-9 agonist for patients with esophageal squamous cell carcinoma].

    Science.gov (United States)

    Katsuda, Masahiro; Iwahashi, Makoto; Matsuda, Kenji; Miyazawa, Motoki; Nakamori, Mikihito; Nakamura, Masaki; Naka, Teiji; Ojima, Toshiyasu; Iida, Takeshi; Yamaue, Hiroki

    2011-11-01

    Patients with advanced carcinoma are thought to have an impaired immune surveillance system. Therefore, the potent helper action is required for the induction of an antitumor immune response in such patients. We evaluated the efficacy of CpG-ODN, which is TLR-9 agonist, as cancer vaccine adjuvant through in vitro experiments. We also conducted a phase I clinical trial for patients with advanced esophageal squamous cell carcinoma (ESCC) using peptide vaccine in combination with CpG-B. In vitro experiments showed that CpG-ODN caused various immune-modifications, suggesting an efficacy of CpG-ODN as peptide vaccine adjuvant. Moreover, the immune monitoring data in phase I clinical trial suggested that CpG-B augmented the generation of antigen-specific T cell responses and innate immunity. These data indicated that the vaccination with cancer-testis antigen derived peptide in combination with CpG-B may be useful as a new immunotherapy for patients with advanced ESCC. PMID:22202246

  12. Coexistence of esophageal superficial carcinoma and multiple leiomyomas: A case report

    Institute of Scientific and Technical Information of China (English)

    Takeshi Iwaya; Go Wakabayashi; Chihaya Maesawa; Noriyuki Uesugi; Toshimoto Kimura; Kenichiro Ikeda; Yusuke Kimura; Shingo Mitomo; Kaoru Ishida; Nobuhiro Sato

    2006-01-01

    Leiomyomas are the most common benign tumors of the esophagus. They usually occur as a single lesion or as two or three nodules. Only two cases of esophageal multiple leiomyomas comprising more than 10 nodules have been reported previously. Moreover, there have been few reports of esophageal squamous cell carcinoma overlying submucosal tumors. We describe a 71-yearold man who was diagnosed as having a superficial esophageal cancer coexisting with two or three leiomyoma nodules. During surgery, 10 or more nodules that had not been evident preoperatively were palpable in the submucosal and muscular layers throughout the esophagus. As intramural metastasis of the esophageal cancer was suspected, we considered additional lymphadenectomy, but had to rule out this option because of the patient's severe anoxemia. Microscopic examination revealed that all the nodules were leiomyomas (20 lesions, up to 3 cm in diameter), and that invasion of the carcinoma cells was limited to the submucosal layer overlying a relatively large leiomyoma.This is the first report of superficial esophageal cancer coexisting with numerous solitary leiomyomas. Multiple minute leiomyomas are often misdiagnosed as intramural metastasis, and a leiomyoma at the base of a carcinoma lesion can also be misdiagnosed as tumor invasion.The present case shows that accurate diagnosis is required for the management of patients with coexisting superficial esophageal cancer and multiple leiomyomas.

  13. HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Lin; Chang-Sheng Deng; Jie Sun; Xian-Gong Zheng; Xing Huang; Yan Zhou; Ping Xiong; Ya-Ping Wang

    2003-01-01

    AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province.METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics.RESULTS: Allele frequency (AF) of HLA-DRB1·0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1·0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles.CONCLUSION: HLA-DRB1·0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1·0901may be susceptible to esophageal carcinoma.

  14. Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas.

    Science.gov (United States)

    Imamhasan, Abdukadir; Mitomi, Hiroyuki; Saito, Tsuyoshi; Hayashi, Takuo; Takahashi, Michiko; Kajiyama, Yoshiaki; Yao, Takashi

    2012-11-01

    Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and detected 22 cases (3%) of basaloid squamous cell carcinoma. These tumors and stage-matched paired conventional squamous cell carcinomas were investigated for clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B-cell lymphoma 2 (bcl-2), β-catenin, and epidermal growth factor receptor. Molecular aberrations in p53, CTNNB1 (the gene encoding β-catenin), and epidermal growth factor receptor (EGFR) were also determined. Patients with basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%, significantly worse than those with well-differentiated squamous cell carcinoma (Pcarcinomas, the basaloid squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin 903, and membranous β-catenin (Pcarcinomas, low-level expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a significant influence on worse survival (Pcarcinoma, a neoplasm with particularly aggressive biologic behavior, should be differentiated from conventional squamous cell carcinomas. In this context, immunohistochemical assessment of several markers might provide a useful adjunct diagnostic tool. Aberrations of p53 and epidermal growth factor receptor genes are possibly involved in progression of esophageal basaloid squamous cell carcinoma.

  15. Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Li Shau-Hsuan

    2012-08-01

    -free survival (P = 0.003, univariately and overall survival (P = 0.037, univariately. In multivariate comparison, absence of preoperative bone scan was independently associated with inferior bone recurrence-free survival (P = 0.009, odds ratio: 5.832 and overall survival (P = 0.029, odds ratio: 1.603. Conclusions Absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival, suggesting that whole-body bone scan should be performed before esophagectomy in patients with esophageal squamous cell carcinoma, especially in patients with advanced stages.

  16. Rule of lymph node metastasis and proper target of postoperative radiotherapy for thoracic esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze the rule of lymph node metastasis in thoracic esophageal carcinoma, and to study the proper radiation target. Methods: From September 1986 to December 1997,549 patients with esophageal carcinoma who had undergone radical resection were divided into surgery alone group (S,275 patients) or surgery plus radiotherapy group(S + R,274 patients). Radiotherapy was begun 3 to 4 weeks after operation. The radiation target included both supra-clavicular areas and the entire mediastinum. The total dose was 50 Gy in 25 fractions over 5 weeks for the supra-clavicular areas and 60 Gy in 30 fractions over 6 weeks for the entire mediastinum. Results: The 5-year overall survival of patients with lymph node metastasis in one anatomic site and two anatomic sites was 31.5% and 13.9% (P=0.013), respectively. For patients with > 2 positive nodes metastasis receiving surgery alone, the corresponding 5-year survival was 24.8% and 4.9% (P=0.046), respectively. The median number of dissected lymph nodes of the upper-, middle-and lower-segment esophageal carcinoma was 13, 17 and 20, respectively. The rate of metastatic lymph node in the para-esophagus region was the highest(61.5%-64.9%), which was not different among the different primary sites (P=0.922). The anastomotic stoma recurrence rate of the upper-segment esophageal carcinoma was higher than that of the middle- or lower-segment carcinomas (16.7%, 3.1%, and 7.7%, χ2=9.02,P<0.05). Conclusions: For the thoracic esophageal carcinoma, the number of anatomic sites of lymph node metastasis is an important factor affecting the survival. The lower rate of lymph node metastasis of the upper segment esophageal carcinoma may be corrected with the less lymph node dissected. The rate of lymph node metastasis in para-esophageal region is not related with the lesion segment. The anastomotic stoma is an important radiotherapy target for upper segment esophageal carcinoma. (authors)

  17. A comparative Analysis by SAGE of Gene Expression Profiles of Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jantine W. P. M. van Baal

    2008-01-01

    Full Text Available Esophageal adenocarcinoma (EA and esophageal squamous cell carcinoma (ESCC are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett’s esophagus (BE, the metaplastic epithelium that predisposes for EA, and compared the transcriptome of ESCC to normal esophageal squamous epithelium. For obtaining the transcriptomes tissue biopsies were used and serial analysis of gene expression (SAGE was applied. Validation of results by RT-PCR and immunoblotting was performed using tissues of an additional 23 EA and ESCC patients. Over 58,000 tags were sequenced. Between EA and BE 1013, and between ESCC and normal squamous epithelium 1235 tags were significantly differentially expressed (p < 0.05. The most up-regulated genes in EA compared to BE were SRY-box 4 and Lipocalin2, whereas the most down-regulated genes in EA were Trefoil factors and Annexin A10. The most up-regulated genes in ESCC compared to normal squamous epithelium were BMP4, E-Cadherin and TFF3. The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified.

  18. Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Junsheng

    2010-07-01

    Full Text Available Abstract Background Glutathione S-transferase pi (GST pi is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Methods Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. Results The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p p p p p = 0.004, respectively and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively. In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p p p p Conclusions Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore, deficiency of GST pi protein expression may be an important mechanism involved in the carcinogenesis and progression of the squamous esophageal carcinoma, and the underlying mechanisms leading to decreased GST pi expression deserve further investigation.

  19. EXPRESSION OF ANNEXIN I IN TUMORIGENESIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    吕宁; 薛丽燕; 林冬梅; 谢永强; 温芃; 何祖根

    2004-01-01

    Objective: To detect the expression of annexin I in esophageal squamous cell carcinoma and precursor lesions,and evaluate its effect on the tumorigenesis. Methods: The immunohistochemistry S-P method was used to determine the expression of annexin I in 135 cases of esophageal squamous cell carcinoma, in which precursor lesions were found in some cases, and in the corresponding normal controls. Results: Of 135 cases, 35 (25.9%) were strongly positive, 60 (44.4%) were weakly positive and 40 (29.6%)negative, while in the corresponding normal controls, 129(95.6%) were strongly positive, 6 (6.4%) weakly positive.The expression of annexin I was decreased in esophageal squamous cell carcinoma (P<0.0001), and the degree and rate of the decrease did not show correlation with age,gender, differentiation, and lymph node metastasis (P>0.05).The expression of annexin I was also decreased in the lesions of dysplasia and carcinoma in situ, with 2 (4.3%) strongly positive, 17 (37.0%) weakly positive and 27(58.7%) negative (P<0.0001). Conclusion: Annexin I may be useful in early detection of esophageal squamous cell carcinoma and in evaluation of predisposition for the risk of cancerization of precursor lesions.

  20. Loss of myeloid-related proteins 8 and myeloid-related proteins 14 expression in human esophageal squamous cell carcinoma correlates with poor differentiation

    Institute of Scientific and Technical Information of China (English)

    Jian-Ping Kong; Fang Ding; Chuan-Nong Zhou; Xiu-Qin Wang; Xiao-Ping Miao; Min Wu; Zhi-Hua Liu

    2004-01-01

    AIM: To study the expression of myeloid-related proteins (MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14expression level and histopathological grade in these tumors.METHODS: In this study, 65 cases of advanced esophageal squamous cell carcinoma were assessed for MRP8 and MRP14 expression using immunohistochemistry. Statistical analysis was performed for the comparison of MRP8 and MRP14 expression in normal and tumor tissues, and their relationship with clinicopathological features.RESULTS: Reduced or absent expression of MRP8 and MRP14was observed in esophageal squamous cell carcinoma, with a significant difference between tumor tissues and normal tissues (P<0.01 and P<0.01 for MRP8 and MRP14, respectively).Poorly differentiated tumors presented a greater decrease than well and moderately differentiated tumors, with a correlation between their protein level and histopathological grading (P<0.001 and P<0.001, respectively). However, no significant association was found between MRP8 and MRP14expression and age or gender (P>0.05).CONCLUSION: These findings suggest that the decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma, being particularly associated with poor differentiation of tumor cells.

  1. Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    Institute of Scientific and Technical Information of China (English)

    Wei He; Ke Li; Feng Wang; Yan-Ru Qin; Qing-xia Fan

    2012-01-01

    AIM:To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis.METHODS:Using real-time polymerase chain reaction (PCR),Western blotting,immunocytochemistry and immunohistochemistry,the expression of OCT4 in three esophageal squamous cancer cell lines,KYSE70,KYSE140 and KYSE450,was characterized.OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features.RESULTS:Immunohistochemically,OCT4 positive immunostaining was observed in cancer cell nuclei.OCT4 was variably expressed in three esophageal squamous cancer cell lines.Among 153 specimens,105 (68.7%)were negative or weakly positive for OCT4 staining;21 (13.7%) were moderately positive and 27 (17.6%)were strongly positive.Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001).CONCLUSION:The expression of OCT4 enables the tumor to have a higher degree of stemness,which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.

  2. Prognostic nomogram integrated systemic inflammation score for patients with esophageal squamouscell carcinoma undergoing radical esophagectomy

    OpenAIRE

    Yingjie Shao; Zhonghua Ning; Jun Chen; Yiting Geng; Wendong Gu; Jin Huang; Honglei Pei; Yueping Shen; Jingting Jiang

    2015-01-01

    Growing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors. This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamouscell carcinoma (ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores. We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The pred...

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

    DEFF Research Database (Denmark)

    Bergheim, I.; Wolfgarten, E.; Bollschweiler, E.;

    2007-01-01

    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, ...

  4. Dysphagia after Colon Interposition Graft for Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    C. Spitali

    2012-01-01

    Full Text Available Colon interposition is an established technique for esophageal reconstruction. We describe the case of primary adenocarcinoma arising in a colonic interposition graft that was performed after total esophagectomy for recurrence adenocarcinoma derived from the Barrett esophagus.

  5. Expression of thymidylate synthase and glutathione-stransferase π in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xing Huang; Feng-Yue Li; Wei Xiao; Zheng-Xiang Song; Rong-Yu Qian; Ping Chen; Eeva Salminen

    2009-01-01

    AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase π (GST-π) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS: Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS: The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-π was also significantly higher in welldifferentiated carcinomas (65.63%) than in poorlydifferentiated carcinomas (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of TS and reduced expression of GST-π.

  6. Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

  7. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sadat Noori

    2012-06-01

    Full Text Available Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences.Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4.Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed.Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated.

  8. Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Hung-Chang Liu; Yu-Jen Chen; Shih-Kai Hung; Charn-Jer Huang; Chung-Chu Chen; Ming-Jen Chen; Chun-Chao Chang; Cheng-Jeng Tai; Chi-Yuan Tzen; Li-Hua Lu

    2005-01-01

    AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer.METHODS: Patients with T3-4 and N0-1 esophageal carcinoma from a number of institutions were non-randomly,prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m2 and 5-fiuorouracil 1 000 mg/m2 for five consecutive days),or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-to-treat patients' outcome of survival.RESULTS: A total of 60 patients (n = 30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematological and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI,27.5-36.4 vs15.2-26.1) and 3-year survival (70.0% vs 33.7%; P = 0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients.CONCLUSION: For locally advanced esophageal cancer,the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.

  9. Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Frédéric Di Fiore; Stéphane Lecleire; Olivier Rigal; Marie-Pierre Galais; Emmanuel Ben Soussan; Isabelle David; Bernard Paillot; Jacques-Henri Jacob; Pierre Michel

    2006-01-01

    AIM: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT)regimen based on the 5FU/CDDP combination.METHODS: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included.Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model.RESULTS: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%).The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P <0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P= 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P< 0.0001), weight loss < 10% (P = 0.034) and WHO performance < 2 (P = 0.046).CONCLUSION: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.

  10. Association between Bmi1 and clinicopathological status of esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ting He; Xiu-Feng Cao; Lv Ji; Bin Zhu; Jin Lv; Dong-Dong Wang; Pei-Hua Lu; Heng-Guan Cui

    2009-01-01

    AIM: To investigate the clinicopathological roles of Bmi1 in esophageal squamous cell carcinoma (ESCC). METHODS: Quantitative real-time polymerase chain reaction and immunohistochemical staining for Bmi1 were performed in cancerous and adjacent noncancerous paraffin-embedded esophageal specimens. RESULTS: The Bmi1 expression level was unaffected by gender and age. The level of Bmi1 mRNA in ESCC was significantly higher than that in the adjacent noncancerous tissues (2.181 ± 2.158 vs 0.931 ± 0.894, P = 0.0152), and its over-expression was aggressively associated with lymph node metastasis (3.580 ± 2.487 vs 1.703 ± 0.758, P = 0.0003), poorer cell differentiation ( P = 0.0000) and advanced pathological stage (3.827 ± 2.673 vs 1.590 ± 0.735, P = 0.0001). The patients were divided into high-expression and low-expression groups based on the median expression level of Bmi1 mRNA, and a shorter overall survival time in the former group was observed. Immunohistochemistry for Bmi1 oncoprotein showed diffusely positive, focally positive and negative expression in 44, 16 and 10 of 70 ESCC cases, respectively, compared with three, two and five of 10 adjacent non-cancerous cases ( P = 0.027). The positive rate of the oncoprotein in samples of histological grade Ⅲ was higher than that of grade Ⅱ ( P = 0.031), but its expression had no relation to the lymph node metastasis and pathological staging. In 70 ESCC samples, Bmi1 showed high intense expression in the cytoplasm and less or even no expression in the nucleus. CONCLUSION: Bmi1 was over-expressed in ESCC. Increased Bmi1 mRNA expression was significantly associated with ESCC progression, and the oncoprotein was largely distributed in the cytoplasm of tumor cells.

  11. Late course accelerated hyperfractionation radiotherapy for elderly patients with esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the clinical results and prognostic factors of late course accelerated hyperfractionation radiotherapy (LCAHR) in the treatment of esophageal carcinoma in the elderly. Methods: 105 over 60 year-old patients with esophageal carcinoma who received radical LCAHR, were retrospectively analysed. Radical tumoricidal dose of 67.9-72.0 Gy was delivered in 39-43 fractions over 42-53 days. Results: The 5-year local control rate was 63.7%. The 5-year disease-free survival and overall survival rate were 22.6% and 34.4%. Acute esophagitis and bronchitis were the most common but acceptable radioreactions Grade 1-2. No significant differences were found either in the clinical response or complication, between the 60-69 year and 70-80 year groups. By multivariate analysis, T stage and KPS score were two independent prognostic factors. Of 67 death cases, 31 died of local relapse, 23 of distant metastases, 8 of both and 5 of other causes. Conclusions: LCAHR toxicity, being tolerable for the older esophageal carcinoma patients, may improve their survival and quality of life

  12. Dosimetric comparison between Volumetric Modulated Arc Therapy (VMAT vs Intensity Modulated Radiation Therapy (IMRT for radiotherapy of mid esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Tejinder Kataria

    2014-01-01

    Conclusion: VMAT can be a better option in treating mid esophageal carcinoma as compared to IMRT. The VMAT plans resulted in equivalent or superior dose distribution with a reduction in the dose to lung and heart.

  13. Specific intronic p53 mutation in esophageal squamous cell carcinoma in Southern Thailand

    Institute of Scientific and Technical Information of China (English)

    Paramee; Thongsuksai; Pleumjit; Boonyaphiphat; Puttisak; Puttawibul; Wanna; Sudhikaran

    2010-01-01

    AIM:To investigate p53 mutations in esophageal cancer in a high-risk population,and correlate them with smoking,alcohol consumption and betel chewing.METHODS:One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma(ESCC) obtained from a university hospital in Songkhla province,Southern Thailand were investigated for p53 mutations in exons 5-8,using polymerase chain reaction-single strand conformation polymorphism analysis,followed by direct sequencing.A polymerase chain reactionrestric...

  14. Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: Report of a case

    Institute of Scientific and Technical Information of China (English)

    Shin Ichi Kosugi; Tatsuo Kanda; Tadashi Nishimaki; Satoru Nakagawa; Kazuhito Yajima; Manabu Ohashi; Katsuyoshi Hatakeyama

    2006-01-01

    We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed.Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 months was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.

  15. A Critical Appraisal of Circumferential Resection Margins in Esophageal Carcinoma

    NARCIS (Netherlands)

    Pultrum, Bareld B.; Honing, Judith; Smit, Justin K.; van Dullemen, Hendrik M.; van Dam, Gooitzen M.; Groen, Henk; Hollema, Harry; Plukker, John Th. M.

    2010-01-01

    In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the opti

  16. Resveratrol induces apoptosis in human esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Yun Yan; Ya-Ni Sun; Ju-Ren Zhu

    2003-01-01

    AIM: To investigate the apoptosis in esophageal cancer cells induced by resveratrol, and the relation between this apoptosis and expression of Bcl-2 and Bax.METHODS: In in vitro experiments, MTr assay was used to determine the cell growth inhibitory rate. Transmission electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of esophageal cancer cell line EC-9706 before and after the resveratrol treatment. Immunohistochemical staining was used to detect the expression of apoptosis-regulated gene Bcl-2 and Bax.RESULTS: Resveratrol inhibited the growth of esophageal cancer cell line EC-9706 in a dose-and time-dependent manner. Resveratrol induced EC-9706 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptotic body formation. TUNEL assay showed that after the for 24 to 96 hours, the AIs were apparently increased with treated time (P<0.05). Immunohistochemical staining showed that after the treatment of EC-9706 cells with proteins were apparently reduced with treated time (P<0.05)and the PRs of Bax proteins were apparently increased with treated time (P<0.05).CONCLUSION: Resveratrol is able to induce the apoptosisin esophageal cancer. This apoptosis may be mediated by down-regulating the apoptosis-regulated gene Bcl-2 and upregulating the expression of apoptosis-regulated gene bax.

  17. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    Science.gov (United States)

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  18. Standardized perfusion value of the esophageal carcinoma and its correlation with quantitative CT perfusion parameter values

    Energy Technology Data Exchange (ETDEWEB)

    Djuric-Stefanovic, A., E-mail: avstefan@eunet.rs [Faculty of Medicine, University of Belgrade, Belgrade (Serbia); Unit of Digestive Radiology (First University Surgical Clinic), Center of Radiology and MR, Clinical Center of Serbia, Belgrade (Serbia); Saranovic, Dj., E-mail: crvzve4@gmail.com [Faculty of Medicine, University of Belgrade, Belgrade (Serbia); Unit of Digestive Radiology (First University Surgical Clinic), Center of Radiology and MR, Clinical Center of Serbia, Belgrade (Serbia); Sobic-Saranovic, D., E-mail: dsobic2@gmail.com [Faculty of Medicine, University of Belgrade, Belgrade (Serbia); Center of Nuclear Medicine, Clinical Center of Serbia, Belgrade (Serbia); Masulovic, D., E-mail: draganmasulovic@yahoo.com [Faculty of Medicine, University of Belgrade, Belgrade (Serbia); Unit of Digestive Radiology (First University Surgical Clinic), Center of Radiology and MR, Clinical Center of Serbia, Belgrade (Serbia); Artiko, V., E-mail: veraart@beotel.rs [Faculty of Medicine, University of Belgrade, Belgrade (Serbia); Center of Nuclear Medicine, Clinical Center of Serbia, Belgrade (Serbia)

    2015-03-15

    Purpose: Standardized perfusion value (SPV) is a universal indicator of tissue perfusion, normalized to the whole-body perfusion, which was proposed to simplify, unify and allow the interchangeability among the perfusion measurements and comparison between the tumor perfusion and metabolism. The aims of our study were to assess the standardized perfusion value (SPV) of the esophageal carcinoma, and its correlation with quantitative CT perfusion measurements: blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) of the same tumor volume samples, which were obtained by deconvolution-based CT perfusion analysis. Methods: Forty CT perfusion studies of the esophageal cancer were analyzed, using the commercial deconvolution-based CT perfusion software (Perfusion 3.0, GE Healthcare). The SPV of the esophageal tumor and neighboring skeletal muscle were correlated with the corresponding mean tumor and muscle quantitative CT perfusion parameter values, using Spearman's rank correlation coefficient (r{sub S}). Results: Median SPV of the esophageal carcinoma (7.1; range: 2.8–13.4) significantly differed from the SPV of the skeletal muscle (median: 1.0; range: 0.4–2.4), (Z = −5.511, p < 0.001). The cut-off value of the SPV of 2.5 enabled discrimination of esophageal cancer from the skeletal muscle with sensitivity and specificity of 100%. SPV of the esophageal carcinoma significantly correlated with corresponding tumor BF (r{sub S} = 0.484, p = 0.002), BV (r{sub S} = 0.637, p < 0.001) and PS (r{sub S} = 0.432, p = 0.005), and SPV of the skeletal muscle significantly correlated with corresponding muscle BF (r{sub S} = 0.573, p < 0.001), BV (r{sub S} = 0.849, p < 0.001) and PS (r{sub S} = 0.761, p < 0.001). Conclusions: We presented a database of the SPV for the esophageal cancer and proved that SPV of the esophageal neoplasm significantly differs from the SPV of the skeletal muscle, which represented a sample of healthy

  19. Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

    International Nuclear Information System (INIS)

    Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer

  20. Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nomura Fumio

    2009-07-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (SCC represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. Methods Tumor markers of esophageal squamous cell carcinoma (SCC were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1 antibodies (s-MKRN1-Abs was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. Results MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25% of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1. Conclusion MKRN1 is a novel SEREX antigen of esophageal SCC, and s

  1. Detection of riboflavin contents in plasma and tumor tissues of patients with esophageal carcinoma and its clinical pathological significance evaluation

    Institute of Scientific and Technical Information of China (English)

    Yong Wu; Nan-Bin Yu

    2016-01-01

    Objective:To study the riboflavin contents in plasma and tumor tissues of patients with esophageal carcinoma and its clinical pathological significance.Methods:Serum samples of healthy volunteers and serum and tissue specimens of patients with esophageal cancer were collected. And riboflavin contents in them were detected. Lsm-4, Bmi-1, Galectin-7, PAR-2, Yap1, nestin, MBP-1, IKK16, beclin-1, RIP-1, DEC-1 and LAST-1 contents in tissue samples were also detected.Results:riboflavin contents in esophageal carcinoma patients’ serum and esophageal cancer tissue were significantly lower than those of healthy volunteers. Lsm-4, Bmi-1, Galectin-7, PAR-2, Yap1 and Nestin contents in esophageal cancer tissue were significantly higher than those in normal tissue. The lower the content of riboflavin in esophageal cancer tissue was, the higher the contents of Lsm-4, Bmi-1, Galectin-7, PAR-2, Yap1 and Nestin were. In esophageal cancer tissue, MBP-1, IKK16, beclin-1, RIP-1, DEC-1 and LAST-1 contents were significantly lower than those in normal tissue, and the lower the content of riboflavin in esophageal cancer tissue, the lower the MBP-1, IKK16, beclin-1, RIP-1, DEC-1, LAST-1 contents.Conclusions:riboflavin contents in plasma and tumor tissues of esophageal cancer patients abnormally decrease and the more obvious the decrease of its content, the higher the proliferation-promoting gene contents, and the lower the proliferation-inhibiting gene contents.

  2. Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m2 D1 and 5-fluorouracil 500 mg/m2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m2 and 5- fluorouracil 100 mg/m2. Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m2. MTD was defined as cisplatin 52.5 mg/m2, 5- fiuorouracil 700 mg/m2. The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m2 D1-5, repeated 4 times every 28 days. (authors)

  3. Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Myoung Sook Kim

    Full Text Available Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH in a significant proportion of primary esophageal squamous cell carcinoma (ESCC samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/beta-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of beta-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/beta-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways.

  4. Somatically Acquired LINE-1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Doucet-O'Hare, Tara T; Sharma, Reema; Rodić, Nemanja; Anders, Robert A; Burns, Kathleen H; Kazazian, Haig H

    2016-09-01

    Squamous cell carcinoma of the esophagus (SCC) is the most common form of esophageal cancer in the world and is typically diagnosed at an advanced stage when successful treatment is challenging. Understanding the mutational profile of this cancer may identify new treatment strategies. Because somatic retrotransposition has been shown in tumors of the gastrointestinal system, we focused on LINE-1 (L1) mobilization as a source of genetic instability in this cancer. We hypothesized that retrotransposition is ongoing in SCC patients. The expression of L1 encoded proteins is necessary for retrotransposition to occur; therefore, we evaluated the expression of L1 open reading frame 1 protein (ORF1p). Using immunohistochemistry, we detected ORF1p expression in all four SCC cases evaluated. Using L1-seq, we identified and validated 74 somatic insertions in eight tumors of the nine evaluated. Of these, 12 insertions appeared to be somatic, not genetically inherited, and sub-clonal (i.e., present in less than one copy per genome equivalent) in the adjacent normal esophagus (NE), while clonal in the tumor. Our results indicate that L1 retrotransposition is active in SCC of the esophagus and that insertion events are present in histologically NE that expands clonally in the subsequent tumor. PMID:27319353

  5. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China)

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  6. Human papilloma virus and esophageal carcinoma in a Latin-American region

    Institute of Scientific and Technical Information of China (English)

    Roberto Herrera-Goepfert; Marcela Lizano; Suminori Akiba; Adela Carrillo-García; Mauricio Becker-D'Acosta

    2009-01-01

    AIM: To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected inone case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased twofold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

  7. Narrow-band imaging without magnification for detecting early esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Edson Ide; Fauze Maluf-Filho; Dalton Marques Chaves; Sergio Eiji Matuguma; Paulo Sakai

    2011-01-01

    AIM: To compare narrow-band imaging (NBI) without image magnification, and chromoendoscopy with Lugol's solution for detecting high-grade dysplasia and intramucosal esophageal squamous cell carcinoma (SCC) in patients with head and neck cancer.RESULTS: Of the 129 patients, nine (7%) were diagnosed with SCC, 5 of which were in situ and 4 which were intramucosal. All carcinomas were detected through NBI and Lugol chromoendoscopy. Only 4 lesions were diagnosed through conventional examination, all of which were larger than 10 mm.CONCLUSION: NBI technology with optical filters has high sensitivity and high negative predictive value for detecting superficial esophageal SCC, and produces results comparable to those obtained with 2.5% Lugol chromoendoscopy.

  8. Esophageal Lymphoepithelioma-Like Carcinoma with Unique Daisy-Like Appearance

    Science.gov (United States)

    Olmez, Sehmus; Can, Alper; Yavuz, Alpaslan; İliklerden, Umit Haluk; Bulut, Gulay

    2015-01-01

    Due to differences in prognosis and management, it is important to subclassify esophageal carcinoma. Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare, with only a few cases reported to date. Review of the literature revealed case reports describing lesions with similar histology. We present a 69-year-old man with a giant pedunculated-polypoid lesion of the esophagus shrinking the lumen. Endoscopic excision of the tumor was performed and final histopathological diagnosis was confirmed to be LELC. In contrast to a previous case with a more aggressive course and a recurrent lesion, our patient died of his disease within 8 months of diagnosis. Here we discuss the endoscopic and radiologic findings of the case and a review of the literature. PMID:26668803

  9. Examestane in advanced or recurrent endometrial carcinoma

    DEFF Research Database (Denmark)

    Lindemann, Kristina; Malander, Susanne; Christensen, René dePont;

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.......We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma....

  10. Factors Predicting Effectiveness of Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

    2016-01-01

    Abstract The aim of the study was to elucidate pretreatment factors that can predict the outcome of neoadjuvant chemoradiotherapy or chemotherapy (NAC(R)T) and help us choose treatment strategies appropriate for individual patients. Few studies have investigated whether clinical data obtainable before the treatment can predict the efficacy of NAC(R)T. Of 1540 patients treated for esophageal squamous cell carcinoma (ESCC) at our department between January 2000 and June 2014, those who underwen...

  11. Prognostic Nomogram for Thoracic Esophageal Squamous Cell Carcinoma after Radical Esophagectomy

    OpenAIRE

    Dan Su; Xinming Zhou; Qixun Chen; Youhua Jiang; Xun Yang; Weihui Zheng; Kaiyi Tao; Jie Wu,; Zhen Yan; Liang Liu; Shaoyuan Wu; Weimin Mao

    2015-01-01

    Nomogram has demonstrated its capability in individualized estimates of survival in diverse cancers. Here we retrospectively investigated 1195 patients with esophageal squamous-cell carcinoma (ESCC) who underwent radical esophagectomy at Zhejiang Cancer Hospital in Hangzhou, China. We randomly assigned two-thirds of the patients to a training cohort (n = 797) and one-third to a validation cohort (n = 398). Cox proportional hazards regression analyses were performed using the training cohort, ...

  12. Clinical significance of preoperative serum tumor markers in esophageal squamous cell carcinoma

    OpenAIRE

    Hongguang Zhao; Wenhu Chen; Jie Wu; Lifang Wang; Weimin Mao

    2014-01-01

    Background: Serum tumor markers (TMs) were seldom reported in esophageal carcinoma (ESCC), and the results were still unsatisfactory. Materials and Methods: We retrospectively analyzed carcinoembryonic antigen, CA125, CA199, CA724 and CA242 in ESCC patients. The preliminary relations between serum TMs and clinicopathological factors or prognosis were analyzed by Fisher′s exact test and Kaplan-Meier method firstly. Then, the cut-off values of these serum TMs were delimited according to lymp...

  13. Challenges of advanced hepatocellular carcinoma.

    Science.gov (United States)

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  14. A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser

    OpenAIRE

    Kazunari Yoshida; Shigeru Suzuki; Seishiro Mimura; Hiroyuki Narahara; Hiroshi Tanimura; Yugo Nagai; Kaichi Isono; Teruo Kozu; Hisayuki Fukutomi; Akira Nakahara; Hiromasa Kashimura; Toshio Hirashima; Yoko Murata; Hiroko Ide; Harubumi Kato

    1998-01-01

    A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60–180 J/cm2 48–72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of inva...

  15. RELATIONSHIP BETWEEN LYMPH NODE METASTASES IN ESOPHAGEAL CARCINOMA AND ITS PROGNOSIS

    Institute of Scientific and Technical Information of China (English)

    肖小炜

    2002-01-01

    Objective: To study the relationship between lymph node metastases in esophageal carcinoma and its prognosis. Methods: We obtained 1500 resected lymph nodes from the specimen of 86 patients with resected esophageal carcinoma and checked these lymph nodes by routine histopathology. Additiionally, frozen tissue sections of 540 lymph nodes classified as tumor-free by routine histopathology werescreened for micrometastases by immunohistology with the monoclonal antibody Ber-EP4. Results: Forty-two patients (49%) had pN0 disease, and 61 patients (71%) had lymph node micrometastases detected by immunohistochemistry, skip metastasesdetected by routine histopathology were present in 26%(11/42) of pN0 and 41%(18/44) of pN1 patients. Skipping of micrometastases detected by immunohistochemistry was found in 71%(61/86). Twenty-six of 42 patients (62%) with tumor staged aspN0 and 35 of 44 patients (80%) with stage pN1 had nodal micrometastasis. The presence of micrometastases was associated with a significantly decreased relapse-free time and overall survival (P<0.0001 and P=0.004, respectively). Conclusion: Lymph node skip metastases are a frequent event in esophageal carcinoma. Extensive lymph node sampling, in conjunction with immunohistochemical detection, will lead to accurate staging and prognosis.

  16. Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.

    Science.gov (United States)

    Shimada, H; Nakajima, K; Ochiai, T; Koide, Y; Okazumi, S I; Matsubara, H; Takeda, A; Miyazawa, Y; Arima, M; Isono, K

    1998-01-01

    The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.

  17. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    Science.gov (United States)

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  18. Relationship between Egr-1 gene expression and apoptosis in esophageal carcinoma and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Ming-Yao Wu; Ying-Rui Liang; Xian-Ying Wu; Chu-Xiang Zhuang

    2002-01-01

    AIM: To study the expression of early growth response gene1 (Egr-1 gene) and Bcl-X/L protein and its relationship with the cell apoptosis in human esophageal carcinoma(EC) and precancerous lesions.METHODS: In situ hybridization(ISH), immunohistochemistry (IHC) and TUNEL method were used respectively to detect Egr-1mRNA, Egr-1 protein, apoptosis related-protein Bcl-X/L and cell apoptosis in situ from 66 cases of esophageal squamous cell carcinoma and their upper cut edge and paracancerous mucosa.RESULTS: Egr-1 gene in situ hybridization, Bcl-X/L immunohistochemistry positive products were located in the cytoplasm, while Egr-1 immunohistochemistry and TUNEL positive signal were located in the nuclei. The apoptosis index(AI) and the frequency of apoptosis occurrence were increased gradually from precancerous lesion to cancer (P<0.01) and the expression of Egr-1mRNA and Egr-1 protein in dysplasia was the highest among all specimens (P<0.01).The AI of Egr-1 positive cancer tissues was much higher than that of Egr-1 negative cancer tissues (P<0.01), while the AI of Bcl-X/L positive cancer tissues was much lower than that of Bcl-X/L negative cancer tissues (P<0.01). The AI and Egr-1 expression were not correlated with invasiveness and lymphatic metastasis in EC.CONCLUSION: Cell apoptosis was present through esophageal carcinogenesis. The expression of Egr-1 mRNA and Egr-1 protein were high in precancerous lesion of esophagus. The AI was increased significantly in Egr-1 positive squamous cell carcinoma. Egr-1 might promote apoptotic effect. Egr-1 expression and cell apoptosis may have an important biological significance in esophageal carcinogenesis.

  19. Prognostic factors influencing morbidity and mortality in esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Cariati Andrea

    2002-01-01

    Full Text Available PURPOSE: In 1980, operative mortality for esophageal resection was 29%. Over the last 15 years, technical and critical care improvements contributed to the reduction of postoperative mortality rate to 8%. The aim of this study is to analyze retrospectively the role of different factors (surgical procedure, stage of the disease, and anesthetic risk on the postoperative mortality of 63 patients that underwent esophagectomy with gastric interposition for cancer. METHODS: Seventy-two patients underwent esophagectomy. The stomach was the esophageal substitute in 63 cases. Surgical procedures included transthoracic esophagectomy in 49 patients and transhiatal esophagectomy in 14 cases. Among the 49 transthoracic esophagectomy patients, there were 18 patients with a high anesthetic risk (ASA III. Among the patients that underwent transhiatal esophagectomy, there were 10 patients with a high anesthetic risk (ASA III. RESULTS: The operative mortality rate was 14% (2/14 in transhiatal esophagectomy group and 22% (11/49 in transthoracic esophagectomy group (P = ns. The postoperative mortality of patients with a high anesthetic risk (ASA III was 47% (8/17 after transthoracic esophagectomy and 10% (1/10 after transhiatal esophagectomy (P <0.05. DISCUSSION: In our experience, the operative mortality was nearly 18% (16.6% after transhiatal esophagectomy and 20.8% after transthoracic esophagectomy. Among the patients with a high anesthetic risk (ASA III that underwent surgery, the postoperative mortality was significantly lower after transhiatal esophagectomy (10% compared to transthoracic esophagectomy (47% (P <0.05.

  20. Pemetrexed plus dendritic cells as third-line therapy for metastatic esophageal squamous cell carcinoma

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    Zhang B

    2016-06-01

    Full Text Available Bin Zhang,1,* Rui Li,2,3,* Chun-Xiao Chang,2,3 Yong Han,2,3 Sheng-Bin Shi,2,3 Jing Tian2,3 1Department of Medical Oncology, Shandong Ji Ning First People’s Hospital, 2Department of Medical Oncology, Shandong Cancer Hospital, Shandong University, Shandong 3Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workAbstract: This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC. All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m2 plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0% had a partial response, ten patients (33.3% had stable disease, and 17 patients (56.7% had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS time was 2.9 months (95% CI, 2.7–3.2, and the median overall survival (OS time was 7.1 months (95% CI, 6.4–7.9. The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9–3.4 and 2.7 months (95% CI, 2.4–3.0, respectively (P=0.017, and median OS times =7.8 months (95% CI, 6.8–8.9 and 6.3 months (95% CI, 5.3–7.3, respectively (P=0.036. No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential

  1. Genetic polymorphism at codon 546 of the human RAD17 contributes to the risk for esophageal squamous cell carcinoma

    Science.gov (United States)

    Yasuda, Yukiko; Sakai, Akiko; Ito, Sachio; Mita, Yuichiro; Sonoyama, Takayuki; Tanabe, Shunsuke; Shirakawa, Yasuhiro; Naomoto, Yoshio; Katayama, Hiroshi; Shimizu, Kenji

    2016-01-01

    Human RAD17, a human homolog of the Schizosaccharomyces pombe cell cycle checkpoint gene RAD17, plays a significant role in activating checkpoint signals in response to DNA damage. We evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of esophageal squamous cell carcinoma in relation to smoking and alcohol consumption history in 154 esophageal squamous cell carcinoma male patients and 695 cancer-free male controls by a case-control study conducted in Japan. The results showed that the hRAD17 Arg/Arg genotype compared to the Leu/Leu and Leu/Arg genotypes was significantly associated with the risk of the esophageal squamous cell carcinoma with an adjusted odds ratios of 2.22 (95% CI: 1.19-4.16 P=0.013). In stratified studies, the risk of esophageal squamous cell carcinoma was markedly higher in light drinkers (less than 23 g ethanol/day) with the Arg/Arg genotype than in heavy drinkers (excess of 23 g ethanol/day) with the Arg/Arg genotype (OR=2.83, 95% CI: 1.05-7.61, P=0.04). We concluded that the genetic variant of hRAD17 Leu546Arg polymorphism exerts a significant effect on esophageal squamous cell carcinoma risk among Japanese men. PMID:27186329

  2. Management of Esophageal Carcinoma Associated with Cirrhosis: A Retrospective Case-Control Analysis

    Directory of Open Access Journals (Sweden)

    Florence Trivin

    2009-01-01

    Full Text Available Objectives. Esophageal carcinoma and cirrhosis have the overlapping etiologic factors. Methods. In a retrospective analysis conducted in 2 Breton institutions we wanted to asses the frequency of this association and the outcome of these patients in a case-control study where each case (cirrhosis and esophageal cancer was paired with two controls (esophageal cancer. Results. In a 10-year period, we have treated 958 esophageal cancer patients; 26 (2.7% had a cirrhosis. The same treatments were proposed to the 2 groups; cases received nonsignificantly different radiation and chemotherapy dose than controls. Severe toxicities and deaths were more frequent among the cases. At the end of the treatment 58% of the cases and 67% of the controls were in complete remission; median and 2-year survival were not different between the 2 groups. All 4 Child-Pugh B class patients experienced severe side effects and 2 died during the treatment. Conclusions. This association is surprisingly infrequent in our population! Child-Pugh B patients had a dismal prognosis and a bad tolerance to radiochemotherapy; Child-Pugh A patients have the same tolerance and the same prognosis as controls and the evidence of a well-compensated cirrhosis has not modified our medical options.

  3. NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway

    Science.gov (United States)

    Ai, Runna; Sun, Yulin; Guo, Zhimin; Wei, Wei; Zhou, Lanping; Liu, Fang; Hendricks, Denver T.; Xu, Yang; Zhao, Xiaohang

    2016-01-01

    ABSTRACT N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however β−catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and β−catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and  β-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression. PMID:27414086

  4. Study on factors influencing survival in patients with radioactive 125Ⅰ seeds implantation combined with surgery therapy on advanced esophageal squamous cell carcinoma by COX model%COX模型对术中125Ⅰ粒子植入治疗中晚期食管鳞癌预后因素的分析

    Institute of Scientific and Technical Information of China (English)

    李义生; 周国志

    2012-01-01

    Objective: To evaluate the safety, efficacy, survival rate and the factors influencing survival in united intraoperative 125I seed implantation in the treatment of advanced esophageal squamous cell carcinoma. Methods: The clinical data were collected from 100 cases of surgical treatment of combined Ⅰ seed implantation in patients with esophageal squamous cell carcinoma (based on preoperative CT staging: Ⅱ -Ⅲ phase) between 2001 -2006 in our hospital, excluding 5 patients performed on palliative resection and bypass surgery, the final 95 patients with e-sophageal cancer radical resection combined with I seed implantation, and their data were analysized. Patients were developed based on TPS dose, surgery under direct vision interstitial implantation of 125I seeds; using 0. 3 -0. 7mCi 10 -40 I25I seeds, total activity in the 7 -28mCi, matching peripheral tumor dose40 -80Gy. The factors influencing postoperative survival in patients were analysized by univariate and multivariate analysis. Results: On the close date of June 30,2011, 95 patients all had been followed up, the survival was observed in 40 patients. The satisfied quality assessment of I seeds was observed. There were no surgery or seeds implantation -related deaths, the local recur-rence rate was 11. 6% and the distant metastasis rate was 41. 1 % . The 1 - year, 3 - year and 5 - year overall surviv-al rates were 90. 5% , 58. 9% and 42. 1% , respectively. The median survival was 38 months (95% CI; 25 -51 months). Univariate survival analysis showed that the factors influencing long - term survival included the age group (P =0.0006) , tumor location (P =0.0013), preoperative CT staging (P =0.0003), particle activity (P = 0. 0026) , tumor matched peripheral dose (P = 0. 0021 ) and pathological stage (P =0. 0001) . Then the prognostic factors including particle activity (P =0. 017) and tumor matched peripheral dose (P = 0. 000) and pathological stage (P =0. 0000) were shown by COX regression analysis

  5. Gene expression profiles at different stages of human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jin Zhou; Li-Qun Zhao; Mo-Miao Xiong; Xiu-Qin Wang; Guan-Rui Yang; Zong-Liang Qiu; Min Wu; Zhi-Hua Liu

    2003-01-01

    AIM: To characterize the gene expression profiles in differentstages of carcinogenesis of esophageal epithelium.METHODS: A microarray containing 588 cancer relatedgenes was employed to study the gene expression profileat different stages of esophageal squamous cell carcinomaincluding basal cell hyperplasia, high-grade dysplasia,carcinoma in situ, early and late cancer. Principle componentanalysis was performed to search the genes which wereimportant in carcinogenesis.RESULTS: More than 100 genes were up or down regulatedin esophageal epithelial cells during the stages of basal cellhyperplasia, high-grade dysplasia, carcinoma in situ, earlyand late cancer. Principle component analysis identified aset of genes which may play important roles in the tumordevelopment. Comparison of expression profiles betweenthese stages showed that some genes, such as P160ROCK,JNK2, were activated and may play an important role inearly stages of carcinogenesis. CONCLUSION: These findings provided an esophagealcancer-specific and stage-specific expression profiles,showing that complex alterations of gene expression underliethe development of malignant phenotype of esophagealcancer cells.

  6. Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    To report our experience with increased dose intensity-modulated radiation and concurrent systemic chemotherapy as definitive treatment of locally advanced esophageal cancer. We analyzed 27 consecutive patients with histologically proven esophageal cancer, who were treated with increased-dose IMRT as part of their definitive therapy. The majority of patients had T3/4 and/or N1 disease (93%). Squamous cell carcinoma was the dominating histology (81%). IMRT was delivered in step-and-shoot technique in all patients using an integrated boost concept. The boost volume was covered with total doses of 56-60 Gy (single dose 2-2.14 Gy), while regional nodal regions received 50.4 Gy (single dose 1.8 Gy) in 28 fractions. Concurrent systemic therapy was scheduled in all patients and administered in 26 (96%). 17 patients received additional adjuvant systemic therapy. Loco-regional control, progression-free and overall survival as well as acute and late toxicities were retrospectively analyzed. In addition, quality of life was prospectively assessed according to the EORTC QLQs (QLQ-OG25, QLQ-H&N35 and QLQ-C30). Radiotherapy was completed as planned in all but one patient (96%), and 21 patients received more than 80% of the planned concurrent systemic therapy. We observed ten locoregional failures, transferring into actuarial 1-, 2- and 3-year-locoregional control rates of 77%, 65% and 48%. Seven patients developed distant metastases, mainly to the lung (71%). The actuarial 1-, 2- and 3-year-disease free survival rates were 58%, 48% and 36%, and overall survival rates were 82%, 61% and 56%. The concept was well tolerated, both in the clinical objective examination and also according to the subjective answers to the QLQ questionnaire. 14 patients (52%) suffered from at least one acute CTC grade 3/4 toxicity, mostly hematological side effects or dysphagia. Severe late toxicities were reported in 6 patients (22%), mostly esophageal strictures and ulcerations. Severe side effects to

  7. Late course accelerated hyperfractionated radiotherapy for clinical T1-2 esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kuai-Le Zhao; Yang Wang; Xue-Hui Shi

    2003-01-01

    AIM: This retrospective study was designed to analyze the results and the failure patterns of late course accelerated hyperfractionated radiotherapy for clinical T1-2NoMo esophageal carcinoma. METHODS: From Aug. 1994 to Feb. 2001, 56 patients with clinical T1-2 esophageal carcinoma received late course accelerated hyperfractionated radiotherapy in Cancer Hospital,Fudan University. All patients had been histologically proven to have squamous cell carcinoma (SCC) and were diagnosed to be T1-2NoMo by CT scan. All patients were treated with conventional fractionation (CF) irradiation during the first twothirds course of the treatment to a dose of about 41.4Gy/23fx/4 to 5 weeks, Which was then followed by accelerated hyperfractionation irradiation using reduced fields, twice daily at 1.SGy per fraction, to a dose about 27Gy/18 fx. Thus the total dose was 67-70Gy/40-43fx/40-49 d. RESULTS: The 1-, 3- and 5-year overall survival was 90.9 %,54.6 %, 47.8 % respectively. The 1-, 3- and 5-year local control rate was 90.9 %, 84.5 % and 84.5 %, respectively.Twenty-five percent (14/56) patients had distant metastasis and/or lymph nodes metastasis alone. Eight point nine percent (5/56) patients had local disease alone. Another 3.6 % (2/56) patients had regional relapse and distant metastasis. CONCLUSION: Late course accelerated hyperfractionated radiotherapy is effective on clinical T1-2 esophageal carcinoma.The main failure pattern is distant metastasis.

  8. Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform

    OpenAIRE

    Lihong Yin; Enchun Pan; Wei Guo; Yuepu Pu; Yi Wang; Xiaobo Li; Yuan Peng; Ran Liu

    2013-01-01

    Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma s...

  9. Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Wang; Guo-Zhen Liu; Ai-Li Song; Rui-Fen Chen; Hai-Yan Li; Yu Liu

    2005-01-01

    AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageal carcinoma and adjacent normal tissues.METHODS: The expression of HSP70 and grp94 in 78human esophageal cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis.RESULTS: Both esophageal cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageal carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8%(56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageal cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01).CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70is related to the differentiation of esophageal carcinoma.

  10. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

    Science.gov (United States)

    Kim, Ryul; Keam, Bhumsuk; Kwon, Dohee; Ock, Chan-Young; Kim, Miso; Kim, Tae Min; Kim, Hak Jae; Jeon, Yoon Kyung; Park, In Kyu; Kang, Chang Hyun; Kim, Dong-Wan; Kim, Young Tae; Heo, Dae Seog

    2016-01-01

    AIM To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients (33.5%) were PD-L1-positive. Positive p16 expression was observed in 21 specimens (10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens (21.0%). Although PD-L1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PD-L1-positivity (OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival (P = 0.656). In contrast, the locoregional relapse rate tended to increase (P = 0.134), and the distant metastasis rate was significantly increased (HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC. CONCLUSION PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC. PMID:27729745

  11. Factors Predicting Effectiveness of Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

    2016-04-01

    The aim of the study was to elucidate pretreatment factors that can predict the outcome of neoadjuvant chemoradiotherapy or chemotherapy (NAC(R)T) and help us choose treatment strategies appropriate for individual patients.Few studies have investigated whether clinical data obtainable before the treatment can predict the efficacy of NAC(R)T.Of 1540 patients treated for esophageal squamous cell carcinoma (ESCC) at our department between January 2000 and June 2014, those who underwent surgical resection of cStage II or more advanced ESCC after NAC(R)T (113 NACRT and 146 NACT patients) were enrolled in this study. Information all available before the treatment was analyzed to extract factors that can predict the effectiveness of NAC(R)T. NAC(R)T was considered effective when Grade 2 or greater treatment efficacy was achieved based on the histological grading system.NACRT was effective in 51 (45%) of 113 patients. The analysis of 35 pretreatment factors showed that female sex (hazard ratio [HR] = 3.650; 1.181-11.236), absence of dyslipidemia (HR = 3.284; 1.341-8.041), and histologically poorly differentiated tumor (HR = 2.431; 1.052-5.619) were factors predicting NACRT effectiveness. On the other hand, NACT was effective in 21 (14%) of 146 patients. The analysis of pretreatment factors showed that absence of dyslipidemia (HR = 10.204; 1.302-83.33) and therapy with docetaxel, cisplatin, and 5-fluorouracil (HR = 2.097; 1.027-4.280) were factors predicting NACT effectiveness.The findings of this study investigating factors that could predict the outcome of NAC(R)T suggest that the prevalence of dyslipidemia influences the outcome of NAC(R)T for ESCC. PMID:27082598

  12. Pemetrexed plus dendritic cells as third-line therapy for metastatic esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Bin; Li, Rui; Chang, Chun-Xiao; Han, Yong; Shi, Sheng-Bin; Tian, Jing

    2016-01-01

    This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs) when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC). All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m(2)) plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0%) had a partial response, ten patients (33.3%) had stable disease, and 17 patients (56.7%) had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS) time was 2.9 months (95% CI, 2.7-3.2), and the median overall survival (OS) time was 7.1 months (95% CI, 6.4-7.9). The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9-3.4) and 2.7 months (95% CI, 2.4-3.0), respectively (P=0.017), and median OS times =7.8 months (95% CI, 6.8-8.9) and 6.3 months (95% CI, 5.3-7.3), respectively (P=0.036). No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential biomarker for predicting the efficacy of pemetrexed plus DCs in the treatment of ESCC.

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

    Institute of Scientific and Technical Information of China (English)

    Ke Li; Wei He; Na Lin; Xin Wang; Qing-Xia Fan

    2009-01-01

    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 rates 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 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.

  14. Up-regulated manganese superoxide dismutase expression increases apoptosis resistance in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    HU Hai; WANG Ming-rong; LUO Man-li; DU Xiao-li; FENG Yan-bin; ZHANG Yu; SHEN Xiao-ming; XU Xin; CAI Yan; HAN Ya-ling

    2007-01-01

    Background Esophageal cancer is one of the most common malignancies in the world.In order to identify the proteins associated with esophageal squamous cell carcinomas(ESCC),we analyzed the protein profiles of ESCC cases with tumor and matched adjacent normal tissues.Methods Two-dimensional electrophoresis(2-DE)was carried out to analyze the protein profiles.Dysregulated protein spots were identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight(MALDI-TOF)and verified by liquid chromatography/electrospray ionization ion trap-mass spectrometry/mass spectrometry(LC-ESI-IT MS).RT-PCR and immunohistochemistry on tissue microarray were performed to confirm the gene dysregulation in esophageal cancerous tissues.RNA interference (RNAi)was used to knock down the gene expression in ESCC cell lines.Apoptosis assay with annexin V-FITC/PI staining was conducted and cells were analyzed by flow cytometry.Results 2-DE showed that two protein spots with approximate molecular weights and different pl were elevated in 12 out of 18 ESCCs as compared to the corresponding normal tissues.Both the two spots were identified as MnSOD by MALDI-TOF and were verified by LC-ESI-IT MS.MnSOD overexpression was detected in 14 tumors out of 24 cases by RT-PCR and 52 tumors out of 116 cases by immunohistochemistry comparing to normal epithelia.siRNA-mediated silencing of MnSOD in KYSE450 and KYSE150 cell lines revealed that MnSOD protected ESCC cells from apoptosis induced by ultraviolet(UV)and doxorubicin(DOX).Conclusions These findings suggest that there existed two isoforms of MnSOD protein in normal and tumor esophageal tissues.MnSOD was overexpressed in ESCC and its up-regulation in esophageal cancer cells was associated with apoptosis resistance.

  15. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Casini

    2011-09-01

    Full Text Available Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered.

  16. Esophageal Carcinoma Histology Affects Perioperative Morbidity Following Open Esophagogastrectomy

    Directory of Open Access Journals (Sweden)

    Charles E. Woodall

    2008-01-01

    Full Text Available Background. Esophagectomy for esophageal cancer is being practiced routinely with favorable results at many centers. We sought to determine if tumor histology is a powerful surrogate marker for perioperative morbidity. Methods. Seventy three consecutive patients managed operatively were reviewed from our prospectively maintained database. Results. Adenocarcinoma (AC was present in 52 (71% and squamous cell (SCC in 21 (29%. The use of neoadjuvant therapy was similar for the AC (34.62% and SCC (42.86% groups. The SCC group had a higher incidence of prior pulmonary disease than the AC group (23.8% versus 5.8%, resp.; =.03. SCC patients were more likely to have a prolonged ICU stay than AC patients (=.004 despite similar complication rates, EBL, and prognostic nutritional index. The SCC group did, however, experience higher grades of complications (=.0053. Conclusions. Presence of SCC was the single best predictor of prolonged ICU stay and more severe complications as defined by this study. Only a past history of pulmonary disease was different between the two histologic subgroups.

  17. Clinical observation of irinotecan-based regimens as second-line treatment in 35 cases of advanced esophageal squamous cell carcinoma%含伊立替康方案二线治疗35例晚期食管癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘捷; 范南峰; 李惠; 郑亮

    2014-01-01

    Objective To evaluate the efficacy and toxicity of irinotecan (CPT-1 1 )as second-line regimens in patients with advanced esophageal squamous cell carcinoma (ESCC).Methods A total of 35 advanced ESCC patients after failure to chemotherapy with paclitaxel and platinum received Irinotecan-based combination chemotherapy as second-line regimen.Of them,20 cases received IP regimen (irinotecan 180 mg/m2 d1,cisplatin 50 mg/m2 d2),15 cases received FOLFIRI regimen (irinotecan 180 mg/m2 d1,5-FU 2 400 mg/m2 continuous infusion over 46 hours,folinic acid (FA)400 mg/m2 d1),all re-peated every 14 days.Results For a total of 35 patients,8 patients achieved PR,12 patients achieved SD,15 patients a-chieved PD.The response rate was 22.8%,and the disease control rate was 57.1%.The median progression-free survival (PFS)and overall survival (OS)was 2.7 and 7.3 months.The most common adverse events (AEs)were myelosuppression, nausea,vomit and diarrhea.Conclusion Irinotecan-based combination chemotherapy as second-line regimen is effective,safe and well-tolerated in patients with advanced esophageal squamous cell carcinoma.It is valuable for further observation in clinical practice.%目的:观察含伊立替康的联合化疗方案在晚期食管癌二线治疗中的临床疗效及毒性反应。方法35例既往经紫杉醇联合铂类一线化疗无效或进展的晚期食管癌患者,二线化疗使用伊立替康+顺铂方案20例(伊立替康180 mg/m2静滴第1天,顺铂50 mg/m2静滴第2天);使用伊立替康+氟尿嘧啶+亚叶酸钙(FOLFIRI)方案15例(伊立替康180 mg/m2静滴第1天,氟尿嘧啶2400 mg/m2持续静滴46 h,亚叶酸钙400 mg/m2静滴第1天),均为双周化疗方案。结果完全缓解(CR)0例,部分缓解(PR)8例,稳定(SD)12例,进展(PD)15例,有效率为22.8%,疾病控制率为57.1%,中位无进展生存期(PFS)2.7个月,中位总生存期(OS)7.3个月。主要毒副反应为血液学毒性及恶心呕吐、腹泻,全组无毒性相关死亡。结

  18. Changes of serum p53 antibodies and clinical significance of radiotherapy for esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Yi Cai; Xiao-Hu Wang; Ying Tian; Li-Ying Gao; Li-Juan Zhang; Zhi-Yan Zhang

    2008-01-01

    AIM: To explore the relationship between serum p53 antibodies (p53-Abs) and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma (EC), and to investigate sequential changing regularity of serum p53-Abs after radiotherapy.METHODS: The serum p53-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay (ELISA). The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy.RESULTS: The level and positive rate of serum p53-Abs in EC patients were significantly higher than those in normal individuals (P<0.05). Serum anti-p53 antibodies were positive in 18 of 46 EC patients (39.1%). The positive rate of p53-Abs in EC was related to histological grade, disease stage and lymph node metastasis (P<0.05), but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d (P<0.05 or P<0.01). The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy (P<0.0001).CONCLUSION: Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.

  19. Inhibitory effect of ubiquitin-proteasome pathway on proliferation of esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Wei-Guo Zhang; Jie-Ping Yu; Qing-Ming Wu; Qiang Tong; Sheng-Bao Li; Xiao-Hu Wang; Guo-Jian Xie

    2004-01-01

    AIM: To investigate the inhibitory effect of ubiquitinproteasome pathway (UPP) on proliferation of esophageal carcinoma cells.METHODS: Esophageal carcinoma cell strain EC9706 was treated with MG-132 to inhibit its UPP specificity. Cell growth suppression was evaluated with 3-(4,5-dimethylthiazole2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. DNA synthesis was evaluated by 3H-thymidine (3H-TdR)incorporation. Morphologic changes of cells were observed under microscope. Activity of telomerase was examined by telomeric repeat amplification protocol (TRAP) of PCRELISA. Cell cycle and apoptosis were detected by flow cytometry (FCM). DNA fragment analysis was used to confirm the presence of apoptosis. Expression of p27kip1was detected by immunocytochemical technique.RESULTS: After exposed to MG-132, the growth and value of 3H-TdR incorporation of EC9706 cells were obviously inhibited. Cells became round, small and exfoliative under microscope. TRAP PCR-ELISA showed that light absorption of cells gradually decreased after exposed to 5 μmol/L of MG-132 for 24, 48, 72 and 96 h (P<0.01). The percentage of cells at G0/G1 phase was increased and that at S and G2/M was decreased (P<0.01). The rate of apoptotic cells treated with 5 μmol/L of MG-132 for 48 and 96 h was 31.7%and 66.4%, respectively. Agarose electrophoresis showed marked ladders. In addition, the positive signals of p27kip1were located in cytoplasm and nuclei in MG-132 group in contrast to cytoplasm staining in control group.CONCLUSION: MG-132 can obviously inhibit proliferation of EC9706 cells and induce apoptosis. The mechanisms include upregulation of p27kip1 expression, G1 arrest and depression of telomerase activity. The results indicate that inhibiting UPP is a novel strategy for esophageal carcinoma therapy.

  20. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    Science.gov (United States)

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (PAvocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

  1. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    Science.gov (United States)

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers. PMID:24901722

  2. A Novel Inflammation-Based Stage (I Stage) in Patients with Resectable Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Peng-Cheng Chen; Ji-Feng Feng

    2016-01-01

    Background. Inflammation plays a key role in cancer. In the current study, we proposed a novel inflammation-based stage, named I stage, for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods. Three hundred and twenty-three patients with resectable ESCC were enrolled in the current study. The I stage was calculated as follows: patients with high levels of C-reactive protein (CRP) (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) (>3.5), and platelet-count-to-lymphocyte ...

  3. pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus

    Institute of Scientific and Technical Information of China (English)

    Simone S Contu; Paulo C Contu; Daniel C Damin; Renato B Fagundes; Fabiano Bevilacqua; Aline S Rosa; Jo(a)o C Prolla; Luis F Moreira

    2007-01-01

    AIM: To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus.METHODS: One hundred and seventy asympto matic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein.RESULTS: Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%).CONCLUSION: Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRBprotein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy.

  4. Expression of ECRG4, a novel esophageal cancer-related gene,downregulated by CpG island hypermethylation in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Mei Yue; Da-Jun Deng; Mei-Xia Bi; Li-Ping Guo; Shih-Hsin Lu

    2003-01-01

    AIM: To study the mechanisms responsible for inactivation of a novel esophageal cancer related gene 4 (ECRG4) in esophageal squamous cell carcinoma (ESCC). METHODS: A pair of primers was designed to amplify a 220 bp fragment, which contains 16 CpG sites in the core promoter region of the ECRG 4 gene. PCR products of bisulfite-modified CpG islands were analyzed by denaturing high-performance liquid chromatography (DHPLC), which were confirmed by DNA sequencing. The methylation status of ECRG 4 promoter in 20 cases of esophageal cancer and the adjacent normal tissues, 5 human tumor cell lines (esophageal cancer cell line-NEC, EC109, EC9706; gastric cancer cell line- GLC; human embryo kidney cell line-Hek293)and 2 normal esophagus tissues were detected. The expression level of the ECRG 4 gene in these samples was examined by RT-PCR. RESULTS: The expression level of ECRG 4 gene was varied.Of 20 esophageal cancer tissues, nine were unexpressed,six were lowly expressed and five were highly expressed compared with the adjacent tissues and the 2 normal esophageal epithelia. In addition, 4 out of the 5 human cell lines were also unexpressed. A high frequency of methylation was revealed in 12 (8 unexpressed and 4 lowly expressed)of the 15 (80%) downregulated cancer tissues and 3 of the 4 unexpressed cell lines. No methylation peak was observed in the two highly expressed normal esophageal epithelia and the methylation frequency was low (3/20) among the 20 cases in the highly expressed adjacent tissues. The methylation status of the samples was consistent with the result of DNA sequencing. CONCLUSION: These results indicate that the inactivation of ECRG 4gene by hypermethylation is a frequent molecular event in ESCC and may be involved in the carcinogenesis of this cancer.

  5. Acute esophagitis for patients with Local-regional Advanced NSCLC treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Y.; Brink, C.; Knap, M.;

    2015-01-01

    and clinical and dosimetric parameters in the patients with local advanced NSCLC receiving IMRT and concomitant chemotherapy (CCT). Materials and Methods: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC enrolled in the multi institution clinical trial NARLAL. All patients were treated with 2......Purpose/Objective: Esophagitis are one of the acute treatment related toxicities to definitive radiotherapy for NSCLC. Most current researches about the risk factors for acute esophagitis are based on 3DCRT. The purpose of this study was to estimate the dose-effect relationship between esophagitis...

  6. Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic stent placement

    Institute of Scientific and Technical Information of China (English)

    You-Tao Yu; Guang Yang; Yan Liu; Bao-Zhong Shen

    2004-01-01

    AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement.METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1 200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement.RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases.CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients' survival and reduce occurrence of re-stenosis.

  7. 内镜下窄带光谱成像技术联合碘染色检查对进展期食管癌的诊断价值%Application of narrow band imaging combined with lugol chromo-endoscopy in the diagnosis of advanced esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    曹长琦; 李士杰; 闫炎; 张集昌; 吴齐

    2013-01-01

    Objective To investigate the value of narrow band imaging (NBI) and lugol chromo-endoscopy (LCE) in the diagnosis of advanced esophageal carcinoma.Methods The clinical data of 162 patients with advanced esophageal carcinoma who received NBI and LCE at the Cancer Hospital of Peking University from November 2010 to May 2012 were retrospectively analyzed.Esophageal mucosa was first examined using white light imaging (WLI),and then followed by NBI and LCE,and the lengths of the lesions were recorded.Biopsy histology was obtained in all abnormal mucosa which were detected by NBI or LCE.Difference in the length of lesions detected by the NBI/LCE and WLI was calculated.Surgical approach and method of anastomosis were recorded for patients who received surgical treatment,and the final treatment method was recorded for patients who did not receive surgical treatment.Difference in the treatment methods was compared before and after endoscopy.Results The length of the lesions detected by the 3 methods was identical in 121 patients,different in 41 patients.The difference ranged between 1 and 3 cm was observed in 22 patients,>3 cm and ≤5 cm in 8 patients,>5 cm and ≤10 cm in 7 patients,> 10 cm in 4 patients.Of the patients in the above mentioned 4 categories,there were 1,2,2,4 patients in each category received neo-adjuvant therapy,and the rest patients received operation.Superficial cancer contiguous to the primary lesion was found in 41 patients,including squamous cell carcinoma in 31 patients,carcinoma-in-situ in 3 patients and severe dysplasia in 7 patients.Of the 153 patients who received surgery,the surgical plan for 12 patients was modified.Intrathoracic anastomosis was changed to cervical anastomosis in 2 patients,anastomosis under the aortic arch was changed to anastomosis above the aortic arch in 3 patients,trans-abdominal operation was changed to thoraco-abdominal operation in 7 patients.Conclusions The combination of NBI and LCE is more accurate to evaluate

  8. HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma

    Science.gov (United States)

    Palumbo, Antonio; Meireles Da Costa, Nathalia; Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; de Sousa, Vanessa Paiva Leite; Martins, Ivanir; Nasciutti, Luiz Eurico; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro

    2016-01-01

    Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression. PMID:27027341

  9. Efficacy and prognostic analysis of chemoradiotherapy in patients with thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis alone

    International Nuclear Information System (INIS)

    The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50–68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival

  10. Translocation of annexin Ⅰ from cellular membrane to the nuclear membrane in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu Liu; Xiao-Hang Zhao; Hui-Xin Wang; Ning Lu; You-Sheng Mao; Fang Liu; Ying Wang; Hai-Rong Zhang; Kun Wang; Min Wu

    2003-01-01

    AIM: To investigate the alteration of the annexin I subcellular localization in esophageal squamous cell carcinoma (ESCC)and the correlation between the translocation and the tumorigenesis of ESCC.METHODS: The protein localization of annexin I was detected in both human ESCC tissues and cell line via the indirect immunofiuorescence strategy.RESULTS: In the normal esophageal epithelia the annexin I was mainly located on the plasma membrane and formed a consecutive typical trammels net. Annexin I protein also expressed dispersively in cytoplasm and the nuclei without specific localization on the nuclear membrane. In esophageal cancer annexin I decreased very sharply with scattered disappearance on the cellular membrane, however it translocated and highly expressed on the nuclear membrane,which was never found in normal esophageal epithelia. In cultured esophageal cancer cell line annexin I protein was also focused on the nuclear membrane, which was consistent with the result from esophageal cancer tissues.CONCLUSION: This observation suggests that the translocation of annexin I protein in ESCC may correlate with the tumorigenesis of the esophageal cancer.

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

    Institute of Scientific and Technical Information of China (English)

    I Bergheim; E Wolfgarten; E Bollschweiler; AH H(o)lscher; C Bode; A Parlesak

    2007-01-01

    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(n = 21)and in controls(n = 10).Protein levels of CYP2E1,CYP2C8,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.CYP2C8,CYP3A4,CYP3A5,and CYP2E1)between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.

  12. Elevated maspin expression is associated with better overall survival in esophageal squamous cell carcinoma (ESCC.

    Directory of Open Access Journals (Sweden)

    Yang Wang

    Full Text Available Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in early stage of tumor progression appear to be complex and remain to be elucidated. In the current study, we examined the expression of maspin in 84 esophageal squamous cell carcinoma (ESCC cases (stages I-III and 55 non-tumor adjacent esophageal tissue specimens by immunohistochemical (IHC staining. The correlation of maspin with clinicopathological parameters was analyzed. Compared to normal esophageal squamous tissue where 80% (47/55 of the cases expressed maspin at a low to moderate level, all ESCC specimens (100% (84/84 were positive for maspin expression at a moderate to high level. ESCC with low or moderate maspin expression had significantly shorter postoperative survival rates compared to those that had high maspin expression (p<0.001. Since the correlation of maspin with ESCC histology and the correlation of maspin with ESCC prognosis seem to be at odds, we further investigated the biological function of maspin in ESCC using the established ESCC cell lines. The expression of maspin in five human esophageal squamous cancer cell lines (T12, E450, KYSE150, EC109, and KYSE510 was examined by the Western blot. ESCC cell line KYSE510 that did not express maspin and was stably transfected by maspin cDNA or an empty vector. The resulting transfected cells were characterized in vitro. Maspin expression significantly inhibited cell proliferation, motility and matrigel invasion. Taken together, our data suggest that the transient up-regulation of maspin in the early development of ESCC may be a defense mechanism against further transition towards more malignant phenotypes, ultimately slowing down ESCC tumor

  13. Detection of esophageal squamous cell carcinoma by cathepsin B activity in nude mice.

    Directory of Open Access Journals (Sweden)

    Wei Ma

    Full Text Available BACKGROUND AND OBJECTIVE: Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice. METHODS: Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109 and one normal human esophageal epithelial cell line (HET-1A for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology. RESULTS: CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro. CONCLUSIONS: CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.

  14. Elevated maspin expression is associated with better overall survival in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Wang, Yang; Sheng, Shijie; Zhang, Jianzhi; Dzinic, Sijana; Li, Shaolei; Fang, Fang; Wu, Nan; Zheng, Qingfeng; Yang, Yue

    2013-01-01

    Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in early stage of tumor progression appear to be complex and remain to be elucidated. In the current study, we examined the expression of maspin in 84 esophageal squamous cell carcinoma (ESCC) cases (stages I-III) and 55 non-tumor adjacent esophageal tissue specimens by immunohistochemical (IHC) staining. The correlation of maspin with clinicopathological parameters was analyzed. Compared to normal esophageal squamous tissue where 80% (47/55) of the cases expressed maspin at a low to moderate level, all ESCC specimens (100% (84/84)) were positive for maspin expression at a moderate to high level. ESCC with low or moderate maspin expression had significantly shorter postoperative survival rates compared to those that had high maspin expression (pESCC histology and the correlation of maspin with ESCC prognosis seem to be at odds, we further investigated the biological function of maspin in ESCC using the established ESCC cell lines. The expression of maspin in five human esophageal squamous cancer cell lines (T12, E450, KYSE150, EC109, and KYSE510) was examined by the Western blot. ESCC cell line KYSE510 that did not express maspin and was stably transfected by maspin cDNA or an empty vector. The resulting transfected cells were characterized in vitro. Maspin expression significantly inhibited cell proliferation, motility and matrigel invasion. Taken together, our data suggest that the transient up-regulation of maspin in the early development of ESCC may be a defense mechanism against further transition towards more malignant phenotypes, ultimately slowing down ESCC tumor progression.

  15. A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Joseph Chok Yan Ip

    2015-01-01

    Full Text Available Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. An in vivo esophageal squamous cell carcinoma (ESCC orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and the in vivo tumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.

  16. Detection of Human Papillomaviral Infection on Kazakh Patients with Esophageal Squamous Cell Carcinoma in Xinjiang

    Institute of Scientific and Technical Information of China (English)

    Ling Chen; Lan Yang; Zhenzhu Sun; Haiyang Zhang; Tao Ren; Xiuyun Tian; Lijuan Pang; Bin Chang; Hongan Li; Feng Li

    2009-01-01

    OBJECTIVE To investigate the detection rate of human papilloma virus (HPV) DNA in the Kazakh esophageal carcinoma (EC) patients of Xinjiang.METHODS We detected the prevalence of a HPV gene in tumor tissues from 318 esophageal squamous cell carcinoma (ESCC).Tumor tissues were kept in formalin and embedded in paraffin.One hundred seventeen samples used crude cell suspension, while the other 201 used the method of DNA extraction with phenol-Tris/chloroform. We analyzed the relevance to EC of Kazakh's in Xinjiang.RESULTS In the ESCC samples of Kazakh's in Xinjiang, total detection rate for HPV DNA was 64.5% (205/318). The positive rate of HPV in group of crude cell suspensions was 82.9% (97/117) compared with the rate of 53.7% (108/201) in the group of DNA extraction. The results in the two groups showed significant diffference (X2 = 5.711, P < 0.05).CONCLUSION HPV DNA infection may be one of the most important factors related to EC of Kazakh's in Xinjiang.

  17. Change and Significance of Mitochondrial DNA Copy Number in Esophageal Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zongwen Liu; Zhihua Zhao; Qiumin Zhao; Shenglei Li; Dongling Gao; Xia Pang; Kuisheng Chen; Yunhan Zhang

    2007-01-01

    OBJECTIVE To compare the differences of mitochondrial DNA (mtDNA)copies among the tissues of esophageal squamous cell carcinoma (ESCC),para-neoplastic tissue and normal mucous membrane of the esophagus,and to study the relationship between the mtDNA and the occurrence and development of esophageal squamous cell carcinoma.METHODS The mtDNA copies of 42 specimens with the ESCC,paraneoplastic mucous tissue and normal mucous membrane of the esophagus were determined using real-time fluorescence quantitative PCR.The mtDNA was analyzed using agarose gel electrophoresis.RESULTS The mtDNA from all of the tissues (42/42) from the ESCC,para-neoplastic tissue and normal esophageal mucous membranes was analyzed.showing thal there were an average mtDNA copy number of 27.1894x106 μg DNA.9.4102x106 μg DNA and 5.9347x106 μg DNA,from the respective tissues.There were significant differences (F=27.83,P<0.05) in mtDNA copy number among the three.A positive band was shown at 403 bp after qel electrophoresis of the PCR products.and the lane where the ESCC mtDNA located was rather bright.which was in accordance with the result of the real-time PCR determination.CONCLUSION An increase in the mtDNA copy number is related to the occurrence and development of ESCC.

  18. Morphological and functional changes of mitochondria in apoptotic esophageal carcinoma cells induced by arsenic trioxide

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    Zhong-Ying Shen; Jian Shen; Qiao-Shan Li; Cai-Yun Chen; Jiong-Yu Chen; Yi Zeng

    2002-01-01

    AIM: To demonstrate that mitochondrial morphological andfunctional changes are an important intermediate link in thecourse of apoptosis in esophageal carcinoma cells inducedby As2O3.METHODS: The esophageal carcinoma cell line SHEEC1,established in our laboratory, was cultured in 199 growthmedium, supplemented with 100mL@ L-1 calf serum and3 mol@L-1 As2O3( the same below). After 2, 4, 6, 12, 24 hof drug adding, the SHEEC1 cells were collected for light-and electron-microscopic examination. The mitochondriawere labeled by Rhodamine fluorescence probe and thefluorescence intensity of the mitochondria was measured byflow cytometer and cytofluorimetric analysis. Further, themitochondrial transmembrane potential ( MTP, ΔΨm )change was also calculated.RESULTS: The mitochondrial morphological change afteradding As2O3 could be divided into three stages. In theearly-stage (2-6h) after adding As2O3, an adaptiveproliferation of mitochondria appeared; in the mid-stage (6-12 h ) e degenerative change was observed; and in the late-stage (12-24 h ) the mitochondria swelled with outermembrana broken down and then calls death with apoptoticchanges of nucleus. The functional change of themitochondria indicated by fluorescent intensity, whichreflected the MTP status of mitochondria, was in accordancewith morphological change of the mitochondria. Thefluorescent intensity increased at early-stage, declined inmid-stage and decreased to the lowest in the late@ stage. 24h after As2O3 adding, the cell nucleus showed typicalapoptotic changes.CONCLUSION: Under the inducement of As2O3, the earlyapoptotic changes of SHEEC1 cells were the apparentmorphological and functional changes of mitochondria,afterwards the nucleus changes followed. lt is consideredthat changes of mitochondria are an important intermediatelink in the course of apoptosis of esophageal carcinomacalls induced by As2O3.

  19. Significance of the prognostic nutritional index in patients with esophageal squamous cell carcinoma

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    Feng JF

    2013-12-01

    Full Text Available Ji-Feng Feng, Qi-Xun Chen Department of Thoracic Surgery, Zhejiang Cancer Hospital, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, People's Republic of China Background: The prognostic nutritional index (PNI is related to the prognosis in many cancers; however, its role in esophageal cancer is still controversial. Further, controversy exists concerning the optimal cut-off points for PNI to predict survival. The aim of this study was to determine the prognostic value of PNI and propose the optimal cut-off points for PNI in predicting cancer-specific survival (CSS in esophageal squamous cell carcinoma (ESCC. Methods: This retrospective study included 375 patients who underwent esophagectomy for ESCC. The PNI was calculated as 10 × serum albumin (g/dL + 0.005 × total lymphocyte count (per mm3. With the help of the fit line on the scatter plot, we classified the patients into three categories according to the PNI, ie, >52, 42–52, and <42. Results: Our study showed that PNI was associated with tumor length (P=0.007, T grade (P=0.001, and N staging (P<0.001. The 5-year CSS in patients with PNI <42, 42–52, and >52 were 11.0%, 39.1%, and 55.2%, respectively (P<0.001. Multivariate analysis showed that PNI was a significant predictor of CSS (42–52 versus >52, P=0.011; <42 versus PNI >52, P<0.001. Conclusion: PNI is a predictive factor for long-term survival in ESCC. The survival rate of ESCC can be discriminated between three groups, ie, PNI ,42, 42–52, and .52. Keywords: esophageal squamous cell carcinoma, prognostic nutritional index, prognostic factor, survival

  20. Clinicopathologic characteristics of esophagectomy for esophageal carcinoma in elderly patients

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    Jian-Yang Ma; Zhu Wu; Yun Wang; Yong-Fan Zhao; Lun-Xu Liu; Ying-Li Kou; Qing-Hua Zhou

    2006-01-01

    AIM: To evaluate the risk of esophagectomy for carcinoma of the esophagus in the elderly (70 years or more)compared with younger patients (<70 years) and to determine whether the short-term outcomes of esophagectomy in the elderly have improved in recent years.METHODS: Preoperative risks, postoperative morbidity and mortality in 60 elderly patients (≥70 years) with esophagectomy for carcinoma of the esophagus were compared with the findings in 1 782 younger patients (<70 years) with esophagectomy between January 1990and December 2004. Changes in perioperative outcome and short-time survival in elderly patients between 1990to 1997 and 1998 to 2004 were separately analyzed.RESULTS: Preoperatively, there were significantly more patients with hypertension, pulmonary dysfunction, cardiac disease, and diabetes mellitus in the elderly patients as compared with the younger patients. No significant difference was found regarding the operation time, blood loss, organs in reconstruction and anastomotic site between the two groups, but elderly patients were more often to receive blood transfusion than younger patients.Significantly more transhiatal and fewer transthoracic esophagectomies were performed in the elderly patients as compared with the younger patients. Resection was considered curative in 71.66% (43/60) elderly and 64.92% (1 157/1 782) younger patients, which was not statistically significant (P>0.05). There were no significant differences in the prevalence of surgical complications between the two groups. Postoperative cardiopulmonary medical complications were encountered more frequently in elderly patients. The hospital mortality rate was 3.3% (2/60) for elderly patients and 1.1% (19/1782) for younger patients without a significant difference. When the study period was divided into a former (1990 to 1997) and a recent (1997 to 2004) period,operation time, blood loss, and percentage ot patients receiving blood transfusion of the elderly patients

  1. The molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells in Vitro

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    景钊

    2012-01-01

    Objective To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells. Methods The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence.

  2. [A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU].

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    Ehara, Kazuhisa; Tsutsumi, Kenji; Kinoshita, Yoshihiro; Ueno, Masaki; Mine, Shinji; Udagawa, Harushi

    2008-08-01

    The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is

  3. Effect of the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma on pulmonary function

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    Xin-Hui Rao; Han-Yun Liu; Jin-Song Liang; Zi-Zheng Zhang; Huan-Rong Zhang

    2015-01-01

    Objective: To explore the effect of the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma on pulmonary function and its clinical efficacy. Methods: A total of 200 esophageal carcinoma patients with complete medical materials, admitted in our hospital from January, 2011 to December, 2014 were included in the study and divided into the observation group and the control group with 100 cases in each group. The patients in the observation group were undergoing the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma, while the patients in the control group were undergoing open esophagectomy for the treatment of esophageal carcinoma. The operation indicators, postoperative complications, short-term efficacy, and the effect of operation on pulmonary function in the two groups were compared. Results: The comparison of operation time, lymph node dissection number, and the occurrence rate of postoperative complications between the two groups was not statistically significant. The intraoperative amount of bleeding, thoracic duct indwelling time, and hospitalization time in the observation group were significantly lower than those in the control group. FEV1 the 5th day after operation in the observation group was not statistically different from that before operation, while in the control group it was statistically different from that before operation. FEV1/FVC after treatment in the observation group was significantly higher than that in the control group. PaO2 and SaO2 after operation in the observation group were not statistically different from those before operation, while PaO2 and SaO2 after operation in the control group were significantly lower than those before operation. Conclusions: The combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma has an accurate efficacy with no obvious

  4. An novel role of sphingosine kinase-1 (SPHK1 in the invasion and metastasis of esophageal carcinoma

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    Zhang Yan-Lan

    2011-09-01

    Full Text Available Abstract Background Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. Methods A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. Results We identified sphingosine kinase 1 (SPHK1 as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%, SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%, SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC. Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P P = 0.016. By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR

  5. c-Myc inhibits TP53INP1 expression via promoter methylation in esophageal carcinoma

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    Weng, Wenhao; Yang, Qinyuan [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Huang, Miaolong [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Qiao, Yongxia [Department of Preventive Medicine, Tongji University, Shanghai City 200092 (China); Xie, Yuan; Yu, Yongchun [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Jing, An, E-mail: Anjing77@gmail.com [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Institute of Cancer Research, Southern Medical University, Guangzhou 510515 (China); Li, Zhi, E-mail: lizhiweng2010@163.com [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China)

    2011-02-11

    Research highlights: {yields} TP53INP1 expression is down-regulated in esophageal carcinoma and is associated with CGI-131 methylation. {yields} Inhibition of CGI-131 methylation upregulates TP53INP1 expression in ESCC cell lines. {yields} Ectopic expression of TP53INP1 inhibits growth of ESCC cells by inducing apoptosis and inhibiting cell cycle progression. {yields} c-Myc binds to the promoter of TP53INP1 in vivo and vitro and recruits DNMT3A to TP53INP1 promoter for CGI-131 methylation. -- Abstract: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a well known stress-induced protein that plays a role in both cell cycle arrest and p53-mediated apoptosis. Loss of TP53INP1 expression has been reported in human melanoma, breast carcinoma, and gastric cancer. However, TP53INP1 expression and its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Our findings are in agreement with previous reports in that the expression of TP53INP1 was downregulated in 28% (10/36 cases) of ESCC lesions, and this was accompanied by significant promoter methylation. Overexpression of TP53INP1 induced G1 cell cycle arrest and increased apoptosis in ESCC cell lines (EC-1, EC-109, EC-9706). Furthermore, our study showed that the oncoprotein c-Myc bound to the core promoter of TP53INP1 and recruited DNA methyltransferase 3A to methylate the local promoter region, leading to the inhibition of TP53INP1 expression. Our findings revealed that TP53INP1 is a tumor suppressor in ESCC and that c-Myc-mediated DNA methylation-associated silencing of TP53INP1 contributed to the pathogenesis of human ESCC.

  6. Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xing Huang; Wei Yan; Zheng-Xiang Song; Rong-Yu Qian; Ping Chen; Eeva Salminen; Jorma Toppari

    2005-01-01

    AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cydin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors.METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immunohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (x200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections.RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immunostaining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t= 13.32 and t= 7.52,respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t= 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping.CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

  7. Clinical Studies of Postoperative Arterial Infusion Chemotherapy in Patients with Pathologic T3 Esophageal Squamous Carcinoma

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    Baodong Liu; Zongjun Dong; Xiuyi Zhi; Qingsheng Xu

    2006-01-01

    OBJECTIVE To evaluate how arterial infusion chemotherapy after radical surgery influences long-term survival of patients with pathologic T3 (pT3) esophageal squamous carcinoma.METHODS We divided 190 patients with pathologic pT3 esophageal squamous carcinoma, confirmed by consecutive radical surgery, into an experimental group (surgery + intra-arterial infusion, 56 T3N0M0 and 52 T3N1M0 cases), and the remaining patients into a control group (surgery alone, 48 T3N0M0 and 34 T3N1M0 cases). The experimental group was sub-grouped into 56 cases (26 T3N0M0 and 30 T3N1M0 cases) receiving 1 or 2 periods of chemotherapy, while 52 cases (30 T3N0M0 and 22 T3N1M0 cases) underwent 3 or more than 3 periods of chemotherapy. We used one to seven courses of selected arterial infusion chemotherapy of cisplatin (80 mg/m2 of body-surface area) and fluorouracil (800 mg/m2) with or without epirubicin at 3~4 weeks post operation. The interval between each period was 3~4 weeks. All cases were followed-up for more than 5 years. Survival rates were calculated by the Kaplan-Meier methods and survival differences between patients with and without selected arterial infusion chemotherapy were compared with the Log-rank test. Prognostic variables were entered into a Cox regression analysis model controlling for age, site, lymph node status, and treatment received.RESULTS The overall survival rates were not significantly different between the experimental group and the control group, but there was better survival for patients who received 3 or more than 3 courses of chemotherapy. Lymph node status (N) was an important factor in the prognosis.CONCLUSION Trans-catheter arterial infusion chemotherapy is a safe and effective method of therapy. Postoperative selective arterial infusion chemotherapy can improve the survival rate in patients with esophageal squamous carcinoma who were previously treated by radical surgery.However, this modality of therapy needs further investigation.

  8. Role of adjuvant chemoradiotherapy in treatment of resectable esophageal carcinoma: a meta-analysis

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    ZHENG Bin; ZHENG Wei; ZHU Yong; LIN Xiao-yan; XU Ben-hua; CHEN Chun

    2013-01-01

    Background The effectiveness and influence of surgery followed by adjuvant chemoradiotherapy (CRT) on the survival of patients with resectable esophageal carcinoma are still under debate.The outcomes of clinical trials have not been consistent.This study aimed to perform a meta-analysis of eligible published clinical trials to compare CRT with surgery without adjuvant chemoradiotherapy (non-CRT) for resectable esophageal carcinoma.Methods Computerized bibliographic and manual searches were undertaken to identify all eligible literature between 1990 and 2012.PubMed,EMBASE,Chinese National Knowledge Infrastructure,and Wanfang databases were our primary sources for published clinical trials.The quality of the methodology and reliability of the data from all of the clinical trials were assessed.All data were extracted by three independent researchers.Results Seven studies that included a total of 523 patients were selected.It was found that CRT significantly improved survival.The odds ratio (OR) in comparing CRT and non-CRT groups was 1.75 (95% confidence intervals (CI):1.17-2.60,P=0.006) for 1-year survival,2.07 (95% Cl:1.45-2.96,P <0.0001) for 3-year survival,and 2.17 (95% CI:1.45-3.26,P=0.0002) for 5-year survival.There have been no CRT treatment-related deaths reported in the literature.The incidence of related complications was high in the cases with CRT.Patients treated with CRT had a lower incidence of local-regional cancer recurrence (OR:0.49,95% Cl:0.31-0.76,P=0.002) and a similar incidence of distant cancer recurrence (OR:0.90,95% CI:0.60-1.34,P=0.60).Conclusions It was found that patients with resectable esophageal carcinoma could gain a survival benefit from CRT.However,CRT was associated with a high incidence of related complications.

  9. The relationship between C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma

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    纪爱芳

    2013-01-01

    Objective To explore the association of C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma(ESCC). Methods Purification of genomic DNA from whole blood was used the

  10. Endoscopic surveillance of head and neck cancer in patients with esophageal squamous cell carcinoma

    Science.gov (United States)

    Kato, Minoru; Ishihara, Ryu; Hamada, Kenta; Tonai, Yusuke; Yamasaki, Yasushi; Matsuura, Noriko; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Multiple squamous cell carcinomas (SCCs) frequently arise in the upper aerodigestive tract, referred to as the field cancerization phenomenon. The aim of this study was to elucidate the detailed clinical features of second primary head and neck (H&N) SCCs arising in patients with esophageal SCC. Patients and methods: A total of 818 patients underwent endoscopic resection for superficial esophageal cancer between January 2006 and December 2013. Of these, 439 patients met our inclusion criteria, and we retrospectively investigated the incidence, primary sites, and stages of second primary H&N SCCs in these patients. Results: A total of 53 metachronous H&N SCCs developed in 40 patients after a median follow-up period of 46 months (range 9 – 109). The cumulative incidence rates of metachronous H&N SCCs at 3, 5, and 7 years were 5.3 %, 9.7 %, and 17.2 %, respectively. These lesions were frequently located at pyriform sinus or in the posterior wall of the pharynx (70 %, 37/53 lesions). Most of the lesions were detected at an early stage, though 4 lesions were associated with lymph node metastasis when their primary sites were detected (1 postcricoid area, 2 posterior wall of hypopharynx, and 1 lateral wall of oropharynx). Conclusions: Patients with esophageal SCC should undergo careful inspection of the pyriform sinus and posterior wall of the pharynx for detection of H&N SCCs. Methods to open the hypopharyngeal space, such as the Valsalva maneuver, should be included in the surveillance program.

  11. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

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    Yan Wusheng

    2012-01-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC, the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB, normal differentiated squamous epithelium (ND, and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and

  12. Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.

    Science.gov (United States)

    Xuan, Xaioyan; Li, Shanshan; Lou, Xi; Zheng, Xianzhao; Li, Yunyun; Wang, Feng; Gao, Yuan; Zhang, Hongyan; He, Hongliu; Zeng, Qingru

    2015-05-01

    Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

  13. Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma

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    He Zu-gen

    2006-12-01

    Full Text Available Abstract Background The development of esophageal squamous cell carcinoma (ESCC progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS and carcinoma in situ (CIS, subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. Methods Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5γ2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. Results In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5γ2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5γ2 and SPARC. Conclusion Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.

  14. Comprehensive clinical study of concurrent chemotherapy breathing IMRT middle part of locally advanced esophageal cancer

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    Jung, Jae Hong; Moon, Seong Kwon [Dept. of Radiation Oncology, College of Medicine, Soonchunhyang University , Asan (Korea, Republic of); Kim, Seung Chul [Dept. of Radiology, Songho College, Hoengseong (Korea, Republic of)

    2015-12-15

    The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity- modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC)

  15. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Sheng-Ta Tsai

    Full Text Available Esophageal squamous cell carcinoma (ESCC accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1 was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.

  16. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-01-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. PMID:27125498

  17. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma

    Science.gov (United States)

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-01-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients. PMID:27599779

  18. Nitric oxide and calcium ions in apoptotic esophageal carcinoma cells induced by arsenite

    Institute of Scientific and Technical Information of China (English)

    Zhong-Ying Shen; Wen-Ying Shen; Ming-Hua Chen; Jian Shen; Wei-Jie Cai; Zeng Yi

    2002-01-01

    AIM: To quantitatively analyze the nitric okide (NO) andCa2+ in apoptosis of esophageal carcinoma cells induced byarsenic trioxide (As2O3).METHODS: The cell line SHEEC1, a malignant esophagealepithelial call induced by HPV in synergy with TPA in ourlaboratory, was cultured in a serum-free medium and treatedwith As2O3. Before and after administration of As2O3, NOproduction in cultured medium was detected quantitativelyusing the Griess Colorimetric method. Intracellular Ca2+ waslabeled using the fluorescent dye Fluo3-AM and detectedunder confocal laser scanning microscope (CLSM), whichwas able to acquire data in real-time enabling Ca2+ dynamicsof individual cells in vitro. The apoptotic cells wareexamined under electron microscopy.RESULTS: Intracellular concentration of Ca2+ increased from1.00 units to 1.09-1.38 units of fluorescent intensity at As2O3treatment and NO products subsequently released fromAs2O3-treated cells increased from 0.98-1.00 × 10-2 mol@ L-1up to 1.48-1.52 × 10-2 mol@ L-1 and maintained in a highlevel contineously. Finally apoptosis of cells occurred,chromatin being agglutinated, cells shrunk, nuclei becameround and mitochondria swelled.CONCLUSION:Ca2+ and NO increased with cell damage andapoptosis in cells treated by As2O3. The Ca2+ is an initialmessenger to the apoptotic pathway. To investigate Ca2+and NO will be a new direction for studying the apoptoticsignaling messenger of the esophageal carcinoma cellsinduced by As2O3.

  19. Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes:an overview

    Institute of Scientific and Technical Information of China (English)

    Jalil Pirayesh Islamian; Mohsen Mohammadi; Behzad Baradaran

    2014-01-01

    Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced effcacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, speciifcally the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. hTis article will brielfy review studies on silencing tumor enhancer genes related to the induction of esophageal cancer.

  20. Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma.

    Science.gov (United States)

    Syed, Nazia; Barbhuiya, Mustafa A; Pinto, Sneha M; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T S Keshava; Kumar, M Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh; Gowda, Harsha

    2015-01-01

    Esophageal squamous-cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early-stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non-neoplastic Het-1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation.

  1. Sorafenib in advanced hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Køstner, Anne Helene; Sørensen, M; Olesen, René Krøjgaard;

    2013-01-01

    Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we...

  2. Experimental gene therapy using p21Waf1 gene for esophageal squamous cell carcinoma by gene gun technology.

    Science.gov (United States)

    Tanaka, Yuichi; Fujii, Teruhiko; Yamana, Hideaki; Kato, Seiya; Morimatsu, Minoru; Shirouzu, Kazuo

    2004-10-01

    In our previous study, the proliferation rate of esophageal squamous cell carcinoma cell lines, which poorly expressed p21Waf1, was found to be regulated by p21Waf1 gene transfection using adenovirus vector. In the present study, in order to examine the effect of p21Waf1 gene therapy in esophageal cancer, we used gene gun technology, which proved to be a powerful method to introduce the p21Waf1 gene into esophageal cancer cells. p21Waf1 transfection to KE3 and YES2 cells (weakly expressed p21Waf1 protein cells) showed a high expression of p21Waf1 protein after applying this gene gun technique. In KE3 and YES2 cells, statistical significant growth inhibition was observed after p21Waf1 transfection compared with LacZ transfection (KE3, p=0.0009; YES2, pgun technique significantly inhibited the low basal p21Waf1 expressed esophageal cancer cell growth in vitro and in vivo. Furthermore, p21Waf1 transfection strongly enhanced the effect of 5Fu suggesting that p21Waf1 may prove beneficial in chemotherapy combined with gene therapy using gene gun technology in patients with esophageal cancer who have a low level of p21Waf1 expressed tumor.

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

    Institute of Scientific and Technical Information of China (English)

    Chun Li; Ming-Yao Wu; Ying-Rui Liang; Xian-Ying Wu

    2003-01-01

    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.

  4. Reduced lung dose during radiotherapy for thoracic esophageal carcinoma: VMAT combined with active breathing control for moderate DIBH

    OpenAIRE

    Gong, GuanZhong; Wang, Ruozheng; Guo, Yujie; Zhai, Deyin; Liu, Tonghai; Lu, Jie; Chen, Jinhu; Liu, Chengxin; Yin, Yong

    2013-01-01

    Background Lung radiation injury is a critical complication of radiotherapy (RT) for thoracic esophageal carcinoma (EC). Therefore, the goal of this study was to investigate the feasibility and dosimetric effects of reducing the lung tissue irradiation dose during RT for thoracic EC by applying volumetric modulated arc radiotherapy (VMAT) combined with active breathing control (ABC) for moderate deep inspiration breath-hold (mDIBH). Methods Fifteen patients with thoracic EC were randomly sele...

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

    Institute of Scientific and Technical Information of China (English)

    Cong-Mei Wu; Tian-Hua Huang; Qing-Dong Xie; De-Sheng Wu; Xiao-Hu Xu

    2003-01-01

    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.

  6. Endoscopic Detection of Early Esophageal Squamous Cell Carcinoma in Patients with Achalasia: Narrow-Band Imaging versus Lugol's Staining

    Directory of Open Access Journals (Sweden)

    Edson Ide

    2013-01-01

    Full Text Available Chromoendoscopy with Lugol's staining remains the gold standard technique for detecting superficial SCC. An alternative technique, such as narrow-band imaging (NBI, for “optical staining” would be desirable, since NBI is a simpler technique and has no known complications. In this study, we compare NBI without magnification and chromoendoscopy with Lugol's staining for detecting high-grade dysplasia and intramucosal esophageal squamous cell carcinoma (SCC in patients with achalasia. This was a prospective observational study of 43 patients with achalasia referred to the Gastrointestinal Endoscopy Unit of the Hospital of Clinics, São Paulo, University Medical School, Brazil, from October 2006 to February 2007. Conventional examinations with white light, NBI, and Lugol staining were consecutively performed, and the suspected lesions were mapped, recorded, and sent for biopsy. The results of the three methods were compared regarding sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood value, and negative likelihood value. Of the 43 patients, one was diagnosed with esophageal squamous cell carcinoma, and it was detected by all of the methods. NBI technology without magnification has high sensitivity and negative predictive value for detecting superficial esophageal squamous cell carcinoma, and it has comparable results with those obtained with Lugol's staining.

  7. Construction of pETNF-P16 plasmid and its expression properties in esophageal carcinoma cells induced by ionizing irradiation

    International Nuclear Information System (INIS)

    Objective: The recombined plasmid pETNF-P16 was constructed to investigate its expression properties in esophageal squamous cell carcinoma cell line EC9706 induced by X-ray irradiation and the feasibility of gene-radiotherapy for esophageal carcinoma. Methods: The recombined plasmid pETNF-P16 was constructed and transfected into EC9706 cells with lipofectamine. ELISA, Western blot, and immunocytochemistry were performed to determine the expression properties of pETNF-P16 in EC9706 after transfection induced by X-ray irradiation. Results: The eukaryotic expression vector pETNF-P16 was successfully constructed and transfected into EC9706 cells. The expressions of TNFα were significantly increased in the transfected cells after different dose of X-ray irradiation than that of 0 Gy group (P<0.05-0.01) and the expressions of TNFα and P16 were significantly higher during 2-48 h after 2 Gy X-ray irradiation than that of control group (P<0.05-0.01). No P16 expression in normal EC9706 cells and strong expression in the transfected group and irradiation induction group were detected. Conclusions: X-ray irradiation induction could significantly enhance the TNFα and P16 expression property in the EC9706 cells transfected with pETNF-P16 plasmid. These results may establish important experimental basis for gene-radiotherapy of esophageal carcinoma. (authors)

  8. Concurrent radiotherapy and chemotherapy with protracted continuous infusion of 5-fluorouracil in inoperable esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. Methods and Materials: Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. Results: For 25 patients receiving a total dose of ≥ 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. Conclusion: The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma

  9. Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Shaoyan

    2011-05-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice. Methods We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development. Results The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis. Conclusions Slug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

  10. Comparison between continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Purpose: To compare the treatment results and toxicity of continuous accelerated hyperfractionated (CAHF) and late-course accelerated hyperfractionated (LCAF) radiotherapy (RT) for esophageal carcinoma. Methods and Materials: Between August 1996 and March 1999, 101 patients with squamous cell carcinoma of the esophagus were randomized into two groups: 49 to the CAHF group and 52 to the LCAF group. Patients in the CAHF group received RT at 1.5 Gy/fraction b.i.d. (6-h interval), 5 d/wk, to a total dose 66 Gy in 44 fractions during 4.4 weeks. The patients in the LCAF group received conventional fractionation RT, 1.8 Gy/fraction, to a dose of 41.4 Gy in 23 fractions during 4.6 weeks, followed by accelerated fractionation RT using reduced fields, b.i.d., at 1.5 Gy/fraction, with a minimal interval of 6 h between fractions. The total dose was 68.4 Gy in 41 fraction during 6.4 weeks. Patient age, gender, performance score, diet, lesion location, lesion length, stage, and fractionation (CAHF or LCAF) were entered into the univariate and multivariate analyses. Results: All patients finished the treatment course, except for 1 patient in the CAHF group because of severe acute esophagitis. The rate of Grade I, II, and III acute bronchitis was 18.4% (9 of 49), 30.6% (15 of 49), and 8.2% (4 of 49) in the CAHF group and 13.5% (7 of 52), 21.2% (11 of 52), and 3.8% (2 of 52) in the LCAF group, respectively. However, the difference between the two groups was not statistically significant (p=0.084). The rate of Grade I, II, III, and IV acute esophagitis was 6.1% (3 of 49), 32.7% (16 of 49), 46.9% (23 of 49), and 14.3% (7 of 49) in the CAHF group and 26.9% (14 of 52), 32.7% (17 of 52), 7.7% (4 of 52), and 1.9% (1 of 52) in the LCAF group, respectively. The difference was statistically significant (p<0.001). The local control rate at 1, 2, and 3 years was 88.7%, 83.9%, and 55.9% in the CAHF group and 80.7%, 71.4%, and 57.1% in the LCAF group, respectively (p=0.1251). The 1-, 2-, and 3

  11. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

    Full Text Available The matrix metalloprotease-1 (MMP-1/protease-activated receptor-1 (PAR-1 signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC, we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9% and 58 (68.2% tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS than those with negative ESCC (P = 0.002 and 0.003, respectively. Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR = 2.836, 95% confidence interval (CI = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068, MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127, and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883 and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681, MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279, and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881 as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  12. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hong-hua; Zhang, Xi; Cao, Pei-guo [Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province (China)

    2011-11-18

    The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  13. Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients

    Institute of Scientific and Technical Information of China (English)

    Kumiko Tahara; Satoshi Tanabe; Kenji Ishido; Katsuhiko Higuchi; Tohru Sasaki; Chikatoshi Katada; Mizutomo Azuma

    2012-01-01

    AIM:To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients.METHODS:We studied 17 patients (15 men and 2 women,21 lesions) with SESC in whom endoscopic mucosal resection (EMR),endoscopic submucosal dissection (ESD),and open surgery were contraindicated from March 1999 through February 2009.None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g.,liver cirrhosis,cerebral infarction,or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy.After conventional endoscopy,an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins.The lesion was then ablated by APC.We retrospectively studied the treatment time,number of APC sessions per site,complications,presence or absence of recurrence,and time to recurrence.RESULTS:The median duration of follow-up was 36 mo (range:6-120 mo).All of the tumors were macroscopically classified as superficial and slightly depressed type (0-Ⅱ c).The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2.The median treatment time was 15 min (range:10-36 min).The median number of treatment sessions per site was 2 (range:1-4).The median hospital stay was 14 d (range:5-68d).Among the 17 patients (21 lesions),2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence.There were no treatment-related complications,such as bleeding or perforation.CONCLUSION:APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease,as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy.

  14. Upregulation of microRNA-98 increases radiosensitivity in esophageal squamous cell carcinoma

    Science.gov (United States)

    Jin, Ying-Ying; Chen, Qing-Juan; Wei, Yang; Wang, Ya-Li; Wang, Zhong-Wei; Xu, Kun; He, Yun; Ma, Hong-Bing

    2016-01-01

    Although radiation resistance is a common challenge in the clinical treatment of esophageal squamous cell carcinoma (ESCC), an effective treatment strategy has yet to be developed. Aberrant expression of microRNAs (miRNAs) is responsible for cancer sensitivity to radiation. In this study, we aimed to identify the miRNAs that are associated with radioresistance in ESCC. We used a miRNA microarray to perform a comparison of miRNA expression in both ESCC parental and acquired radioresistance cell lines. qRT-PCR was used to confirm the alterations. Cell radiosensitivity was determined with a survival fraction assay. Functional analyses of the identified miRNA in ESCC cells with regard to metastasis and apoptosis were performed by transwell assays and flow cytometry. The miRNA targets were identified with pathway analysis and confirmed with a luciferase assay. miR-98 was recognized as the most downregulated miRNA in established radioresistant cell line. AmiR-98 mimic enforced the expression of miRNA-98 and made ESCC cells sensitive to radiotherapy, while anti-miR-98 reversed this process. Optimal results were achieved by decreasing cellular proliferation, decreasing cell migration and inducing apoptosis. The luciferase target gene analysis results showed that the overexpression of miRNA-98 inhibited tumor growth and resistance tolerance by directly binding to the BCL-2 gene. Our study indicated that increasing miRNA-98 expression can be used as a potential radiosensitive therapeutic strategy for treating esophageal cancer cells. PMID:27422937

  15. High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations.

    Directory of Open Access Journals (Sweden)

    Chi Hoon Maeng

    Full Text Available BACKGROUND: Given the high incidence of metastatic esophageal squamous cell carcinoma, especially in Asia, we screened for the presence of somatic mutations using OncoMap platform with the aim of defining subsets of patients who may be potential candidate for targeted therapy. METHODS AND MATERIALS: We analyzed 87 tissue specimens obtained from 80 patients who were pathologically confirmed with esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens were prepared from primary cancer sites in 70 patients and from metastatic sites in 17 patients. In order to test the concordance between primary and metastatic sites from the patient for mutations, we analyzed 7 paired (primary-metastatic specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor content was >70%. RESULTS: In total, we have detected 20 hotspot mutations out of 80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K, five H1047R and one H1047L (N = 10, 11.5% followed by MLH1 V384D (N = 7, 8.0%, TP53 (R306, R175H and R273C (N = 3, 3.5%, BRAF V600E (N = 1, 1.2%, CTNNB1 D32N (N = 1, 1.2%, and EGFR P733L (N = 1, 1.2%. Distributions of somatic mutations were not different according to anatomic sites of esophageal cancer (cervical/upper, mid, lower. In addition, there was no difference in frequency of mutations between primary-metastasis paired samples. CONCLUSIONS: Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients.

  16. Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males

    Institute of Scientific and Technical Information of China (English)

    Chia-Fang Wu; Deng-Chyang Wu; Hon-Ki Hsu; Ein-Long Kao; Jang-Ming Lee; Cheng-Chieh Lin; Ming-Tsang Wu

    2005-01-01

    AIM: To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwanese men.METHODS: Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan.ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP.RESULTS: Compared to those with ADH2*2/*2,individuals with ADH2*1/*2 and ADH2*1/*1 had 2.28-and 7.14-fold, respectively, increased risk of developing esophageal cancer (95%CI = 1.11-4.68 and 2.76-18.46)after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2*1/*2 (adjusted OR (AOR)= 5.25, 95%CI = 2.47-11.19), when compared to those with ALDH2*1/*1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2*1/*1 and ALDH2*1/*2, compared to those with ADH2*1/*2 or ADH2*2/*2 and ALDH2*1/*1 (AOR = 36.79,95%CI = 9.36-144.65). Furthermore, we found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk.CONCLUSION: Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.

  17. Processed food consumption and risk of esophageal squamous cell carcinoma: A case-control study in a high risk area.

    Science.gov (United States)

    Song, Qingkun; Wang, Xiaorong; Yu, Ignatius Tak-sun; Huang, Chengyu; Zhou, Xiaoqiao; Li, Jun; Wang, Dong

    2012-11-01

    This study was conducted to investigate the association between consumption of processed foods and esophageal cancer risk. A population-based case-control study was designed. For the present study, 254 patients with esophageal squamous cell carcinoma with pathological diagnoses were selected from Yanting during 2008 and 2010 and 254 community-based controls were selected from the same area, individually matched with cases by age and sex. Data on demographic, lifestyle and dietary factors were collected using food frequency questionnaires. A conditional logistic regression model was used to estimate the odds ratio (OR) with adjustments for potential confounders. Compared to the frequency of 3 times/week of preserved vegetables had a significant association with esophageal cancer (OR = 5.01, 95% confidence interval [CI] 2.07, 12.17). In stratified analyses, the OR of increasing intake of preserved vegetables for esophageal cancer were 2.02 in men (95% CI 1.18, 3.48), 3.15 in women (95% CI 1.28, 7.75), 2.41 (95% CI 1.45 4.01) in the persons <65 years old and 1.28 (95% CI 0.35, 4.65) in persons ≥65 years old. Consumption of pickled vegetables was not associated significantly with esophageal cancer risk. Intake of salted meat with a frequency of ≥1 time/week meant that the OR increased to 2.57 (95%CI 1.02, 6.43), but no significant trend or association in subgroup analysis was observed. Preserved vegetable consumption was associated with increased risk of esophageal cancer, while no association was found with pickled vegetables.

  18. Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Hua Zhou; Bin Zhang; Kemp H Kernstine; Li Zhong

    2011-01-01

    AIM: To evaluate the diagnostic values of serum autoantibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoantibodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS: The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-β-D-Thiogalactopyranoside (IPTG) induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples (OD450 = 1.69 ± 0.08 vs OD450 = 1.55 ± 0.10, P < 0.001). The area under the receiver operating characteristic (ROC) curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples (OD450 = 1.62 ± 0.06 vs OD450 = 1.55 ± 0.10, P < 0.001), the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION: Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma.

  19. Genome-wide analysis of the effect of esophageal squamous cell carcinoma on human umbilical vein endothelial cells.

    Science.gov (United States)

    Jin, Guoguo; Yang, Yi; Liu, Hangfan; Liu, Kangdong; Zhao, Jimin; Chen, Xinhuan; Zhang, Xiaoyan; Zhang, Yanyan; Lu, Jing; Dong, Ziming

    2016-07-01

    A large volume of data indicates that controlling tumor-associated angiogenesis is a promising therapy against cancer. However, angiogenesis is a complex process, little is known about the differential gene expression in the process of normal endothelial cell differentiation toward tumor vascular endothelial cells induced by tumor microenvironment. The aim of this study is to investigate the effect of tumor microenvironment simulated by the supernatant of esophageal squamous cancer cells (KYSE70) on normal endothelial cells (HUVECs) at the whole genome level. The gene expression profile was studied through gene ontology and signal pathway analysis. Compared with the normal HUVECs, a total of 3769 differentially expressed genes in induced HUVECs were detected, including 1609 upregulated genes and 2160 downregulated genes. Moreover, the microarray data analysis showed that 11 significant biological processes and 10 significant signaling pathways changed most, which are associated with angiogenesis and cell differentiation. According to the different expression levels in the microarrays and their functions, four differentially expressed genes involved in tumor angiogenesis and cell differentiation (IL6, VEGFA, S1PR1, TYMP) were selected and analyzed by qRT-PCR. The qRT-PCR results were consistent with the microarray data. Furthermore, we simulated the tumor microenvironment by human esophageal carcinoma tissue homogenate to investigate its effect on HUVECs, the qRT-PCR results indicated that the above genes were highly expressed in HUVECs after induction by esophageal carcinoma tissue homogenate. In conclusion, tumor microenvironment impact on normal endothelial cells differentiated toward tumor vascular endothelial cells, and the selected genes, which are associated with tumor angiogenesis, would be anti-angiogenesis targets against esophageal carcinoma.

  20. Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients with inoperable thoracic esophageal squamous cell carcinoma?

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    Full Text Available BACKGROUND AND PURPOSE: The benefit of concurrent chemoradiotherapy (CCRT in elderly patients with inoperable esophageal squamous cell carcinoma (SCC is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients. METHODS AND MATERIALS: Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73. RESULTS: No treatment-related deaths occurred and no patients experienced any acute grade 4 non-hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008. Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients ≤ 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years. CONCLUSION: Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit.

  1. Epigastric Distress Caused by Esophageal Candidiasis in 2 Patients Who Received Sorafenib Plus Radiotherapy for Hepatocellular Carcinoma: Case Report.

    Science.gov (United States)

    Chen, Kuo-Hsin; Weng, Meng-Tzu; Chou, Yueh-Hung; Lu, Yueh-Feng; Hsieh, Chen-Hsi

    2016-03-01

    Sorafenib followed by fractionated radiotherapy (RT) has been shown to decrease the phagocytic and candidacidal activities of antifungal agents due to radiosensitization. Moreover, sorafenib has been shown to suppress the immune system, thereby increasing the risk for candida colonization and infection. In this study, we present the 2 hepatocellular carcinoma (HCC) patients suffered from epigastric distress caused by esophageal candidiasis who received sorafenib plus RT. Two patients who had received sorafenib and RT for HCC with bone metastasis presented with hiccups, gastric ulcer, epigastric distress, anorexia, heart burn, and fatigue. Empiric antiemetic agents, antacids, and pain killers were ineffective at relieving symptoms. Panendoscopy revealed diffuse white lesions in the esophagus. Candida esophagitis was suspected. Results of periodic acid-Schiff staining were diagnostic of candidiasis. Oral fluconazole (150 mg) twice daily and proton-pump inhibitors were prescribed. At 2-weak follow-up, esophagitis had resolved and both patients were free of gastrointestinal symptoms. Physicians should be aware that sorafenib combined with RT may induce an immunosuppressive state in patients with HCC, thereby increasing their risk of developing esophagitis due to candida species.

  2. The Correlation of p53 and nm23-H1 Expression with Invasivenes and Metastasis in Esophageal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    LIULigang; PANTiecheng; 等

    2002-01-01

    Objective:To study the relationship between expression of p53 and nm23-H1 and differentiation,invasiveness and metastasis in human esophageal carcinoma,and the correlation between expression of p53 and nm23-H1.Methods:Expression of p53 and nm23-H1 in 50 patients with squamous cell carcinoma of esophagus was detected by using immunohistochemical S-P methods.Results:35 caes(70%) and 32 cases(64%) of esophageal squamous cell carcinoma were positive for nm23-H1 protein and p53 protein,respectivel.The expression of nm23-H1 was related to lymphatic metastasis(P0.05).The lymphatic metastasis location positive group had a very lower expression of nm23-H1 and the negative rage was 70.8% ,but the negative group had a higher expression and the positive rate was 65.4% ,The expression of p53 was related to tumor differentiation and invasiveness(P0.05).Among the three grups,the high differentiation group had the lowest expression of p53 and the positive rate was 29.2%,but the low differentiation group had the highest positvie rate(71.4%) ,As for tmor invasiveness,the group of outer membrane of esophagus infiltrated had the highest p53 proten positive rate (56%) .but in the group of mucous or submucous layer infiltrated p53 protein was not detectable.The low expression of nm23-H1 and the high expression of p53 were also correlated.The expression of nm23-H1 and p53 were both correlated with TNM stage of esophageal carcinoma (P<0.05).The better esophageal carcinomas differentiated,the lower nm23-H1 expressed and higher p53 expressed.Conclusion Low expression of nm23-H1 and high expression of p53 play an important role in the progression of squamous cell carcinoma of esophagus.Nm 23-H1 might be a gene marker in the prophecy of patients' prognosis and benefit tumor treatment clinically.

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

    Institute of Scientific and Technical Information of China (English)

    Andrzej D(a)browski; Wojciech Kwa(s)niewski; Tomasz Skoczylas; Wieslawa Bednarek; Dorota Ku(z)ma; Anna Go(z)dzicka-Józefiak

    2012-01-01

    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

  4. Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Wen Hao; Sheng-Tao Zhu; Yuan-Long He; Peng Li; Yong-Jun Wang; Shu-Tian Zhang

    2012-01-01

    AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and explore its role in ESCC carcinogenesis.METHODS: Seven ESCC cell lines (KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human esophageal epithelial cell line (Het-1A), 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction (RT-PCR) was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expression and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2'-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.RESULTS: SFRP2 mRNA was expressed in the immortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2'-deoxycytidine could restore the expression of SFRP2 mRNA in the three ESCC cell lines lacking SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 ± 0.398 vs 1.51 ± 0.399, P < 0.01). SFRP2 methylation was higher in tumor tissue than in paired normal tissue (95% vs 65%, P < 0.05). The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by introducing pcDNA3.1/v5 his

  5. Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile

    Institute of Scientific and Technical Information of China (English)

    Andres Castillo; Claudia Backhouse; Jorge Argandona; Tetsuhiko Itoh; Karem Shuyama; Yoshito Eizuru; Suminori Akiba; Francisco Aguayo; Chihaya Koriyama; Miyerlandi Torres; Edwin Carrascal; Alejandro Corvalan; Juan P Roblero; Cecilia Naquira; Mariana Palrna

    2006-01-01

    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, P16INK4A 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 10 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 p16positive 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.

  6. Epigenetic inactivation of SPINT2 is associated with tumor suppressive function in esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Dongli [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); The Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Fan, Qingxia [The Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Chen, Xinfeng; Li, Feng [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Wang, Liping [The Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Huang, Lan [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Dong, Wenjie; Chen, Xiaoqi [The Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Zhang, Zhen [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Liu, Jinyan; Wang, Fei [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); The School of Life Sciences, Zhengzhou University, Zhengzhou 450052, Henan (China); Wang, Meng [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); The Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Zhang, Bin [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); The Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago 60611 (United States); and others

    2014-03-10

    Hepatocyte growth factor activator inhibitor type 2 (SPINT2), a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor suppressor gene silenced by promoter methylation. We aimed to investigate whether SPINT2 might act as an esophageal squamous cell carcinoma (ESCC) tumor suppressor gene. Four ESCC cell lines, Fifty-two ESCC tissues and twenty-nine neighboring non-cancerous tissues were included in this study. The expression of SPINT2 was monitored by real time PCR. Bisulfite genomic sequencing and methylation-specific PCR were used to analyze methylation status. The effect of SPINT2 on cell proliferation and apoptosis in EC109 and EC9706 cells was observed by CCK-8 assay and flow cytometric analysis. We found that silencing of SPINT2 was associated with promoter methylation in ESCC cell lines. The densely methylated SPINT2 promoter region was confirmed by bisulfite genomic sequencing. Ectopic expression of SPINT2 inhibited cell proliferation through inducing cell apoptosis in vitro. Furthermore, methylation-specific PCR analysis revealed that SPINT2 promoter methylation was prominent in carcinoma tissues (52.08%) compared with neighboring non-cancerous tissues (22.58%). Kaplan–Meier analysis showed that patients with SPINT2 hypermethylation had shorter survival time. The tumor suppressor gene of SPINT2 is commonly silenced by promoter hypermethylation in human ESCC and SPINT2 hypermethylation is correlated with poor overall survival, implicating SPINT2 is an underlying prognostic marker for human ESCC. - Highlights: • We firstly found SPINT2 gene may be transcriptionally repressed by promoter hypermethylation in ESCC cells. • SPINT2 overexpressing cells induced proliferation inhibition through promoting apoptosis. • mRNA expression of SPINT2 was significantly higher in ESCC tissues than in neighboring non-cancerous tissues. • Promoter hypermethylation of SPINT2 is significantly linked to TNM stage and poor overall survival.

  7. Study on RIZ1 gene promoter methylation status in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shang-Wen Dong; Peng Zhang; Yi-Mei Liu; Yuan-Tao Cui; Shuo Wang; Shao-Jie Liang; Zhun He; Pei Sun; Yuan-Guo Wang

    2012-01-01

    AIM: To investigate the promoter region methylation status of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) in the human esophageal squamous cell carcinoma (ESCC) cell lines and tissues and verify the relationship between methylation of RIZ1 and oncogen-esis, tumor progression and metastasis etc of ESCC.METHODS: Methylation-specific polymerase chain reaction (MSP) was used to investigate the promoter region methylation status of RIZ1 in 6 ESCC cell lines. One cell line where RIZ1 promoter region methylation was detected was selected for the next study, where the cell line was treated with 5-aza-CdR. Real-time polymerase chain reaction was used to investigate its influence on the transcription of RIZ1. Experiments using frozen pathological specimens from 47 ESCC patients were performed using the same MSP methodology.RESULTS: Promoter methylation of RIZ1 gene was detected in TE13, CaEs17 and EC109 cell lines and the cell line TE13 was chosen for further study. The expression of RIZ1 mRNA in TE-13 was up-regulated after treatment with 5-aza-CdR. The rate of methylation in carcinomas tissues was significantly higher than those in matched neighboring normal and distal ending normal tissue, and the deviation of data was statistically significant (x2 = 24.136, P < 0.01). Analysis of the gender, age familial history, tumour deviation, tumour saturation, lymph gland displacement and clinical staging of 47 samples from ESCC patients showed that the fluctuation of data was not statistically significant.CONCLUSION: Promoter methylation may play an important role in the epigenetic silencing of RIZ1 gene expression in human ESCC. RIZ1 is considered to be a potential tumor suppressor gene and may be a biological parameter for testing early stage human ESCC.

  8. CT and MR imaging for detecting neoplastic invasion of esophageal inlet

    OpenAIRE

    Chen, Bin; Yin, Shan-Kai; Zhuang, Qi-Xin; Cheng, Ying-Sheng

    2005-01-01

    AIM: Direct neoplastic invasion of esophageal inlet is an uncommon but significant sequela of advanced head and neck carcinomas. The aim of this study was to seek an optimal CT or MRI criterion for determining the neoplastic esophageal inlet involvement in order to help tumor staging and surgical planning.

  9. Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir, India.

    Science.gov (United States)

    Dar, Nazir A; Shah, Idrees A; Bhat, Gulzar A; Makhdoomi, Muzamil A; Iqbal, Beenish; Rafiq, Rumaisa; Nisar, Iqra; Bhat, Arshid B; Nabi, Sumaiya; Masood, Akbar; Shah, Sajad A; Lone, Mohd M; Zargar, Showkat A; Islami, Farhad; Boffetta, Paolo

    2013-09-01

    Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case-control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.

  10. Plasma DNA methylation of Wnt antagonists predicts recurrence of esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ji-Bin Liu; Fu-Lin Qiang; Jing Dong; Jin Cai; Shu-Hui Zhou; Min-Xin Shi; Ke-Ping Chen; Zhi-Bin Hu

    2011-01-01

    AIM: To detect the effects of plasma DNA methylation of Wnt antagonists/inhibitors on recurrence of esophageal squamous cell carcinoma (ESCC).METHODS: We used methylation-specific polymerase chain reaction to detect hypermethylation of the promoter of four Wnt antagonists/inhibitors (SFRP-1, WIF-1, DKK-3 and RUNX3) using DNA from the plasma of ESCC patients (n = 81) and analyzed the association between promoter hypermethylation of Wnt pathway modulator genes and the two-year recurrence of ESCC.RESULTS: Hypermethylation of SFRP-1, DKK-3 and RUNX-3 was significantly associated with an increased risk of ESCC recurrence (P = 0.001, 0.003 and 0.001 for SFRP-1, DKK-3 and RUNX3, respectively). Patients carrying two to three methylated genes had a significantly elevated risk of recurrence compared with those not carrying methylated genes (odds ratio = 15.69, 95% confidential interval: 2.97-83). The area under the receiver operating characteristic curve (AUC) was 77.1 for ESCC recurrence prediction (sensitivity = 66.67 and specificity = 83.3). When combining methylated genes and the clinical stage, the AUC was 83.69, with a sensitivity of 76.19 and a specificity of 83.3.CONCLUSION: The status of promoter hypermethylation of Wnt antagonists/inhibitors in plasma may serve as a non-invasive prognostic biomarker for ESCC.

  11. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis

    Science.gov (United States)

    Liu, Wenjin; Snell, Jeff M.; Jeck, William R.; Wilkerson, Matthew D.; Parker, Joel S.; Patel, Nirali; Mlombe, Yohannie B.; Mulima, Gift; Liomba, N. George; Wolf, Lindsey L.; Shores, Carol G.; Gopal, Satish; Sharpless, Norman E.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses. PMID:27734031

  12. Radiosensitization in esophageal squamous cell carcinoma. Effect of polo-like kinase 1 inhibition

    International Nuclear Information System (INIS)

    This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone. (orig.)

  13. Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis

    Science.gov (United States)

    Qin, Hai-De; Liao, Xiao-Yu; Chen, Yuan-Bin; Huang, Shao-Yi; Xue, Wen-Qiong; Li, Fang-Fang; Ge, Xiao-Song; Liu, De-Qing; Cai, Qiuyin; Long, Jirong; Li, Xi-Zhao; Hu, Ye-Zhu; Zhang, Shao-Dan; Zhang, Lan-Jun; Lehrman, Benjamin; Scott, Alan F.; Lin, Dongxin; Zeng, Yi-Xin; Shugart, Yin Yao; Jia, Wei-Hua

    2016-01-01

    The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets. PMID:27058444

  14. Interaction between Esophageal Squamous Cell Carcinoma and Adipose Tissue in Vitro.

    Science.gov (United States)

    Nakayama, Atsushi; Aoki, Shigehisa; Uchihashi, Kazuyoshi; Nishijima-Matsunobu, Aki; Yamamoto, Mihoko; Kakihara, Nahoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji

    2016-05-01

    Esophageal squamous cell carcinoma (ESCC) develops within the squamous epithelial layer and invades the submucosa to the subadventitia that has adipose tissue (AT). AT seems critical to ESCC progression, but the underlying mechanism is unknown. We aimed to address the association between ESCC and AT in vitro. ESCC cells were cultured on rat or human subcutaneous AT-embedded or -non-embedded collagen gel. AT promoted the growth of ESCC cells and inhibited their apoptosis. AT promoted the expression of the squamous differentiation marker involucrin in ESCC cells. AT accelerated the expression of invasion-related factors in poorly differentiated ESCC cells only. AT promoted the expression of phosphorylated-insulin-like growth factor-1 receptor in ESCC cells, whereas it inhibited that of the human epidermal growth factor receptor 2. Insulin-like growth factor-1, but not leptin, adiponectin, or resistin, promoted and inhibited the growth and apoptosis of ESCC cells, respectively. In turn, ESCC cells decreased the production of these adipokines in AT and the number of preadipocytes and mesenchymal stem cell-like cells, which developed from AT. These results suggest that i) AT may influence the progression of ESCC with increased growth or invasion and decreased apoptosis through insulin-like growth factor-1/insulin-like growth factor-1 receptor signaling, ii) AT may affect human epidermal growth factor receptor 2-targeted therapy; and iii) the cancer cells may affect adipokine production in AT. PMID:26952643

  15. Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-Jia Ren; Qing-Yun Zhang

    2006-01-01

    AIM: To investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features.METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RTPCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples.The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%)than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC.CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion.The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.

  16. Preoperative sorting of circulating T lymphocytes in patients with esophageal squamous cell carcinoma: Its prognostic significance

    Institute of Scientific and Technical Information of China (English)

    Tadahiro Nozoe; Yoshihiko Maehara; Keizo Sugimachi

    2005-01-01

    AIM: To elucidate the immunologic parameters for the outcome of patients with malignant tumors, especially esophageal squamous cell carcinoma (ESCC) associated with high malignant potential.METHODS: Clinicopathologic features were compared between patients with lower and higher CD4 and CD8values as well as CD4/CD8 ratio in peripheral blood.RESULTS: The survival rate of patients with higher CD4 value was significantly better than that in patients with lower CD4 value (P = 0.039). The survival rate of patients with higher CD8 value was significantly worse than that of patients with lower CD8 value (P = 0.026).Similarly, the survival rate of patients with higher CD4/CD8 ratio was significantly better than that of patients with lower CD4/CD8 ratio (P = 0.042). Additionally,multivariate analysis demonstrated that lower CD8and lower CD4/CD8 ratio were factors independently associated with worse prognosis of patients.CONCLUSION: All the immunologic parameters can predict the outcome of patients with ESCC.

  17. Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Xiaoping Huang; Jun Qi; Cai Yan; Xin Xu; Yaling Han; Mingrong Wang

    2008-01-01

    Androgen-induced proliferation shutoff gene AS3, also known as APRIN, is a growth inhibitory gene that is in itially implicated inprostate cancer. This gene is required for androgen-dependent growth arrest and is a primary target for 1,25(OH)2D3 and androgens. Alle-lic loss at AS3 locus has been linked to a variety of cancers. However, the correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma (ESCC) is not well established. In this study, the genomic and expression alterations of AS3 in ESCC and their clinical significance are evaluated. Loss of beterozygosity (LOH) analysis using an AS3 intragenic mierosatellite marker D13S171 revealed 72% allelic loss at AS3 locus in ESCC, which is significantly correlated with higher pathological grade (P=0.042).RT-PCR examination showed that AS3 mRNA obviously decreased in 44% tumors and its down-regulation was correlated with the sex of patients (P=0.03). Furthermore, the correlation between genomic and expression alterations of AS3 gene was analyzed in 18 ESCC specimens, which indicated that the consistency between allelic loss and decreased mRNA expression of AS3 was relatively poor. The results of this study indicate that the aberrant expression of AS3 may be involved in the tumorigenesis of esophagus and is responsible for the male predominance of ESCC.

  18. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

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    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

  19. BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin-Tong; Bao, Ci-Hang; Jia, Yi-Bin; Wang, Nana [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Ma, Wei [Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan 750000 (China); Liu, Fang [Medical Imaging, Shandong Medical College, Jinan 250002 (China); Wang, Cong; Wang, Jian-Bo; Song, Qing-Xu [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Cheng, Yu-Feng, E-mail: qlcyf1965@126.com [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-10-03

    Highlights: • BIIB021 downregulated radioresistant proteins in ESCC cell lines. • BIIB021 increased radiation-induced apoptotic cells. • BIIB021 enhanced G{sub 2} arrest in ESCC cell lines. • BIIB021 is a good candidate for radiosensitizer in radiotherapy of ESCC patients. - Abstract: BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G{sub 2} arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.

  20. Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Garcia Jose

    2010-06-01

    Full Text Available Abstract Background Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC. Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation. Methods We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line. Results The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation. Conclusions These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.

  1. TET family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Murata, Asuka; Baba, Yoshifumi; Ishimoto, Takatsugu; Miyake, Keisuke; Kosumi, Keisuke; Harada, Kazuto; Kurashige, Junji; Iwagami, Shiro; Sakamoto, Yasuo; Miyamoto, Yuji; Yoshida, Naoya; Yamamoto, Manabu; Oda, Shinya; Watanabe, Masayuki; Nakao, Mitsuyoshi; Baba, Hideo

    2015-09-15

    Mammalian DNA is epigenetically marked by 5'-cytosine methylation (5-methylcytosine [5-mC]). The Ten-eleven translocation (TET) enzymes (TET1, TET2, and TET3) are implicated in DNA demethylation, through dioxygenase activity that converts 5-mC to 5-hydroxymethylcytosine (5-hmC). Although decreased TET is reportedly associated with decreased 5-hmC levels in various cancers, functions of 5-hmC and TET expression in esophageal squamous cell carcinoma (ESCC) are unclear. We used ELISA and immunohistochemistry tests to analyze 5-hmC status in ESCC tissues, RT-qPCR to analyze TET family mRNA expression in normal and tumor tissues, and pyrosequencing to quantify LINE-1 (i.e., global DNA methylation) levels. ELISA and immunohistochemical testing showed 5-hmC levels were significantly lower in ESCC than in paired normal tissues (P ESCCs than paired normal tissues (P ESCCs (P = 0.003, r = 0.33). 5-hmC levels were also significantly associated with LINE-1 methylation level (P = 0.0002, r = 0.39). Patients with low 5-hmC levels had shorter overall survival than those with higher levels, although not significantly so (P = 0.084). In conclusion, 5-hmC expression was decreased in ESCC tissues, and was associated with TET2 expression level. TET2 reduction and subsequent 5-hmC loss might affect ESCC development.

  2. Circular RNA has_circ_0067934 is upregulated in esophageal squamous cell carcinoma and promoted proliferation

    Science.gov (United States)

    Xia, Wenjia; Qiu, Mantang; Chen, Rui; Wang, Siwei; Leng, Xuechun; Wang, Jie; Xu, Youtao; Hu, Jingwen; Dong, Gaochao; Xu, Prof Lin; Yin, Rong

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly types of cancer worldwide especially in Eastern Asia and the prognosis of ESCC remain poor. Recent evidence suggests that circular RNAs (circRNAs) play important roles in multiple diseases, including cancer. In this study, we characterized a novel circRNA termed hsa_circ_0067934 in ESCC tumor tissues and cell lines. We analyzed a cohort of 51 patients and found that hsa_circ_0067934 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues. The high expression level of hsa_circ_0067934 was associated with poor differentiation (P = 0.025), I-II T stage (P = 0.04), and I-II TNM stage (P = 0.021). The in vitro silence of hsa_circ_0067934 by siRNA inhibited the proliferation and migration of ESCC cells and blocked cell cycle progression. Cell fraction analyses and fluorescence in situ hybridization detected that hsa_circ_0067934 was mostly located in the cytoplasm. Our findings suggest that hsa_circ_0067934 is upregulated in ESCC tumor tissue. Our data suggest that hsa_circ_0067934 represents a novel potential biomarker and therapeutic target of ESCC. PMID:27752108

  3. Macrolide analog F806 suppresses esophageal squamous cell carcinoma (ESCC) by blocking β1 integrin activation.

    Science.gov (United States)

    Li, Li-Yan; Jiang, Hong; Xie, Yang-Min; Liao, Lian-Di; Cao, Hui-Hui; Xu, Xiu-E; Chen, Bo; Zeng, Fa-Min; Zhang, Ying-Li; Du, Ze-Peng; Chen, Hong; Huang, Wei; Jia, Wei; Zheng, Wei; Xie, Jian-Jun; Li, En-Min; Xu, Li-Yan

    2015-06-30

    The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.

  4. Blue Laser Imaging-Bright Improves Endoscopic Recognition of Superficial Esophageal Squamous Cell Carcinoma

    Science.gov (United States)

    Tomie, Akira; Yagi, Nobuaki; Kitae, Hiroaki; Majima, Atsushi; Horii, Yusuke; Kitaichi, Tomoko; Onozawa, Yuriko; Suzuki, Kentaro; Kimura-Tsuchiya, Reiko; Okayama, Tetsuya; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Naito, Yuji; Itoh, Yoshito

    2016-01-01

    Background/Aims. The aim of this study was to evaluate the endoscopic recognition of esophageal squamous cell carcinoma (ESCC) using four different methods (Olympus white light imaging (O-WLI), Fujifilm white light imaging (F-WLI), narrow band imaging (NBI), and blue laser imaging- (BLI-) bright). Methods. We retrospectively analyzed 25 superficial ESCCs that had been examined using the four different methods. Subjective evaluation was provided by three endoscopists as a ranking score (RS) of each image based on the ease of detection of the cancerous area. For the objective evaluation we calculated the color difference scores (CDS) between the cancerous and noncancerous areas with each of the four methods. Results. There was no difference between the mean RS of O-WLI and F-WLI. The mean RS of NBI was significantly higher than that of O-WLI and that of BLI-bright was significantly higher than that of F-WLI. Moreover, the mean RS of BLI-bright was significantly higher than that of NBI. Furthermore, in the objective evaluation, the mean CDS of BLI-bright was significantly higher than that of O-WLI, F-WLI, and NBI. Conclusion. The recognition of superficial ESCC using BLI-bright was more efficacious than the other methods tested both subjectively and objectively.

  5. Application of serum tumor markers for predicting chemotherapy efficacy and prognosis in advanced esophageal squamous cell carcinoma%血清肿瘤标志物在晚期食管鳞状细胞癌疗效评价和预后判定中的作用

    Institute of Scientific and Technical Information of China (English)

    龚磊; 龚继芳; 张晓东

    2011-01-01

    Objective To assess the predictive and prognostic role of the alteration of serum carcinoembryonic antigen (CEA),squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment (CYFRA21-1) during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC).Methods The serum levels of CEA,CYFRA21-1 and SCC-Ag were measured in 50 patients with advanced ESCC at baseline and after first line chemotherapy.The data was correlated with objective efficacy and overall survival.To evaluate the role of tumor marker change in predicting response to therapy,receiver operating characteristic (ROC) curves were constructed.Results CEA,SCC-Ag and CYFRA21-1 increased higher than the cutoffs in 22.0 %,34.0 %,and 44.0 % of tested patients,respectively.Statistically significant correlations were observed between CYFRA21-1 and SCC responses and objective efficacy evaluated by RECIST criteria (Z =3.181,2.389; P = 0.001,0.017).Based on the ROG curve analysis,a post treatment 32 % and 38 % increase in serum concentration was used as cut-off level for defining CYFRA21-1 and SCC-Ag change,respectively.When the cut-off levels were used to predict chemotherapy efficacy,the accuracy for CYFRA21-1 and SCC-Ag were 76 % and 70 %.In the univariate survival analysis,a statistically significant prognostic impact on survival from the change of CYFRA21-1 and SCC-Ag was observed.Conclusion CYFRA21-1 and SCC-Ag are useful for diagnosis,predicting chemotherapy objective efficacy and prognosis in advanced ESCC.%目的 探讨血清肿瘤标志物在晚期食管鳞状细胞癌(简称:鳞癌)中的表达及其在化疗疗效评价和预后判断中的意义.方法 测定50例晚期食管鳞癌患者一线化疗前后血清标志物的水平.按照实体瘤的疗效评价标准(RECIST标准)评效.通过建立受试者工作特性曲线(ROC曲线)求最佳临界值.用Kaplan-Meier法行生存分析.结果 50例患者治疗前的血清肿瘤标志物阳性率以细胞角蛋白19

  6. Post-ablation lymphocytic esophagitis in Barrett esophagus with high grade dysplasia or intramucosal carcinoma.

    Science.gov (United States)

    Kissiedu, Juliana; Thota, Prashanthi N; Gohel, Tushar; Lopez, Rocio; Gordon, Ilyssa O

    2016-06-01

    In patients who have undergone ablation therapy for treatment of Barrett's esophagus with dysplasia, histologic features of eosinophilic esophagitis, but not lymphocytic esophagitis, have been described. We evaluated for histologic evidence of eosinophilic esophagitis and lymphocytic esophagitis and correlated with endoscopic findings in this population. A single-institution Barrett's esophagus registry was searched for patients who had received radiofrequency ablation, cryotherapy, or both for treatment of Barrett's esophagus with dysplasia. Clinical and endoscopic data were collected and biopsies were reviewed for inflammation and reactive changes at three time points: pre-intervention, first surveillance after ablation therapy, and most recent surveillance. Of the 173 patients initially identified, 102 met the inclusion criteria. Intraepithelial eosinophils were increased at first surveillance (60%, P=0.096) and last surveillance (69%, P=0.048) compared with pre-intervention (50%), although histologic evidence of post-ablation eosinophilic esophagitis was not significant. Prevalence of lymphocytic esophagitis was significantly higher at first surveillance (17%, P=0.02) and at last surveillance (43%, Pcryotherapy were identified as independent risk factors for developing histologic lymphocytic esophagitis. This is the first report that histologic evidence of lymphocytic esophagitis increased over time in patients undergoing ablation for Barrett's esophagus with dysplasia. Though the pathophysiology of lymphocytic esophagitis remains unknown, patients in our study with a history of smoking, hyperlipidemia, or cryotherapy were more likely to develop post-ablation lymphocytic esophagitis. PMID:26965580

  7. Comparison of endoscopic submucosal implantation vs. surgical intramuscular implantation of VX2 fragments for establishing a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma.

    Directory of Open Access Journals (Sweden)

    Jin Huang

    Full Text Available PURPOSE: This study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC by endoscopic and surgical implantation of VX2 tumors. METHODS: Fragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed. RESULTS: Both the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32 vs. 97.1% (33/34] and tumor growth [86.7% (26/30 vs. 81.8% (27/33], and the variation in the results was not statistically significant (P>0.05. Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26 vs. 29.6% (8/27] and of intra-luminal tumor growth [73.1% (19/26 vs. 37.0% (10/27], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26 vs. 81.5% (22/27]; all of these results were statistically significant (P0.05. CONCLUSION: The endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.

  8. Discovery of a Good Responder Subtype of Esophageal Squamous Cell Carcinoma with Cytotoxic T-Lymphocyte Signatures Activated by Chemoradiotherapy.

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    Yosuke Tanaka

    Full Text Available Definitive chemoradiotherapy (CRT is a less invasive therapy for esophageal squamous cell carcinoma (ESCC. Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL activation signatures were preferentially found in long-term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre- and post-treatment biopsy specimens of 30 ESCC patients and 121 pre-treatment ESCC biopsy specimens. In the complete response (CR cases, 999 overexpressed genes including at least 234 tumor-specific CTL-activation associated genes such as IFNG, PRF1, and GZMB, were found in post-treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-activated cases, designating them as I-type, from other cases. However, despite the better CR rate in the I-type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-type was significantly better than that of the CDH2-positive cases in the I-type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested to cooperatively enhance the effect of CRT in the CDH2-negative I-type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics.

  9. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.

    Science.gov (United States)

    Jia, Kun; Li, Wei; Wang, Feng; Qu, Haixia; Qiao, Yuanyuan; Zhou, Lanping; Sun, Yulin; Ma, Qingwei; Zhao, Xiaohang

    2016-04-26

    Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21-1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application. PMID:26993605

  10. Expression of YY1 correlates with progression and metastasis in esophageal squamous cell carcinomas

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    Luo J

    2014-09-01

    Full Text Available Judong Luo,1,* Xin Jiang,1,* LiLi Cao,2,* Kejun Dai,1 Shuyu Zhang,3,4 Xin Ge,3,4 Xifa Zhou,1 Xujing Lu1 1Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, People's Republic of China; 2Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; 3School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, 4Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X, Soochow University, Suzhou, People's Republic of China  *These authors contributed equally to this work Objective: Esophageal squamous cell carcinoma (ESCC is one of the deadliest cancers worldwide. Yin Yang 1 (YY1 is a ubiquitous and multifunctional zinc-finger transcription factor that plays important biological functions in cell homeostasis and tumorigenesis. The purpose of this study was to investigate the expression of YY1 in different ESCC tissues and the potential relationship with clinicopathological features. Methods: One hundred and four ESCC tissues were collected in this study. The protein levels of YY1 were measured by immunohistochemistry. TE-1 cell invasion in vitro was assessed using the Transwell assay. Results: There were no obvious differences between expression levels in patients over age 64 and those younger than 64, and no noticeable distinction was observed between males and females. However, the YY1 protein level was significantly higher in ESCC tissues with lymph node metastasis than those without lymph node metastasis (P=0.042. Furthermore, the expression of the YY1 protein was stronger in stage III–IV patients than in stage I–II patients (P=0.002, but the protein levels between different histological grades (well, moderate, or poor showed no statistical significance. Similarly, there was no

  11. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah

    2012-10-26

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  12. Tubo gástrico isoperistáltico no tratamento paliativo do carcinoma irressecável do esôfago Gastro-esophageal isoperistaltic bypass as palliative treatment of the irresectable esophageal cancer

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    Alexandre Cruz Henriques

    2001-12-01

    nos pacientes portadores de carcinoma irressecável do esôfago, a derivação da obstrução através de um tubo gástrico isoperistáltico atinge seu objetivo primeiro que é aliviar a disfagia até o momento do óbito. A morbidade é alta, porém a maioria das complicações tem evolução benigna. A mortalidade é aceitável levando-se em conta a gravidade do carcinoma do esôfago.The goal of the treatment in patients with advanced esophageal carcinoma is to alleviate dysphagia. BACKGROUND: The objective of this study is to report the authors' experience with gastric esophageal bypass using isoperistaltic gastric tube followed by radiotherapy, in the treatment of patients with unresectable esophageal carcinoma. METHOD: From 1990 to 1999, 30 patients underwent bypass surgery. Twenty four patients (80% were male and six (20% female, age ranged from 27 to 69 years, with a mean age of 49.3 years. Diagnosis was confirmed by esophagogastroduodenoscopy and biopsy in all patients. Those with tumors greater than 6 cm at esophagography or with signs of invasion of the respiratory sistem at bronchoscopy were considered unresectable. Bypass surgery was carried out after medical assessment and preoperative evaluation. Surgery was performed by two teams, one at the cervical area and another at the abdominal area. Surgical time ranged from 3 to 4 hours. After hospital discharge, patients were referred to radiotherapy. RESULTS: There was no operative mortality. Postoperative mortality was 10%, one case of pulmonary thromboembolism and two cases of pneumonia. Thirteen patients (43.3% developed cervical anastomotic leak and eleven had spontaneous resolution; one required a new operation and another patient died at postoperative day 14, with an open fistula. Eight patients (26.6% had anastomotic stenosis, and all of them had a good outcome with endoscopic dilation. Deglutition was reestablished in all patients until death, excluding those who died as a result of postoperative

  13. Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hansen, L.V.; Laerum, O.D.; Illemann, M.;

    2008-01-01

    present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia and...... carcinoma in situ the expression of C4.4A is abruptly and coordinately weakened. Double immunofluorescence staining of normal and dysplastic tissue showed that C4.4A colocalizes with the epithelial cell surface marker E-cadherin in the suprabasal cells and has a complementary expression pattern compared to...

  14. [Current status and future prospect of internal medicine treatment for advanced esophageal cancer].

    Science.gov (United States)

    Wang, F; Fan, Q X

    2016-09-23

    Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research. Molecular targeted drugs have become a new developmental direction in cancer treatment because of their high specificity and antitumor activity, but the effects on esophageal cancer remain controversial. With the development of immune check point blockade treatment, breakthrough has been made in tumor immunotherapy, which has become an important means in cancer comprehensive treatment and shown a good prospect of treatment.

  15. Radiological Imaging in Patients with Esophageal Carcinoma%食管癌的影像学表现

    Institute of Scientific and Technical Information of China (English)

    Barbara Krug; Claudia Morgenroth

    2004-01-01

    Diagnostic imaging is carried out in patients with esophageal carcinoma in order to decide on the therapeutical procedure, to control therapy, to document complications and to assess concomitant diseases.Chest X-rays and esophagograms give a 2-dimensional view of the X-ray absorption in 3-dimensional examination volumes, the diagnostic accuracy thus being limited by overshadowing. Because of the robust examination technique, the broad availability and the low costs chest X-rays are usually used for short-term controls under therapy and follow-up. Esophagography is carried out in order to asses the exact location and length of a known esophageal carcinoma prior to therapy and in order to assess peristaltic disturbances and fistulas. CT and MRI provide tomographic images with a spatial resolution of up to 1 mm3 allowing the reconstruction of high-resolution images not only in the transversal but also in any other plain. The diagnostic accuracy of esophagography is comparatively high in T1-T3 stages (80%-90%). T1 and T2tumors cannot be diagnosed by CT and MRI, because both methods do not visualize the mucosa (unlike esophagography and endoscopy) and the esophageal wall layers (unlike EUS). Infiltration depth tends to be overestimated in T1 and T2 carcinomas and to be underestimated in T3 and T4 cancers. CT and MRI cannot detect metastases in normally sized lymph nodes and cannot accurately differentiate between benign and malignant lymphadenopathy in enlarged nodes with a reported sensitivities and specifities of 60% and 74%, respectively. However, further prospective studies using up to date CT and MR technology are needed to assess the present diagnostic situation. CT and MRI do not only visualize the mediastinum,but also the lungs, the pleura and the skeleton as well as the neck and the abdomen thus providing a comprehensive overview of the TNM stage in 3 body regions.

  16. Analysis of Clinicopathologic Features of Esophageal Carcinoma Patients Undergoing Surgery-a Report of 4,329 Cases

    Institute of Scientific and Technical Information of China (English)

    Wei Liu; Liyun Guan; Yumin Ping; Xianli Meng; Rui Wang; Junfeng Liu; Xiaoling Wang; Xishan Hao; Ying Jin; Haixin Li; Linan Song; Shijie Wang; Peizhong Wang; Yong Chen; Qian Fan

    2008-01-01

    OBJECTIVE To investigate the clinicopathological features of esophageal carcinoma (EC) patients, and to analyze epidemiologic characteristics and the current situation of esophageal cancioma in the southern area of Hebei Province.METHODS A total of 4329 patients with esophageal cancinoma,undergoing surgery in the Fourth Hospital of Hebei Medical University during a period from January 1996 to December 2005,were selected. Collection and statistical analysis of the pathologic data were performed using a SAS 6.0 software package.RESULTS Over the past ten years, there has been a tendency for an increase in the mean age of EC onset (P < 0.05), a downtrend in the percentage of squamous cancer (SqCa) (P < 0.05) and an uptrend in the frequency of small cell carcinoma (P < 0.05). In clinical stages, there was a drop in the percentage of Stage-Ⅱsquamous EC patients (P < 0.05), and an increase in that of Stage-Ⅳ patients (P < 0.05). There were statistical differences in sex, age,pathologic types, depth of infiltration, ratio of stages and lymph node metastasis, etc. Among the superior, middle and inferior segments of the EC diseased region (P < 0.05).CONCLUSION It was relatively late for the EC patients from this area to see a doctor, resulting in a drop in the ratio of SqCa and an ascensus in that of small cell cancer. However, due to a low incidence of adenocarcinoma, no obvious ascending tendency was found in the frequency of this carcinoma over the past ten years.

  17. Anti-tumor Effect and Its Mechanisms of Ursolic Acid on Human Esophageal Carcinoma Cell Eca-109 in Vivo

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-qing; SHEN Yi; DUANG Hong

    2008-01-01

    Objective:To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo.Methods:A transplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established.40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid(25-100 mg·kg-1.d-1)was injected into abdominal cavity respectively once everyday and lasted for fourteen days.The changes of tumor volume were measured continuously and tumor inhibition rate was calculated.The morphological changes of apoptosis were observed by electron microscope.The expressions of COX-2,bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry.At last the PGE2 level of transplanted tumors was detected by radioimmunoassay.Results:Treatment of nude mice with 25,50,or 100 mg·kg-1.d-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses.The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups,while the Bax increased.The PGE2 level of transplanted tumors was decreased in ursolic acid groups with a dose-related manner.Conclusion:Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo,which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.

  18. DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang,China

    Institute of Scientific and Technical Information of China (English)

    Ilyar; Sheyhidin

    2010-01-01

    AIM:To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma(ESCC). METHODS:A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects.Genotypes of 69 single nucleotide polymorphisms(SNPs)of metabolic enzyme(aldehyde dehydrogenase-2,ALDH2; alcohol dehydrogenase-1 B,ADHB1;Cytochrome P450 2A6,CYP2A6)and DNA repair capacity genes(excision repair cross complementing group 1,E...

  19. Investigation of tumor suppressing function of CACNA2D3 in esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available BACKGROUND: Deletion of 3p is one of the most frequent genetic alterations in esophageal squamous cell carcinoma (ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs within these regions. In this study, one TSG, CACNA2D3 at 3p21.1, was characterized. METHODS: Expression of CACNA2D3 in ESCCs was tested by quantitative real-time PCR and tissue microarray. The mechanism of CACNA2D3 downregulation was investigated by methylation-specific polymerase chain reaction (MS-PCR. The tumor suppressive function of CACNA2D3 was characterized by both in vitro and in vivo tumorigenic assays, cell migration and invasion assays. RESULTS: CACNA2D3 was frequently downregulated in ESCCs (24/48, 50%, which was significantly associated with promoter methylation and allele loss (P<0.05. Tissue microarray result showed that downregulation of CACNA2D3 was detected in (127/224, 56.7% ESCCs, which was significantly associated with lymph node metastasis (P = 0.01, TNM staging (P = 0.003 and poor outcome of ESCC patients (P<0.05. Functional studies demonstrated that CACNA2D3 could inhibit tumorigenicity, cell motility and induce apoptosis. Mechanism study found that CACNA2D3 could arrest cell cycle at G1/S checkpoint by increasing expressions of p21 and p53 and decreasing expression of CDK2. In addition, CACNA2D3 could upregulate intracellular free cytosolic Ca(2+ and subsequently induce apoptosis. CONCLUSION: CACNA2D3 is a novel TSG responsible to the 3p21 deletion event and plays a critical suppressing role in the development and progression of ESCC.

  20. Involved-field radiotherapy for esophageal squamous cell carcinoma: theory and practice

    International Nuclear Information System (INIS)

    Esophageal carcinoma (EC) is characterized by a high rate of lymph node metastasis and its spread pattern is not always predictable. Chemoradiotherapy has an important role in the treatment of EC in both the inoperable and the pre-operative settings. However, regarding the target volume for radiation, different clinical practices exist. Theoretically, in addition to the clinical target volume administered to the gross lesion, it might seem logical to deliver a certain dose to the uninvolved regional lymph node area at risk for microscopic disease. However, in practice, it is difficult because of the intolerance of normal tissue to radiotherapy (RT), particularly if all regions containing the cervical, mediastinal, and upper abdominal nodes are covered. To date, the use of elective nodal irradiation (ENI) is still controversial in the field of radiotherapy. Some investigators use involved-field radiotherapy (IFRT) in order to reduce treatment-related toxicities. It is thought that micrometastases can be controlled, to some extent, by chemotherapy and the abscopal effects of radiation. It is the presence of overtly involved lymph nodes rather than the micrometastatic nodes negatively affects survival in patients with EC. In another hand, lymph nodes stationed near primary tumors also receive considerable incidental irradiation doses that may contribute to the elimination of subclinical lesions. These data indicate that an irradiation volume covering only the gross tumor is appropriate. When using ENI or IFRT, very few patients experience solitary regional node failure and out-of-field lymph node failure is not common. Primary tumor recurrence and distant metastases, rather than regional lymph node failure, affect the overall survival in patients with EC. The available evidence indicates that the use of ENI seems to prevent or delay regional nodal relapse rather than improve survival. In a word, these data suggest that IFRT is feasible in EC patients

  1. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3

    Directory of Open Access Journals (Sweden)

    Zhao Lei

    2012-12-01

    Full Text Available Abstract Background Epidermal growth factor receptor (EGFR is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC. The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody on ESCC radiotherapy (RT and underlying mechanisms. Methods Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3 in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model. Results Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (PP>0.05. In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029, and also with IGFBP-3 up-regulation in tumor tissue. Conclusions Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.

  2. Potential transcriptional regulatory regions exist upstream of the human ezrin gene promoter in esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Shuying Gao; Yanpeng Dai; Meijun Yin; Jing Ye; Gang Li; Jie Yu

    2011-01-01

    We previously demonstrated that the region -87/+ 134 of the human ezrin gene (VIL2) exhibited promoter activity in human esophageal carcinoma EC109 cells, and a further upstream region -1324/-890 positively regulated transcription.In this study, to identify the transcriptional regulatory regions upstream of the VIL2 promoter, we cloned VIL2 - 1541/- 706 segment containing the -1324/-890, and investigated its transcriptional regulatory properties via luciferase assays in transiently transfected cells.In EC109 cells, it was found that VIL2 -1541/-706 possessed promoter and enhancer activities.We also localized transcriptional regulatory regions by fusing 5′- or 3′-deletion segments of VIL2 -1541/-706 to a luciferase reporter.We found that there were three positive and one negative transcriptional regulatory regions ithin VIL2 -1541/-706 in EC109 cells.When these regions were separately located upstream of the luciferase gene without promoter, or located upstream of the VIL2 promoter or SV40 promoter directing the luciferase gene, only VIL2 -1297/-1186 exhibited considerable promoter and enhancer activities, which were lower than those of -1541/-706.In addition, transient expression of Sp1 increased ezrin expression and the transcriptional activation of VIL2 -1297/-1186.Other three regions,although exhibiting significantly positive or negative transcriptional regulation in deletion experiments, showed a weaker or absent regulation.These data suggested that more than one region upstream of the VIL2 promoter participated in VIL2 transcription, and the VIL2 -1297/-1186, probably as a key transcriptional regulatory region, regulated VIL2 transcription in company with other potential regulatory regions.

  3. Bmi-1 confers adaptive radioresistance to KYSE-150R esophageal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guanyu [Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Liu, Luying [Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou (China); Sharma, Sherven [David Geffen School of Medicine at UCLA, and the Department of Veterans Affairs, Los Angeles, CA (United States); Liu, Hai; Yang, Weifang; Sun, Xiaonan [Department of Radiotherapy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Dong, Qinghua, E-mail: dongqinghua@zju.edu.cn [Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Adaptive radioresistant KYSE-150R cells expressed high level of Bmi-1. Black-Right-Pointing-Pointer Bmi-1 depletion sensitized KYSE-150R cells to RT. Black-Right-Pointing-Pointer Bmi-1 depletion increased the generation of ROS in KYSE-150R cells exposed to radiation. Black-Right-Pointing-Pointer Bmi-1 depletion impaired DNA repair capacities in KYSE-150R cells exposed to radiation. -- Abstract: Radiotherapy (RT) is a major modality of cancer treatment. However, tumors often acquire radioresistance, which causes RT to fail. The exact mechanisms by which tumor cells subjected to fractionated irradiation (FIR) develop an adaptive radioresistance are largely unknown. Using the radioresistant KYSE-150R esophageal squamous cell carcinoma (ESCC) model, which was derived from KYSE-150 parental cells using FIR, the role of Bmi-1 in mediating the radioadaptive response of ESCC cells to RT was investigated. The results showed that the level of Bmi-1 expression was significantly higher in KYSE-150R cells than in the KYSE-150 parental cells. Bmi-1 depletion sensitized the KYSE-150R cells to RT mainly through the induction of apoptosis, partly through the induction of senescence. A clonogenic cell survival assay showed that Bmi-1 depletion significantly decreased the radiation survival fraction in KYSE-150R cells. Furthermore, Bmi-1 depletion increased the generation of reactive oxygen species (ROS) and the expression of oxidase genes (Lpo, Noxo1 and Alox15) in KYSE-150R cells exposed to irradiation. DNA repair capacities assessed by {gamma}-H2AX foci formation were also impaired in the Bmi-1 down-regulated KYSE-150R cells. These results suggest that Bmi-1 plays an important role in tumor radioadaptive resistance under FIR and may be a potent molecular target for enhancing the efficacy of fractionated RT.

  4. Irradiated fibroblasts promote epithelial–mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Ci-Hang; Wang, Xin-Tong [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Ma, Wei [Department of Radiation Oncology, Cancer Hospital, Genaral Hospital of Ningxia Medical University, Yinchuan 750000 (China); Wang, Na-Na; Nesa, Effat un; Wang, Jian-Bo; Wang, Cong; Jia, Yi-Bin; Wang, Kai [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Tian, Hui [Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan 250012 (China); Cheng, Yu-Feng, E-mail: qlcyf1965@126.com [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2015-03-06

    Recent evidence suggested that nonirradiated cancer-associated fibroblasts (CAFs) promoted aggressive phenotypes of cancer cells through epithelial–mesenchymal transition (EMT). Hepatoma-derived growth factor (HDGF) is a radiosensitive gene of esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the effect of irradiated fibroblasts on EMT and HDGF expression of ESCC. Our study demonstrated that coculture with nonirradiated fibroblasts significantly increased the invasive ability of ESCC cells and the increased invasiveness was further accelerated when they were cocultured with irradiated fibroblasts. Scattering of ESCC cells was also accelerated by the supernatant from irradiated fibroblasts. Exposure of ESCC cells to supernatant from irradiated fibroblasts resulted in decreased E-cadherin, increased vimentin in vitro and β-catenin was demonstrated to localize to the nucleus in tumor cells with irradiated fibroblasts in vivo models. The expression of HDGF and β-catenin were increased in both fibroblasts and ESCC cells of irradiated group in vitro and in vivo models. Interestingly, the tumor cells adjoining the stromal fibroblasts displayed strong nuclear HDGF immunoreactivity, which suggested the occurrence of a paracrine effect of fibroblasts on HDGF expression. These data suggested that irradiated fibroblasts promoted invasion, growth, EMT and HDGF expression of ESCC. - Highlights: • Irradiated CAFs accelerated invasiveness and scattering of ESCC cell lines. • Irradiated CAFs promoted EMT of ESCC cells. • Irradiated fibroblasts induced nuclear β-catenin relocalization in ESCC cells. • Irradiated fibroblasts increased HDGF expression in vitro and in vivo.

  5. TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Li, Juan; Zhu, Shu-Chai; Li, Shu-Guang; Zhao, Yan; Xu, Jin-Rui; Song, Chun-Yang

    2015-08-01

    Transketolase-like-1 (TKTL1), which is a rate-limiting enzyme in the non-oxidative part of the pentose-phosphate pathway, has been demonstrated to promote carcinogenesis through enhanced aerobic glycolysis. Dysregulation of TKTL1 expression also leads to poor prognosis in patients with urothelial and colorectal cancer. However, the expression pattern and underlying cellular functions in human esophageal squamous cell carcinoma (ESCC) remain largely unexplored. In this study, we measured TKTL1 expression in ESCC cell lines and paraffin-embedded ESCC tumor tissues. Our results revealed that TKTL1 expression was upregulated in all of the four ESCC cell lines and in 61.25% (98/160) of ESCC specimens detected, while only 27.5% (11/40) in normal epithelium. Silencing of TKTL1 expression decreased cell proliferation through inhibiting the expression of MKI67 and cyclins including Ccna2, Ccnb1, Ccnd1 and Ccne1. Meanwhile, down-regulation of TKTL1 also associated with increased apoptotic ratio and altered protein expression of Bcl-2 family in ESCC cells. Furthermore, knockdown of TKTL1 significantly reduced the invasive potential of ESCC cells through up-regulation of anti-metastasis genes (MTSS1, TIMP2 and CTSK) and down-regulation of pr-metastasis genes (MMP2, MMP9, MMP10 and MMP13). Taken together, our results indicate that TKTL1 is associated with a more aggressive behavior in ESCC cells and suppresses its expression or enzyme activity might represents a potential target for developing novel therapies in human ESCCs.

  6. Thioridazine Sensitizes Esophageal Carcinoma Cell Lines to Radiotherapy-Induced Apoptosis In Vitro and In Vivo

    Science.gov (United States)

    Li, Hongxia; Juan, Li; Xia, Leiming; Wang, Yi; Bao, Yangyi; Sun, Guoping

    2016-01-01

    Background Radiotherapy is one of the primary treatments for esophageal squamous cell carcinoma (ESCC). Identification of novel radio-sensitizing agents will improve the therapeutic outcome of radiotherapy. This study aimed to determine the radio-sensitizing effect of the antipsychotic agent thioridazine in ESCC and explored the underlying mechanisms. Material/Methods ECA-109 and TE-1 ESCC cells were treated with thioridazine and radiotherapy alone and in combination. Cell survival was measured by MTT assay. Cell cycle and apoptosis were monitored by flow cytometry. Western blot analysis was used to analyze the expression of phospho-PI3K, phosphor-AKT, phospho-mTOR, Caspase-3, Caspase-9, Bax, Bcl-2, Bal-xl, Bak, and p53. The xenograft mouse model was used to study the in vivo anticancer effect of thioridazine and irradiation. Results Combined treatment with thioridazine and irradiation significantly reduced viability of ESCC cells compared with thioridazine or irradiation treatment alone. Thioridazine and irradiation treatment induced G0/G1 phases cell cycle arrest through down-regulation of CDK4 and cyclinD1. In addition, thioridazine and irradiation treatment induced apoptosis through up-regulation of cleaved capase-3 and 9, as well as an increase in the expression of Bax and Bak and a decrease in the expression of Bcl-2 and Bcl-xl. Furthermore, thioridazine and irradiation treatment inhibited the PI3K-AKT-mTOR pathway and up-regulated the expression of p53. In xenograft mice, thioridazine and irradiation reduced ESCC tumor growth. Conclusions Thioridazine sensitizes ESCC cells to radiotherapy. Thioridazine may play a role in ESCC radiation therapy as a promising radiosensitizer. PMID:27453171

  7. Association of mu-opioid receptor expression with lymph node metastasis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Y-F; Xu, Q-X; Liao, L-D; Xu, X-E; Wu, J-Y; Wu, Z-Y; Shen, J-H; Li, E-M; Xu, L-Y

    2015-01-01

    The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau-b-test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log-rank test). Our results suggest that the cytoplasmic MOR1 may be a high-risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.

  8. Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran.

    Directory of Open Access Journals (Sweden)

    Behnoush Abedi-Ardekani

    Full Text Available BACKGROUND: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. METHODOLOGY/PRINCIPAL FINDINGS: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%, including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs. Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. CONCLUSION/SIGNIFICANCE: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis.

  9. S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Dong Chen; Xue-Feng Zheng; Ze-You Yang; Dong-Xiao Liu; Guo-You Zhang; Xue-Long Jiao; Hui Zhao

    2012-01-01

    AIM:To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs).METHODS:Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis,n =28; non-metastasis,n =20) by reverse transcription-polymerase chain reaction,quantitative polymerase chain reaction and immunohistochemistry.To explore the influence of S100A4 on esophageal cancer invasion and metastasis,S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo.RESULTS:We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated,and more importantly,that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis.It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin,leading to increased cell migration in vitro,whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression.Moreover,the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely.In addition,nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo.CONCLUSION:S100A4 may be involved in ESCC progression by regulate E-cadherin expression,vectorbased RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.

  10. Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fauzia; Z; Khan; Ryan; B; Perumpail; Robert; J; Wong; Aijaz; Ahmed

    2015-01-01

    An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in non-alcoholic fatty liver disease(NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis(NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma(HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

  11. Esophageal cancer

    DEFF Research Database (Denmark)

    Mortensen, M. B.

    2007-01-01

    The distribution of adenocarcinomas and squamous cell carcinomas in esophageal cancer (EC) has changed, and focus directed towards tumors of the distal esophagus and the esophagogastric junction. The genetic events leading to EC are not fully clarified, but important risk factors have been...

  12. Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model

    Science.gov (United States)

    Osei-Sarfo, Kwame; Scognamiglio, Theresa; Gudas, Lorraine J.

    2015-01-01

    Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (β-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethanol alone increased the numbers of epithelial cells expressing solute carrier family 2 (facilitated glucose transporter, member 1) (SLC2A1) and carbonic anhydrase IX (CAIX), and increased the phosphorylation of p38. Thus, we identified both 4-NQO- and ethanol-specific targets in the initial stages of esophageal carcinogenesis, which should lead to the development of potential markers and therapeutic targets for human ESCC. PMID:25714027

  13. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    Science.gov (United States)

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence.

  14. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    Science.gov (United States)

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence. PMID:25731408

  15. 术中125I粒子植入联合术后化学治疗中晚期食管鳞癌%125I radioactive seeds implantation combined with postoperative chemotherapy in treatment of advanced esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吕进; 曹秀峰; 朱斌; 王冬冬; 纪律; 王山; 安红银

    2011-01-01

    目的 探讨术中125I粒子植入联合术后化学治疗治疗胸段中晚期食管鳞癌(ESCC)的安全性及疗效.方法 前瞻性队列研究,入组时间为2000年1月至2005年12月.根据ESCC术前CT分期标准,南京医科大学附属南京第一医院肿瘤外科和盐城市肿瘤医院胸外科298例Ⅱ~Ⅲ期胸段ESCC患者通过计算机随机数字法分为术中125I粒子植入联合术后化学治疗组(A组,98例)、术后放射化学治疗组(B组,100例)及单纯根治术组(C组,100例).三组均行食管癌根治术.再根据术后pTNM分期标准,最终实际入组Ⅱb~Ⅲ期胸段ESCC患者233例,三组分别为78例、75例、80例.依据治疗计划系统(TPS)所确定的剂量,A组于术中直视下植入125I粒子.选用0.5 mCi的125I粒子10~22粒,总活度在5~11 mCi,肿瘤匹配周边剂量60~70 Gy,术后通过影像学手段(CT、X线片)行粒子验证和质量评估.观察患者术后并发症,通过CT监测肿瘤影像学、局部复发情况,随访术后1、3、5、10年生存率.结果 A组术后粒子验证无移位、脱落,质量评估满意.A、B、C组局部复发率分别为11.5%、13.3%、38.8%,比较差异有统计学意义(P<0.05).3组并发症比较差异无统计学意义(P>0.05).3组1年生存率对比差异无统计学意义(P>0.05),A、B、C组3、5、10年总体及无进展生存率分别为64.8%,37.7%,25.1%;63.3%,36.9%,24.9%;43.6%,25.0%,12.6%)及63.5%,37.4%,15.1%;62.5%,36.6%,14.4%;42.5%,25.6%,6.2%;3组比较差异均有统计学意义(P<0.05).结论 术中125I粒子植入联合术后化疗与术后放化疗治疗中晚期食管鳞癌疗效相当,是简单、安全、有效的方法,可降低局部复发率、延长患者生存期.%Objective To evaluate the safety and efficacy of 125I radioactive seeds implantation combined with postoperative chemotherapy as a treatment option for thoracic advanced esophageal squamous cell carcinoma(ESCC). Methods A prospective cohort study was carried out

  16. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    Science.gov (United States)

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  17. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.

    Science.gov (United States)

    Shimada, Hideaki; Nabeya, Yoshihiro; Tagawa, Masatoshi; Okazumi, Shin-ichi; Matsubara, Hisahiro; Kadomatsu, Kenji; Muramatsu, Takashi; Ikematsu, Shinya; Sakuma, Sadatoshi; Ochiai, Takenori

    2003-07-01

    High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 +/- 342 pg/ml vs. 154 +/- 76 pg/ml, P esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK (>/= 300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival.

  18. Clinical significance and prognostic value of TRIM24 expression in esophageal squamous cell carcinoma

    Science.gov (United States)

    Chi, Jun; Yang, Qing; Xie, Xiao-Feng; Yang, Xian-Zi; Zhang, Mei-Yin; Wang, Hui-Yun; Xu, Guo-Liang

    2016-01-01

    Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RARα. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RARα in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RARα expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC. PMID:27689360

  19. Improved longitudinal length accuracy of gross tumor volume delineation with diffusion weighted magnetic resonance imaging for esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    To analyze the longitudinal length accuracy of gross tumor volume (GTV) delineation with diffusion weighted magnetic resonance imaging for esophageal squamous cell carcinoma (SCC). Forty-two patients from December 2011 to June 2012 with esophageal SCC who underwent radical surgery were analyzed. Routine computed tomography (CT) scan, T2-weighted MRI and diffusion weighted magnetic resonance imaging (DWI) were employed before surgery. Diffusion-sensitive gradient b-values were taken at 400, 600, and 800 s/mm2. Gross tumor volumes (GTV) were delineated using CT, T2-weighted MRI and DWI on different b-value images. GTV longitude length measured using the imaging modalities listed above was compared with pathologic lesion length to determine the most accurate imaging modality. CMS Xio radiotherapy planning system was used to fuse DWI scans and CT images to investigate the possibility of delineating GTV on fused images. The differences between the GTV length according to CT, T2-weighted MRI and pathology were 3.63 ± 12.06 mm and 3.46 ± 11.41 mm, respectively. When the diffusion-sensitive gradient b-value was 400, 600, and 800 s/mm2, the differences between the GTV length using DWI and pathology were 0.73 ± 6.09 mm, -0.54 ± 6.03 mm and −1.58 ± 5.71 mm, respectively. DWI scans and CT images were fused accurately using the radiotherapy planning system. GTV margins were depicted clearly on fused images. DWI displays esophageal SCC lengths most precisely when compared with CT or regular MRI. DWI scans fused with CT images can be used to improve accuracy to delineate GTV in esophageal SCC

  20. Effect of Traditional Chinese Medicine on Survival and Quality of Life in Patients with Esophageal Carcinoma after Esophagectomy

    Institute of Scientific and Technical Information of China (English)

    LU Ping; LIANG Qiu-dong; LI Rong; NIU Hong-rui; KOU Xiao-ge; XI Hong-jun

    2006-01-01

    Objective: To explore the effect and possible mechanism of traditional Chinese medicine (TCM) on survival and quality of life (QOL) in patients with esophageal carcinoma after esophagectomy.Methods: Adopting prospective controlled method of study, the authors had 128 post-esophagectomy patients, hospitalized from February 2001 to February 2002, randomly divided into 3 groups: the TCM group,treated with TCM drugs alone; the chemotherapy group, with chemotherapy alone applied; and the synthetic group, treated with chemotherapy combined with Chinese medicine. Their survival rate and QOL were compared. Results: In the TCM group, the chemotherapy group and the synthetic group, the respective 3-year relapse and remote metastasis rate were 71.4 %, 76.7 %, 53.4 %, respectively (χ2 = 6.53, P<0.05); the 1-year survival rate 42.9%, 46.5%, 72.1%; 2-year survival rate 28.6%, 27.9%, 55.8%, and 3-year survival rate 26. 2%, 23. 1%, 37. 2%, respectively. And the QOL improving rate was 69.0%, 37.2%,58.1%, respectively, all showing significant difference among them (χ2 = 6. 10, all P<0.05). Moreover,immune function was increased in the TCM and the synthetic groups. Conclusion: Integrative Chinese and Western medicinal treatment was the beneficial choice for post-operational patients with esophageal carcinoma. However, long time use of simple Chinese medicine was also advisable, especially for those in poverty.

  1. Effects of Oxymatrine on the Apoptosis of Human Esophageal Carcinoma Eca109 Cell Line and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    Yi JIN; Jianli HU; Qiong WANG; Zhenyu LI; Yeshan CHEN

    2008-01-01

    The effects of Oxymatrine (Oxy) on the proliferation and apoptosis of human esophageal carcinoma Eca109 cell line and the mechanism were investigated. The human esophageal carcinoma Eca109 cells were cultured in vitro. The Oxy-induced apoptosis of Eca109 cells was assayed by using flow cytometry. The expressions of p-ERK1/2, Cyclin D1, p21waf/cip1, Bax and Bcl-2 were detected by Western blot. Flow cytometry revealed that Oxy could induce the apoptosis of Eca109 cells. Western blot showed that Oxy of different concentrations suppressed the expressions of p-ERK1/2, cyclin D1 and Bc1-2, but up-regulated the expression of p21waf/cip1 and Bax, and the ratio of Bax/Bcl-2 was increased It was suggested the Oxy could induce the apoptosis of Eca109-cells, which might be related to the upregulation of p21waf/cip1 and the downregulation of p-ERK1/2 Cyclin D1 and p21waf/cip1. The possible pathway may be related to Bcl-2/Bax.

  2. Effect and mechanism of RUNX3 gene on biological characteristics of human esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Chen, Huaxia; Wang, Zhou; Wang, Shuai; Zhang, Zhiping; Shi, Shanshan

    2015-01-01

    The aim of this study was to investigate the role of RUNX3 in esophageal squamous cell carcinoma (ESCC) cells biological behavior and the relationship between the expression of RUNX3 and MMP-9, TIMP-1, ICAM-1. RUNX3 levels in 90 esophageal squamous cell carcinoma specimens using immunohistochemical staining to examine the correlation between RUNX3 expression and clinical stage of ESCC. Furthermore, the role of RUNX3 in ESCC progression was evaluated in vitro by siRNA-mediated knockdown of RUNX3 or lentivirus-mediated over-expression of RUNX3 in ESCC cell lines. The expression and activities of MMP-9, TIMP-1, and ICAM-1 were analyzed. We found decreased expression of RUNX3 in ESCC tissue to be significantly related to T stage of tumor (p cells resulted in promoting cell growth, migration, and invasion. Additionally, MMP-9 and ICAM-1 were upregulated in RUNX3-knockdown cells. Notably, RUNX3 over-expression in Kyse150 cells could significantly decrease MMP-9 and ICAM-1. Tumorigenesis in vivo was significantly determined. The study indicates that low expression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells migration, invasion, and tumorigenesis, which may be caused by RUNX3's interaction with MMP-9 and ICAM-1; RUNX3 may be a potential therapeutic target for ESCC.

  3. The Discovery and Validation of Biomarkers for the Diagnosis of Esophageal Squamous Dysplasia and Squamous Cell Carcinoma.

    Science.gov (United States)

    Couch, George; Redman, James E; Wernisch, Lorenz; Newton, Richard; Malhotra, Shalini; Dawsey, Sanford M; Lao-Sirieix, Pierre; Fitzgerald, Rebecca C

    2016-07-01

    The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are esophageal squamous cell carcinomas (ESCC). Endoscopic screening is undertaken in high incidence areas. Biomarker analysis could reduce the subjectivity associated with histologic assessment of dysplasia and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publicly available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus. Each gene was ranked by a support vector machine separation score. Expression profiles were examined, before validation by qPCR and IHC. We found that 800 genes were overexpressed in ESCC compared with normal esophagus (P < 10(-5)). Of the top 50 genes, 33 were expressed in ESCC epithelium and not in normal esophagus epithelium or stroma using the Protein Atlas website. These were taken to qPCR validation, and 20 genes were significantly overexpressed in ESCC compared with normal esophagus (P < 0.05). TNFAIP3 and CHN1 showed differential expression with IHC. TNFAIP3 expression increased gradually through normal esophagus, mild, moderate and severe dysplasia, and SCC (P < 0.0001). CHN1 staining was rarely present in the top third of normal esophagus epithelium and extended progressively towards the surface in mild, moderate, and severe dysplasia, and SCC (P < 0.0001). Two novel promising biomarkers for ESCC were identified, TNFAIP3 and CHN1. CHN1 and TNFAIP3 may improve diagnostic accuracy of screening methods for ESCC. Cancer Prev Res; 9(7); 558-66. ©2016 AACR. PMID:27072986

  4. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Wen-ying DENG

    2015-09-01

    Full Text Available Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer.Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because of Ⅳ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP parameters, including blood flow (BF, blood volume (BV, mean transit time (MTT, and permeability surface (PS before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS of 2 groups.Results: The efficacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF in combined group was obviously lower than that in single chemotherapy group after treatment (P<0.01. Compared with treatment before in combined group, BF, BV and PS decreased while MTT increased after treatment (P<0.05. However, there were no significant differences in single chemotherapygroup before and after treatment (P>0.05. The median OS was 30 months (95%CI: 20.935-39.065 for combined group and 21 months (95%CI: 15.109-26.591 for single chemotherapy group, respectively (P=0.048. The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively.Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

  5. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    DENG Wen-ying; LI Ning; LUO Su-xia

    2015-01-01

    Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer. Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because ofⅣ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan) and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP) parameters, including blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS) before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS) of 2 groups. Results:The efifcacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF) in combined group was obviously lower than that in single chemotherapy group after treatment (P0.05). The median OS was 30 months (95%CI: 20.935-39.065) for combined group and 21 months (95%CI: 15.109-26.591) for single chemotherapy group, respectively (P=0.048). The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively. Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

  6. CT灌注成像在食管癌中的应用%Application of CT perfusion in esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    闫圆圆; 李文武

    2011-01-01

    OBJECTIVE: To sum up the domestic and abroad articles correlated with the development of CT perfusion in esophageal carcinoma. METHODS: "esophageal carcinoma, CT, perfusion" were searched as key words by Medline and CNKI series full-text detabases retrieval system from 01-1991 to 01-2010. Totally 61 English papers and 11 Chinese papers were obtained. Choice criteria: 1) Theoretical basis of CT perfusion. 2) Significance of CT perfusion parameters. 3) Value of CT perfusion in diagnosis and therapy of esophageal carcinoma. By extraction of the choice criteria, 24 closely related papers are selected. RESULTS: DCT perfusion parameters such as BV(bold volume) and TTP (time to peak) are positively correlated with microvessel density (MVD) of esophageal carcinoma. 2) PS (permeability surface) and PEI (peak enhancement intensity) are significantly deviated before and after radiotherapy. 3)BV and BF(blood flow) are positively correlate and MTT is negtively correlated with sensitivity of patients to radiotherapy and chemotherapy. 4) CT perfusion can be used in locoregional and distant disease detection and staging. CONCLUSIONS: CT perfusion takes an important part in assessing angiogenesis of esophageal carcinoma and in predicting the response to radiotherapy and chemotherapy. In addition,CT perfusion is a new method for locoregional and distant disease detection and staging.%目的:总结国内外CT灌注技术及其在食管癌中的应用进展.方法:应用Medline和CNKI期刊全文数据库系统,以“食管癌、计算机体层成像、灌注”为关键词,检索1991-01-2010-01的相关文献,共检索到英文文献61篇和中文文献11篇.纳入标准:1)CT灌注技术的理论基础;2)食管癌灌注参数的意义;3)CT灌注在食管癌诊断、治疗中的价值.根据纳入标准分析24篇文献.结果:1)食管癌CT灌注参数血容量(BV)和峰值到达时间(TTP)与食管癌微循环情况有良好相关性;2)放疗前后的食管癌CT灌注参数毛

  7. p53 negativity, CDC25B positivity, and metallothionein negativity are predictors of a response of esophageal squamous cell carcinoma to chemoradiotherapy

    Institute of Scientific and Technical Information of China (English)

    Fumiko Sunada; Masayuki Itabashi; Hisanao Ohkura; Toshiyuki Okumura

    2005-01-01

    AIM: Esophageal squamous cell carcinoma is generally sensitive to chemoradiotherapy (CRT), but some cases are not. Using a retrospective analysis, we aimed to identify the predictors of the response by esophageal squamous cell carcinoma to definitive CRT.METHODS: The intensities of expression of p53, Ki67,Bcl-2, Bax, cyclin D1, VEGF, CDC25B, and metallothionein (MT)were evaluated immunohistochemically in the biopsy specimens obtained before CRT, and the intensities of their expression were tested for correlations with the clinical effects of CRT.RESULTS: The esophageal squamous cell carcinomas with negative p53, positive CDC25B, and negative MT expression were found to be significantly more sensitive to CRT. In addition, p53 positivity and CDC25B positivity respomd well to CRT.CONCLUSION: Esophageal squamous cell carcinomas with negative p53,positive CDC25B, and negative MT expressions respond well to CRT. Even with p53 positivity,if with CDC25B positivity, CRT can be expected.

  8. Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population

    Directory of Open Access Journals (Sweden)

    Song Zhengbo

    2012-12-01

    Full Text Available Abstract Background Tumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2 without lymph-node metastases in esophageal squamous cell carcinoma. Methods We enrolled 201 patients with esophageal squamous cell carcinoma (SCC who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC tumor, node, metastasis (TNM staging system published in 2009. Results The overall survival (OS rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (PP = 0.04, as did the other current TNM factors. Conclusion Tumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.

  9. Prognostic significance of circulating tumor cells in esophageal carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Qiao GL

    2016-03-01

    Full Text Available Guang-Lei Qiao,1 Wei-Xiang Qi,2 Wei-Hua Jiang,1 Ying Chen,1 Li-Jun Ma1 1Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 2Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China Purpose: The prognostic significance of circulating tumor cells (CTCs in esophageal carcinoma (EC is controversial. We aim to assess its association with clinicopathological and prognostic relevance in EC by using a meta-analysis.Methods: We searched PubMed, Cochrane Database, Embase databases, and the references in relevant studies that assessed the clinicopathological or prognostic relevance of CTCs in peripheral blood of patients with EC. Statistical analyses were conducted by using Stata software to calculate the pooled odds ratio (OR, hazard ratio (HR, and 95% confidence intervals (CIs using fixed or random-effects models according to the heterogeneity of included studies. The subgroup analyses were performed according to ethnicity, histological type, and detection method.Results: Sixteen trials containing 1,260 patients were included for analysis. Pooled results showed that presence of CTCs was significantly associated with poor overall survival (HR =1.71, 95% CI [1.30, 2.12], P<0.001 and progression-free survival (HR =1.67, 95% CI [1.19, 2.15], P<0.001 in EC patients. Subgroup analysis indicated that presence of CTCs was closely associated with worse overall survival (Asian: HR =1.66, 95% CI [1.24, 2.08], P<0.001; squamous cell carcinoma [SCC]: HR =1.66, 95% CI [1.24, 2.08], P<0.001; no polymerase chain reaction [PCR]: HR =2.08, 95% CI [1.40, 2.76], P<0.001 and progression-free survival (Asian: HR =1.63, 95% CI [1.15, 2.12], P<0.001; SCC: HR =1.63, 95% CI [1.15, 2.12], P<0.001; PCR: HR =1.63, 95% CI [1.15, 2.12], P<0.001. Additionally, ORs showed that presence of CTCs was significantly correlated with tumor node metastasis (TNM staging (overall: OR =1

  10. Integration of human papillomavirus 18 DNA in esophageal carcinoma 109 cells

    Institute of Scientific and Technical Information of China (English)

    Ke Zhang; Jin-Tao Li; Shu-Ying Li; Li-Hua Zhu; Ling Zhou; Yi Zeng

    2011-01-01

    AIM: To detect human papillomavirus (HPV) DNA in esophageal carcinoma (EC) 109 cells and investigate the relationship between HPV and EC. METHODS: Genomic DNA and total RNA from EC109 cells were isolated. HPV DNA was detected by poly-merase chain reaction (PCR) with the general primer sets of MyO9/ll and GP5 +/6 + for the HPV LI gene and type-specific primer sets for HPV18 E6 and HPV18 E6-E7. Reverse transcription (RT) of mRNA isolated from EC109 cells was performed to produce a cDNA. And then a PCR-based protocol for the amplification of papillomavirus oncogene transcripts was used to analyze HPV18 DNA and integrated transcripts of HPV18 in the chromosomes of EC109 cells. The final nested PCR products were cloned into a pMD-18T vector and se-quenced to analyze the chromosomal location of HPV integration. RESULTS: HPV18 DNA was detected in EC109 cells by PCR using the general primer sets of MyO9/ll and GP5 +/6 + for HPV LI and the type-specific primer sets for HPV18 E6 and E6-E7 to generate products of 450 bp, 150 bp, 335 bp and 944 bp, respectively. Approximately 600 bp of integrated HPV18-specific transcript was identified. The final nested PCR product of integrated HPV18 DNA was cloned into a pMD-18T vector and sequenced to analyze the chromosomal location of HPV integration. Sequence alignment showed that the HPV18 sequence from EC109 cells was identical to that of the encoded early protein E7-E1 of the standard HPV18 strain X05015, and another partial gene sequence was identical to a partial sequence of human chromosome 8. CONCLUSION: Integration of the HPV genome into the host cell chromosome suggests that persistent HPV infection is vital for malignant cell transformation and carcinogenesis.

  11. Radiosensitization in esophageal squamous cell carcinoma. Effect of polo-like kinase 1 inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jenny Ling-Yu [National Taiwan University, Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei (China); National Taiwan University Hospital Hsin-Chu Branch, Department of Radiation Oncology, Hsin-Chu (China); National Taiwan University Hospital and National Taiwan University Cancer Center, Department of Oncology, Taipei (China); Chen, Jo-Pai [National Taiwan University Hospital and National Taiwan University Cancer Center, Department of Oncology, Taipei (China); National Taiwan University Hospital Yun-Lin Branch, Department of Oncology, Yun-Lin (China); Huang, Yu-Sen [National Taiwan University, Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei (China); National Taiwan University Hospital, Department of Medical Imaging, Taipei (China); National Taiwan University Hospital Yun-Lin Branch, Department of Medical Imaging, Yun-Lin (China); Tsai, Yuan-Chun; Tsai, Ming-Hsien; Jaw, Fu-Shan [National Taiwan University, Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei (China); Cheng, Jason Chia-Hsien; Kuo, Sung-Hsin [National Taiwan University Hospital and National Taiwan University Cancer Center, Department of Oncology, Taipei (China); National Taiwan University, Graduate Institute of Oncology, Taipei (China); Shieh, Ming-Jium [National Taiwan University, Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei (China); National Taiwan University Hospital and National Taiwan University Cancer Center, Department of Oncology, Taipei (China)

    2016-04-15

    This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone. (orig.) [German] Diese Studie untersucht die Wirksamkeit der Polo-like -Kinase 1-(PLK1-)Inhibition auf die Strahlenempfindlichkeit in vitro und in vivo beim oesophagealen Plattenepithelkarzinom durch eine pharmakologische Herangehensweise mit dem hochwirksamen PLK1-Inhibitor Volasertib. Menschliche Zelllinien des oesophagealen Plattenepithelkarzinoms (ESCC), KYSE 70 und KYSE 150, wurden verwendet, um den synergistischen Effekt von Volasertib und Bestrahlung in vitro zu bewerten. Hierzu wurden Zellviabilitaets- und Koloniebildungsuntersuchungen sowie Zellwachstumsanalysen, Immunblots und ektopische In-vivo-Tumormodelle herangezogen. Volasertib verminderte die ESCC

  12. Establishment and characterization of a paclitaxel‑resistant human esophageal carcinoma cell line.

    Science.gov (United States)

    Wang, Cong; Guo, Liu-Bin; Ma, Jun-Yuan; Li, Yong-Mei; Liu, Hong-Min

    2013-11-01

    The aim of this study was to establish a new paclitaxel (PTX)-resistant human esophageal squamous carcinoma (ESCC) cell line and investigate its biological characteristics. The resistant cell line (EC109/Taxol) was developed in vitro by intermittent exposure of the human ESCC cell line EC109 to a high concentration of PTX with time-stepwise increment over a period of 6 months. The MTT assay was performed to test the drug resistance of EC109 and EC109/Taxol cells. The morphological features were observed using inverted microscopy and apoptosis was measured by flow cytometry (FCM) and Hoechst 33258 fluorescence staining. Cell growth curves and colony formation of EC109 and EC109/Taxol cells were compared. FCM was also used to determine the distribution of the cell cycle. The protein levels of Bcl-2, Bax, Procaspase-3 and P-gp were detected by western blotting. P-gp activity was evaluated by Rh123 accumulation and efflux assay. In vivo resistance characterization was investigated. EC109/Taxol cells were 67.2-fold resistant to PTX in comparison with EC109 cells, and also exhibited cross-resistance to 5-fluorouracil (5-FU), cisplatin (CDDP) and epirubicin (EPI). FCM and Hoechst 33258 fluorescence staining confirmed that EC109 cells treated with PTX showed significantly higher percentage of apoptotic cells compared to EC109/Taxol cells. Simultaneously, EC109/Taxol cells exhibited changes in morphology, proliferation rate, doubling time, cell cycle distribution and colony formation rate were detected as compared with EC109 cells. The resistant cell line overexpressed Bcl-2, Procaspase-3 and P-gp protein, and showed decreased Bax expression. Further, EC109/Taxol cells did not change PTX resistance in vivo. This is the first report on the establishment of an EC109/Taxol cell line with higher resistance. Bcl-2, Bax, Procaspase-3 and P-gp are involved in the resistance of cell lines to PTX, which are invaluable tools to study the resistance of anticancer drugs and to identify

  13. Genomic imbalances in esophageal carcinoma cell lines involve Wnt pathway genes

    Institute of Scientific and Technical Information of China (English)

    Jacqueline Brown; Hannelie Bothma; Robin Veale; Pascale Willem

    2011-01-01

    AIM: To identify molecular markers shared across South African esophageal squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy number analysis. METHODS: We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software. RESULTS: We detected common translocation breakpoints involving chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or interruption of the EPHA3 gene. The most significant amplifications involved the following chromosomal regions and genes: 11q13.3 ( CCND1, FGF3, FGF4, FGF19, MYEOV), 8q24.21( C-MYC, FAM84B), 11q22.1-q22.3 ( BIRC2, BIRC3), 5p15.2 ( CTNND2), 3q11.2-q12.2 ( MINA) and 18p11.32 ( TYMS, YES1). The significant deletions included 1p31.2-p31.1 ( CTH, GADD45α, DIRAS3), 2q22.1 ( LRP1B), 3p12.1-p14.2 ( FHIT), 4q22.1-q32.1 ( CASP6, SMAD1), 8p23.2-q11.1 ( BNIP3L) and 18q21.1-q21.2 ( SMAD4, DCC). The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC. CONCLUSION: The finding that a significant number of genes that were amplified (FGF3 , FGF4 , FGF19 , CCND1 and C-MYC ) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.

  14. MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma.

    Science.gov (United States)

    Bujas, T; Marusic, Z; Peric Balja, M; Mijic, A; Kruslin, B; Tomas, D

    2011-03-21

    In the present study we analyzed immunohistochemical expression of MAGE-A 3/4 and NY-ESO-1 in 55 samples of esophageal squamous cell carcinomas (ESCC) and their respective lymph node metastases. To our knowledge this is the first study to assess and compare the expression of these antigens in ESCC lymph node metastases. Fifty (90.9%) primary ESCC were positive for MAGE-A 3/4 and 53 (96.6%) were positive for NY-ESO-1. MAGE-A 3/4 was expressed in all lymph node metastases and the intensity of expression was high in a majority of cases. NY-ESO-1 was negative in 2 (7.1%) lymph nodes metastases, while the reaction was predominantly moderate in the positive group. In primary tumors MAGE-A 3/4 showed a significantly higher intensity of expression compared to NY-ESO-1 (P=0.047), while in lymph node metastases the intensity of expression was not significantly different (P=0.387). Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression. Intensity of MAGE-A 3/4 (P=0.461) and NY-ESO-1 (P=0.414) expression in primary tumors was not significantly different compared to the expression in their respective lymph nodes metastases. Expression of MAGE-A 3/4 in primary tumors showed significant positive correlation with primary tumor expression of NY-ESO-1 (P=0.021) but no significant correlation with the expression of MAGE-A 3/4 in lymph node metastases (P=0.056). Expression of NY-ESO-1 in primary tumors showed significant positive correlation with the expression of NY-ESO-1 in lymph node metastases (P=0.001) and significant negative correlation with patients’ age (PESO-1 in primary tumors and lymph node metastases showed no significant correlation with prognostic parameters such as tumor grade and TNM stage (P>0.05). We have shown different levels of MAGE-A 3/4 and NY-ESO-1 expression in almost all specimens of primary tumor and lymph node metastases, suggesting that ESCC may be possible target

  15. Impact on cellular immunocompetence by late course accelerated hyperfractionation radiotherapy assisted with cisplatin in the treatment of esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the therapeutic results of late course accelerated hyperfractionation radiotherapy (LCAHR) combined with concomitant cisplatin administration as a sensitizer, and to assess the effects on cell-mediated immunocompetence in the treatment of esophageal carcinoma. Methods: From Jan. to Nov. 199, 104 patients with squamous cell carcinoma (SCC) of the esophagus were randomized to receive LCAHR alone (Group A, 53 patients) or LCAHR plus cisplatin (Group B, 51 patients). For both groups, the same radiation technic was given with the conventional fractionation in the first 3 weeks and 1.5 Gy twice daily, a minimum inter fraction interval of 6 hours, 5 days per week in the final 2 weeks. The total dose was 60 Gy/35 fs/5 wk. For the B group patients, cisplatin was given synchronously with 20 mg once daily for 5 days in the 1 st and 5 th weeks. The CD4, CD8 and CD56 expressions in peripheral blood lymphocytes (PBL) were quantitatively assessed with flow cytometry before and during the treatment. Results: The CD4/CD8 ratio of PBL decreased significantly after treatment completion (P < 0.01 in Group A and P < 0.01 in Group B). Whereas the percentage of positive CD56 PBL increased dramatically (P < 0.01 in two groups). There were no evidence that CD expression difference had any statistical or clinical significance. Conclusion: Immunosuppression may be present on cell-mediated immuno-activity (CD4/CD8) and NK cell (CD56)immuno-enhancement may be obtainable on immuno-surveillance, when esophageal carcinoma is being treated by LCAHR with or without cisplatin

  16. Patterns of failure after complete resection of thoracic esophageal squamous cell carcinoma: implications for postoperative radiation therapy volumes

    International Nuclear Information System (INIS)

    Objective: To analyze intrathoracic or extrathoracic recurrence pattern after surgical resection of thoracic esophageal squamous cell carcinoma (TESCC) and its help for further modify and improvement on the target of postoperative radiation therapy. Methods: One hundred and ninety-five patients who had undergone resection of TESCC at the Cancer Hospital, Chinese Academy of Medical Sciences enrolled from April 1999 to July 2007. Sites of failure on different primary location of esophageal cancer were documented. Results: Patients with upper or middle thoracic esophageal cancer had higher proportion of intrathoracic recurrence. Patients with lower thoracic esophageal cancer had more intrathoracic recurrence and abdominal lymph node metastatic recurrence. Histological lymph node status has nothing to do with intrathoracic recurrence, supraclavicular lymph node (SLN) metastasis or distant metastasis (χ2 =1.58, 0.06, 0.04, P =0.134, 0.467, 0.489, respectively), whereas the chance of abdominal lymph node metastases in N positive patients was significantly higher than that in N0 patients (28.7%: 10.6%, χ2 =9.94, P =0.001), and so did in middle thoracic esophageal cancer (20.0%: 5.6%, χ2 =5.67, P =0.015). Anatomic recurrence rate of patients with proximal resection margin no more than 3 cm was significantly higher compared to those more than 3 cm (25.0%: 11.3%, χ2=5.65, P=0.019). Conclusions: Mediastinum is the most common recurrence site.According to recurrence site, the following radiation targets are recommended: when tumor was located at the upper or middle thoracic esophagus with negative N status, the mediastinum, the tumor bed and the supraclavicular region should be included as postoperative RT target; when tumor was located at the middle thoracic esophagus with positive N or located at the lower thoracic esophagus, the abdominal lymph node should be added.If the proximal resection margin was no more than 3 cm, the anastomotic-stoma should be included. (authors)

  17. Production of a human single-chain variable fragment antibody against esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming-Yan Xu; Xiao-Hu Xu; Geng-Zhen Chen; Xiao-Ling Deng; Jonathan Li; Xiao-Jun Yu; Mei-Zhen Chen

    2004-01-01

    AIM: To construct a phage display library of human singlechain variable fragment (scFv) antibodies associated with esophageal cancer and to preliminarily screen a scFv antibody against esophageal cancer.METHODS: Total RNA extracted from metastatic lymph nodes of esophageal cancer patients was used to construct a scFv gene library. Rescued by M13K07 helper phage, the scFv phage display library was constructed. esophageal cancer cell line Eca 109 and normal human esophageal epithelial cell line (NHEEC) were used for panning and subtractive panning of the scFv phage display library to obtain positive phage clones. Soluble scFv was expressed in E.coli HB2151 which was transfected with the positive phage clone, then purified by affinity chromatography.Relative molecular mass of soluble scFv was estimated by Western blotting, its bioactivity was detected by cell ELISA assay. Sequence of scFv was determined using the method of dideoxynucleotide sequencing.RESULTS: The size of scFv gene library was approximately 9×106 clones. After four rounds of panning with Eca109 and three rounds of subtractive panning with NHEEC cells, 25 positive phage clones were obtained. Soluble scFv was found to have a molecular mass of 31 ku and was able to bind to Eca109 cells, but not to HeLa and NHEEC cells. Variable heavy (VH) gene from one of the positive clones was shown to be derived from the γ chain subgroup Ⅳ of immunoglobulin, and variable light (VL) gene from the κchain subgroup I of immunoglobulin.CONCLUSION: A human scFv phage display library can be constructed from the metastatic lymph nodes of esophageal cancer patients. A whole human scFv against esophageal cancer shows some bioactivity.

  18. Recent advances in multidisciplinary management ofhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Asmaa I Gomaa; Imam Waked

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC)is increasing, and it is currently the second leadingcause of cancer-related death worldwide. Potentiallycurative treatment options for HCC include resection,transplantation, and percutaneous ablation, whereaspalliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemictreatments. Due to the diversity of available treatmentoptions and patients' presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.

  19. Advances in Management of Hepatocellular Carcinoma.

    Science.gov (United States)

    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  20. Overexpression of GPR39 contributes to malignant development of human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Tang Hong

    2011-02-01

    Full Text Available Abstract Background By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC. Methods The mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells. Results We found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54% and protein level (121/207, 58.5%, which was significantly associated with the lymph node metastasis and advanced TNM stage (P GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells. Conclusions The present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC.

  1. Endoscopic assessment and management of early esophageal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ghassan; M; Hammoud; Hazem; Hammad; Jamal; A; Ibdah

    2014-01-01

    Esophageal carcinoma affects more than 450000people worldwide and the incidence is rapidly increasing.In the United States and Europe,esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence.Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages.Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus.These risk factors include chronic gastroesophageal reflux disease,hiatal hernia,advanced age,male sex,white race,cigarette smoking,and obesity.The annual risk of esophageal cancer is approximately 0.25%for patients without dysplasia and 6%for patients with high-grade dysplasia.Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa.The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option.The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia.Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation,photodynamic therapy and cryoablation.Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion.Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor,positive lymph node and submucosal invasion.Surgical resection should be offered to patients with deep submucosal invasion.

  2. Preemptive analgesic effects of flurbiprofen axetil in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach

    Institute of Scientific and Technical Information of China (English)

    WANG Yan; ZHANG Hong-bin; XIA Bin; WANG Gong-ming; ZHANG Meng-yuan

    2012-01-01

    Background Systemic non-steroidal anti-inflammatory drugs have been evaluated for their possible preemptive analgesic effects.The efficacy of flurbiprofen axetil for preemptive analgesia in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach needs further investigation.The aim of this study was to research the preemptive analgesic effects of flurbiprofen axetil in thoracic surgery,and the influence of preoperative administration on postoperative respiratory function.Methods This randomized,double-blind,controlled trial enrolled 60 patients undergoing radical resection of esophageal carcinoma via the left thoracic approach.Anesthesia management was standardized.Each patient was randomly assigned to receive either 100 mg flurbiprofen axetil intravenously 15 minutes before incision (PA group) or intravenous normal saline as a control (C group).Postoperative analgesia was with sufentanil delivered by patient-controlled analgesia pump.Postoperative sufentanil consumption,visual analog scale pain scores,plasma levels of interleukin-8,and oxygenation index were measured.Results Compared with the preoperative baseline,postoperative patients in the PA group had no obvious increase in pain scores (P >0.05),but patients in the C group had significantly increased pain scores (P<0.05).Pain scores in the C group were significantly higher at 24 hours postoperatively than preoperatively.Intergroup comparisons showed lower visual analog scale scores at 2-24 hours postoperatively in the PA group than the C group (P <0.05).Sufentanil consumption and plasma interleukin-8 levels at 2 and 12 hours postoperatively were significantly lower in the PA group than the C group (P <0.05).The oxygenation index at 2 and 12 hours postoperatively was significantly higher in the PA group than the C group (P<0.05).Conclusions Intravenous flurbiprofen axetil appears to have a preemptive analgesic effect in patients undergoing radical resection of

  3. Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

    Directory of Open Access Journals (Sweden)

    Wu Xianhua

    2012-08-01

    Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

  4. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.)....

  5. Dietary intake of minerals and risk of esophageal squamous cell carcinoma: results from the Golestan Cohort Study123

    Science.gov (United States)

    Hashemian, Maryam; Poustchi, Hossein; Abnet, Christian C; Boffetta, Paolo; Dawsey, Sanford M; Brennan, Paul J; Pharoah, Paul; Etemadi, Arash; Kamangar, Farin; Sharafkhah, Maryam; Hekmatdoost, Azita; Malekzadeh, Reza

    2015-01-01

    Background: Dietary factors have been hypothesized to affect the risk of esophageal cancer via different mechanisms, but the intake of minerals is understudied and the evidence is conflicting. Objective: The objective was to evaluate the associations of dietary intake of minerals with risk of esophageal squamous cell carcinoma (ESCC). Design: We used data from the Golestan Cohort Study, which was launched in a high-risk region for esophageal cancer in Iran. Participants were enrolled in 2004–2008 and were followed to 2014. Intakes of minerals were assessed with a validated food-frequency questionnaire. A Cox proportional hazards model was used to estimate HRs and 95% CIs of ESCC for dietary intakes of selected minerals. Results: We identified 201 ESCC cases among 47,405 subjects. Calcium intake was significantly inversely associated with the risk of ESCC (HR per 100-mg/d increase: 0.88; 95% CI: 0.81, 0.96; P = 0.005; quartile 4 vs. quartile 1 HR: 0.49; 95% CI: 0.29, 0.82; P-trend = 0.013). Zinc intake was also inversely associated with ESCC, but the quartile association did not reach significance (HR per 1-mg/d increase: 0.87; 95% CI: 0.77, 0.98; P = 0.027; quartile 4 vs. quartile 1 HR: 0.56; 95% CI: 0.28, 1.12; P-trend = 0.097). The relations between dietary intakes of selenium, magnesium, and copper and risk of ESCC were nonlinear (P-nonlinear trend = 0.001, 0.016, and 0.029, respectively). There was no relation between dietary intake of manganese and the risk of ESCC. Conclusion: The results suggest that higher intakes of calcium and zinc are associated with a lower risk of ESCC in a high-risk region of Iran. PMID:26016858

  6. Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform

    Directory of Open Access Journals (Sweden)

    Lihong Yin

    2013-04-01

    Full Text Available Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors.

  7. HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.

    Science.gov (United States)

    Ge, Xiao-Song; Ma, Hua-Juan; Zheng, Xiao-Hui; Ruan, Hong-Lian; Liao, Xiao-Yu; Xue, Wen-Qiong; Chen, Yuan-Bin; Zhang, Ying; Jia, Wei-Hua

    2013-12-01

    Long non-coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well-known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time-polymerase chain reaction (qPCR). WIF-1 playing an important role in Wnt/β-catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF-1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/β-catenin signaling pathway. This newly identified HOTAIR/WIF-1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC. PMID:24118380

  8. Consumption of salted meat and its interactions with alcohol drinking and tobacco smoking on esophageal squamous-cell carcinoma.

    Science.gov (United States)

    Lin, Sihao; Wang, Xiaorong; Huang, Chengyu; Liu, Xudong; Zhao, Jin; Yu, Ignatius T S; Christiani, David C

    2015-08-01

    Etiology of esophageal cancer has not yet been clearly documented, especially in high-risk regions. To evaluate the association between salted meat intake and esophageal squamous-cell carcinoma (ESCC) and to explore its joint effects with alcohol drinking and smoking, a population-based case-control study was conducted in a high ESCC risk area in China, including 942 incident ESCC cases and 942 age- and sex-matching controls. A validated food frequency questionnaire was used to collect information on dietary factors, alcohol drinking and tobacco smoking. Conditional logistic regressions were applied to estimate the association between salted meat intake and ESCC and its interactions with alcohol drinking and smoking, with adjustment for other confounders, including total energy intake. Salted meat intake was associated with an increased risk of ESCC, showing an exposure-response relationship (p for trend alcohol drinking or smoking had a greater risk than salted meat alone, which was more than additive. The strongest association was seen in the combination of all the three factors, particularly at the highest level of salted meat intake (odds ratio = 29.27, 95% confidence interval: 13.21-64.89). Salted meat intake is strongly associated with ESCC and its interactions with alcohol drinking and/or smoking highlights the significance of reducing salted meat intake among smokers and drinkers with respect to ESCC prevention.

  9. Pneumonia and Pleural Empyema due to a Mixed Lactobacillus spp. Infection as a Possible Early Esophageal Carcinoma Signature

    Science.gov (United States)

    Chaini, Eleftheria; Chainis, Nikolaos D.; Ioannidis, Anastasios; Magana, Maria; Nikolaou, Chryssoula; Papaparaskevas, Joseph; Liakata, Melina-Vassiliki; Katopodis, Panagiotis; Papastavrou, Leonidas; Tegos, George P.; Chatzipanagiotou, Stylianos

    2016-01-01

    Lactobacilli are human commensals found in the gastrointestinal and genitourinary tract. Although generally conceived as non-pathogenic microorganisms, the existence of several reports implicating them in certain severe pathological entities renders this species as opportunistic pathogens. The case of a 58-year-old woman with mixed Lactobacillus infection is described. The patient was admitted in an outpatient clinic with community acquired pneumonia, and on the third day of hospitalization she presented rapid pneumonia deterioration. Subsequent imaging techniques revealed increased pleural empyema in alignment with the general deterioration of her clinical condition. Pleural fluid culture revealed the presence of Lactobacillus delbrueckii and Lactobacillus gasseri and the infection was successfully treated with clindamycin. Five months after hospital discharge and an overall good condition, the patient developed signs of dysphagia and upon re-admission an inoperable esophageal carcinoma was diagnosed. The patient succumbed to the cancer 11 months later. Herein, we report for the first time a mixed respiratory infection due to lactobacilli, possibly associated with a formerly unveiled esophageal malignancy. PMID:27734016

  10. The unusual yin-yang fashion of RIZ1/RIZ2 contributes to the progression of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cui Yuantao

    2016-08-01

    Full Text Available Retinoblastoma protein-interacting zinc finger gene RIZ encodes two different protein products, RIZ1 and RIZ2. Observations suggest that RIZ1 is a tumor suppressor, while RIZ2 acts as a negative regulator of RIZ1 and may play a positive role in oncogenesis. The imbalance amount of RIZ1 and RIZ2 may be involved in cancer development. In this study we detected the expression levels of RIZ1 and RIZ2 mRNA in human esophageal squamous cell carcinoma (ESCC tissue specimens, reexpressed RIZ1 in the human ESCC cell line EC109 in which RIZ1 mRNA level was not detected, examined the changes of RIZ1 and RIZ2 mRNA expression, investigated the changes of proliferation, and apoptosis of the cells. We found that RIZ1 mRNA expression is commonly decreased or at undetectable level in human esophageal squamous cancer tissue specimens compared to the normal tissue specimens, while RIZ2 is usually expressed. With the forced expression of RIZ1, RIZ2 mRNA expression did not change, The ESCC cell proliferation was inhibited and apoptosis was induced. This unusual yinyang fashion of RIZ1/RIZ2 may contribute to the progression of ESCC.

  11. κ-Opioid receptor in the nucleus is a novel prognostic factor of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Yong-Fa; Xu, Qing-Xia; Liao, Lian-Di; Xu, Xiu-E; Wu, Jian-Yi; Shen, Jian; Wu, Zhi-Yong; Shen, Jin-Hui; Li, En-Min; Xu, Li-Yan

    2013-09-01

    Opioid receptors, members of the G-protein-coupled receptor superfamily, appear to be involved in cancer progression. However, the expression and significance of opioid receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, we demonstrated by flow cytometry that μ, δ, and κ-opioid receptors (MOR, DOR, and KOR) are expressed to various degrees in ESCC cell lines. The KOR protein was further examined by several methods in ESCC cell lines and tissues. Immunocytochemical staining localized KOR to the cell membrane in KYSE180 cells and the nucleus in EC109 cells, whereas no signal or weak staining of the cytoplasm was observed in KYSE150 cells. The expression of KOR was confirmed in ESCC cells by Western blotting. Furthermore, immunohistochemistry staining showed that KOR was up-regulated in ESCC tissues compared with nontumorous esophageal epithelium (P = .004, χ(2) test). Moreover, high nuclear KOR expression was significantly correlated with lymph node metastasis in 256 ESCC cases (R = 0.144; P = .030, Kendall τB test). Patients with high nuclear KOR expression in ESCC had a significantly poorer prognosis (P = .001, log-rank test). Multivariate Cox analysis revealed that KOR in the nucleus was an independent prognostic factor (hazard ratio, 1.789; 95% confidence interval, 1.177-2.720; P = .006). Our results suggest that KOR is involved in the carcinogenesis or progression of ESCC and that nuclear KOR may be indicative of prognosis.

  12. Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xiong Wang; Yuan-Long He; Sheng-Tao Zhu; Shuo Yang; Shu-Tian Zhang

    2011-01-01

    AIM: To identify the novel methylation-silenced gene pentraxin 3 (PTX3) in esophageal squamous cell carcinoma (ESCC). METHODS: PTX3 mRNA expression was examined in six human ESCC cell lines, one human immortalized normal esophageal epithelial cell line, primary ESCC tumor tissue, and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction (RT-PCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. Methylation specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate gene. RESULTS: In the majority of ESCC cell lines, we found that PTX3 expression was down-regulated due to gene promoter hypermethylation, which was further confirmed by bisulphite genomic sequencing. Demethyl-ation treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell lines. Methylation was more common in tumor tissues (85%) than in adjacent nontumor tissues (25%) (P < 0 .01). CONCLUSION: PTX3 is down-regulated through promoter hypermethylation in ESCC, and could potentially serve as a biomarker of ESCC.

  13. Overexpression of LRIG1 regulates PTEN via MAPK/MEK signaling pathway in esophageal squamous cell carcinoma

    Science.gov (United States)

    Jiang, Xiaofang; Li, Huiwu

    2016-01-01

    The present study aimed to evaluate the role of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) in the regulation of phosphatase and tensin homolog (PTEN) expression in esophageal carcinogenesis. LRIG1 was overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines, and the effect of LRIG1 overexpression on the mRNA and protein expression levels of PTEN was evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. Furthermore, the effects of LRIG1 overexpression on the cell cycle distribution and apoptosis of ESCC cells were examined by flow cytometry. Various cell signaling pathway inhibitors were used to assess the effects of LRIG1 on downstream signaling in ESCC cell lines. In addition, the association between LRIG1 and PTEN expression was examined in 48 samples from patients with ESCC. LRIG1 overexpression was demonstrated to downregulate PTEN expression in ESCC cell lines, and promote their proliferation and inhibit apoptosis. In addition, LRIG1-mediated suppression of PTEN expression was inhibited by the U0126 inhibitor, which suggests that LRIG1 may inhibit the activation of PTEN signaling molecules by triggering the mitogen-activated protein kinase (MAPK)/MAPK kinase 1 (MEK) signaling pathway. In conclusion, the present study demonstrated that overexpression of LRIG1 significantly and adversely affected the survival of ESCC cells, and that the MAPK/MEK signaling pathway may be responsible for the repression of PTEN expression and function. PMID:27698691

  14. Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Knap, Marianne;

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...

  15. Primary management of esophageal carcinoma with radiation therapy and surgery and correlation of failure pattern based on autopsy findings

    International Nuclear Information System (INIS)

    This paper reports a study of forty-seven patients with esophageal carcinoma who were treated definitively with radiation therapy (n = 18) and radical surgery (n = 18) or received palliative treatment (n = 11) at the Medical College of Virginia between 1967 and 1982. The average intervals between diagnosis and death were 5, 7, and 4 months, respectively. Autopsy revealed that 80% with radiation therapy and 50% in the surgery group had persistent local-regional disease. Eleven of 36 had adrenal metastasis and eight of 36 had a second primary in the head, neck, lung or prostate. The data show a significant incidence of persistent disease in spite of negative surgical margins. Additional treatment with chemotherapy or postoperative radiation therapy should be considered

  16. Comparison of conformal and intensity-modulated techniques for simultaneous integrated boost radiotherapy of upper esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wei-Hua Fu; Lu-Hua Wang; Zong-Mei Zhou; Jian-Rong Dai; Yi-Min Hu; Lu-Jun Zhao

    2004-01-01

    AIM: To compare intensity-modulated radiotherapy (IMRT)with conformal radiotherapy (CRT) by investigating the dose profiles of primary tumors, electively treated regions, and the doses to organs at risk.METHODS: CRT and IMRT plans were designed for five patients with upper esophageal carcinoma. For each patient,target volumes for primary lesions (67.2 Gy) and electively treated regions (50.4 Gy) were predefined. An experienced planner manually designed one CRT plan. Four IMRT plans were generated with the same dose-volume constraints, but with different beam arrangements. Indices including dose distributions, dose volume histograms (DVHs) and conformity index were compared.RESULTS: The plans with three intensity-modulated beams were discarded because the doses to spinal cord were lager than the tolerable dose 45Gy, and the dose on areas near the skin was up to 50Gy. When the number of intensity beams increased to five, IMRT plans were better than CRT plans in terms of the dose conformity and homogeneity of targets and the dose to OARs. The dose distributions changed little when the beam number increased from five to seven and nine.CONCLUSION: IMRT is superior to CRT for the treatment of upper esophageal carcinoma with simultaneous integrated boost (SIB). Five equispaced coplanar intensity-modulated beams can produce desirable dose distributions. The primary tumor can get higher equivalent dose by SIB technique.The SIB-IMRT technique shortens the total treatment time,and is an easier, more efficient, and perhaps a less errorprone way in delivering IMRT.

  17. Diagnostic sensitivity of serum carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, and beta-human chorionic gonadotropin in esophageal carcinoma (receiver operating characteristic curve analysis

    Directory of Open Access Journals (Sweden)

    Bhawna Bagaria

    2015-01-01

    Full Text Available Background: Esophageal carcinomas are very lethal disease relatively unresponsive to therapy. The continued development of new and more effective chemotherapeutic agents and regimens offers hope that in the future, this carcinoma may be amenable to either more effective palliative treatment or possibly increased cure. We, therefore, aimed to evaluate the marker with best diagnostic sensitivity in esophageal carcinoma. Materials and Methods: Serum carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, alpha-fetoprotein (AFP, and beta-human chorionic gonadotropin (β-HCG levels were assessed in healthy subjects (n = 50 and patients (n = 50 initially diagnosed of esophageal carcinoma by endoscopic examination and biopsy before receiving any therapy. The data were analyzed using SPSS software version 10.0 (SPSS Inc. USA and MedCalc to estimate mean ± standard deviation, the significance of the observed differences (P value, for calculating sensitivity and for plotting receiver operating characteristic curves. Results: Sensitivity of CEA, CA19-9, AFP, and β-HCG detected in esophagus cancer was 38%, 18%, 10%, and 26% respectively. Conclusion: From the above studied markers, CEA has the highest sensitivity followed by β-HCG, CA19-9 and AFP. Although the sensitivity of tumor markers in esophagus cancer is low, they may be useful additional parameter in the prediction of neoplasms involved at the early stage of tumor growth.

  18. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  19. Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Wang, Li; Xing, Jie; Cheng, Rui; Shao, Ying; Li, Peng; Zhu, Shengtao; Zhang, Shutian

    2015-01-01

    Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.

  20. Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.

  1. [Effect of surgical trauma on NK cell activity in esophageal carcinoma after transmediastinal dissection vs. transthoracic en bloc resection].

    Science.gov (United States)

    Bruns, C; Schäfer, H; Wolfgarten, B; Pichlmaier, H

    1996-01-01

    In order to assess the impact of surgical trauma involved in the therapy of esophageal carcinoma on the cellular immune system, a perspective study was performed involving perioperative hematological parameters. The activity of natural killer cells and the serum concentrations of interleukin-2, interleukin-6 and TNF-alpha were measured in 12 cases of transmediastinal dissection and 10 cases of transthoracic en bloc esophageal resection and compared to values of a control group of thoracic and abdominal surgical patients with non-malignant maladies. Natural killer cells assume a central role in the non-specific immunological response in tumor patients. Their main function is the destruction of tumor cells via cytotoxic activities amplified by the release of interleukin-2 and TNF-alpha. Natural killer cell activity was measured prior to surgery and on postoperative days 4 and 10 using a standardized europium chloride release assay, utilizing K562 target cells. Lymphokines interleukin-2, interleukin-6, and TNF-alpha were also measured on postoperative days 1 and 7 using standardized ELISA assays. The activity of natural killer cells in our patient group sank significantly (P < 0.05) on postoperative day 4 and likewise in the control group and both study groups, activity sank to the original values. In the control group, natural killer cell activity averaged 45% of preoperative values, in comparison with an average of 63% following transmediastinal esophageal carcinoma resection (one cavity procedure), and transthoracic en bloc resection (two cavity procedure). On postoperative day 10, all groups displayed a significant reacceleration of natural killer cell activity (P < 0.05). Whereas transthoracic en bloc resection patients only reached 61% of preoperative values, transmediastinal dissection patients assumed 75%, and 77% was achieved by control group members. Transthoracic en bloc resection of the esophagus led to a more extreme reduction in cytotoxic cellular

  2. Insulin enhances apoptosis induced by cisplatin in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy

    Institute of Scientific and Technical Information of China (English)

    Yang Yang; Wen Fengbiao; Dang Lifeng; Fan Yuxia; Liu Donglei; Wu Kai; Zhao Song

    2014-01-01

    Background Chemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC).We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.Methods The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay.The times T1,when the number of living cells reached a plateau and T2,when the number of living cells reached a new plateau after the addition of insulin were found.T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC).Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively.Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively.Western blotting analysis was used to estimate the protein expression levels of AKT,mTOR,PI3K,PTEN,autophage related indicator LC3-Ⅱ and autophage related protein Beclin1 changes that occurred in the course of treatment.Results A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin.Insulin can increase the apoptosis induced by cisplatin.Apoptotic ratio of T1 plateau cells ((32.6±4.3)%) is significantly less than T2 plateau ((47.5±5.6)%).MDC fluorescent intensity at T1 plateau (104.9±13.2) was significantly higher than intensity at T2 plateau (82.6±10.3).After cotreatment with insulin,the expression level of LC3-Ⅱ,Beclin1 and PTEN in T2 plateau cells were significantly downregulated,but AKT,mTOR and PI3K expressions significantly upregulated compared with T1 plateau.Conclusions Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy.The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells,which may be attributed to the anticancer effects of cisplatin.

  3. Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shi Y

    2013-05-01

    Full Text Available Yan Shi, Rui Qin, Zhi-Kuan Wang, Guang-Hai DaiDepartment of Multimodality Therapy of Oncology, General Hospital of CPLA, Beijing, People's Republic of ChinaAbstract: Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX combined with cisplatin (DDP in patients with metastatic esophageal squamous cell carcinoma (ESCC. Patients with histologically confirmed ESCC were treated with Nab-PTX 250 mg/m2 and DDP 75 mg/m2 intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles. Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confidence interval: 4.0 to 8.4 months and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months. Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%, neutropenia (63.6%, leucopenia (48.5%, anemia (24.2% and sensory neuropathy (24.2%. In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC.Keywords: esophageal squamous cell carcinoma, nanoparticle albumin-bound paclitaxel, chemotherapy, metastasis

  4. Explore the related risk factors of acute respiratory failure after resection of esophageal carcinoma%食管癌术后急性呼吸衰竭的相关危险因素

    Institute of Scientific and Technical Information of China (English)

    白山

    2014-01-01

    Objective:To investigate the related risk factors of acute respiratory failure after resection of esophageal carcinoma,in order to improve the quality of life of patients after resection of esophageal carcinoma.Methods:108 cases with esophageal carcinoma were selected from February 2012 to December 2013.Analyse their clinical data retrospectively.All the patients were divided into two groups according to whether the occurrence of acute respiratory failure.48 patients in the acute respiratory failure group(ARF group) and 60 patients in the control group.Comparison of patient age,operation time,smoking history(>500/year) and other clinical information in two groups.Using univariate analysis and logistic multivariate analysis,to analyses the risk factors of acute respiratory failure after the operation of esophageal carcinoma.Results:In 108 patients with esophageal cancer,there were 48 patients occurred acute respiratory failure,and the incidence was 44.44% .Multivariate logistic analysis showed that the risk factors of acute respiratory failure after the operation of esophageal carcinoma including advanced age,smoking history, preoperative diabetes,operation time,postoperative combined thoracic complications,plasma albumin concentration decreased, second thoracotomy after operation and postoperative pain.Conclusion:Doctors and nurses should provide more targeted treatment and nursing care for patients with these risk factors,in order to improve the prognosis of patients.%目的:探讨食管癌术后急性呼吸衰竭的相关危险因素,改善食管癌患者的术后生存质量。方法:回顾性分析2012年2月-2013年12月收治食管癌患者108例的临床资料,依据术后是否发生急性呼吸衰竭进行分组,其中急性呼吸衰竭组(ARF)48例和对照组60例,比较两组患者的年龄、手术时间、吸烟史(>500支/年)等临床资料,采用单因素分析和logistic多因素分析食管癌患者术后急性呼吸衰竭的相

  5. In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To develop a fusion vaccine of esophageal carcinoma cells and dendritic cells (DC) and observe its protective and therapeutic effect against esophageal carcinoma cell line 109 (EC109). METHODS: The fusion vaccine was produced by fusing traditional polyethyleneglycol (PEG), inducing cytokine, sorting CD34+ magnetic microbead marker and magnetic cell system (MACS). The liver, spleen and lung were pathologically tested after injection of the fusion vaccine. To study the therapeutic and protective effect of the fusion vaccine against tumor EC109, mice were divided immune group and therapeutic group. The immune group was divided into P, E, D and ED subgroups, immunized by phosphate buffered solution (PBS), inactivated EC109,DC and the fusion vaccine respectively, and attacked by EC109 cells. The tumor size, weight, latent period and mouse survival period were recorded and statistically analyzed. The therapeutic group was divided into four subgroups: P, inactivated EC109,D and ED subgroups, which were attacked by EC109 and then treated with PBS, inactivated EC109,DC,and EC109-DC respectively. Pathology and flow cytometry were also used to study the therapeutic effect of the fusion vaccine against EC109 cells. RESULTS: Flow cytometry showed that the expression of folate receptor (FR), EC109, D Cs (D) in human nasopharyngeal carcinoma cell line (HNE1) (B) was 78.21%,89.50%,and 0.18%,respectively.The fusion cells were highly expressed. No tumor was found in the spleen, lung and liver after injection of the fusion vaccine. Human IgG was tested in peripheral blood lymphocytes (PBL). In the immune group, the latent period was longer in EC109-DC subgroup than in other subgroups, while the tumor size and weight were also smaller than those in ED subgroup. In the therapeutic group, the tumor size and weight were smaller in ED subgroup than in P, inactivated EC109 and DC subgroups. CONCLUSION: Fusion cells are highly expressed not only in FR but also in CD80.The fusion

  6. 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

    Institute of Scientific and Technical Information of China (English)

    Zi-Bo Song; Shan-Shan Gao; Xin-Na Yi; Yan-Jie Li; Qi-Ming Wang; Ze-Hao Zhuang; Li-Dong Wang

    2003-01-01

    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.

  7. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    OpenAIRE

    Ryuichi Kita; Toru Kimura; Hiroki Nishikawa; Yukio Osaki

    2012-01-01

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of ...

  8. Study on etiology of esophageal carcinoma:retrospect and prospect%食管癌病因学研究的回顾与展望

    Institute of Scientific and Technical Information of China (English)

    胡盛平; 杨红珊; 沈忠英

    2001-01-01

    Esophageal carcinoma is one of the top frequently occur malignant cancers, especially in Chinese.Studies on esophageal carcinoma have suggested that genetic predisposition, dietary or environmental factors, such as nitrosamine, tobacco smoking, malnutrition, trace element deficieny and fungus toxin could be important in the carcinogenesis of this cancer.%食管癌是最常见的十大恶性肿瘤之一,尤其多发生于中国人。是由环境因素和基因变异相互作用而致的多基因病。本文回顾了食管癌病因学研究的历程,并展望了其未来研究方向。

  9. INTERVENTION CHEMOTHERAPY IN COMPREHENSIVE TREATMENT OF ADVANCED NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the use of interventional chemotherapy in comprehensive treatment for advanced nasopharyngeal carcinoma. Methods: Interventional chemotherapy with multi-drugs including cisplatin (DDP) 100 mg, 5-fluorouracil (5-FU) 1000 mg and bleomycin (BLM) 16 mg was used to treat 30 cases with advanced nasopharyngeal carcinoma before radiotherapy. 50 cases that received radiotherapy alone were used as a control group. The methods, time and dose schedule of radiotherapy were similar in the two groups. Results: The primary lesions in 16 cases and the cervical lymph nodes in 12 cases were reduced in size after interventional chemotherapy. Radiation doses of those in complete response in their primary lesion and cervical lymph nodes were lower than that of the control group (P<0.05). The complete response rate of study group was 83.3% and that of control group was 72.0% (P<0.05). Conclusion: Interventional chemotherapy plus radiotherapy is a valuable treatment method in advanced nasopharyngeal carcinoma.

  10. A case of Esophageal small cell carcinoma with multiple liver metastases responding to chemotherapy with Irinotecan plus Cisplatin

    International Nuclear Information System (INIS)

    We report a case of small cell esophageal carcinoma (SCEC) with multiple liver metastases treated with some success by chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP). Radiologic and endoscopic examination of a 75-year-old man with multiple liver tumors disclosed a 4.0-cm type 2 tumor in the middle third of the esophagus. An endoscopically obtained biopsy specimen was diagnosed as undifferentiated small cell carcinoma. Multiple liver metastases were confirmed but lymph node metastases and distant metastases other than those in the liver were not detected. After six courses of chemotherapy with CPT-11 plus CDDP, the primary lesion showed complete response and liver metastases showed partial response. However, because all lesions almost immediately relapsed or progressed, arterial infusion chemotherapy for liver metastases and radiation for the primary lesion were given as second-line treatment. The primary lesion showed complete response with radiation. Arterial infusion chemotherapy prevented the progression of liver metastases once, but the patient died of liver failure at last. No distant lesions including metastatic lymph nodes were confirmed over the course of his illness, and the patient survived for a year after first diagnosis. Although the prognosis of SCEC is quite unfavorable due to highly aggressive behavior, a better prognosis is possible with effective chemotherapy and second-line treatment is important in improving prognosis

  11. The K–Cl Cotransporter KCC3 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Atsushi Shiozaki

    2014-01-01

    Full Text Available The objectives of the present study were to investigate the role of K–Cl cotransporter 3 (KCC3 in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC. Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN, and the survival rate of patients with a CN>MT score was lower than that of patients with a CN≤MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

  12. Expression of peanut agglutinin-binding mucin-type glycoprotein in human esophageal squamous cell carcinoma as a marker

    Directory of Open Access Journals (Sweden)

    Balakrishnan Ramathilakam

    2003-11-01

    Full Text Available Abstract Background The TF (Thomson – Friedenreich blood group antigen behaves as an onco-foetal carcinoma-associated antigen, showing increased expression in malignancies and its detection and quantification can be used in serologic diagnosis mainly in adenocarcinomas. This study was undertaken to analyze the sera and tissue level detectable mucin-type glycoprotein (TF-antigen by Peanut agglutinin (PNA and its diagnostic index in serum as well tissues of human esophageal squamous cell carcinoma as marker. Results We examined 100 patients for serological analysis by Enzyme Linked Lectin Assay (ELISA and demonstrated a sensitivity of 87.5%, specificity of 90% and a positive predictive value of 95%. The immuno-histochemical localization of TF antigen by Fluorescence Antigen Technique (FAT in 25 specimens of normal esophageal squamous epithelium specimens and 92 specimens with different grades of, allowed a quicker and more precise identification of its increased expression and this did not correlate with gender and tumor size. There was a positive correlation between membrane bound TF antigen expression with different histological progression, from well differentiated to poorly differentiated, determined by PNA binding. Specimens showed morphological changes and a pronounced increase in PNA binding in Golgi apparatus, secretory granules of the cytosol of well differentiated and an increased cell membrane labeling in moderately and poorly differentiated, when compared with ESCC and normal tissues. Conclusion The authors propose that the expression of TF-antigen in human may play an important role during tumorigenesis establishing it as a chemically well-defined carcinoma-associated antigen. Identification of the circulating TF-antigen as a reactive form and as a cryptic form in the healthy individuals, using PNA-ELLA and Immunohistochemical analysis of TF antigen by FAT is positively correlated with the different histological grades as a simple

  13. Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma

    OpenAIRE

    He, Jing; Zhou, Mingxia; CHEN, XINFENG; Yue, Dongli; Yang, Li; Qin, Guohui; Zhang, Zhen; Gao, Qun; Wang, Dan; Zhang, Chaoqi; Huang, Lan; Wang, Liping; Zhang, Bin; Yu, Jane; Zhang, Yi

    2016-01-01

    Background Growing evidence suggests that SALL4 plays a vital role in tumor progression and metastasis. However, the molecular mechanism of SALL4 promoting esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Methods The gene and protein expression profiles- were examined by using quantitative real-time PCR, immunohistochemistry and western blotting. Small hairpin RNA was used to evaluate the role of SALL4 both in cell lines and in animal models. Cell proliferation, apoptosis a...

  14. Postoperative Radiation Therapy With or Without Concurrent Chemotherapy for Node-Positive Thoracic Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Junqiang; Pan, Jianji [Department of Radiation Oncology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou (China); Liu, Jian, E-mail: liujianfj@yahoo.com.cn [Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou (China); Li, Jiancheng [Department of Radiation Oncology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou (China); Zhu, Kunshou [Department of Surgery, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou (China); Zheng, Xiongwei [Department of Pathology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou (China); Chen, Mingqiang [Department of Radiation Oncology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou (China); Chen, Ming [School of Graduate, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Purpose: To retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions. Methods and Materials: We retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m{sup 2}, average days 1-3, plus paclitaxel 135 mg/m{sup 2}, day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone. Results: The 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups. Conclusions: Our results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

  15. Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    YAN Hong-jiang; WANG Ren-ben; ZHU Kun-li; JIANG Shu-mei; ZHAO Wei; XU Xiao-qing; FENG Rui

    2012-01-01

    Background Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response.The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT.Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer.The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT.Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays.The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed.Overall survival (OS) was estimated by univariate and multivariate analysis.Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P=0.001 and P=0.023,respectively).It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P=0.041).By Logistic regression analysis,the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P=0.002).The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P=0.001).In multivariate analysis,a low level of CYFRA21-1 was the most significant independent predictor of good OS (P=0.007).Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT.CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

  16. PIK3CA gene mutations and overexpression: implications for prognostic biomarker and therapeutic target in Chinese esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available To evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese esophageal squamous cell carcinoma (ESCC patients, and their correlation with clinicopathological characteristics and clinical outcomes.Direct sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in 406 Chinese ESCC patients. PIK3CA expression was evaluated using immunohistochemistry analysis. The associations of PIK3CA gene mutations and PIK3CA expression with clinicopathological characteristics and clinical outcome were examined.Thirty somatic point mutations (30/406, 7.4% were identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA mutations were not correlated with clinicopathological characteristics or clinical outcomes. However in the ESCC patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival (multivariate hazard ratio (HR = 10.493, 95% CI: 2.432-45.267, P = 0.002. Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in cancer tissue (P<0.001. PIK3CA overexpression was independently associated with higher risk of local recurrence (multivariate HR  = 1.435, 95% CI: 1.040-1.979, P = 0.028. In female ESCC patients, PIK3CA overexpression was independently correlated with worse overall survival (multivariate HR  = 2.341, 95% CI: 1.073-5.108, P = 0.033.Our results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.

  17. MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma cells by targeting BMI1.

    Science.gov (United States)

    Wang, Ting; Chen, Tengfei; Niu, Hua; Li, Chang; Xu, Chun; Li, Yuanyuan; Huang, Rui; Zhao, Jun; Wu, Shuyan

    2015-07-01

    MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes. In the present study, we found that the expression level of miR-218 was significantly reduced in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. Moreover, its expression was found to correlate with the clinicopathological stage of ESCC; miR-218 expression was lower in the stage III tissue samples than in the stage I and II tissue samples. Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis. Western blot analysis and luciferase reporter assay revealed that miR-218 decreased BMI1 expression by binding to the putative binding sites in its 3'-untranslated region (3'-UTR). The BMI1 mRNA expression levels were markedly increased and negatively correlated with the miR-218 expression level in the ESCC tissues. Functional analyses revealed that the restoration of miR-218 expression inhibited ESCC cell proliferation, migration and invasion and promoted apoptosis. The knockdown of BMI1 by siRNA showed the same phenocopy as the effect of miR-218 on ESCC cells, indicating that BMI1 was a major target of miR-218. In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC. Therefore, miR-218 may prove to be a useful biomarker for monitoring the initiation and development of ESCC, and may thus be an effective therapeutic target in ESCC.

  18. Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

    Science.gov (United States)

    Zeng, Rong; Huang, Jun-Peng; Li, Xu Feng; Xiong, Wei-Bin; Wu, Gang; Jiang, Zhao-Jing; Song, Shu-Jie; Li, Ji-Qiang; Zheng, Yan-Fang; Zhang, Ji-Ren

    2016-04-01

    EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

  19. Cyclooxygenase-2, a Potential Therapeutic Target, Is Regulated by miR-101 in Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Ying Shao

    Full Text Available Cyclooxygenase-2 (COX-2 is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC. There are no reports on whether microRNAs (miRNAs regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC.Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8, transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA. The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC.Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001, as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001. Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001. The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR-101.Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC.

  20. Early response to neoadjuvant chemotherapy in advanced esophageal cancer evaluated by computed tomography predicts the utility of a second cycle of chemotherapy

    OpenAIRE

    MOTOORI, MASAAKI; Yano, Masahiko; Yasuda, Takushi; Miyata, Hiroshi; PENG, YINGFENG; YAMASAKI, MAKOTO; SHIRAISHI, OSAMU; Tanaka, Koji; Ishikawa, Osamu; SHIOZAKI, HITOSHI; Doki, Yuichiro

    2013-01-01

    Multi-course neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment for advanced esophageal cancer. However, non-responders may continue to receive ineffective treatment, since there are no definitive criteria for early discontinuation of NACT. In this study, we analyzed 103 advanced esophageal cancer patients treated with 2 cycles of NACT followed by surgery. Patients with >20% decrease in the size of the primary tumor as evaluated by computed tomography (CT) following ...

  1. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.

  2. High pathologic complete remission rate from induction docetaxel, platinum and fluorouracil (DCF) combination chemotherapy for locally advanced esophageal and junctional cancer.

    Science.gov (United States)

    Noronha, Vanita; Joshi, Amit; Jandyal, Sunny; Jambhekar, Nirmala; Prabhash, Kumar

    2014-09-01

    Adding docetaxel to the cisplatin/5-fluorouracil induction regimen for locally advanced esophageal and GEJ cancer may increase the pathologic complete remission (pCR) rate, leading to an improved outcome. Institutional ethics committee approved the protocol of retrospective analysis of patients with locally advanced esophageal and GEJ carcinoma, who received 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil (DCF) induction chemotherapy with primary growth factors and prophylactic antibiotics. Following chemotherapy, a restaging scan was performed. If disease was deemed resectable, surgery was performed. Between February 2010 and October 2013, 31 patients received induction DCF. Ninety-four percent patients had squamous histology. Response rate was 81 %: complete remission (CR)-23 % and partial remission-58 %. Eighty-seven percent patients underwent surgery; R0 resection rate was 67 %. pCR occurred in 26 %. Common grade 3/4 toxicities included anemia-23 %, neutropenia-42 %, febrile neutropenia-39 %, diarrhea-39 %, hyponatremia-55 % and hypokalemia-39 %. There were no toxic deaths. At a median follow-up of 34 months (95 % CI 31.3-36.6), estimated median progression-free survival (PFS) was 27 months (95 % CI 11-39) and the overall survival (OS) at 1 year, 2 years and 3 years was 80, 68 and 55 %, respectively. Patients who attained pCR had a significant longer PFS and OS; median PFS and OS were not reached in patients with pCR and were 15 months (95 %CI 8.4-21.5 months), P = 0.012 and 25 months (95 %CI 10.3-39.7), P = 0.023, respectively, in patients who did not attain a pCR. DCF induction chemotherapy leads to pCR of 26 %, which rivals that obtained from chemoradiotherapy. Toxicity is substantial but manageable with adequate supportive care.

  3. Prospective randomized study on inductive chemotherapy plus radiotherapy for patients with upper and middle esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of radiotherapy combined with inductive chemotherapy for patients with upper and middle esophageal cancer. Methods: 162 patients with upper and middle esophageal cancer were randomized into two groups, with 82 treated by inductive chemotherapy combined with radiotherapy (C + R) and 80 by radiotherapy alone (R). The chemotherapy regimen included 5-fluorouracil 500 mg/m2 on d1-d5 by continuous infusion for 120 hours, cisplatin 60 mg/m2 on dl and bleomycin A5 8 mg on d1, d3, d5 intravenously. Three to seven days after chemotherapy, the patients were irradiated with anteroposterior (AP) and posteroanterior (PA) fields to a dose of 40-44 Gy in 4.0-4.4 weeks followed by a boost of 24-28 Gy in 2.4-2.8 weeks through oblique fields. Results: The 5- and 10-year survival rates were 22.0%, 15.9% for the C + R group and 13.8%, 8.8% for the R group. The difference was statistically significant (P = 0.034). The toxic and side effects were tolerable and similar in the two groups. Nineteen patients (23%) in the C + R group and thirty-one (39%) in the R group died from distant metastasis and/or lymph node metastasis, even though the difference was not statistically significant (x2 = 3.47, P > 0.05). Conclusions: Inductive chemotherapy with 5-fluorouracil, cisplatin, bleomycin A5 plus radiotherapy may improve the outcome of esophageal cancer, with the toxic and side effects of the combined modality severer than radiation along, but they are well tolerated

  4. Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai'an population, China

    Institute of Scientific and Technical Information of China (English)

    LIU Ran; YIN Li-hong; PU Yue-pu

    2007-01-01

    Background Cytochrome P450 2E1 (CYP2E1) has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 Rsal and Dral polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA.Methods Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79healthy controls matched in age, gender and residence were recruited for the control study. An Rsal polymorphism in the 5'-flanking region and a Dral polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR.Results No significant association of Rsal or Dral polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated (OR=1.67, 95% CI: 0.89-3.15, P=0.11; OR=1.11, 95% CI: 0.59-2.09,P=0.74, respectively). With SHEsis software, no linkage disequilibrium was detected between Rsal and Dral polymorphism (D'=0.528,r2=0.27). When combined Rsal polymorphism with Dral polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found (OR=5.77, 95% CI: 1.65-20.22). Compared with the normal controls, the mRNA levels with Rsal polymorphism, Dral polymorphism, or any combined genotypes in cases showed no statistical difference.Conclusions This study suggests that carryingc2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.

  5. Value of endoscopic methylene blue and Lugol's iodine double staining and detection of GST-n and telomerase in the early diagnosis of esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xuan Zhu; Shuang-Hong Zhang; Kun-He Zhang; Bi-Ming Li; Jiang Chen

    2005-01-01

    AIM: To explore the expressions of GST-n and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue(MB) and Lugol's iodine double staining.METHODS: Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol's iodine in proper order and the areas stained blue and brown,and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining,biopsy specimen was obtained. GST-n and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively.RESULTS: After MB and Lugol's iodine staining, the area between both the colors was obtained in 64 of the 72patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology(P<0.005). The expression of GST-n and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-n and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium (P<0.005). The expression in hyperplasia was slightly higher than that in normal epithelium.With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased (P<0.025).Expression of GST-n was correlated with that of telomerase activity in dysplasia and carcinoma ((ψ) = 0.4831, P<0.005;(ψ) = 0.3031, P<0.025, respectively); but there was no correlation between them in normal epithelium and hyperplasia.CONCLUSION: The expression of GST-n and telomerase may be an early event in the carcinogenesis of esophagus.They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol's iodine double staining and detection of GST-n and

  6. High immunosuppressive burden in advanced hepatocellular carcinoma patients

    OpenAIRE

    Lugade, Amit A.; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2013-01-01

    The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

  7. Maximum standardized uptake value on PET/CT in preoperative assessment of lymph node metastasis from thoracic esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Amos JM Ela Bella; Ya-Rui Zhang; Wei Fan; Kong-Jia Luo; Tie-Hua Rong; Peng Lin; Hong Yang; Jian-Hua Fu

    2014-01-01

    The presence of lymph node metastasis is an important prognostic factor for patients with esophageal cancer. Accurate assessment of lymph nodes in thoracic esophageal carcinoma is essential for selecting appropriate treatment and forecasting disease progression. Positron emission tomography combined with computed tomography (PET/CT) is becoming an important tool in the workup of esophageal carcinoma. Here, we evaluated the effectiveness of the maximum standardized uptake value (SUVmax) in assessing lymph node metastasis in esophageal squamous cell carcinoma (ESCC) prior to surgery. Fifty-nine surgical patients with pathologically confirmed thoracic ESCC were retrospectively studied. These patients underwent radical esophagectomy with pathologic evaluation of lymph nodes. They al had 18F-FDG PET/CT scans in their preoperative staging procedures. None had a prior history of cancer. The pathologic status and PET/CT SUVmax of lymph nodes were col ected to calculate the receiver operating characteristic (ROC) curve and to determine the best cutoff value of the PET/CT SUVmax to distinguish benign from malignant lymph nodes. Lymph node data from 27 others were used for the validation. A total of 323 lymph nodes including 39 metastatic lymph nodes were evaluated in the training cohort, and 117 lymph nodes including 32 metastatic lymph nodes were evaluated in the validation cohort. The cutoff point of the SUVmax for lymph nodes was 4.1, as calculated by ROC curve (sensitivity, 80%; specificity, 92%;accuracy, 90%). When this cutoff value was applied to the validation cohort, a sensitivity, a specificity, and an accuracy of 81%, 88%, and 86%, respectively, were obtained. These results suggest that the SUVmax of lymph nodes predicts malignancy. Indeed, when an SUVmax of 4.1 was used instead of 2.5, FDG-PET/CT was more accurate in assessing nodal metastasis.

  8. Esophageal carcinoma extending into the spinal canal - case report and review of the literature; Carcinoma do esofago com invasao do canal medular - relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Urban, Linei A.B.D.; Rogacheski, Enio; Ledesma, Jorge A. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia]. E-mail: radiohc@terra.com.br; Zaparolli, Mauricio; Duarte, Maria Cecilia B. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas; Sakamoto, Danielle G. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Anatomia Patologica

    2002-06-01

    The authors report the case of a 62-year-old male with a 4 month history of weight loss and a 2 day complaint of weakness and paraesthesia on the lower limbs. A computed tomography myelogram revealed a mass in the posterior mediastinum associated with destruction of the vertebral body, spinal canal extension and irregular esophageal wall thickening. The patient was later submitted to a barium esophagogram that showed an irregular filling defect. A biopsy confirmed the presence of a squamous cell carcinoma. This is the first report in the Latin-American literature (Lilacs) of a patient with an esophageal carcinoma with spinal canal extension and spinal cord compression syndrome at initial presentation. (author)

  9. 食管鳞癌K-ras、EGFR和B-raf突变的初步研究%A preliminary study on K-ras, EGFR, and B-raf mutations of esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Huili Ma; Yongfei Xue; Changsheng Li; Jingwei Zhang; Zhonghai Ren

    2011-01-01

    Objective:Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients'life.Meanwhile,molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts.However,little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma.This paper,therefore,intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR,K-ras and B-raf in the esophageal squamous cell carcinoma tissues.Methods:Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected.Pyrophosphate was used for observing the mutations of EGFR,K-ras and B-raf in the esophageal squamous cell carcinoma tissues.Results:Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes,codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes.No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35),all of codon 12 in K-ras genes were wild-type without any mutation,while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35).Conclusion:In treating esophageal squamous cell carcinoma patients,all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.

  10. Aldesleukin in advanced renal cell carcinoma.

    Science.gov (United States)

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

  11. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-01-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800–1800 cm−1) and high-wavenumber (HW)(2800–3600 cm−1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy. PMID:26243571

  12. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-08-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm-1) and high-wavenumber (HW)(2800-3600 cm-1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.

  13. The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.

    Science.gov (United States)

    Yang, Pei-Wen; Chiang, Tzu-Hsuan; Hsieh, Ching-Yueh; Huang, Ya-Chuan; Wong, Li-Fan; Hung, Mien-Chie; Tsai, Jui-Chang; Lee, Jang-Ming

    2015-12-01

    Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

  14. Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

    International Nuclear Information System (INIS)

    Transforming growth factor β (TGFβ) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFβ receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages. Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas. The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor. The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma

  15. Oral verrucous carcinoma arising from lichen planus and esophageal squamous cell carcinoma in a patient with hepatitis C virus-related liver cirrhosis-hyperinsulinemia and malignant transformation: A case report.

    Science.gov (United States)

    Nagao, Yumiko; Sata, Michio

    2013-01-01

    Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral cancer. In Japan, the association of OLP with hepatitis C virus (HCV) infection is well documented. In the present study, a case of oral verrucous carcinoma arising from OLP coexisting vulvo-vaginal-gingival syndrome and esophageal squamous cell carcinoma (SCC) in a patient with HCV-related liver cirrhosis is reported. A 71-year old, non-smoking Japanese woman presented with lesions of OLP affecting the bilateral buccal mucosa, tongue, gingival, palate, oral floor and lower lip. Ten years later, an exophytic mass developed in the mandibular alveolar mucosa, the right buccal mucosa and the right lower lip. Pathological diagnosis confirmed the presence of verrucous carcinoma. However, she developed esophageal rather than oral cancer. The oral cancer was resected surgically three times and the patients underwent radiotherapy. The esophageal cancer was removed by endoscopic submucosal dissection. The risk of carcinogenesis increased as hyperinsulinemia continued. The results suggested that it is necessary to monitor for malignant changes in patients with OLP lesions and HCV infection. In addition, treatment requires the cooperation of various medical specialists, as well as an oral surgeon. PMID:24648893

  16. Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

    Directory of Open Access Journals (Sweden)

    Sho Sato

    Full Text Available BACKGROUND: Refluxogenic effects of smoking and alcohol abuse may be related to the risk of esophageal squamous cell carcinoma (ESCC. The present study attempts to clarify the effects of continuous taurocholic acid (TCA exposure, which is neither mutagenic nor genotoxic, on ESCC progression. METHODS: A squamous carcinoma cell line (ESCC-DR was established from a tumor induced in a rat model of gastroduodenal reflux. ESCC-DR cells were incubated with 2 mM TCA for ≥2 months. The effects of continuous TCA exposure were evaluated in vitro on cell morphology, growth, and invasion and in vivo on xenograft tumor growth in nude mice. Moreover, the mean level of secreted transforming growth factor (TGF-β1 and vascular endothelial growth factor (VEGF proteins in cell culture supernatants and mRNA synthesis of TGF-β1 and VEGF-A of ESCC cells were measured. The angiogenic potential was further examined by a migration assay using human umbilical vein endothelial cells (HUVECs. RESULTS: Continuous TCA exposure induced marked formation of filopodia in vitro. Expression levels of angiogenic factors were significantly higher in the cells treated with TCA than in control cells. Tumor xenografts derived from cells pre-exposed to TCA were larger and more vascularized than those derived from control cells. In addition, TCA exposure increased HUVEC migration. CONCLUSION: Continuous TCA exposure enhanced ESCC progression due to reduced cell loss in vivo. Cell loss was inhibited by TCA-induced vascular endothelial cell migration, which was mediated by TGF-β1 and VEGF-A released from ESCC cells.

  17. A novel tumor suppressor gene ECRG4 interacts directly with TMPRSS11A (ECRG1 to inhibit cancer cell growth in esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhou Yun

    2011-02-01

    Full Text Available Abstract Background The esophageal carcinoma related gene 4 (ECRG4 was initially identified and cloned from human normal esophageal epithelium in our laboratory (GenBank accession no.AF325503. ECRG4 has been described as a novel tumor suppressor gene associated with prognosis in esophageal squamous cell carcinoma (ESCC. Methods In this study, binding affinity assay in vitro and co-immunoprecipitation experiment in vivo were utilized to verify the physical interaction between ECRG4 and transmembrane protease, serine 11A (TMPRSS11A, also known as ECRG1, GenBank accession no. AF 071882. Then, p21 protein expression, cell cycle and cell proliferation regulations were examined after ECRG4 and ECRG1 co-transfection in ESCC cells. Results We revealed for the first time that ECRG4 interacted directly with ECRG1 to inhibit cancer cell proliferation and induce cell cycle G1 phase block in ESCC. Binding affinity and co-immunoprecipitation assays demonstrated that ECRG4 interacted directly with ECRG1 in ESCC cells. Furthermore, the ECRG4 and ECRG1 co-expression remarkably upregulatd p21 protein level by Western blot (P Conclusions ECRG4 interacts directly with ECRG1 to upregulate p21 protein expression, induce cell cycle G1 phase block and inhibit cancer cells proliferation in ESCC.

  18. Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma. Early results of a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei-Wei [Fudan University, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai (China); Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Department of Radiation Oncology, Shanghai (China); Zhu, Zheng-Fei; Zhao, Kuai-Le; Mao, Jing-Fang; Wu, Kai-Liang; Yang, Huan-Jun; Fan, Min; Zhao, Sen [Fudan University, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai (China); Fu, Xiao-Long [Fudan University Cancer Hospital, Department of Radiation Oncology, Shanghai (China); Fudan University, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai (China); Welsh, James [The University of Texas MD Anderson Cancer Center, Departments of Radiation Oncology, Houston, Texas (United States)

    2014-11-15

    The safety and efficacy of using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with esophageal squamous cell carcinoma were evaluated in a single-institution phase II setting. Between June 2007 and October 2009, 45 patients underwent concurrent chemoradiotherapy (n = 27) or radiotherapy alone (n = 18). Two planning target volumes (PTV) were defined for the SIB: PTV{sub C} and PTV{sub G}, with prescribed doses of 50.4 Gy to the PTV{sub C} (1.8 Gy/fraction) and 63 Gy to the PTV{sub G} (2.25 Gy/fraction), both given in 28 fractions. At a median follow-up interval of 20.3 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 42.2 and 40.7 %, respectively. The median overall survival time was 21 months; locoregional control rates were 83.3 % at 1 year and 67.5 % at 3 years. According to CTCAE (version 3.0) criteria, none of the patients developed grade 4-5 toxicity. The most common grade 2 and 3 radiation-related toxicity was radiation esophagitis, occurring in 64 % of all patients (but only 13 % as grade 3). No patient developed grade > 2 pulmonary complications. SIB-IMRT is a feasible therapeutic approach for esophageal carcinoma patients and provides encouraging locoregional control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies. (orig.) [German] Die Wirksamkeit und Effektivitaet einer intensitaetsmodulierten Radiotherapie mit einem simultan integrierten Boost (SIB-IMRT) fuer Patienten mit Oesophaguskarzinom wurde in einer Single-Institution-Phase-II-Studie bewertet. Zwischen Juni 2007 und Oktober 2009 wurden 45 Patienten mit einer simultanen Radiochemotherapie (n = 27) oder einer alleinigen Strahlentherapie (n = 18) behandelt. Zwei Planungszielvolumen (PTV) wurden fuer die SIB definiert: PTV{sub C} und PTV{sub G}, mit vorgeschriebenen Dosen von 50,4 Gy fuer PTV{sub C} (1,8 Gy/Fraktion) und 63 Gy

  19. HPV Infection in Esophageal Squamous Cell Carcinoma and Its Relationship to the Prognosis of Patients in Northern China

    Directory of Open Access Journals (Sweden)

    Fangli Cao

    2014-01-01

    Full Text Available Purpose. Human papillomavirus (HPV as a risk factor for esophageal squamous cell carcinoma (ESCC has previously been studied, but importance of HPV status in ESCC for prognosis is less clear. Methods. A total of 105 specimens with ESCC were tested by in situ hybridization for HPV 16/18 and immunohistochemistry for p16 expression. The 5-year overall survival (OS and progression-free survival were calculated in relation to these markers and the Cox proportional hazards model was used to determine the hazard ratio (HR of variables in univariate and multivariate analysis. Results. HPV was detected in 27.6% (29 of the 105 patients with ESCC, and all positive cases were HPV-16. Twenty-five (86.2% of the 29 HPV-positive tumors were stained positive for p16. HPV infected patients had better 5-year rates of OS (65.9% versus 43.4% among patients with HPV-negative tumors; P = 0.002 by the log-rank test and had a 63% reduction in the risk of death (adjusted HR = 0.37, 95% CI = 0.16 to 0.82, and P = 0.01. Conclusions. HPV infection may be one of many factors contributing to the development of ESCC and tumor HPV status is an independent prognostic factor for survival among patients with ESCC.

  20. Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma.

    Science.gov (United States)

    Thépot, Amélie; Hautefeuille, Agnès; Cros, Marie-Pierre; Abedi-Ardekani, Behnoush; Pétré, Aurélia; Damour, Odile; Krutovskikh, Vladimir; Hainaut, Pierre

    2010-11-01

    TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of DeltaNp63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA in ESCC cell lines resulted in a similar shift, characterized by increased expression of component of tight junctions, decreased cell-to-cell communication and downregulation of cell proliferation. These results indicate that DeltaNp63 may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion patterns compatible with cell proliferation. PMID:20127860

  1. Invasive and prognostic significance of pRB in esophageal squamous cell carcinoma: a meta-analysis.

    Science.gov (United States)

    Wang, M-T; Zhang, J-J; Xu, L-Y; Cao, J; Chen, S; Ma, C-S; Fang, Z-M; Meng, L-Y; Lan, B; Li, E-M

    2013-01-01

    This paper investigates the association between protein retinoblastoma (pRB) loss and the T,N stage and prognosis in esophageal squamous cell carcinomas (ESCCs) using meta-analysis. We conducted a meta-analysis of 16 studies, comprising 1,117 patients to clarify this issue. All the studies searched by the electronic literature PubMed and http://www.KJEBM.com, which had been published during the period from January 1996 to January 2012 according to the inclusion criteria. Summary odds ratios (OR) were calculated using fixed or random-effects models. The summary odds ratios (ORs) for pRB inactive were 0.64 (95% confidence interval [CI]:0.45-0.91, P = 0.01) for T1/T2 versus T3/T4 tumors; summary OR = 0.69 (95% CI:0.51-0.94, P = 0.02) for N0 versus N1 tumors. The association between pRB loss and prognosis was examined in nine studies, and the summary hazard ratio was 1.39 (95% CI:1.11-1.74, P = 0.004). pRB inactive was significant associated with T3/T4 tumors and N1 stage as well as adverse prognosis for ESCCs. It appears warranted to prospectively validate that pRB loss may be used for subdividing the T,N stage evaluation of patients with ESCCs, and these patients may be the preponderant people for individualized treatment or target therapy.

  2. miR-1179 promotes cell invasion through SLIT2/ROBO1 axis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Lixin; Wang, Yongfang; Rong, Yaxiong; Xu, Lianhong; Chu, Ying; Zhang, Ying; Yao, Yonghua

    2015-01-01

    MiR-1179, a new identified miRNA highly associated with metastasis of colorectal cancer which was never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of miR-1179 and the candidate target gene in tissues from 40 patients with ESCC. Transwell, Dual-luciferase reporter assay and immunocytochemistry assay were employed to detect the function role of miR-1179 in vitro. We found that miR-1179 was up-regulated in human ESCC tumor tissues. Bioinformatics analysis indicated that SLIT2 acting as a new potential target of miR-1179 which was confirmed by luciferase reporter assay. Down-regulation of miR-1179 suppressed cell invasion in vitro with an increasing level of SLIT2 and ROBO1, besides, the up-regulation of SLIT2 decreased cell invasion through ROBO1. Taken together, these findings will shed light the role to mechanism of miR-1179 in regulating cell invasion via SLIT2/ROBO1 axis.

  3. High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaoyu Liao

    2015-07-01

    Full Text Available Lysosomal-associated membrane protein 3 (LAMP3, identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR. LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC. Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001. LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037. Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010 and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006. In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.

  4. Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells.

    Science.gov (United States)

    Hao, Jia-Jie; Gong, Ting; Zhang, Yu; Shi, Zhi-Zhou; Xu, Xin; Dong, Jin-Tang; Zhan, Qi-Min; Fu, Song-Bin; Wang, Ming-Rong

    2013-01-15

    Chromosomal rearrangements and involved genes have been reported to play important roles in the development and progression of human malignancies. But the gene rearrangements in esophageal squamous cell carcinoma (ESCC) remain to be identified. In the present study, array-based comparative genomic hybridization (array-CGH) was performed on the ESCC cell line KYSE150. Eight disrupted genes were detected according to the obviously distinct unbalanced breakpoints. The splitting of these genes was validated by dual-color fluorescence in-situ hybridization (FISH). By using rapid amplification of cDNA ends (RACE), genome walking and sequencing analysis, we further identified gene disruptions and rearrangements. A fusion transcript DTL-1q42.2 was derived from an intrachromosomal rearrangement of chromosome 1. Highly amplified segments of DTL and PTPRD were self-rearranged. The sequences on either side of the junctions possess micro-homology with each other. FISH results indicated that the split DTL and PTPRD were also involved in comprising parts of the derivative chromosomes resulted from t(1q;9p;12p) and t(9;1;9). Further, we found that regions harboring DTL (1q32.3) and PTPRD (9p23) were also splitting in ESCC tumors. The data supplement significant information on the existing genetic background of KYSE150, which may be used as a model for studying these gene rearrangements.

  5. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Ferdous Rastgar Jazii; Zahra Najafi; Reza Malekzadeh; Thomas P Conrads; Abed Ali Ziaee; Christian Abnet; Mansour Yazdznbod; Ali Asghar Karkhane; Ghasem H Salekdeh

    2006-01-01

    AIM: To assess the proteome of normal versus tumor tissue in squamous cell carcinoma of the esophagus(SCCE) in Iranian patients and compare our results with former reports by using proteomics.METHODS: Protein was extracted from normal and tumor tissues. Two dimensional electrophoresis was carried out and spots with differential expression were identified with mass spectrometry. RNA extraction and RT-PCR along with immunodetection were performed.RESULTS: Fourteen proteins were found whose expression levels differed in tumor compared to normal tissues. Mass spectrometric analysis resulted in the identification of β-tropomyosin (TMβ), myosin light chain 2 (and its isoform), myosin regulatory light chain 2,peroxyredoxin 2, annexin I and an unknown polypeptide as the down regulated polypeptides in tumor tissue. Heat shock protein 70 (HSP70), TPM4-ALK fusion oncoprotein 2, myosin light polypeptide 6, keratin I, GH16431p and calreticulin were the up-regulated polypeptides found in tumor tissue. Several of these proteins, such as TMβ,HSP70, annexin I, calreticulin, TPM4-ALK and isoforms of myosins, have been well recognized in tumorigenesis of esophageal or other types of cancers.CONCLUSION: Our study not only supports the involvement of some of the formerly reported proteins in SCCE but also introduces additional proteins found to be lost in SCCF, including TMβ.

  6. Intake of fruit and vegetables and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies.

    Science.gov (United States)

    Liu, Jun; Wang, Jian; Leng, Ye; Lv, Changxing

    2013-07-15

    Quantification of the association between the intake of fruit and vegetables and risk of esophageal squamous cell carcinoma (ESCC) is controversial even though several studies have explored this association. We summarized the evidence from observational studies in categorical, linear and non-linear dose-response meta-analyses. Eligible studies published up to 31 July 2012 were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Random-effects models were used to calculate summary relative risks (SRRs) and the corresponding 95% confidence intervals (CIs). A total of 32 studies involving 10,037 cases of ESCC were included in this meta-analysis. The SRRs for the highest vs. lowest intake were 0.56 (95% CI: 0.45-0.69) for vegetable intake and 0.53 (95% CI: 0.44-0.64) for fruit intake (pheterogeneity vegetables (pnon-linearity =0.041). There was no evidence of publication bias. These data support the hypothesis that intakes of vegetables and fruit may significantly reduce the risk of ESCC. Further investigation with prospective designs, validated questionnaires and good control of important confounders is warranted.

  7. Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition.

    Science.gov (United States)

    Cui, Fei; Wu, Duoguang; He, Xiaotian; Wang, Wenjian; Xi, Jingle; Wang, Minghui

    2016-08-01

    The biology of esophageal squamous cell carcinoma (ESCC) remains poorly understood. Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether SPRY4-IT1 is involved in ESCC remains poorly understood. To investigate the role of SPRY4-IT1 in ESCC, we evaluated the SPRY4-IT1 expression levels in a series of ESCC patients and a panel of ESCC cell line using qRT-PCR. CCK8 and colony formation assay were performed to assess the effect of SPRY4-IT1siRNA on cell proliferation, migration, and invasion of ESCC cell lines. SPRY4-IT1 expression was upregulated in ESCC tissues and the higher expression of SPRY4-IT1 was significantly correlated with tumor grade, depth of invasion, and lymph node metastasis. Moreover, silencing of SPRY4-IT1 expression inhibited ESCC cell proliferation, colony formation, migration, and invasion. Therefore, our study indicates that SPRY4-IT1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC.

  8. MicroRNA-338-3p suppresses tumor growth of esophageal squamous cell carcinoma in vitro and in vivo.

    Science.gov (United States)

    Li, Xinyu; Li, Zhihong; Yang, Guiyun; Pan, Zhenxiang

    2015-09-01

    Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal squamous cell carcinoma (ESCC) and are crucial in tumorigenesis, among which miR‑338‑3p has been examined to be downregulated in patients with ESCC. However, the role of miR‑338‑3p in ESCC remains to be elucidated. In the present study, the role of miR‑338‑3p on the growth and survival of an ESCC cell line was determined with several in vitro approaches and in nude mouse models. It was determined that miR‑338‑3p expression was frequently downregulated in ESCC tissue compared with corresponding adjacent non‑tumor tissue, and that its expression was significantly correlated with tumor stage and metastasis. Overexpression of miR‑338‑3p in ESCC cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell arrest at the G0/G1 stage and cell apoptosis in vitro. In addition, it was demonstrated that overexpression of miR‑338‑3p significantly suppresses tumor growth of xenograft tumors in mice (PESCC, and its dysregulation may be involved in the initiation and development of human ESCC. In addition, it was suggested that miR‑338‑3p may be a potential therapeutic agent for treatment of ESCC.

  9. Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Yin, Yachao; Dou, Xiaoyan; Duan, Shimiao; Zhang, Lei; Xu, Quanjing; Li, Hongwei; Li, Duojie

    2016-09-30

    Radiation therapy is one of the most important methods of contemporary cancer treatment. Cells in the G2 and M phases are more sensitive to radiation therapy, and cell division cycle 25 homolog C (CDC25C) is essential in shifting the cell cycle between these two phases. In this study, the knockdown of CDC25C in human esophageal squamous carcinoma EC9706 cells was mediated by transfecting shRNA against human CDC25C-subcloning into pGV248. The levels of CDC25C mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Moreover, cell proliferation and radiosensitivity were measured. Stable CDC25C-knockdown EC9706 cell lines were successfully established. Furthermore, the proliferation of both control and CDC25C-shRNA-EC9706 cells was inhibited after the cells were treated with increasing X-ray doses, and the proliferation of the control cells was affected more significantly (p<0.05). Moreover, cell colony formation assays allowed us to reach the same conclusion. Taken together, our experiments demonstrated that the knockdown of CDC25C can reduce both the radiotherapy sensitivity and the proliferation activity of EC9706 cells. Thus, CDC25C might be a potential biomarker for radiotherapy treatment. PMID:27188256

  10. Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Cong; Li, Qingbao; Liu, Fang; Chen, Xuan; Nesa, Effat Un; Guan, Shanghui; Liu, Bowen; Han, Lihui; Tan, Bingxu; Wang, Ding; Chen, Pengxiang; Liu, Xiaoyue; Zhang, Han; Sun, Ying; Cheng, Yufeng

    2016-09-01

    We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC. PMID:27152453

  11. P73、ER、PR在食管癌及癌前病变中的表达及临床意义%Expression of p73, ER and PR in esophageal carcinoma and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    樊圣; 艾杰; 王军

    2006-01-01

    Objective: To test the expression of mutant p73, p53, ER and PR proteins in the esophageal normal mucosa, hyperplasia, dysplasia and squamous cell carcinoma, and research the clinically pathological significance and the correlation, for the early diagnosis, prognostic measure and therapy in clinic. Methods: With Immunohistochemistry, it was examined to show these tumor markers' expression in different epithelial lesions of 40 esophageal squamous cell carcinomas, 14 dysplasias, 14 hyperplasias and 14 normal mucosas. Results: The expression of p73 was 55%, 21%, 0% and 0% in the esophageal carcinoma, dysplasia, hyperplasia and normal mucosa, respectively. The significant difference in expression of p73 (P<0.001)was observed between the esophageal normal mucosia, hyperplasia, dysplasia and esophageal squamous cell carcinoma with Fisher's exact test. Difference in expression of p73 (P<0.05) was observed between the esophageal squamous cell carcinoma and dysplasia with χ2 test. The expression of p73 showed non-correlation with the patient's age, sex, tumor's grade, lymph-node metastasis and invasive depth (P>0.05); Similarly, the expression of mutant p53 was 67.5%, 35.7%, 7% and 0%, respectively; In like manner, the expression of ER was 55%, 21.4%, 14.2% and 0%, respectively; The expression of PR was 57.5%,14.28%, 0%and 0%, respectively. The significant difference in expression of PR (P<0.001) was observed with Fisher's exact test. Difference in expression of PR (P<0.05) was observed between the esophageal squamous cell carcinoma and dysplasia with χ2 test. The expression of PR (P<0.05) was correlated with lymph-node metastasis, and showed non-correlation with the patient's age, sex, tumor's grade, and invasive depth (P>0.05). Moreover, over-expression of mutant p53 and p73 showed significant correlation with ER and PR protein's positive expression (P<0.05). Conclusion: P73 protein may become a new tumor's marker to diagnose esophageal squamous cell

  12. Evolution of systemic therapy of advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Thomas Yau; Pierre Chan; Richard Epstein; Ronnie T Poon

    2008-01-01

    Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients.Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.

  13. CT ASSESSMENT OF RESECTABILITY PRIOR TO TRANSHIATAL ESOPHAGECTOMY FOR ESOPHAGEAL GASTROESOPHAGEAL JUNCTION CARCINOMA

    NARCIS (Netherlands)

    VANOVERHAGEN, H; LAMERIS, JS; BERGER, MY; KLOOSWIJK, AIJ; TILANUS, HW; VANPEL, R; SCHUTTE, HE

    1993-01-01

    The ability of preoperative CT to assess resectability and to stage carcinoma of the esophagus and gastroesophageal junction was studied in 71 patients who underwent transhiatal esophagectomy. Patients with preoperatively proven distant metastases who did not have surgery were not included in the pr

  14. Target volume delineation in individualized radiotherapy of non-surgical esophageal carcinoma%非手术食管癌个体化放疗的靶区勾画进展

    Institute of Scientific and Technical Information of China (English)

    营巧玲; 李前文; 杜云翔

    2014-01-01

    Individualized radiotherapy is the ideal model of radiation therapy, based on tailoring the treatment in a large num-ber of individual clinical, pathological and molecular genetic level. Two key problems exist in the implementation of individualized ra-diotherapy, one is how to identify and individually delineate the target volume of esophageal carcinoma, and the other is how to individ-ually implement the precise exposure. Due to technological advances and the renovation of equipment in radiotherapy for esophageal car-cinoma, the individualized implementation of the precise exposure has become possible. In recent years, with the advent of functional imaging, molecular imaging and other new technologies, it points out the future research direction of individualized tumor target volume delineation. This article reviewed the definition of the target volume in the individual radiotherapy of non-surgical esophageal carcinoma, which involves the application of new technologies such as anatomical imaging, functional imaging, hypoxia, molecular im-aging to individually identify and delineat the tumor target volume, including gross tumor volume, clinical tumor volume, planning tar-get volume, biological target volume and etc.%个体化放疗的实施取决于两个关键环节,首先是靶区的个体化识别和勾画,另一个是射线的个体化施照。由于放疗设备的更新和精确放疗技术的快速发展,实现射线个体化的精确施照成为可能。近年来,随着功能影像和分子显像等新技术的出现,指明了肿瘤个体化放疗靶区勾画的研究方向。本文对非手术食管癌患者个体化放疗的靶区勾画进行综述,内容涉及应用解剖影像、功能影像、乏氧和分子显像等新技术个体化识别和勾画非手术食管癌的放疗靶区,包括大体肿瘤靶区、临床靶区、计划靶区、生物靶区等。

  15. Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Lian Wang; Zhongxing Liao; Helen Liu; Jaffer Ajani; Stephen Swisher; James D Cox; Ritsuko Komaki

    2006-01-01

    AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer.METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed.RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%).tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%)of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula.CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

  16. 14-3-3σ confers cisplatin resistance in esophageal squamous cell carcinoma cells via regulating DNA repair molecules.

    Science.gov (United States)

    Lai, Kenneth K Y; Chan, Kin Tak; Choi, Mei Yuk; Wang, Hector K; Fung, Eva Y M; Lam, Ho Yu; Tan, Winnie; Tung, Lai Nar; Tong, Daniel K H; Sun, Raymond W Y; Lee, Nikki P; Law, Simon

    2016-02-01

    Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in Asia. Cisplatin is commonly used in chemoradiation for unresectable ESCC patients. However, the treatment efficacy is diminished in patients with established cisplatin resistance. To understand the mechanism leading to the development of cisplatin resistance in ESCC, we compared the proteomes from a cisplatin-resistant HKESC-2R cell line with its parental-sensitive counterpart HKESC-2 to identify key molecule involved in this process. Mass spectrometry analysis detected 14-3-3σ as the most abundant molecule expressed exclusively in HKESC-2R cells, while western blot result further validated it to be highly expressed in HKESC-2R cells when compared to HKESC-2 cells. Ectopic expression of 14-3-3σ increased cisplatin resistance in HKESC-2 cells, while its suppression sensitized SLMT-1 cells to cisplatin. Among the molecules involved in drug detoxification, drug transportation, and DNA repair, the examined DNA repair molecules HMGB1 and XPA were found to be highly expressed in HKESC-2R cells with high 14-3-3σ expression. Subsequent manipulation of 14-3-3σ by both overexpression and knockdown approaches concurrently altered the expression of HMGB1 and XPA. 14-3-3σ, HMGB1, and XPA were preferentially expressed in cisplatin-resistant SLMT-1 cells when compared to those more sensitive to cisplatin. In ESCC patients with poor response to cisplatin-based chemoradiation, their pre-treatment tumors expressed higher expression of HMGB1 than those with response to such treatment. In summary, our results demonstrate that 14-3-3σ induces cisplatin resistance in ESCC cells and that 14-3-3σ-mediated cisplatin resistance involves DNA repair molecules HMGB1 and XPA. Results from this study provide evidences for further work in researching the potential use of 14-3-3σ and DNA repair molecules HMGB1 and XPA as biomarkers and therapeutic targets for ESCC.

  17. Advances in dosimetry and biological predictors of radiation-induced esophagitis

    Directory of Open Access Journals (Sweden)

    Yu Y

    2016-01-01

    Full Text Available Yang Yu,1 Hui Guan,1 Yuanli Dong,1 Ligang Xing,2 Xiaolin Li2 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan, 2Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong Province, People’s Republic of China Objective: To summarize the research progress about the dosimetry and biological predictors of radiation-induced esophagitis.Methods: We performed a systematic literature review addressing radiation esophagitis in the treatment of lung cancer published between January 2009 and May 2015 in the PubMed full-text database index systems.Results: Twenty-eight eligible documents were included in the final analysis. Many clinical factors were related to the risk of radiation esophagitis, such as elder patients, concurrent chemoradiotherapy, and the intense radiotherapy regimen (hyperfractionated radiotherapy or stereotactic body radiotherapy. The parameters including Dmax, Dmean, V20, V30, V50, and V55 may be valuable in predicting the occurrence of radiation esophagitis in patients receiving concurrent chemoradiotherapy. Genetic variants in inflammation-related genes are also associated with radiation-induced toxicity.Conclusion: Dosimetry and biological factors of radiation-induced esophagitis provide clinical information to decrease its occurrence and grade during radiotherapy. More prospective studies are warranted to confirm their prediction efficacy. Keywords: lung cancer, esophagitis, radiation injuries, predictors

  18. p53功能失活在食管鳞癌中的表达及意义%Significance of Functional Inactivation of p53 in Esophageal Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    李小东; 戎铁华; 傅剑华; 龙浩

    2001-01-01

    目的:建立一种评价肿瘤生物学特性的新方法棗p53功能失活检测法,并探讨p53功能失活与食管鳞癌TNM分期(tumor,nodes,metastasisstaging)和组织学分级的关系。方法:采用p53功能测定法对45例新鲜食管鳞癌组织和正常食管组织进行p53功能检测(p53基因突变检测作为对照),将检测结果与患者的TNM分期和组织学分级进行统计学分析。结果:p53功能失活率为64%,明显高于p53基因突变率49%。p53功能失活和食管鳞癌的TNM分期有关,分期越高,p53功能失活率越高;p53功能失活和食管鳞癌的组织学分级有关,分级越高,p53功能失活率越高。结论:p53功能失活有望成为一种评价食管鳞癌生物学特性的新指标;p53功能失活与食管鳞癌的TNM分期和组织学分级有关。%Objective: The current study was designed to establish a new method to evaluate biological activity of carcinoma— functional status of p53, and investigate the relationship between functional inactivation of p53 and the TNM(tumor,nodes,metastasis) staging or histological classification of squamous cell carcinoma of esophagus. Methods: A total of 45 samples of fresh esophageal tissues of squamous cell carcinoma and normal esophageal tissues were examined for functional inactivation of p53 by detection of functional inactivation of p53 ( comparison with detection of p53 gene mutation ) . Then the analyses of detected results and the TNM stagings or the histological classifications of the carcinoma were statistically analyzed in SPSS. Results: The rate of functional inactivation of p53 (64% ) seemed to be obviously higher than that of p53 gene mutation (49% ) with a significant difference (P=0.046). There was a significant relationship between functional inactivation of p53 and the TNM staging of esophageal squamous cell carcinoma. Its rate tended to be increased with the advance of the TNM staging; there was a significant

  19. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    OpenAIRE

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic r...

  20. Study of consolidation chemotherapy in advanced epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Ning-hai; Huang Hui-fang; Pan Lin-ya; Shen Keng; Wu Ming; Yang Jia-xin

    2007-01-01

    Objective: A prospective randomized study was designed to evaluate the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.Methods: 50 patients with advanced epithelial ovarian carcinoma treated in our hospital during the period from March 2000 to October 2005 were enrolled in this study.All patients had achieved clinical complete remission by means of standard treatments, and were randomly divided into consolidation chemotherapy group and control group.Relapse rate, and disease-free survival(DFS) time were analyzed in both groups.Results: 24 patients were assigned in consolidation chemotherapy group, and 26 patients in control group.Tumor relapse interval in consolidation group was (26.5±7.4) months, vs.(16.8±7.0) months in control group respectively, P=0.001.Time to relapse(TTR) in consolidation group was (19.2±6.8) months, vs.(10.0±6.9)months in control group, P=0.002.Analysis of DFS time and overall survival time, Log Rank test:P=0.042 and P= 0.062, respectively.Conclusions: Consolidation chemotherapy could be the relevant factor that postpones tumor relapse interval and prolongs DFS time in advanced epithelial ovarian carcinoma patients who had achived chlinical complete remission.But so far the statistic result of our clinical study is beyond the conclusion that consolidation chemotherapy can decrease relapse rate or increase survival rate.Muhicenter randomized clinical trial should be performed to confirm the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.

  1. Identification of Biomarkers for Esophageal Squamous Cell Carcinoma Using Feature Selection and Decision Tree Methods

    Directory of Open Access Journals (Sweden)

    Chun-Wei Tung

    2013-01-01

    Full Text Available Esophageal squamous cell cancer (ESCC is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

  2. Alterations in expression, proteolysis and intracellular localizations of clusterin in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Zhi He; Xiao-Hang Zhao; Zhen-Mei Song; Kun Wang; Liang-Hong Teng; Fang Liu; You-Sheng Mao; Ning Lu; Shang-Zhong Zhang; Min Wu

    2004-01-01

    AIM: To investigate biogenesis and intracellular localizations of clusterin to elucidate the potential molecular mechanisms implicated in tumorigenesis of esophageal mucosa.METHODS: Semi-quantitative RT-PCR for multi-region alteration analysis, Western blot for different transcriptional forms and immunohistochemical staining for intracellular localizations of clusterin were carried out in both tissues and cell lines of ESCC.RESULTS: The N-terminal deletions of the clusterin gene and the appearance of a 50-53 ku nuclear clusterin, an uncleaved, nonglycosylated, and disulfide-linked isoform,were the major alterations in cancer cells of esophagus.Naturally the 40 ku clusterin was located in the connective tissue of the lamina propria of epithelial mucosa and right under the basal membrane of epithelia, but it was disappeared in stromal mucosa of esophagus and the pre-matured clusterin was found positive in cancerous epithelia.CONCLUSION: The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.

  3. Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus. Nine Japanese institutions trial

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kaoru [Iwate Medical Univ., Morioka (Japan). School of Medicine; Iizuka, Toshifumi; Ando, Nobutoshi; Ide, Hiroko

    1996-10-01

    A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1{sub (LYM)}), were enrolled in the study for treatment with cisplatin (70 mg/m{sup 2}) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m{sup 2}) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer. (author)

  4. Neoadjuvant chemotherapy and radiation therapy in advanced stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    To assess the feasibility and the toxicity of the neoadjuvant chemotherapy on the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. We analyzed 77 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with neoadjuvant chemotherapy followed by radiation therapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC stage 111-2, stage IV-75. Sixty-six patients received infusion of 5-FU (1000 mg/m2, on Day 1-5) and cisplatin (100 mg/m2, on Day 1), eleven patients received infusion of 5.FU (1000 mg/m2, on Day 1-5) and carboplatin (300 mg/m2, on Day 1) as neoadjuvant chemotherapy prior to radiation therapy. The median follow-up for surviving patients was 44 months. The overall chemotherapy response rates were 87%. The toxicities of chemotherapy were mild. Only 3 patients experienced Grade 3 toxicities (1 for cytopenia, 2 for nausea/vomiting). The degree of radiation induced mucositis was not severe, and ten patients developed Grade 2 mucositis. The 5-year overall survival rates were 68% and the 5-year disease free survival rates were 65%. The 5-year freedom from distant metastasis rates were 82% and 5-year locoregional control rates were 75%. This single institution experience suggests that neoadjuvant chemotherapy improves overall survival and disease free survival for patients with advanced stage nasopharyngeal carcinoma without increase of toxicity

  5. Effect of radiotherapy on serum SCC, CEA, CRFRA21-1, TAG72, CA199 and lymphocyte subsets in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sha Sha; Bo Yu; Zhong-Qin Shu; Xiao-Wei Gu; Wei-Dong Mao; Lin-Yun Xia; Jian-Jun Qin

    2016-01-01

    Objective:To study the effect of radiotherapy on serum SCC, CEA, CRFRA21-1, TAG72, CA199 and lymphocyte subsets in patients with esophageal squamous cell carcinoma. Methods: A total of 60 patients with esophageal squamous cell carcinoma in our hospital from January 2013 to January 2016 were selected as experiment group and 40 healthy subjects were selected as control group. Patients in experiment group were treated with 6MV X-ray radiation therapy. Serum SCC, CEA, CRFRA21-1, TAG72, CA199 and the cell percentage of peripheral blood CD4+, CD8+ were compared in control group and the experimental group before and after 1 month radiotherapy.Results:Before treatment, the levels of serum SCC, CEA and CRFRA21-1 in the experimental group were significantly higher than those in the control group (P0.05). Before treatment, the cell percentage of peripheral blood CD4+, CD8+ and the ratio of CD4+/CD8+ in experimental group was significantly lower than that of the control group, the percentage of peripheral blood CD8+ in the experimental group was significantly higher than that in the control group (P0.05), and in the experimental group, the proportion of CD4+ cells and the tatio of CD4+/CD8+in peripheral blood was significantly lower than that of the control group, the proportion of CD8+ was significantly higher than that of the control group (P<0.05).Conclusions: Radiotherapy can significantly reduce the serum SCC, CEA, CRFRA21-1, TAG72 and CA199 levels of the patients with esophageal squamous cell carcinoma, but have less influence on the T lymphocyte subsets.

  6. Randomized clinical trial on seven-day-per-week continuous accelerated irradiation for patients with esophageal carcinoma:Preliminary report on tumor response and acute toxicity

    Institute of Scientific and Technical Information of China (English)

    Su-Ping Sun; Ya-Zhou Liu; Tao Ye; Wen Zhang; Wen-Bin Shen; Jing-Lei Shi; Hai-Ting Xu; Wei-Dong Wang

    2006-01-01

    AIM: Tumor response and normal tissue toxicity of seven-day-per-week continuous accelerated irradiation (CAIR) for patients with esophageal carcinoma were evaluated and compared to conventional irradiation (CR).METHODS: Sixty patients with squamous cell carcinoma of the esophagus were randomized into two groups:the CAIR group (30 patients) and the CR group (30 pa(RT) with 2 Gy/fraction per day at 7 d/wk with a total dose of 50-70 Gy (average dose 64.2 Gy). The overall time of irradiation was 3.6-5.0 wk (average 4.6 wk). RT in the CR group was 2 Gy/fraction per day at 5 d/wk with a total dose of 40-70 Gy (average dose 61.7 Gy).The overall time of irradiation was 4.0-7.0 wk (average 6.4wk).RESULTS: The data showed that the immediate tumor response to RT was better in the CAIR group than in the CR group. Efficiency rates (CR plus PR) were 82.8%(24/29) and 58.6% (17/29), respectively (P = 0.047). In both groups the incidences of esophagitis and tracheitis were insignificant (P = 0.376, 0.959), and no patient received toxicity that could not be tolerated.CONCLUSION: CAIR shortens overall treatment time and is well tolerated by patients. It may be superior to CR in enhancing the local response of tumor, but its remote effect for esophageal carcinoma awaits further follow-up.

  7. Gallium-67 imaging in candidal esophagitis

    Energy Technology Data Exchange (ETDEWEB)

    Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. (Beth Israel Medical Center, New York, NY (USA))

    1990-01-01

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.

  8. Gallium-67 imaging in candidal esophagitis

    International Nuclear Information System (INIS)

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis

  9. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies

    OpenAIRE

    Abnet, Christian C.; Wang, Zhaoming; SONG, XIN; Hu, Nan; Zhou, Fu-You; Freedman, Neal D.; Li, Xue-Min; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Dawsey, Sanford M.; Liao, Linda M.; Lee, Maxwell P.; DING, Ti

    2012-01-01

    Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) o...

  10. Increased serum cell-free DNA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma

    OpenAIRE

    TOMOCHIKA, SHINOBU; Iizuka, Norio; Watanabe, Yusaku; TSUTSUI, MASAHITO; Takeda, Shigeru; Yoshino, Shigefumi; ICHIHARA, KIYOSHI; Oka, Masaaki

    2010-01-01

    Distant metastasis hinders a favorable outcome for patients with esophageal squamous cell carcinoma (ESCC) by limiting the surgical cure. The levels of cell-free DNA (cfDNA) in the blood have served as a predictor for metastasis and recurrence in distant organs in liver cancer. Thus, this study tested the clinical efficacy of serum cfDNA levels as a predictive marker for distant metastasis of ESCC. We investigated cfDNA levels in a cohort of 101 ESCC patients and 46 age- and gender-matched co...

  11. The effect of tumor length, maximum diameters and volume on the response of N0 stage thoracic esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of GTV volume on response of esophageal carcinoma. Methods: From Jan. 2004 to Dec. 2008, 72 cases newly diagnosed N0 stage thoracic esophageal carcinomas were included in this retrospective study. All treatment plans were set up and designed by CT simulator and 3D TPS. They received dose 56-70 Gy/27-33 F/6-7 w with 6 MV X-ray. The GTV, the tumor length and maximum diameters were measured on the treatment planning system with the X-ray. RECIST standard was applied to evaluate the radiotherapy response of esophageal carcinoma. The effectiveness of related prognostic factors on survival was evaluated by univariate analyses. Results: The short-term response with CR were 79% with length < 5 cm, 48% with 5-7 cm and 26% with length >7 cm(P =0.003). The 1-, 2-, 3-and 5-year survival rates were 93%, 79%, 69%, 69%; 91%, 61%, 46%, 46% and 80%, 46%, 28%, 22% (P =0.037). The short-term response with CR were 56% with maximum diameters ≤3 cm and 33% with maximum diameters > 3 cm(P =0.033). The 1-, 2-, 3-and 5-year survival rates were 91%, 72%, 55%, 37% and 80%, 45%, 30%, 30% (P =0.037). The short-term response with CR were 52% with GTV volume ≤40 cm3 and 30% with GTV volume >40 cm3 (P =0.059). The 1-, 2-, 3-and 5-year survival rates were 91%, 67%, 51%, 41% and 80%, 43%, 27%, 27% (P =0.047). In the multivariate analysis, the length of GTV was likely to be the most important factor for the short-term response (P =0.005, 0.014). Conclusions: GTV volume, the tumor length and maximum diameters are factors for short-term response of N0 stage esophageal carcinoma.The GTV length is independent prognostic factor. The GTV length is the worse the prognosis will be. (authors)

  12. Role of Brg1 in progression of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shahram Torkamandi

    2014-11-01

    Full Text Available Objective(s: Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Materials and Methods: Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR. Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Results: Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line compared with normal esophageal tissue of ESCC patients. Rate of transfection in KYSE30 was also between 40 to 50%, using the pSilencer-Brg1shRNA (1:1 ratio. Conclusion: Our data indicated that chromatin remodeling machinery is a novel aspect in tumor biology of ESCC, and overexpression of Brg1 as an important member of SWI/SNF might be involved in the migration and invasion of ESCC tumoral cells.

  13. Effects of 5-azacytidine on RUNX3 gene expression and the biological behavior of esophageal carcinoma cells.

    Science.gov (United States)

    Wang, Shuai; Liu, Hong; Wang, Zhou; Chen, Hua-Xia

    2014-04-01

    The present study investigated the effects of 5-azacytidine (5-azaC) on the expression level of the human runt-related transcription factor 3 (RUNX3) gene and the biological behavior of esophageal carcinoma Eca109 cells. The effect of the demethylation reagent 5-azaC on the viability of Eca109 cells was detected by the MTT assay, which demonstrated that 5-azaC inhibited the viability of Eca109 cells in a time- and dose-dependent manner. Although demethylation of other genes may occur following treatment with 5-azaC, we focused on the RUNX3 gene. When treated with 5-azaC at hypoxic levels, the expression of RUNX3 increased and the methylation degree of the RUNX3 gene was decreased significantly in Eca109 cells. 5-azaC at 50 µM demonstrated the highest RUNX3-induction activity, inducing RUNX3 mRNA and protein expression, and decreasing the degree of methylation of the RUNX3 gene. Methylation specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. The abilities of migration and invasion of Eca109 cells were inhibited by 5-azaC. The growth of Eca109 cells treated with 5-azaC in vivo was detected by a tumorigenesis experiment. 5-azaC inhibited the growth of Eca109 xenografts in nude mice. Taken together, our findings demonstrated that the RUNX3 gene is hypermethylated in Eca109 cells and that 5-azaC induces the expression of the RUNX3 gene by demethylation, which inhibits the proliferation, migration and invasion of Eca109 cells. PMID:24535051

  14. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

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    Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC

  15. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

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    Dong, Wenjie, E-mail: dongwenjie200581@126.com [Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University (China); Shen, Ruizhe; Cheng, Shidan [Department of Gastroenterology, Rui-jin Hospital, Shanghai Jiao Tong University, Shanghai (China)

    2014-10-31

    Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

  16. Association of single nucleotide polymorphisms in ERCC2 gene and their haplotypes with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Yougai; Wang, Longzhi; Wang, Peng; Song, Chunhua; Wang, Kaijuan; Zhang, Jianying; Dai, Liping

    2014-05-01

    Esophageal squamous cell carcinoma (ESCC), one of the leading causes of cancer death worldwide, occurs at a relatively high frequency in China. To investigate whether common excision repair cross-complementing rodent repair group 2 (ERCC2) variants (rs3916874 G>C, rs238415 C>G, rs1618536 G>A, rs1799793 G>A, and rsl3181 A>C) were associated with ESCC risk, a case-control study was conducted, including 405 cases with ESCC and 405 age and sex 1:1 matched cancer-free controls. The result showed that rsl3181 AC/CC genotypes was associated with an increased risk of ESCC (OR: 1.45, 95% CI: 1.05-2.00), and two ERCC2 haplotypes Grs3916874Crs238415Grs1618536Grs1799793Crsl3181 (Hap5) and Grs3916874Grs238415Ars1618536Grs1799793Crsl3181 (Hap7) were associated with increased risk of ESCC (OR: 2.16, 95 % CI: 1.27-3.57 for Hap5 and OR: 3.72; 95 % CI: 1.89-6.63 for Hap7, respectively), while Grs3916874Grs238415Grs1618536Grs1799793Arsl3181 (Hap4) was associated with decreased risk of ESCC (OR: 0.47, 95% CI: 0.35-0.71). Gene-environment interaction analysis by multifactor dimensionality reduction (MDR) software showed that there was an interaction among rs238415, rs1618536, and family history of cancer with a P value under 0.0001 (OR: 3.23: 95% CI: 2.37-4.40). These results suggested that genetic variations in the ERCC2 gene were associated with risk of ESCC, and there was a significant interaction between gene polymorphisms and family history of cancer in the etiology of ESCC.

  17. A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of esophageal squamous cell carcinoma.

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    Jian Zhang

    Full Text Available BACKGROUND: Accumulated evidences demonstrated that single nucleotide polymorphisms (SNPs in mRNA 3'-untranslated region (3'-UTR may impact microRNAs (miRNAs-mediated expression regulation of oncogenes and tumor suppressors. There is a TNFAIP2 3'-UTR rs8126 T>C genetic variant which has been proved to be associated with head and neck cancer susceptibility. This SNP could disturb binding of miR-184 with TNFAIP2 mRNA and influence TNFAIP2 regulation. However, it is still unclear how this polymorphism is involved in development of esophageal squamous cell carcinoma (ESCC. Therefore, we hypothesized that the functional TNFAIP2 rs8126 SNP may affect TNFAIP2 expression and, thus, ESCC risk. METHODS: We investigated the association between the TNFAIP2 rs8126 variant and ESCC risk as well as the functional relevance on TNFAIP2 expression in vivo. Genotypes were determined in a case-control set consisted of 588 ESCC patients and 600 controls. The allele-specific regulation on TNFAIP2 expression by the rs8126 SNP was examined in normal and cancerous tissue specimens of esophagus. RESULTS: We found that individuals carrying the rs8126 CC or CT genotype had an OR of 1.89 (95%CI  = 1.23-2.85, P = 0.003 or 1.38 (95%CI  = 1.05-1.73, P = 0.017 for developing ESCC in Chinese compared with individual carrying the TT genotype. Carriers of the rs8126 CC and CT genotypes had significantly lower TNFAIP2 mRNA levels than those with the TT genotypes in normal esophagus tissues (P<0.05. CONCLUSIONS: Our data demonstrate that functional TNFAIP2 rs8126 genetic variant is a ESCC susceptibility SNP. These results support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of cancer risk.

  18. miR-218 suppresses tumor growth and enhances the chemosensitivity of esophageal squamous cell carcinoma to cisplatin.

    Science.gov (United States)

    Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; She, Ying-Jun; Bi, Xiao-Bao; Song, Xing-Rong

    2015-02-01

    A growing body of evidence suggests that microRNA-218 (miR-218) acts as a tumor suppressor and is involved in tumor progression, development and metastasis and confers sensitivity to certain chemotherapeutic drugs in several types of cancer. However, our knowledge concerning the exact roles played by miR-218 in esophageal squamous cell carcinoma (ESCC) and the underlying molecular mechanisms remain relatively unclear. Thus, the aims of this study were to detect the expression of miR-218 in human ESCC tissues and explore its effects on the biological features and chemosensitivity to cisplatin (CDDP) in an ESCC cell line (Eca109), so as to provide new insights for ESCC treatment. Here, we found increased expression of miR-218 in the ESCC tissues compared with that in the matched non-tumor tissues, and its expression level was correlated with key pathological characteristics including clinical stage, tumor depth and metastasis. We also found that enforced expression of miR-218 significantly decreased cell proliferation, colony formation, migration and invasion, induced cell apoptosis and arrested the cell cycle in the G0/G1 phase, as well as suppressed tumor growth in a nude mouse model. In addition, our results showed that miR-218 mimics increased the sensitivity to the antitumor effect of CDDP in the human Eca109 cells. Importantly, this study also showed that miR-218 regulated the expression of phosphorylated PI3K, AKT and mTOR, which may contribute to suppressed tumor growth of ESCC and enhanced sensitivity of ESCC cells. These findings suggest that miR-218 is a potential therapeutic agent for the treatment of ESCC.

  19. NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China

    Institute of Scientific and Technical Information of China (English)

    Jian-Hui Zhang; Ming He; Li-Wei Zhang; Ming-Li Wu; Shi-Jie Wang; Yan Li; Rui Wang; Helen Geddert; Wei Guo; Deng-Gui Wen; Zhi-Feng Chen; Li-Zhen Wei; Gang Kuang

    2003-01-01

    AIM: To investigate the association of the NQO1 (C609T)polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China.METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls.RESULTS: The NQO1 C609T C/C, c/r and T/T genotype frequency among healthy controls was 31.5 %, 52.1% and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (X2=4.79, P=0.028). The NQO1T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes,with an age, sex and smoking status adjusted odds ratio (OR)of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 %CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC.CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.

  20. Advances in dosimetry and biological predictors of radiation-induced esophagitis

    Science.gov (United States)

    Yu, Yang; Guan, Hui; Dong, Yuanli; Xing, Ligang; Li, Xiaolin

    2016-01-01

    Objective To summarize the research progress about the dosimetry and biological predictors of radiation-induced esophagitis. Methods We performed a systematic literature review addressing radiation esophagitis in the treatment of lung cancer published between January 2009 and May 2015 in the PubMed full-text database index systems. Results Twenty-eight eligible documents were included in the final analysis. Many clinical factors were related to the risk of radiation esophagitis, such as elder patients, concurrent chemoradiotherapy, and the intense radiotherapy regimen (hyperfractionated radiotherapy or stereotactic body radiotherapy). The parameters including Dmax, Dmean, V20, V30, V50, and V55 may be valuable in predicting the occurrence of radiation esophagitis in patients receiving concurrent chemoradiotherapy. Genetic variants in inflammation-related genes are also associated with radiation-induced toxicity. Conclusion Dosimetry and biological factors of radiation-induced esophagitis provide clinical information to decrease its occurrence and grade during radiotherapy. More prospective studies are warranted to confirm their prediction efficacy. PMID:26869804

  1. Relationship between P-glycoprotein and CD44 expression in esophageal carcinoma%食管癌细胞P-糖蛋白与CD44表达相关性研究

    Institute of Scientific and Technical Information of China (English)

    许沈华; 凌雨田; 朱赤红

    2006-01-01

    Objective: To investigate the relationship between P-glycoprotein (P-gp) and adhesion molecule CD44 expression as well as their clinical significance in esophageal carcinoma.Methods: To examine the expressed level of P-gp and CD44 by flow cytometry (FCM) in the operated samples of 70 cases with esophageal carcinoma and their normal mucosa of esophageal incision,and to evaluate their relationship with clinicopathological factors.Results: Among the 70 cases with esophageal carcinoma,the expression of P-gp in the 27 cases (38.6%) was negative (positive cells <25%); 11 cases (15.7%) were 25%-40%expression of P-gp positive cells; 14 cases (20%) were 41%-60% expression of P-gp positive cells; 18 cases (25.7%) were the high expression (positive cells >60%) of P-gp.Of the cases with the tumor sizes being more than 4 cm,the expression of CD44showed a significant difference (P<0.05) in 25 cases with P-gp positive,compared with 19 cases with P-gp negative.Of the cases with high-mild differentiated esophageal carcinoma,the expression of CD44 showed a significant difference (P<0.05) in 22 cases with P-gp positive,compared with 17 cases with P-gp negative.Of the cases with clinical Ⅲ--Ⅳ stage,the expression of CD44 showed a significant difference (P<0.05) in 26 cases with P-gp positive,compared with 10 cases with P-gp negative.Of the cases with lymph node metastasis,the CD44 expression showed a significant difference (P=0.050)in 27 cases with P-gp positive,compared with 11 cases with P-gp negative.Of the cases of the patients' age being more than 56 years,the expression of CD44 showed a significant difference (P<0.01) in 27 cases with P-gp positive,compared with 12 cases with P-gp negative.When the P-gp and CD44 expression were positive,the clinical Ⅱ stage and Ⅲ-Ⅳ stage in esophageal carcinoma was showed a significant difference (P<0.05).Conclusion: When the CD44 and P-gp both have the positive high expression,it will be significantly associated with the

  2. Narrow Band Imaging with Magnification Can Pick Up Esophageal Squamous Cell Carcinoma More Efficiently Than Lugol Chromoendoscopy in Patients after Chemoradiotherapy

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    Itsuko Asada-Hirayama

    2013-01-01

    Full Text Available Aim. Little is known about the usefulness of narrow band imaging (NBI for surveillance of patients after chemoradiotherapy for esophageal neoplasia. Its usefulness in detecting esophageal squamous cell carcinoma (SCC or high-grade intraepithelial neoplasia (HGIN in these patients was retrospectively compared to Lugol chromoendoscopy. Patients and Methods. We assessed the diagnostic ability of NBI with magnification based on the biopsy specimens obtained from iodine-unstained lesions. Seventy-two iodine-unstained lesions were biopsied and consecutively enrolled for this study. The lesions were divided into NBI positive and NBI negative. Sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV, and accuracy of NBI with magnification and PPV of Lugol chromoendoscopy was calculated using histological assessment as a gold standard. Results. Forty-six endoscopic examinations using NBI with magnification followed by Lugol chromoendoscopy were performed to 28 patients. The prevalence of SCC and HGIN was 21.4%. Sensitivity, specificity, PPV, NPV, and accuracy of NBI were 100.0%, 98.5%, 85.7%, 100%, and 98.6%, respectively. On the contrary, PPV of Lugol chromoendoscopy were 8.3%. Compared to Lugol chromoendoscopy, NBI with magnification showed equal sensitivity and significantly higher PPV (. Conclusion. NBI with magnification would be able to pick up esophageal neoplasia more efficiently than Lugol chromoendoscopy in patients after chemoradiotherapy.

  3. Overexpression of S-adenosylhomocysteine hydrolase (SAHH) in esophageal squamous cell carcinoma (ESCC) cell lines: effects on apoptosis, migration and adhesion of cells.

    Science.gov (United States)

    Li, Qinghua; Mao, Lihong; Wang, Ruili; Zhu, Liqiang; Xue, Lexun

    2014-01-01

    S-adenosylhomocysteine hydrolase (SAHH) is the sole enzyme that catalyses the hydrolysis of S-adenosylhomocysteine (SAH) in methylation reaction. Previous studies have shown that its inhibition or deficiency leads to several human disorders such as severe coagulopathy, hepatopathy and myopathy. However, the effects of SAHH on esophageal squamous cell carcinoma (ESCC) cells have not been explored so far. To determine whether SAHH is involved in carcinogenesis of the esophagus, we investigated the expression of SAHH in ESCC and normal esophageal epithelial cells and found that SAHH was downregulated in ESCC cells compared with normal esophageal epithelial cells (P ESCC cells promoted cell apoptosis, inhibited cell migration and adhesion, but did not affect the cell proliferation and cell cycle. Furthermore, an interaction of SAHH with receptor of activated C kinase 1 (RACK1) protein was detected by coimmunoprecipitation and an increased RACK1, which is caused by overexpression of SAHH, was verified by Western blotting. The findings mentioned above demonstrate that SAHH can promote apoptosis, inhibit migration and adhesion of ESCC cells suggesting that it may be involved in carcinogenesis of the esophagus.

  4. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

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    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  5. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  6. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Daisuke [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Kato, Kazunori, E-mail: kzkatou@juntendo.ac.jp [Department of Biomedical Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585 (Japan); Department of Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2013-05-17

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  7. Percutaneous endoscopic gastrostomy for nutritional palliation of upper esophageal cancer unsuitable for esophageal stenting

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    Ana Grilo

    2012-09-01

    Full Text Available CONTEXT: Esophageal cancer is often diagnosed at an advanced stage and has a poor prognosis. Most patients with advanced esophageal cancer have significant dysphagia that contributes to weight loss and malnutrition. Esophageal stenting is a widespread palliation approach, but unsuitable for cancers near the upper esophageal sphincter, were stents are poorly tolerated. Generally, guidelines do not support endoscopic gastrostomy in this clinical setting, but it may be the best option for nutritional support. OBJECTIVE: Retrospective evaluation of patients with dysphagia caused advanced esophageal cancer, no expectation of resuming oral intake and with percutaneous endoscopic gastrostomy for comfort palliative nutrition. METHOD: We selected adult patients with unresecable esophageal cancer histological confirmed, in whom stenting was impossible due to proximal location, and chemotherapy or radiotherapy were palliative, using gastrostomy for enteral nutrition. Clinical and nutritional data were evaluated, including success of gastrostomy, procedure complications and survival after percutaneous endoscopic gastrostomy, and evolution of body mass index, albumin, transferrin and cholesterol. RESULTS: Seventeen males with stage III or IV squamous cell carcinoma fulfilled the inclusion criteria. Mean age was 60.9 years. Most of the patients had toxic habits. All underwent palliative chemotherapy or radiotherapy. Gastrostomy was successfully performed in all, but nine required prior dilatation. Most had the gastrostomy within 2 months after diagnosis. There was a buried bumper syndrome treated with tube replacement and four minor complications. There were no cases of implantation metastases or procedure related mortality. Two patients were lost and 12 died. Mean survival of deceased patients was 5.9 months. Three patients are alive 6, 14 and 17 months after the gastrostomy procedure, still increasing the mean survival. Mean body mass index and laboratory

  8. Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas

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    YANG Yan-li; XU Kan-lun; ZHOU Yan; GAO Xin; CHEN Li-rong

    2012-01-01

    Background Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane.The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC,and help to identify patients who may benefit from EGFR targeted therapies.Methods Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 cases of normal esophageal tissue.Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC,eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue.Results The IHC-positive rates of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 normal esophageal tissues were 97% (102/105),44% (7/16),and 18% (2/11) respectively.The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P <0.05).Among the 105 cases of ESCC,overexpression of EGFR was found in 90 cases (86%),of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+.In ESCC,the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P<0.05),but not with other parameters.The FISH-positive rates of EGFR in 80 cases of ESCC,the eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue were 31.3% (25/80),0 (0/8) and 0 (0/8) respectively.In ESCC,EGFR gene amplification was found in 17 (21%) cases,high polysomy in 8 (10%) cases,disomy in 34 cases,low trisomy in 17 cases,and high trisomy in four cases.EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P <0.05).EGFR FISH-positive was significantly associated with overexpression of EGFR.Conclusion Protein

  9. Occurrence of multipolar mitoses and association with Aurora-A/-B kinases and p53 mutations in aneuploid esophageal carcinoma cells

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    Münch Claudia

    2011-04-01

    Full Text Available Abstract Background Aurora kinases and loss of p53 function are implicated in the carcinogenesis of aneuploid esophageal cancers. Their association with occurrence of multipolar mitoses in the two main histotypes of aneuploid esophageal squamous cell carcinoma (ESCC and Barrett's adenocarcinoma (BAC remains unclear. Here, we investigated the occurrence of multipolar mitoses, Aurora-A/-B gene copy numbers and expression/activation as well as p53 alterations in aneuploid ESCC and BAC cancer cell lines. Results A control esophageal epithelial cell line (EPC-hTERT had normal Aurora-A and -B gene copy numbers and expression, was p53 wild type and displayed bipolar mitoses. In contrast, both ESCC (OE21, Kyse-410 and BAC (OE33, OE19 cell lines were aneuploid and displayed elevated gene copy numbers of Aurora-A (chromosome 20 polysomy: OE21, OE33, OE19; gene amplification: Kyse-410 and Aurora-B (chromosome 17 polysomy: OE21, Kyse-410. Aurora-B gene copy numbers were not elevated in OE19 and OE33 cells despite chromosome 17 polysomy. Aurora-A expression and activity (Aurora-A/phosphoT288 was not directly linked to gene copy numbers and was highest in Kyse-410 and OE33 cells. Aurora-B expression and activity (Aurora-B/phosphoT232 was higher in OE21 and Kyse-410 than in OE33 and OE19 cells. The mitotic index was highest in OE21, followed by OE33 > OE19 > Kyse-410 and EPC-hTERT cells. Multipolar mitoses occurred with high frequency in OE33 (13.8 ± 4.2%, followed by OE21 (7.7 ± 5.0% and Kyse-410 (6.3 ± 2.0% cells. Single multipolar mitoses occurred in OE19 (1.0 ± 1.0% cells. Distinct p53 mutations and p53 protein expression patterns were found in all esophageal cancer cell lines, but complete functional p53 inactivation occurred in OE21 and OE33 only. Conclusions High Aurora-A expression alone is not associated with overt multipolar mitoses in aneuploid ESCC and BAC cancer cells, as specifically shown here for OE21 and OE33 cells, respectively

  10. Efficacy analysis on simplified intensity-modulated radiotherapy with high or conventional dose and concurrent chemotherapy for patients with N1 esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the feasibility of simplified intensity-modulated radiotherapy (sIMRT) and concurrent chemotherapy against neck and upper thoracic esophageal carcinoma with lymph node metastasis. Methods: sIMRT plans were designed for 44 patients of neck and upper thoracic esophageal carcinoma with lymph node metastasis, 20 of which underwent high dose sIMRT (hsIMRT group) and 24 underwent conventional dose sIMRT (csIMRT group). Three target volumes were defined: PGTVnd, target volume of lymph node lesion, irradiated to 68.1 Gy (2.27 Gy × 30 fractions) for the hsIMRT group, and 60 Gy (2.0 Gy ×30 fractions) the csIMRT group; PTV1, the target volume of primary lesion, to be irradiate to 63.9 Gy (2.13 Gy × 30 fractions) for the hsIMRT group and 60 Gy (2.0 Gy × 30 fractions) for the csIMRT group; PTV2, the prophylactically irradiated volume, to be irradiated to 54 Gy (1.8 Gy ×30) for both groups. The sIMRT plan included 5 equiangular coplanar beams. All patients received DDP + 5-FU regimen concurrently with radiotherapy at 1 -5 d and 29- 33 d, respectively. Chemotherapy was repeated for two cycles 28 days after the radiotherapy was finished. Results: The treatment was completed for all patients within 6 weeks. During the treatment only one patient with grade 3 acute bronchitis was observed in the hsIMRT group. The complete response (CR) rate for the lymph node lesion of the hsIMRT group was 75% (15/20), significantly higher than that of the csIMRT group [45.8% (11/24), χ2=3.84, P<0.05]. The 1-, 2-, and 3-year progression-free survival rates of the hsIMRT group were 60%, 40%, and 25%, respectively, all significantly higher than those of the csIMRT group (41.7%, 25%, and 8.3% respectively, χ2=4.11, P<0.05). However, there were not significant differences in the total survival rate, and the CR and PR of the esophageal lesion between these 2 groups. The major toxicity observed was grade Ⅰ -Ⅱ leukoctyopenia. Conclusions: sIMRT generates desirable dose

  11. Loss of Protein Tyrosine Phosphatase Receptor J Expression Predicts an Aggressive Clinical Course in Patients with Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Qiao, Dongfeng; Li, Ming; Pu, Juan; Wang, Wanwei; Zhu, Weiguo; Liu, Haiyan

    2016-07-01

    Protein Tyrosine Phosphatase Receptor J (PTPRJ) has been reported to be a tumor suppressor in various human cancers. The aim of this study was to investigate the clinical significance of PTPRJ in ESCC patients and its effects on biological behaviors of ESCC cells. PTPRJ expression, at mRNA and protein levels, were respectively detected by quantitative real-time PCR, western blot and immunohistochemistry, based on 106 newly diagnosed ESCC patients. The associations between PTPRJ expression and clinicopathological characteristics of ESCC patients were statistically analyzed. Then, the effects of PTPRJ in migration and invasion were determined by wound healing and transwell assays based on ESCC cell line transfected with siRNA or expression vector of PTPRJ. Expression of PTPRJ at mRNA and protein levels were both significantly lower in ESCC tissues than those in normal esophageal mucosa. Immunohistochemistry showed that PTPRJ protein was localized in the cytoplasm of cancer cells in ESCC tissues. In addition, PTPRJ downregulation was found to be closely correlated with advanced tumor stage (P = 0.01) and poor differentiation (P = 0.03). Moreover, knockdown of PTPRJ in KYSE510 cells could significantly promote cell migration and invasion (both P ESCC patients. PTPRJ may function as a tumor suppressor and play an important role in the regulation of ESCC cell motility, suggesting its potentials as a therapeutic agent for human ESCC.

  12. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation

    Directory of Open Access Journals (Sweden)

    Ji Kai

    2012-11-01

    Full Text Available Abstract Background To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC patients with a dose of 60 Gy/30f. Methods Thirty-nine patients with medically inoperable T1–4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT with involved-field radiation (IFI. The conformal clinical target volume (CTV was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Results Under a 60 Gy dosage, the median Dmean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Conclusions Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions.

  13. Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China

    Institute of Scientific and Technical Information of China (English)

    Yan-Ru Qin; Li-Dong Wang; Zong-Min Fan; Dora Kwong; Xin-Yuan Guan

    2008-01-01

    AIM: To characterize cytogenetic alterations in esophageal squamous cell carcinoma (ESCC) and its metastasis.METHODS: A total of 37 cases of primary ESCC and 15 pairs of primary ESCC tumors and their matched metastatic lymph nodes cases were enrolled from Linzhou, the high incidence area for ESCC in Henan, northern China. The comparative genomic hybridization (CGH) was applied to determine the chromosomal aberrations on the DNA extracted from the frozen ESCC and metastatic lymph node samples from these patients.RESULTS: CGH showed chromosomal aberrations in all the cases. In 37 cases of primary ESCC, chromosomal profile of DNA copy number was characterized by frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%), 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In 15 pairs of primary ESCC tumors and their matched metastatic lymph node cases, the majority of the chromosomal aberrations in both primary tumor and metastatic lymph node lesions were consistent with the primary ESCC cases, but new candidate regions of interest were also detected. The most significant finding is the gains of chromosome 6p with a minimum high-level amplification region at 6pl2-6ql2 in 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P = 0.05) and 20p with a minimum high-level amplification region at 20pl2 in 11 metastatic lymph nodes but only in 5 corresponding primary tumors (P < 0.05). Another interesting finding is the loss of chromosome 10p and 10q in 8 and 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P < 0.05).CONCLUSION: Using the CGH technique to detect chromosomal aberrations in both the primary tumor and its metastatic lymph nodes of ESCC, gains of 8q, 3q and 5p and loss of 3p, 8p, 9q and 13q were specifically implicated in ESCC in Linzhou population. Gains of 6p and 20p and loss of 10pq may contribute to the lymph node metastasis of ESCC. These findings suggest that the gains and losses

  14. Aspirin inhibits the proliferation of tobacco-related esophageal squamous carcinomas cell lines through cyclooxygenase 2 pathway

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiao-Zhi; LIU Hai-bo; DING Xin-chun; LI Peng; ZHANG Shu-tian; YU Zhong-lin

    2007-01-01

    Background Cigarette smoking has been verified as the risk factor of esophageal squamous cell carcinoma(ESCC).Overexpression of cyclooxygenase 2(COX-2)is shown in ESCC.The objective of this study was to investigate the effects of cigarette smoking ethanol extract(EE)on the proliferation of the human ESCC cell Iines,and to explore the correlation between the proliferation rate of human ESCC cell lines and the expression pattern of COX-2.Whether aspirin can inhibit the proliferation of the ESCC cell lines pretreated with EE.and regulate the mRNA expression levels of COX-2 are also examined.Methods Two human ESCC cell Iines were selected.EC109 was poorly differentiated and EC9706 was highly differentiated.EC109 and EC9706 were treated with EE and aspirin for different time course.The cell growth of ESCC was measured by MTT reduction assay and the expression of COX-2 was measured by RT-PCR and Western blot analysis.Results EE promoted the proliferation of EC109 and EC9706 in dose- and time-dependent manners.In the concentration range (10-100 μg/ml for EE)and in the time range(24-72 hours)after addition of EE,the cell proliferation was prominent in an up-scaled manner respectively.Aspirin could inhibit the proliferation of cell lines EC109 and EC9706.pretreated with EE for 5 hours,in a dose-dependent manner.In the concentration range (0.5-8.0 mmol/L for aspirin),the cell growth inhibition was prominent in an up-scaled manner accordingly (P<0.05).The effect of EE on cell proliferation was correlated with the up-regulation of COX-2 gene.However,the cell growth inhibition of aspirin was correlated with the down-regulation of COX-2 gene.Conclusions EE can stimulate the proliferation of human ESCC cell lines EC109 and EC9706,most likely through up-regulating the expression of COX-2.Aspirin can inhibit the proliferation of ESCC cell lines induced by EE,which suggests it may be advantageous in the chemoprevention and therapy of human tobacco-related ESCC.And its effect is

  15. KPNA2 is a promising biomarker candidate for esophageal squamous cell carcinoma and correlates with cell proliferation.

    Science.gov (United States)

    Ma, Shouzhi; Zhao, Xiaohang

    2014-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignant cancers worldwide, with a poor 5-year prognosis. Karyopherin α 2 (KPNA2) is a nuclear membrane protein that mediates nucleus-to-cytoplasm shuttling. Its expression is elevated in multiple forms of cancer, and it can be secreted into the serum. However, the concentration of KPNA2 in serum from ESCC patients and the role of KPNA2 in ESCC cells remains unclear. The aim of the present study was to determine the concentration of KPNA2 in serum from ESCC patients and to investigate the effect of KPNA2 silencing on ESCC cell proliferation. KPNA2 protein expression was detected at the tissue level by immunohistochemistry, in cell lines by western blotting and at the serum level by enzyme linked immunosorbent assay (ELISA). Cell proliferation was determined by cell growth curve and colony formation assay. Stages of the cell cycle were analyzed by flow cytometry. The effect of KPNA2 knockdown on E2F1 translocation was determined by subcellular fractionation. KPNA2 was overexpressed in both ESCC tissues and cell lines compared with controls. The concentration of KPNA2 in serum from ESCC patients was significantly higher than that from healthy controls. The AUC was determined to be 0.804. The sensitivity and specificity of the assay were 76.7 and 75.0%, respectively. To determine the significance of KPNA2 function, small interfering RNA (siRNA) against KPNA2 was used to knock down KPNA2 levels in the ESCC using siRNA in the Kyse510 cell line. KPNA2 siRNA inhibited Kyse510 cell proliferation and colony formation ability and induced a G2/M phase arrest. The nuclear translocation of E2F1 was also reduced in siRNA-treated Kyse510 cells. The KPNA2 protein levels were high in ESCC tumors, and siRNA against KPNA2 could inhibit the growth of ESCC cells, suggesting it may be a new potent marker and therapeutic target for ESCC.

  16. Authentication of newly established human esophageal squamous cell carcinoma cell line (YM-1) using short tandem repeat (STR) profiling method.

    Science.gov (United States)

    Ayyoob, Khosravi; Masoud, Khoshnia; Vahideh, Kazeminejad; Jahanbakhsh, Asadi

    2016-03-01

    Cross-contamination during or early after establishment of a new cell line could result in the worldwide spread of a misidentified cell line. Therefore, newly established cell lines need to be authenticated by a reference standard method. This study was conducted to investigate the authenticity of a newly established epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM-1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC epithelial cells were cultured from the fresh tumor tissue of an adult female patient. Growth characteristics and epithelial originality of YM-1 cells were studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and ESCC donor tumor sample on two different days to prevent probable DNA contamination. STR profiling was performed using AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration as the passage number increases, STR profiling was performed again on harvested cells at passage 51. YM-1 cells grew as a monolayer with a population doubling time of 40.66 h. Epithelial originality of YM-1 cells was confirmed using ICC/IF staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample was the same with YM-1 cells at passage 22. However, STR profile of the donor tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re-profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at D18S51 locus. This suggests that long-term culture of cell lines may alter their DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR profiling databases confirmed unique identity of YM-1 cell line. This study provides an easy, fast, and reliable procedure for authentication of newly established cell lines, which helps in preventing the spread of misidentified cells and improving the reproducibility and validity of experiments, consequently.

  17. The expression of macrophage migration inhibitory factor in carcinoma of gastro-esophageal junction tissue%胃食管接合部癌组织中MIF的表达

    Institute of Scientific and Technical Information of China (English)

    郭豫兰; 赵劲松; 廖克龙; 杨康

    2012-01-01

    目的:研究巨噬细胞移动抑制因子(MIF)在胃食管接合部癌组织中的表达及意义.方法:免疫组化检测40例胃食管接合部癌组织中MIF蛋白表达水平,分析与临床病理的相关性.结果:MIF蛋白在胃食管接合部癌组织中存在异常的高水平表达,与癌细胞的分化程度、肿瘤TNM分期密切相关.结论:MIF可能参与了胃食管接合部癌的发病机制,可以作为早期诊断、预测预后的潜在的指标之一.%Objective: To explore the expression of macrophage migration inhibitory factor(MIF) in carcinoma of gastro - esophageal junction. Methods;To examine the expression level of MIF in forty patients with carcinoma of gas-tro -esophageal junction by immunohistochemistry staining, and analyze the clinical pathology significance. Results: MIF was overexpressed in carcinoma of gastro - esophageal junction specimens, the expression of MIF closely correla-ted with tumor differentiation and the tumor TNM staging. Conclusion: MIF contributed to the pathogenesis of carcino-ma of gastro - esophageal junction, and MIF can be conductd as one potential index to pretest the prognosis and early diagnosis of carcinoma of gastro - esophageal junction.

  18. Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings. One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification. The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no

  19. Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.

    Science.gov (United States)

    Jing, Rongrong; Chen, Wen; Wang, Huimin; Ju, Shaoqing; Cong, Hui; Sun, Baolan; Jin, Qin; Chu, Shaopeng; Xu, Lili; Cui, Ming

    2015-11-01

    The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker

  20. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas.

    Science.gov (United States)

    Ishikawa, Nobuhisa; Takano, Atsushi; Yasui, Wataru; Inai, Kouki; Nishimura, Hitoshi; Ito, Hiroyuki; Miyagi, Yohei; Nakayama, Haruhiko; Fujita, Masahiro; Hosokawa, Masao; Tsuchiya, Eiju; Kohno, Nobuoki; Nakamura, Yusuke; Daigo, Yataro

    2007-12-15

    Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.

  1. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Hiroki, E-mail: h-nishikawa@osaka-med.jrc.or.jp; Osaki, Yukio; Kita, Ryuichi; Kimura, Toru [Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027 (Japan)

    2012-02-21

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  2. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Directory of Open Access Journals (Sweden)

    Ryuichi Kita

    2012-02-01

    Full Text Available Transcatheter methods such as transcatheter arterial chemoembolization (TACE and hepatic arterial infusion chemotherapy (HAIC have an important role in the treatment for advanced hepatocellular carcinoma (HCC. Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  3. Early prediction of treatment response by serum CRP levels in patients with advanced esophageal cancer who underwent definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Serum C reactive protein (CRP) has been shown to be associated with the progression of esophageal cancer. The purpose of this study was to examine the relationship between treatment response and serum CRP levels in time course during definitive chemoradiotherapy (CRT) in terms of early prediction of CRT response by serum CRP. The subjects of this study were 36 patients with cT3/cT4 esophageal squamous cell carcinoma who underwent definitive CRT in our hospital. Serum CRP levels during definitive CRT (pretreatment, 1W, 2W and 3W after CRT initiation) were compared between CR and non-CR group. In addition, partition model was constructed to discriminate CR with non-CR and the prediction accuracy was evaluated. The patients were consisted of 28 males and 8 females. At pretreatment diagnosis, tumors were categorized as T3 (n=21) and T4 (n=15). Thirty four patients received FP-based chemotherapy and 2 patients received docetaxel-based chemotherapy. Treatment responses were categorized as CR (n=8), partial response (PR) (n=14), no change (NC) (n=2) and progressive disease (PD) (n=12). Serum CRP levels at the time of 2W after CRT initiation (CRT2W) in CR group were low compared to those in non-CR group (p=0.071). The partition model was constructed based on CRP levels at CRT2W. The prediction accuracies to discriminate CR from non-CR by CRP ≤0.1 were 50%, 82%, and 75% in sensitivity, specificity and accuracy, respectively. Serum CRP is a useful biomarker for an early prediction of CRT response. (author)

  4. Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Irami Araújo-Filho

    2006-12-01

    Full Text Available BACKGROUD: There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7% were intestinal-type and 22 (39.3% diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6% and atrophic mucosa in 36 patients (64.3%. All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was

  5. Genomic alterations in advanced esophageal cancer may lead to subtype-specific therapies.

    Science.gov (United States)

    Forde, Patrick M; Kelly, Ronan J

    2013-01-01

    The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8-12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease.

  6. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  7. Monitoring of Tumor Response to Neoadjuvant Radio-Chemotherapy of Esophageal Carcinoma by F-18-FDG-PET%F-18-FDG-PET监测新辅助疗法食管癌的反应

    Institute of Scientific and Technical Information of China (English)

    Peter Theissen; Paul M.Schneider; Stephan E.Baldus; Alexandra Jost; Markus Dietlein; Rolf P.Müller; Arnulf H.H(o)lscher; Harald Schicha

    2004-01-01

    Introduction: For clinical assessment of neoadjuvant radiochemotherapy of esophageal cancer reliable in-vivo methods are necessary. Therefore, the capabilities of F-18-Fluorodesoxyglucose-PET in comparison to histomorphological grading of tumor regression were studied. Methods: In 33 patients with locally advanced esophageal carcinoma (uT3, uN0-1, cM0) F-18-FDG-PET was performed before and 2weeks after radiochemotherapy. All tumors were resected by transthoracic en-bloc esophagectomy 3-4 weeks after induction therapy. A subgroup of 11 patients underwent weekly PET scan during neoadjuvant therapy.PET was performed in a dedicated scanner 1.3 h after administration of 370 MBq F-18-FDG. Data analysis based on maximum SUV data derived from individual regions of interest in pre- and posttherapeutic images. PET data were compared to histomorphological grading parameters for tumor regression whithin the resected tissues. Results: The comparison of histopathological tumor regression after neoadjuvant therapy and PET SUV differences showed a significant X2 P-value of 0.006. There was a significant decrease of the SUV data from 9.1±3.5 to 4.3±1.9 (P<0.0001). In therapy responders SUV was diminished by 59% and in non-responders by 34 %. Longitudinal SUV measurement during neoadjuvant therapy showed a strong SUV decrease already after one and two weeks (P=-0.021 and 0.003). Conclusion: The recent data of the FDG-PET follow-up after neoadjuvant therapy show that PET is able to predict therapy response.Longitudinal PET data advocate that it may be possible to recognize response also very early during radiochemotherapy.

  8. Effect of Contrast Agent on IMRT Treatment Plan for Esophageal Carcinoma%造影剂对食管癌调强放疗计划的影响

    Institute of Scientific and Technical Information of China (English)

    林志安; 张清罗; 侯如蓉; 潘惠敏

    2012-01-01

    Objective To evaluate the effect of contrast agent on IMRT treatment plan for esophageal carcinoma. Meth-ods Ten patients of esophageal carcinoma treated with IMRT,were planned by CT image with contrast agent or not. Isodose dis-tribution of PTV and dose-volume histogram of organ at risk were compared. Results The maximum dose,, the minimum dose、 the mean dose and the median dose of PTV have a mean increase of 30 cGy in plan with contrast agent than in plan without contrast agent. No significant difference was found in the maximum dose of spinal corcKthe V20 and V30 of lung 、the conforms! index and the homogeneity index between the two plans. The mean dose of heart and lung were spared more in plan without contrast agent. Conclusion On the IMRT treatment plan for esophageal carcinoma, contrast agent has little effect and can be neglected.%目的 探讨增强造影剂对食管癌调强放疗计划的影响.方法 对10例食管癌进行CT平扫与增强造影,分别设计调强放疗计划,比较2个计划靶区剂量分布和危及器官的剂量体积受量.结果 增强影像计划的靶区最大剂量、最小剂量、平均剂量及中位剂量,较平扫影像计划的平均高30 cGy,适形度指数和均匀性指数的比较无差异,增强影像计划的双肺平均剂量、心脏平均剂量受量高.2种计划的双肺V20、V30和脊髓最大剂量比较无差异.结论 造影剂对食管癌调强放疗剂量有影响,但影响较小,可以直接在增强影像上设计放疗计划.

  9. Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Teik Hin Tan

    2016-07-01

    Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

  10. Technical advances in external radiotherapy for hepatocellular carcinoma.

    Science.gov (United States)

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-08-28

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  11. Technical advances in external radiotherapy for hepatocellular carcinoma

    Science.gov (United States)

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  12. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Elshamy Maged R

    2005-08-01

    Full Text Available Abstract Background Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemotherapy as treatment modalities in the specific indication of operable patients with advanced ovarian carcinoma (no medical contraindication to debulking surgery. Patients and methods A total of 59 patients with stage III or IV epithelial ovarian carcinomas were evaluated between 1998 and 2003. All patients were submitted to surgical exploration aiming to evaluate tumor resectability. Neoadjuvant chemotherapy was given (in 27 patients where optimal cytoreduction was not feasible. Conversely primary debulking surgery was performed when we considered that optimal cytoreduction could be achieved by the standard surgery (32 patients. Results Optimal cytoreduction was higher in the NACT group (72.2% than the conventional group (62.4%, though not statistically significant (P = 0.5. More important was the finding that parameters of surgical aggressiveness (blood loss rates, ICU stay and total hospital stay were significantly lower in NACT group than the conventional group. The median overall survival time was 28 months in the conventional group and 25 months in NACT group with a P value of 0.5. The median disease free survival was 19 months in the conventional group and 21 months in NACT group (P = 0.4. In multivariate analysis, the pathologic type and degree of debulking were found to affect the disease free survival significantly. Overall survival was not affected by any of the study parameters. Conclusion Primary chemotherapy followed by interval debulking surgery

  13. Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

    International Nuclear Information System (INIS)

    To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors

  14. A preliminary study on ras protein expression in human esophageal cancer and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Chang Wei Feng; Zhi Guo Zhao; Qi Zhou; Li Dong Wang

    2000-01-01

    @@INTRODUCTION The esophageal carcinoma is a common malignant tumor in Linzhou City (Linxian) of Henan Province in northern China. Although the etiology and natural history of esophageal carcinoma are not clear, a substantial amount of evidence has been provided to suggest that the development of human esophageal squamous cell carcinomas (SCC) is a multistage progressive process[1-4] An early indicator of abnormality in persons predisposed to esophageal SCC is an increased proliferation of esophageal epithelial cells,morphologically manifested as basal cell hyperplasia (BCH), and dysplasia (DYS), and carcinoma in situ, which could be considered precancerous lesions of esophageal SCC[1-4].

  15. Expression of PED/PEA-15 mRNA and protein in esophageal carcinoma%食管癌中PED/PEA-15mRNA及蛋白表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    庄晓飞; 张弘广; 王春利; 郭石平; 马炎炎; 解立武

    2013-01-01

    Objective To investigate the expression of PED/PEA-15 mRNA and protein in esophageal carcinoma tissue and their clinical significances.Methods The expression of PED/PEA-15 mRNA was detected by RT-PCR,and the expression of PED/PEA-15 protein was measured by immunohistochemistry in 50 cases of esophageal carcinoma,50 cases of corresponding paracarcinoma tissue,and 50 cases of corresponding normal esophageal tissue.Results The expression of PED/PEA-15 mRNA was 1.14±0.49 in esophageal carcinoma,which was significantly higher than that in para-carcinoma tissue (0.59±0.31) and normal esophageal carcinoma tissue (0.53±0.22) (F =44.085,P < 0.001).The immunohistochemistry results showed that PED/PEA-15 protein expression was significantly higher than that in para-carcinoma tissue and normal esophageal tissue (x2 =36.967,P < 0.001; x2 =26.272,P < 0.001).The expression of PED/PEA-15 mRNA and protein were significantly associated with pathological grade,clinical stage of esophageal carcinoma (P < 0.05),but were not significantly correlated to the age of onset,gender,pathological types (P > 0.05).Conclusion The expression of PED/PEA-15 mRNA and protein are increased in esophageal carcinoma,which may play an important role in the occurrence and development of esophageal carcinoma.%目的 探讨PED/PEA-15 mRNA及蛋白在食管癌组织中的表达情况及其临床意义.方法 应用半定量反转录-聚合酶链反应(RT-PCR)检测50例食管癌、相应癌旁组织和正常食管组织中PED/PEA-15基因的相对表达量,并通过免疫组织化学检测PED/PEA-15蛋白的表达.结果 半定量RT-PCR显示,PED/PEA-15基因在食管癌组织中均呈高表达,癌旁组织及正常食管组织呈低表达或不表达,相对表达量分别为1.14±0.49、0.59±0.31和0.53±0.22,PED/PEA-15 mRNA在食管癌组织中表达较癌旁组织、正常食管组织升高(F=44.085,P<0.01).免疫组织化学结果显示,食管癌组织中PED/PEA-15蛋白阳性表达率

  16. Endoscopic Stent Treatment of Advanced Esophageal Cancer%内镜直视下中晚期食道癌的支架治疗

    Institute of Scientific and Technical Information of China (English)

    杜桂英; 陶中原

    2012-01-01

    Objective: To explore the approach and the therapeutic effect of endoscopic stent treatment of advanced esophageal cancer. Methods: Endoscopic stent implantation was carried out on patients diagnosed advanced esophageal cancer with endoscopy and pathological examination, who was unwilling to operate or unresectable. Results: Total 91 patients were treated with 97 stents, the success rate was 100% and efficiency was 100%. Conclusion: Endoscopic esophageal stenting is an effective method for the treatment of advanced esophageal cancer.%目的:探讨中晚期食道癌内镜下治疗的方法和疗效。方法:经过内镜检查和病理诊断的中晚期食道癌,不愿意或失去手术机会的患者进行内镜直视下支架的置入术。结果:91例患者置/L97个支架,成功率100%,有效率100%。结论:内镜直视下食道支架置入是治疗中晚期食道癌的有效方法。

  17. A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery

    Science.gov (United States)

    Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

    2016-01-01

    The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients. PMID:26959879

  18. A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

    Science.gov (United States)

    Wang, Di; Yang, Xin-lu; Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

    2016-04-01

    The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.

  19. Association of Polymorphisms in X-Ray Repair Cross Complementing 1 Gene and Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Yu-Xia Yun

    2015-01-01

    Full Text Available Objectives. To investigate the association between three single nucleotide polymorphisms (SNPs in the X-ray repair cross complementing 1 gene (XRCC1 and the risk of esophageal squamous cell carcinoma (ESCC in Chinese population. Methods. A case-control study including 381 primary ESCC patients recruited from hospital and 432 normal controls matched with patients by age and gender from Chinese Han population was conducted. The genotypes of three XRCC1 polymorphisms at −77T>C (T-77C, codon 194 (Arg194Trp, and codon 399 (Arg399Gln were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP. Unconditional logistic regression model and haplotype analysis were used to estimate associations of these three SNPs in XRCC1 gene with ESCC risk. Results. Polymorphisms at these three sites in XRCC1 gene were not found to be associated with risk for developing ESCC; however the haplotype Ccodon 194Gcodon 399C-77T>C was significantly associated with reduced risk of ESCC (OR: 0.62, 95% CI: 0.40–0.96 upon haplotype analysis. Conclusion. These results suggested that the gene-gene interactions might play vital roles in the progression on esophageal cancer in Chinese Han population and it would be necessary to confirm these findings in a large and multiethnic population.

  20. Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating beta-catenin/TCF pathway.

    Science.gov (United States)

    Wang, Yihua; Zhou, Xiaobo; Zhu, Hongxia; Liu, Shuang; Zhou, Cuiqi; Zhang, Guo; Xue, Liyan; Lu, Ning; Quan, Lanping; Bai, Jinfeng; Zhan, Qimin; Xu, Ningzhi

    2005-10-01

    Esophageal squamous cell carcinoma (ESCC) has a multifactorial etiology involving environmental and/or genetic factors. End-binding protein 1 (EB1), which was cloned as an interacting partner of the adenomatous polyposis coli (APC) tumor suppressor protein, was previously found overexpressed in ESCC. However, the precise role of EB1 in the development of this malignancy has not yet been elucidated. In this study, we analysed freshly resected ESCC specimens and demonstrated that EB1 was overexpressed in approximately 63% of tumor samples compared to matched normal tissue. We report that overexpression of EB1 in the ESCC line EC9706 significantly promotes cell growth, whereas suppression of EB1 protein level by RNA interference significantly inhibited growth of esophageal tumor cells. In addition, EB1 overexpression induced nuclear accumulation of beta-catenin and promoted the transcriptional activity of beta-catenin/T-cell factor (TCF). These effects were partially or completely abolished by coexpression of APC or DeltaN TCF4, respectively. Also, we found that EB1 affected the interaction between beta-catenin and APC. Furthermore, EB1 overexpression was correlated with cytoplasmic/nuclear accumulation of beta-catenin in primary human ESCC. Taken together, these results support the novel hypothesis that EB1 overexpression may play a role in the development of ESCC by affecting APC function and activating the beta-catenin/TCF pathway.

  1. Activating transcription factor 4 mediates a multidrug resistance phenotype of esophageal squamous cell carcinoma cells through transactivation of STAT3 expression.

    Science.gov (United States)

    Zhu, Hongwu; Chen, Xiong; Chen, Bin; Chen, Bei; Fan, Jianyong; Song, Weibing; Xie, Ziying; Jiang, Dan; Li, Qiuqiong; Zhou, Meihua; Sun, Dayong; Zhao, Yagang

    2014-11-01

    Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.

  2. Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition.

    Science.gov (United States)

    Zhang, Chun-Yang; Li, Ren-Ke; Qi, Yu; Li, Xiang-Nan; Yang, Yang; Liu, Dong-Lei; Zhao, Jia; Zhu, Deng-Yan; Wu, Kai; Zhou, Xu-Dong; Zhao, Song

    2016-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-β-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.

  3. U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population.

    Science.gov (United States)

    Du, Jiangbo; Xue, Wenjie; Ji, Yong; Zhu, Xun; Gu, Yayun; Zhu, Meng; Wang, Cheng; Gao, Yong; Dai, Juncheng; Ma, Hongxia; Jiang, Yue; Chen, Jiaping; Hu, Zhibin; Jin, Guangfu; Shen, Hongbing

    2015-12-01

    Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TLSNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P telomeres may be risk factors for ESCC in the Chinese population.

  4. beta-Catenin/TCF pathway plays a vital role in selenium induced-growth inhibition and apoptosis in esophageal squamous cell carcinoma (ESCC) cells.

    Science.gov (United States)

    Zhang, Wei; Yan, Shuang; Liu, Mei; Zhang, Guo; Yang, Shangbin; He, Shun; Bai, Jinfeng; Quan, Lanping; Zhu, Hongxia; Dong, Yan; Xu, Ningzhi

    2010-10-01

    Epidemiological and experimental studies have indicated selenium could reduce the risk of some cancers. In our present study, growth inhibition and apoptosis were detected upon methylseleninic acid (MSA) treatment in human esophageal squamous cell carcinoma cell lines EC9706 and KYSE150. MSA reduced beta-catenin protein levels, while there was no significant change observed on transcriptional levels. Moreover, we found MSA accelerated the degradation of beta-catenin and activated glycogen synthase kinase 3beta (GSK-3beta). Some targets of beta-catenin/TCF pathway and apoptosis-related genes altered after MSA treatment. Notably, utilizing the inducible 293-TR/beta-catenin cell line, we found the apoptotic phenotypes induced by MSA were partially reversed by the overexpression of beta-catenin. Overall, our data indicate the effects induced by MSA in ESCC cells may act on the inhibition of beta-catenin/TCF pathway.

  5. Flowers of Camellia nitidissima cause growth inhibition, cell-cycle dysregulation and apoptosis in a human esophageal squamous cell carcinoma cell line

    Science.gov (United States)

    Dai, Lu; Li, Ji-Lin; Liang, Xin-Qiang; Li, Lin; Feng, Yan; Liu, Hai-Zhou; Wei, Wen-Er; Ning, Shu-Fang; Zhang, Li-Tu

    2016-01-01

    The present study aimed to investigate the chemo-preventive effect of Camellia nitidissima flowers water extract (CNFE) on the Eca109 human esophageal squamous cell carcinoma (ESCC) cell line. The antiproliferative effect on Eca109 cells was determined using the trypan blue exclusion assay. The effects of CNFE on apoptosis and cell cycle arrest were investigated by flow cytometry. CNFE inhibited cell growth in both a dose- and time-dependent manner in Eca109 cells. CNFE also caused dose- and time-dependent apoptosis of these cells. Treatment of cells with CNFE resulted in dose-dependent G0/G1 phase arrest of the cell cycle. The data demonstrated that CNFE serves antiproliferative effects against human ESCC Eca109 cells by inducing apoptosis and interrupting the cell cycle. These results suggested that CNFE has the potential to be a chemoprotective agent for ESCC. PMID:27314447

  6. Therapeutic options for intermediate-advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zong-Ming Zhang; Jin-Xing Guo; Zi-Chao Zhang; Nan Jiang; Zhen-Ya Zhang; Li-Jie Pan

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies, ranking the sixth in the world, with 55% of cases occurring in China. Usually, patients withHCC did not present until the late stage of the disease,thus limiting their therapeutic options. Although surgical resection is a potentially curative modality for HCC,most patients with intermediate-advanced HCC are not suitable candidates. The current therapeutic modalities for intermediate-advanced HCC include: (1) surgical procedures,such as radical resection, palliative resection,intraoperative radiofrequency ablation or cryosurgical ablation, intraoperative hepatic artery and portal vein chemotherapeutic pump placement, two-stage hepatectomy and livertransplantation; (2) interventional treatment,such as transcatheter arterial chemoembolization,portal vein embolization and image-guided locoregional therapies; and (3) molecularly targeted therapies. So far, how to choose the therapeutic modalities remains controversial. Surgeons are faced with the challenge of providing the most appropriate treatment for patients with intermediate-advanced HCC. This review focuses on the optional therapeutic modalities for intermediateadvanced HCC.

  7. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  8. THE CURATIVE EFFECT OF THE RADICAL CORRECTION OF CARCINOMA OF GASTRIC CARDIA AND ESOPHAGEAL CARCINOMA ON GASTROESOPHAGEAL REFLUX%贲门癌、食管下段癌预防术后返流的术式研究

    Institute of Scientific and Technical Information of China (English)

    张力军

    2014-01-01

    Objective To explore the curative effect of the radical correction of carcinoma of gastric cardia and esophageal carcinoma on gastroesophageal reflux .Methods 100 cases of carcinoma of gastric cardia and esophageal carcinoma were divided into the observation group and the contrast group by using random sim-ple blind control study .The contrast group was treated with conventional esophagogastrostomy .After the observation group received routine double stapling technique ,the cardiac structure was established by half wrapping the gastric wall sutured at stoma and by overhanging and embedding pleura mediastinalis outside lower esophagus ,the gastric greater curvature was lifted to be fixed with pleura mediastinalis to form the structure of undus of stomach ,and the transverse suture of 1/3 circle about 3cm under anterior gastric wall stoma was used to make stomach full-thickness bulge under stoma .Postoperative reflux esophagitis was observed .Results More than 35 cases showed no reflux and less than 15 cases got reflux in the observation group while less than 20 cases got no reflux and more than 30 cases got reflux( P<0 .01) .Conclusion The combined use of routine esophagus-stomach anastomosis and the augmentation technique of half w rapping lower esophagus and forming full-thickness inward bulging under anterior gastric wall can effectively re-duce the occurrence of gastroesophageal reflux after the radical correction of carcinoma of gastric cardia and e-sophageal carcinoma .%目的:探讨贲门癌、食管下段癌根治术预防胃食管返流的有效方法。方法采用随机单盲对照研究,将100例贲门癌、食管下段癌患者分为观察组和对照组。对照组采用常规食管胃吻合法,观察组在常规吻合器吻合后,将胃壁半包绕缝合在吻合口及食管下段外加纵隔胸膜悬吊包埋建立类似贲门样结构,将胃大弯侧向上提与纵隔胸膜固定形成胃底样结构,胃前壁吻合口下方约3cm

  9. Insights into anticancer activity and mechanism of action of a ruthenium(II) complex in human esophageal squamous carcinoma EC109 cells.

    Science.gov (United States)

    Guo, Liubin; Lv, Gaochao; Qiu, Ling; Yang, Hui; Zhang, Li; Yu, Huixin; Zou, Meifen; Lin, Jianguo

    2016-09-01

    A ruthenium(II) complex [Ru(p-cymene)(NHC)Cl2] (NHC=1,3-bis(4-(tert-butyl)benzylimidazol-2-ylidene), referred to as L-4, has been designed and synthesized recently in order to look for new anticancer drugs with high efficacy and low side effects. The anticancer activity and mechanism of action of L-4 in human esophageal squamous carcinoma EC109 cells were systematically investigated. The results revealed that L-4 exerted strong inhibitory effect on the proliferation of EC109 cells, and it arrested EC109 cells at G2/M phase, accompanied with the up-regulation of p53 and p21 and the down-regulation of cyclin D1. The results also showed that the reactive oxygen species (ROS)-dependent apoptosis of EC109 can be induced by L-4 via inhibiting the activity of glutathione reductase (GR), decreasing the ratio of glutathione to oxidized glutathione (GSH/GSSG), and leading to the generation of reactive oxygen species. The mitochondria-mediated apoptosis of EC109 induced by L-4 was also observed from the increase of Bax/Bcl-2 ratio, overload of Ca(2+), disruption of mitochondrial membrane potential (MMP), redistribution of cytochrome c, and activation of caspase-3/-9. However, the effects of L-4 on the cell viability, GR activity, GSH/GSSG ratio, reactive oxygen species level, mitochondria dysfunction and apoptosis induction were remarkably attenuated by adding the reactive oxygen species scavenger, NAC. Therefore, it was concluded that L-4 can inhibit the proliferation of EC109 cells via blocking cell cycle progression and inducing reactive oxygen species-dependent and mitochondria-mediated apoptosis. These findings suggested that the ruthenium(II) complex might be a potential effective chemotherapeutic agent for human esophageal squamous carcinoma (ESCC) and worthy of further investigation. PMID:27262377

  10. Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma.

    Science.gov (United States)

    Saito, Tsuyoshi; Mitomi, Hiroyuki; Imamhasan, Abdukadir; Hayashi, Takuo; Mitani, Keiko; Takahashi, Michiko; Kajiyama, Yoshiaki; Yao, Takashi

    2014-02-01

    Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of typical squamous cell carcinoma (SCC) associated with poor survival. A characteristic feature is nuclear accumulation of β-catenin, without a mutation of the gene. We studied the methylation status of Wnt antagonist genes, such as secreted frizzled-related protein (sFRP) gene family members, Wnt inhibitory factor-1 (WIF-1), Dickkopf-1 (Dkk-1), and human Dapper protein-1 (HDPR-1), and alterations of the APC, Axin1, and Axin2 genes in 30 cases of esophageal BSCC. β-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression was examined by immunohistochemistry. APC, Axin1, and Axin2 gene mutations were detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least 1 alteration in these genes. Methylation of the sFRP-2 promoter region was observed in all cases, and methylation was frequent in sFRP-1 and sFRP-5, but infrequent in Dkk-1, WIF-1, sFRP-4, and HDPR-1. sFRP-2 expression was almost completely absent in 25 cases (83 %), consistent with the methylation status. Nuclear accumulation of β-catenin was observed in all cases. sFRP-5 expression was associated with a low nuclear β-catenin labeling index. These results show that sFRP-2 is a target gene of hypermethylation in esophageal BSCC and suggest that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/β-catenin signaling pathway. PMID:24464051

  11. Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma

    Science.gov (United States)

    Kanamoto, Ayako; Ninomiya, Itasu; Harada, Shinichi; Tsukada, Tomoya; Okamoto, Koichi; Nakanuma, Shinichi; Sakai, Seisho; Makino, Isamu; Kinoshita, Jun; Hayashi, Hironori; Oyama, Katsunobu; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Fushida, Sachio; Ohta, Tetsuo

    2016-01-01

    Esophageal carcinoma is one of the most aggressive malignancies, and is characterized by poor response to current therapy and a dismal survival rate. In this study we investigated whether irradiation induces epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) TE9 cells and whether the classic histone deacetylase (HDAC) inhibitor valproic acid (VPA) suppresses these changes. First, we showed that 2 Gy irradiation induced spindle cell-like morphologic changes, decreased expression of membranous E-cadherin, upregulated vimentin expression, and altered the localization of β-catenin from its usual membrane-bound location to cytoplasm in TE9 cells. Irradiation induced upregulation of transcription factors including Slug, Snail, and Twist, which regulate EMT. Stimulation by irradiation resulted in increased TGF-β1 and HIF-1α expression and induced Smad2 and Smad3 phosphorylation. Furthermore, irradiation enhanced CD44 expression, indicating acquisition of cancer stem-like cell properties. In addition, irradiation enhanced invasion and migration ability with upregulation of matrix metalloproteinases. These findings indicate that single-dose irradiation can induce EMT in ESCC cells. Second, we found that treatment with 1 mM VPA induced reversal of EMT caused by irradiation in TE9 cells, resulting in attenuated cell invasion and migration abilities. These results suggest that VPA might have clinical value to suppress irradiation-induced EMT. The reversal of EMT by HDAC inhibitors may be a new therapeutic strategy to improve the effectiveness of radiotherapy in ESCC by inhibiting the enhancement of invasion and metastasis.

  12. TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

    Directory of Open Access Journals (Sweden)

    Martel-Planche Ghislaine

    2011-10-01

    Full Text Available Abstract Background Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC in this area. Results We have analyzed TP53 mutations, the presence of human papilloma virus (HPV DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2 and Nitrotyrosine (NTyR in 28 cases (13 males and 15 females of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in TP53 exons 5 to 8 (39%. All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively. No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking was found. Conclusion Our findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of TP53 mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia.

  13. Significant association among the Fas -670 A/G (rs1800682) polymorphism and esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Liu, Tao; Zuo, Li; Li, Lin; Yin, Lei; Liang, Kai; Yu, Hongyuan; Ren, Hui; Zhou, Wen; Jing, Hongwei; Liu, Yang; Kong, Chuize

    2014-11-01

    The Fas gene plays a key role in regulation of apoptotic cell death, and corruption of this signaling pathway has been shown to participate in immune escape and tumorgenesis. Single-nucleotide polymorphism in the promoter of Fas gene at position -670 A/G may affect its expression and play an important role in the pathology of many kinds of cancer. The association between Fas -670 A/G polymorphism and cancer risk is still controversial and ambiguous. Therefore, we conducted a meta-analysis of the currently literature to clarify this relationship. We conducted a search in the PubMed, EMbase, CNKI, and WanFang databases, covering all papers published by May 5, 2014. Overall, 59 case-control studies with 17,035 cases and 23,155 controls were retrieved based on the search criteria for cancer susceptibility related to -670 A/G polymorphism in Fas gene. Odds ratios (OR) and 95% confidence intervals (CI) revealed association strengths. Although no significant relationship was detected between Fas -670 A/G polymorphism and whole cancer risk, in the ethnicity subgroup, significant associations were found in three types of cancer: prostate cancer (OR = 1.06, 95% CI = 1.01-1.11 for A-allele vs. G-allele); hepatocellular carcinoma (OR = 0.89, 95% CI = 0.80-0.99 for AG vs. GG); esophageal cancer (OR = 0.95, 95% CI = 0.92-0.99 for AA + AG vs. GG). Moreover, lower cancer risk was found in smokers carried A-allele, when compared to smokers carried the GG genotype. The Fas -670 A/G polymorphism may be associated with esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility from our meta-analysis. Studies with larger samples and gene-environment interactions are warranted to understand the role of Fas -670 A/G polymorphism for cancer risk.

  14. CT-guided {sup 125}I brachytherapy for mediastinal metastatic lymph nodes recurrence from esophageal carcinoma: Effectiveness and safety in 16 patients

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fei, E-mail: gaof@sysucc.org.cn [State Key Laboratory of Oncology in South China, Guangzhou 510060 (China); Department of Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060 (China); Li, Chuanxing, E-mail: licx@sysucc.org.cn [State Key Laboratory of Oncology in South China, Guangzhou 510060 (China); Department of Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060 (China); Gu, Yangkui, E-mail: guyk@sysucc.org.cn [State Key Laboratory of Oncology in South China, Guangzhou 510060 (China); Department of Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060 (China); Huang, Jinhua, E-mail: huangjh@sysucc.org.cn [State Key Laboratory of Oncology in South China, Guangzhou 510060 (China); Department of Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060 (China); Wu, Peihong, E-mail: vivian-link@163.com [State Key Laboratory of Oncology in South China, Guangzhou 510060 (China); Department of Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060 (China)

    2013-02-15

    Objectives: To retrospectively evaluate effectiveness and safety of CT-guided {sup 125}I brachytherapy in 16 patients with mediastinal metastatic lymph nodes recurrence from esophageal carcinoma. Materials and methods: Sixteen metastatic lymph nodes in 16 patients were percutaneously treated in 19 {sup 125}I brachytherapy sessions. Each metastatic lymph node was treated with computed tomographic (CT) guidance. Follow-up contrast material-enhanced CT or positron emission tomographic (PET) scans were reviewed and the treatment's effectiveness was evaluated. Results: Months are counted from the first time of {sup 125}I brachytherapy and the median duration of follow-up was 11 months (range, 5–16 months). The local control rates after 3, 6, 10 and 15 months were 75.0, 50.0, 42.9 and 33.3% respectively. At the time of writing, four patients are alive without evidence of recurrence at 16, 9, 16 and 9 months. The 4 patients presented good control of local tumor and no systemic recurrence, and survived throughout the follow-up period. The other 12 patients died of multiple hematogenous metastases 5–15 months after brachytherapy. A small amount of local hematoma occurred in 2 patients that involved applicator insertion through the lung. Two patients presented pneumothorax with pulmonary compression of 30 and 40% after the procedure and recovered after drainage. One patient had minor displacement of radioactive seeds. Severe complications such as massive bleeding and radiation pneumonitis did not occur. Conclusion: {sup 125}I radioactive seed implantation is effective and may be safely applied to mediastinal metastatic lymph nodes recurrence from esophageal carcinoma.

  15. DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ng, Hoi Yan; Ko, Josephine Mun-Yee; Yu, Valen Zhuoyou; Ip, Joseph Chok Yan; Dai, Wei; Cal, Santiago; Lung, Maria Li

    2016-06-15

    Esophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr-AKT, abolished the apoptosis-sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three-dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway.

  16. Hepatocellular carcinoma:current management and recent advances

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the iffth most common cancer in the world, and the third most common cause of cancer-related death. Without speciifc treatment, the prognosis is very poor. The goal of management is"cancer control"-a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances. DATA SOURCES:A MEDLINE database search was performed to identify relevant article using the keywords"hepatocellular carcinoma", "hepatectomy", "liver transplantation", and"local ablative therapy". Additional papers and book chapters were identiifed by a manual search of the references from the key articles. RESULTS:Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results. CONCLUSIONS:Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC.

  17. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin

  18. Clinical Significance of EGFR Expression in Esophageal Squamous Cell Carcinoma%EGFR蛋白在食管鳞癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    吴金训; 余英豪; 刘伟

    2012-01-01

    目的 评价表皮生长因子受体(EGFR)过表达与食管鳞癌患者临床病理参数的相关性及其临床意义.方法 收集2004年1月至2010年6月在南京军区福州总医院手术切除临床资料完整的食管鳞癌标本1034例,采用EliVisionTM plus免疫组织化学染色检测癌组织中EGFR蛋白表达.结果 EGFR在食管鳞癌组织中阳性表达率为74.9%,癌旁非肿瘤性黏膜未见EGFR蛋白过表达;EGFR蛋白表达与患者性别、年龄、肿瘤大小、肉眼分型、TNM分期、浸润深度、淋巴结转移及远处转移均无相关性(P>0.05),而高、中分化胃癌中EGFR的表达显著高于低、未分化胃癌(P<0.05).结论 EGFR蛋白表达与食管鳞癌患者的临床病理参数无明显相关性,不能作为评估食管鳞癌恶性生物学行为的指标,但EGFR过表达为食管鳞癌的靶向治疗研究提供了新思路,EGFR基因可能成为靶向治疗的新靶点.%Objective To evaluate the correlation between EGFR overexpression and esophageal squamous cell carcinoma clinical pathological parameters and the clinical significance. Methods 1034 cases of esophageal squamous cell carcinoma samples with complete clinical data from surgical resection at Fuzhou General Hospital of Nanjing Military Command during Jan. 2004 and Jun. 2010 were collected,EGFR protein expression of which were examined with EliVisionTM plus immunohistochemical staining. Results Out of 1034 esophageal squamous cell carcinoma samples examined by IHC,a total of 774( 74.9% )cases were positive for EGFR overexpression,and no positive cases were observed in adjacent non-neoplastic mucosa. There were no relationship between EGFR overexpression and gender,age,tumor size,gross type differentiation,TNM staging,invasion depth,lymph node metastasis and distant metastasis( P >0. 05 ). The positive rates of EGFR in well differentiated adenocarcinomas was higher than poorly differentiated adenocarcinomas( P < 0. 05 ). Conclusion There are no

  19. 食管癌CT灌注参数与MVD相关性分析%Esophageal carcinoma:MSCT perfusion parameters and microvessel density

    Institute of Scientific and Technical Information of China (English)

    周胜利; 袁刚; 白玲; 黄连庆; 王宗盛

    2012-01-01

    目的:分析食管癌多层螺旋CT(MSCT)灌注成像参数与肿瘤微血管密度(MVD)问的相关性,探讨MSCT灌注成像在评价肿瘤血管生成中的应用价值.方法:79例经手术病理证实的食管癌患者行MSCT灌注成像,绘制兴趣区(ROI)的时间一密度曲线(TDC),计算血流量(BF)、血容量(BV)、平均通过时间(MTT)、毛细血管通透性(PS);切取同层肿瘤组织切片,测定微血管密度,分析不同分化程度、组织学分型及浸润深度的肿瘤组织的CT灌注参数差异及各参数与MVD之间的相关性.结果:79例食管癌BF、BV、MTT、PS平均值分别为(93.07±54.31)ml/(min·100g)、(6.35±1.77)ml/100g、(9.17±7.07)s、(12.71±7.79)ml/(min·100g);MVD计数为(24.69±8.61)条/高倍视野.BF、BV值与MVD呈正相关(P<0.05,r值分别为0.445、0.341),不同侵及深度的肿瘤组织的BF值的差异有统计学意义(P=0.034).结论:MSCT灌注成像可间接反映活体食管癌血管生成情况,为治疗方案的制定、疗效判定及预后评估提供依据.%To correlate multi slice computed tomography (MSCT) perfusion parameters with micro vessel density (MVD) and to explore the value of MSCT perfusion in the evaluation of tumor angiogenesis of esophageal carcino ma. Methods:Seventy nine patients with pathologically confirmed esophageal carcinoma underwent perfusion MSCT exami nation,tumor blood flow (BF) ,blood volume (BV) ,mean transit time (MTT) and permeability surface area product (PS)microvessel density (MVD). Perfusion MSCT measurements were correlated with MVD. Results:Mean BF,BV,MTT and PS were (93. 07 ± 54. 31)ml/(min·100g) ,(6. 35 ± 1. 77)ml/100g, (9. 17±7. 07) s and (12. 71 ± 7. 79)ml/(min ·100g),re spectively. The mean value of MVD was (24. 69±8. 61)item/hpf in 79 patients with esophageal carcinoma. BF (r=0. 445, P<0.05) and BV (r=0. 341, P<0. 05) correlated positively with MVD. Conclusion. MSCT perfusion is a feasible tech of esophageal carcinoma for treatment plan

  20. Understanding the sensory irregularities of esophageal disease.

    Science.gov (United States)

    Farmer, Adam D; Brock, Christina; Frøkjaer, Jens Brøndum; Gregersen, Hans; Khan, Sheeba; Lelic, Dina; Lottrup, Christian; Drewes, Asbjørn Mohr

    2016-08-01

    Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future. PMID:26890720

  1. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.