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Sample records for advanced esophageal squamous

  1. 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.

  2. 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

  3. 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...

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

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    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.

  5. 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.

  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. 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

  8. 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

  9. 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, 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

  10. 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

  11. 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 ...

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

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    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.

  13. Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of esophageal squamous cancers

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    Shi, Yaoping; Wang, Jianfeng; Bai, Zhibin; Li, Yonggang; Qiu, Longhua; Zhai, Bo; Zhang, Feng; Yang, Xiaoming

    2016-01-01

    Despite recent advances in surgical technique and treatment strategies for esophageal cancer (EC), to effectively manage the advanced (metastatic or disseminated) and recurrent EC still remain a great challenge. The aim of this study was to determine the feasibility of using intra-esophagus radiofrequency hyperthermia to enhance local HSV-TK/ganciclovir-mediated suicide gene therapy of an innovative animal models with orthotopic esophageal squamous cancers. Human esophageal squamous cancer (ESCa) cells were labeled with lentivirus/luciferase. ESCa cells and nude rats with orthotopic ESCa were divided into in four groups (n = 6/group) and treated with: i) combination therapy of MR imaging-heating-guidewire-mediated radiofrequency hyperthermia ((RFH, 42°C) plus local HSV-TK/GCV; ii) HSV-TK/GCV alone; iii) RFH alone; and (iv) phosphate-buffered saline (PBS). Bioluminescence optical imaging and transcutaneous ultrasound imaging were used to follow up bioluminescence signal and size changes of tumors among different groups over two weeks, which were correlated with subsequent histology. We demonstrated that combination therapy of RFH with gene therapy resulted in the lowest cell proliferation (37.5±8.6%, Pbioluminescence optical imaging photon signal intensity (0.81±0.17, P<0.01) of orthotopic esophageal cancers, compared with groups treated with gene therapy alone, RFH alone and PBS. Our study indicated that intra-esophageal radiofrequency hyperthermia could enhance the HSV-TK-mediated effect on esophageal squamous cancers. PMID:27725910

  14. 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

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    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

  15. 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.

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

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    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.

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

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    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.

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

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    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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Identification of human papillomavirus in esophageal squamous papillomas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort.METHODS: Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by ,amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. RESULTS: The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. CONCLUSION: This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP.

  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. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. 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.

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

    OpenAIRE

    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. ...

  13. 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, ...

  14. 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.

  15. 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.

  16. [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

  17. 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.

  18. 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

  19. Microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence

    Institute of Scientific and Technical Information of China (English)

    Jian-Chun Cai; Di Liu; Kai-Hua Liu; Hai-Ping Zhang; Shan Zhong; Ning-Sao Xia

    2008-01-01

    AIM: To investigate the microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence.METHODS: Forty-one specimens were obtained from esophageal cancer (EC) patients. Histopathological assessment identified 23 squamous cell carcinomas (SCC) and 18 adenocarcinomas (ADC), including only 8 ADC with Barrett esophageal columnar epithelium (metaplasia) and dysplasia adjacent to ADC. Paraffinembedded normal squamous epithelium, Barrett esophageal columnar epithelium (metaplasia), dysplasia and esophageal tumor tissues were dissected from the surrounding tissues under microscopic guidance. DNA was extracted using proteinase K digestion buffer, and DNA was diluted at 1:100, 1:1000, 1:5000, 1:10000 and 1:50000, respectively. Seven microsatellite markers (D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci) were used in this study. Un-dilution and dilution polymerase chain reactions (PCR) were performed, and microsatellite analysis was carried out.RESULTS: No statistically significant difference was found in microsatellite instability (MSI) and loss of heterozygosity (LOH) of un-diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci.CONCLUSION: The sequence of metaplasia-dysplasia-adenocarcinoma is associated with microsatellite alterations, including MSI and LOH. The MSI and LOH may be the early genetic events during esophageal carcinogenesis, and genetic alterations at the D3S1616, D5S346 and D3S123 loci may play a role in the progress of microsatellite alterations.

  20. 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...

  1. 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.

  2. 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.

  3. 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 ...

  4. 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.

  5. 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.

  6. 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...

  7. 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, ...

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

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    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.

  9. 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

  10. 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

  11. 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.

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

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    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.

  13. 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

  14. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    Science.gov (United States)

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer. PMID:27220342

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

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    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.

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

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    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

  17. 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

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

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    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

  19. 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.

  20. 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

  1. Clinicopathologic Features of Advanced Squamous NSCLC.

    Science.gov (United States)

    Socinski, Mark A; Obasaju, Coleman; Gandara, David; Hirsch, Fred R; Bonomi, Philip; Bunn, Paul; Kim, Edward S; Langer, Corey J; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Spigel, David R; Stinchcombe, Thomas E; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-09-01

    Lung cancer remains the leading cause of cancer-related death worldwide. NSCLC accounts for more than 85% of all lung cancers, and the prognosis for advanced-stage disease is typically poor. In recent years, the importance of histologic subtypes of NSCLC has been recognized, and the distinction between squamous and other NSCLC histologic subtypes is now critical to patient management. Squamous cell lung cancer (sqCLC) represents approximately 25% to 30% of NSCLC. The prognosis for patients with advanced NSCLC is poorer for those with sqCLC than for those with adenocarcinoma. This is partly due to a number of clinical characteristics that distinguish sqCLC from other NSCLC histologic subtypes, such as smoking history, comorbid diseases, age, and molecular profile. Together, these factors make sqCLC an especially challenging disease to manage. Herein, we review some of the key clinicopathologic features of sqCLC. Understanding these features to optimally address many of the unique therapeutic challenges of this disease is likely to be central to ultimately improving outcomes for patients with squamous NSCLC.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. 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

  11. 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 ...

  12. 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

  13. Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Kumar Anupam; Chatopadhyay Tusharkant; Siddhartha Datta Gupta; Ralhan Ranju

    2006-01-01

    AIM: Disabled-2 (D4B2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein.METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR.RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001).Promoter hypermethylation of DAB2 was observed in 2of 10 (20%) DAB2 immuno-negative ESCCs.CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.

  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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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)

  5. 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

  6. 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

  7. 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.

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

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    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.

  9. 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.

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

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    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  12. 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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  14. 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

  15. 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

  16. 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.

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

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    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.

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

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    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.

  19. Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County

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    Yang Fang

    2011-06-01

    Full Text Available Abstract Background The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC and the possibility of predicting those at higher risk. Methods A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH, 262 patients with esophageal squamous cell dysplasia (ESCD, 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants. Results The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 1*1 genotype, the ALDH 2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG of the two combined genotypes was 1.83 (95%CI: 1.55-2.16, indicating a strong genetic association with the risk of carcinogenic progression in the esophagus. Conclusions The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.

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

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    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.

  1. 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.

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

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    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

  3. 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.

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

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    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.

  5. Role of serum angiopoietin-2 level in screening for esophageal squamous cell cancer and its precursors

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    ZHOU Ying-zhi; FANG Xue-qiang; LI Hao; DIAO Yu-tao; YANG Yan-fang; ZHAO De-li; WU Kan; LI Hui-qing

    2007-01-01

    Background Angiopoietin-2 (Ang-2) is one of the critical regulators of tumor angiogenesis. Studies have shown a significant correlation of Ang-2 expression to tumor invasion and metastasis in various human cancers, but little is known about the serum Ang-2 (sAng-2) levels in esophageal squamous cell cancer (ESCC) and its precursors. In this study, we aimed to investigate its role in screening for ESCC and its precursors.Methods We carried out a free endoscopic screening in Feicheng City, a high ESCC incidence area in Shandong Province of China. Serum samples were collected as follows: 91 from normal subjects, 44 from patients with esophagitis,85 from patients with hyperplasia, and 13 from patients with early ESCC. In addition, 28 serum samples were obtained from patients with invasive ESCC undergoing surgery in People's Hospital of Feicheng City. All the subjects of the five groups were diagnosed by histopathology. The sAng-2 levels were tested and compared, and the diagnostic power in early or/and invasive ESCC was calculated in terms of sensitivity and other parameters.Results The sAng-2 levels were (22.0±5.5), (21.3±3.2), (20.5±3.3), (24.0±5.0), and (29.8±5.0) U/ml in normal,esophagitis, hyperplasia, early ESCC, and invasive ESCC groups respectively. It was significantly higher in early ESCC than inhyperplasia group (P=0.009). The invasive ESCC group showed the highest Ang-2 level among all groups (all P=0.000). The sensitivities of sAng-2 to early and invasive ESCC were 23.1% and 78.6% respectively.Conclusion sAng-2 level is related to carcinogenesis and progression of ESCC, but it can not be used to screen for early ESCC.

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

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    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.

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

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    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.

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

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    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.

  9. 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

  10. Restoring KLF5 in esophageal squamous cell cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival.

    Science.gov (United States)

    Tarapore, Rohinton S; Yang, Yizeng; Katz, Jonathan P

    2013-05-01

    Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.

  11. Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

    Institute of Scientific and Technical Information of China (English)

    Carlo Calabrese; Davide Trerè; Lorenzo Montanaro; Giuseppina Liguori; Elisa Brighenti; Mauela Vici; Paolo Gionchetti; Fernando Rizzello; Massimo Campieri; Massimo Derenzini

    2011-01-01

    AIM: To elucidate cell proliferation in erosive reflux disease (ERD) and non-erosive reflux disease (NERD), we evaluated markers in squamous epithelial cells. METHODS: Thirty-four consecutive patients with gastroesophageal- reflux-disease-related symptoms (21 NERD and 13 ERD) were evaluated for the enrolment into the study. All patients underwent 24-h pH monitoring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only. RESULTS: Real-time RT-PCR showed that, in patients with ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 (P = 0.011). Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients (2.31 ± 2.87 vs 0.66 ± 1.11). The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%. CONCLUSION: We confirmed reduced epithelial proliferation in ERD compared with NERD patients, and that individuals who develop ERD are characterized by weaker epithelial cell proliferation.

  12. 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.

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

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    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

  14. 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.

  15. Advances on Driver Oncogenes of Squamous Cell Lung Cancer

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    Wei HONG

    2014-05-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC of the lung is the most frequent histologic subtype in non-small cell lung cancer. Several molecular alterations have been defined as "driver oncogenes" responsible for both the initiation and maintenance of the malignancy. The squamous cell carcinoma of the lung has recently shown peculiar molecular characteristics which relate with both carcinogenesis and response to targeted drugs. So far, about 40% of lung squamous cell carcinoma has been found harbouring driver oncogenes, in which fibroblast growth factor receptor 1 (FGFR1 plays important roles. In this review, we will report the mainly advances on some latest driver mutations of squamous cell lung cancer.

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

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    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.

  17. 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

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

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    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.

  19. 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.

  20. 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.

  1. 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.

  2. Identification of Biomarkers for Esophageal Squamous Cell Carcinoma Using Feature Selection and Decision Tree Methods

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    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.

  3. 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

  4. 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.)

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

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    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.

  20. 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.

  1. A comprehensive genomic characterization of esophageal squamous cell carcinoma:from prognostic analysis to in vivo assay

    Institute of Scientific and Technical Information of China (English)

    Yuan-Bin Chen; Wei-Hua Jia

    2016-01-01

    Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide and is char‑acterized by numerous genetic mutations. TNM staging is not sufcient for predicting patient outcomes. Addition‑ally, ESCC shows poor responsiveness to chemotherapy and radiation. Thus, there is an urgent need to find efcient therapy targets. Previous ESCC high‑throughput genomic studies have lacked intensive survival analysis, particularly for copy number variation (CNV) and the genes involved. Main body: In the study“Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis”recently published in the American Journal of Human Genetics, we comprehensively analyzed the effects of CNVs, mutations, and relative gene expression on patient outcomes. To validate our findings for our 67 sequencing samples, we collected a 321‑patient retrospective cohort with detailed 5‑year follow‑up information and carried out univariate and multivariate survival analyses. In addition, the biological functions of the survival predictors in ESCC were investigated both in vitro and in vivo. Conclusions: We found the independent ESCC survival predictors and potential therapy targets. Nevertheless, the effects of numerous low‑frequency mutations need to be explored using larger sample sequencing. Overall, con‑structing multi‑gene prognostic signatures will remain a great challenge in the future.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

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    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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. [Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].

    Science.gov (United States)

    Fujii, T; Tanaka, Y; Tanaka, T; Matono, S; Sueyoshi, S; Fujita, H; Shirouzu, K; Kato, S; Yamana, H

    2001-10-01

    p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.

  15. 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

  16. 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.

  17. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

    International Nuclear Information System (INIS)

    To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group). The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study. For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome

  18. 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)

  19. 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.

  20. 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.

  1. 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

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

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    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.

  3. Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt.

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    Lee, Hwan Hee; Ye, Shuai; Li, Xiu Juan; Lee, Kwang Bok; Park, Man Hee; Kim, Soo Mi

    2014-01-01

    Despite the fact that paclitaxel and doxorubicin are widely used as chemotherapy agents against several types of cancer, their combined effects on esophageal squamous cell carcinoma (ESCC) have never been fully elucidated. The present study was designed to investigate the biological effects of paclitaxel and doxorubicin in ESCC cells. Combination treatment with paclitaxel and doxorubicin significantly inhibited the proliferation of TE-12 cells in a dose-and time-dependent manner compared to treatment with paclitaxel or doxorubicin alone. FACS analysis showed that the percentage of cells in the G2/M phase was significantly increased at 12 h after treatment with the combination. Increased p-cdc2, p-Wee1 and p53 protein levels were observed, while Akt activation was suppressed by combination treatment with paclitaxel and doxorubicin. In addition, treatment with paclitaxel plus doxorubicin significantly increased apoptosis as indicated by increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-7 and -9 levels. These results suggest that combination treatment with paclitaxel and doxorubicin induced G2/M cell cycle arrest and apoptosis in human ESCC cells by suppressing Akt activity. These findings highlight the potent apoptotic effect of combination therapy with paclitaxel and doxorubicin in ESCC cells and the potential clinical benefits of these two drugs in esophageal cancer. PMID:24247637

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

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    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.

  5. 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.

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

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    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

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

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    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.

  8. Learning curve and interobserver agreement of confocal laser endomicroscopy for detecting precancerous or early-stage esophageal squamous cancer.

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    Jing Liu

    Full Text Available Confocal laser endomicroscopy (CLE can provide in vivo subcellular resolution images of esophageal lesions. However, the learning curve in interpreting CLE images of precancerous or early-stage esophageal squamous cancer is unknown. The goal of this study is to evaluate the diagnostic accuracy and inter-observer agreement for differentiating esophageal lesions in CLE images among experienced and inexperienced observers and to assess the learning curve.After a short training, 8 experienced and 14 inexperienced endoscopists evaluated in sequence 4 sets of high-quality CLE images. Their diagnoses were corrected and discussed after each set. For each image, the diagnostic results, confidence in diagnosis, quality and time to evaluate were recorded.Overall, diagnostic accuracy was greater for the second, third, fourth set of images as compared with the initial set (odds ratio [OR] 2.01, 95% CI 1.22-3.31; 7.95, 3.74-16.87; and 6.45, 3.14-13.27, respectively, with no difference between the third and fourth sets in accuracy (p = 0.67. Previous experience affected the diagnostic accuracy only in the first set of images (OR 3.70, 1.87-7.29, p<0.001. Inter-observer agreement was higher for experienced than inexperienced endoscopists (0.732 vs. 0.666, p<0.01.CLE is a promising technology that can be quickly learned after a short training period; previous experience is associated with diagnostic accuracy only at the initial stage of learning.

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

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    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

  10. Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma.

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    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

  11. 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

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

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    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

  13. 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.

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

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    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

  15. Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer patients.

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    Łukaszewicz-Zając, M; Mroczko, B; Kozłowski, M; Nikliński, J; Laudański, J; Szmitkowski, M

    2012-04-01

    It has been suggested that interleukin 6 (IL-6) plays a potential role in the growth and progression of tumors, including esophageal cancer (EC). The aim of the study was to compare clinical significance of serum IL-6 with classic tumor markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) - in EC patients in relation to its histological types - squamous cell carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The diagnostic criteria and prognostic values for markers were defined. The levels of all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The percentage of elevated results was substantially higher for IL-6 (86%) than for CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on distant metastases and patients' survival in EC and were significantly higher in ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area under receiver operating characteristic curve (0.92) was larger than for CEA (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91, 0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than classic tumor markers in the diagnosis of EC, especially in patients with ESCC.

  16. Comprehensive Analysis of MicroRNA and mRNA Expression in Normal and Tumorous Human Esophageal Squamous Cell Lines Using Microarray Datasets

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    Ichiro Akagi

    2014-01-01

    Full Text Available Despite the undisputed importance of altered microRNA (miRNA expression in various cancers, there is limited information on the clinicopathologic significance of cancer-related miRNAs in esophageal squamous cell carcinoma (ESCC. Previously, it was reported that the expression of several miRNAs was dysregulated in ESCC. However, the target genes of these miRNAs have not been identified. Furthermore, additional miRNAs in humans have been discovered recently, indicating that revised miRNA and gene expression profiling for ESCC are necessary. Here, we provide datasets from microarray analyses to identify miRNA and mRNA expression comprehensively in Het-1A, a normal human esophageal squamous cell line, and three human ESCC cell lines.

  17. 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

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

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    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.

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

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    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.

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

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    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...

  1. Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus. Nine Japanese institutions trial

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    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)

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

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    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...

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

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

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    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.

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

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    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.

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

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    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.

  8. Surgery within multimodal therapy concepts for esophageal squamous cell carcinoma (ESCC): the MRI approach and review of the literature

    International Nuclear Information System (INIS)

    Background: Radical esophagectomy with lymphadenectomy remains the only curative therapy for patients with resectable esophageal squamous cell cancer (ESCC), however, combined treatment modalities may improve survival. Based upon more than 1300 consecutive esophageal resections, we present our current multidisciplinary ESCC approach with analysis in the context of recently published RCTs. Methods: Subject to tumor staging, patients with resectable ESCC receive either a neoadjuvant radiochemotherapy (uT3N+) or are referred to primary surgery (uT1/2N0). By Medline searches (1997-2009), all published RCTs containing multimodal ESCC therapy concepts were identified and a systematic review was generated. Results: From July 2007 to June 2009, 62 patients with ESCC were treated in our department (40 multimodal treatment concept, 21 primary surgery, 1 definite radiochemotherapy). The R0 resection rate was 78%, in hospital mortality 4.8%. 60% of patients showed a good response to neoadjuvant treatment. 18-month follow-up data revealed absence of tumor recurrence in 7 patients (18%). Our approach is aligned to the current published literature including 12 studies in this review. In line with our institutional experience, neodjuvant radiochemotherapy tends to improve overall survival and increases the likelihood of R0 resection. However, postoperative morbidity and mortality rates are increased. Adjuvant treatment failed to demonstrate any improvement in prognosis. For palliation, concurrent radiochemotherapy is the treatment of choice. Conclusion: The MRI approach can be aligned to the most recent published data. Surgical resection remains the principle treatment for patients with resectable ESCC. Although multimodal therapy concepts tend to improve survival rates, postoperative morbidity and mortality rates are increased. (authors)

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

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    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.

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

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    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.

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

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    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.

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

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    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. Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

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    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.

  14. Influence of negative lymph node in No 7 on survival of patients with middle thoracic esophageal squamous cell carcinoma

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    Zhang JL

    2016-03-01

    Full Text Available Jinling Zhang,1 Xueyuan Heng,1 Yi Luo,2 Qingxi Fu,1 Zhengrong Li,1 Fengyuan Che,1 Baosheng Li31Cancer Center, LinYi People Hospital, Affiliated to Shandong University, School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; 3Department of Radiation Oncology (Chest Section, Shandong’s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of ChinaBackground: The overall survival (OS of patients with thoracic esophageal cancer is poor because of the high rate of lymph node metastases. However, recent studies found that the negative lymph node (LN may also influence the patients’ OS. The purpose of this study is to investigate which negative LN stations play a key role in OS prediction.Method: Our study included the retrospective records of 99 patients, who were identified with middle thoracic esophageal squamous cell cancer after esophagectomy. The maximum follow-up time was 6 years. Cox regression models were employed to determine the association between the negative LN and OS of patients. After applying Kaplan–Meier method to calculate OS of patients with positive and negative LNs, the log-rank tests were used to assess the difference between them.Result: The hazard ratio of the total number of negative LNs was 0.937 (P=0.001, and the length of tumor was 1.166 (P=0.038. Multivariate regression results showed that the numbers of positive LNs in No 3 and 7 stations and negative LNs in No 109 and 7 stations were significantly related to OS, and their P-values were 0.017, 0.001, 0.020, and 0.022, respectively. The OS of the patients who had positive and negative LNs in No 7 station was significantly different (P=0.028.Conclusion: No 7 is the most important among the negative LN stations which prolong OS. More attention should be paid to this area when

  15. 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.

  16. 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

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    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells

    Directory of Open Access Journals (Sweden)

    Wang YY

    2015-02-01

    Full Text Available Yan-Yang Wang,1,2 Yin-Xue Yang,3 Ren Zhao,1 Shu-Ting Pan,2,4 Hong Zhe,1 Zhi-Xu He,5 Wei Duan,6 Xueji Zhang,7 Tianxin Yang,8 Jia-Xuan Qiu,4 Shu-Feng Zhou2,51Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 5Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, People’s Republic of China; 6School of Medicine, Deakin University, Waurn Ponds, VIC, Australia; 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 8Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USAAbstract: Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl, B-cell lymphoma 2 (Bcl-2

  9. 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...

  10. 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.

  11. 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.

  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

    2015-01-01

    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

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

    International Nuclear Information System (INIS)

    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

  19. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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.

  1. A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  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. 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.

  5. 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

  6. 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

  7. 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.

  8. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    OpenAIRE

    Sanambar Sadighi; Amanolah Keyhani; Iraj Harirchi; Ata Garajei; Mahdi Aghili; Ali Kazemian; Maziar Motiee Langroudi; Kazem Zendehdel; Nariman Nikparto

    2015-01-01

    To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SP...

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  10. [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

  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. Tratamento endoscópico do câncer epidermóide do esôfago Endoscopic treatment of squamous cell esophageal cancer

    Directory of Open Access Journals (Sweden)

    Fauze Maluf-Filho

    2006-06-01

    esophageal cancer. DATA SOURCE: Relevant publications cited at PubMed database in the last 10 years were analyzed and compared with the experience developed at the Gastrointestinal Endoscopy Division of the Department of Gastroenterology of the University of São Paulo School of Medicine. Mucosectomy and advanced tumor tunnelization were the most important developments in that area. DATA SYNTHESIS: Endoscopic mucosal resection of early epidermoid cancer of the esophagus is indicated when the lesion is confined to the epithelium (m1 or to the lamina propria (m2. The described 5-year survival rate after endoscopic mucosal resection of intramucosal epidermoid tumor of the esophagus approaches 95%. Based on the available evidence, it seems reasonable to indicate endoscopic mucosal resection as a first-choice treatment for patients with intramucosal epidermoid esophageal carcinoma. There are a variety of endoscopic palliative methods for dysphagia relief in advanced esophageal cancer. CONCLUSIONS: The choice will vary according to the anatomical features and location of the tumor, patient preferences, local and expertise availability. The technical success rate for placement of metal stents across the malignant stenosis is close to 100%. The rate of long-term palliation of dysphagia approaches 80% which makes expandable metal stents the treatment of choice for palliation of obstructive symptoms caused by advanced squamous cell cancer of the esophagus.

  13. Narrow Band Imaging with Magnification Can Pick Up Esophageal Squamous Cell Carcinoma More Efficiently Than Lugol Chromoendoscopy in Patients after Chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

    Science.gov (United States)

    Noronha, Vanita; Prabhash, Kumar; Joshi, Amit; Patil, Vijay Maruti; Talole, Sanjay; Nakti, Dipti; Sahu, Arvind; Shah, Srushti; Ghosh-Laskar, Sarbani; Patil, Prachi S; Mehta, Shaesta A; Jambhekar, Nirmala; Mahajan, Abhishek; Purandare, Nilendu

    2016-01-01

    There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

  20. 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.

  1. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation

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    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.

  2. 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

  3. Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.

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    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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma.

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    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

  10. 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.

  11. 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.

  12. miR-483-3p plays an oncogenic role in esophageal squamous cell carcinoma by targeting tumor suppressor EI24.

    Science.gov (United States)

    Ma, Jiaojiao; Hong, Liu; Xu, Guanghui; Hao, Junfeng; Wang, Rui; Guo, Hao; Liu, Jinqiang; Zhang, Yujie; Nie, Yongzhan; Fan, Daiming

    2016-04-01

    microRNAs (miRNAs), through negatively regulating their target genes, influence the development and progression of many cancers. Previously, we found miR-483 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues, and its overexpression was negatively correlated with the prognosis and positively correlated with multidrug resistance of ESCC, but whether it could affect the biological role of proliferation and migration in ESCC cell lines is unknown. In the present study, we found miR-483-3p was overexpressed in ESCC cell lines as compared with the normal esophageal squamous epithelial cell line. Functional experiments in vitro showed that miR-483-3p could promote the proliferation, migration, transformation of cell cycle from G1 phase to G2 phase of ESCC cells and could inhibit cells' sensitivity to chemotherapy drugs. Nude mouse tumorigenicity assay indicated that miR-483-3p could promote the growth of ESCC cells in vivo. Western blot assay showed that ectopic expression of miR-483-3p in ESCC cells could downregulate the protein level of etoposide induced 2.4 (EI24), which is a tumor suppressor and has not been reported in ESCC. Luciferase reporter assay demonstrated that EI24 was a direct target of miR-483-3p. Collectively, our study demonstrated that miR-483-3p could promote ESCC progression at least in part through directly targeting EI24, supplying a potential strategy for miRNA-based ESCC therapy.

  13. 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)

    was enhanced, suggesting that hypoxia had been induced. Comparison of cancer drug resistance using cisplatin and doxorubicin in 3-D-cultured esophageal cancer cells showed that cancer drug resistance had increased. These results indicate that 3-D culture of esophageal squamous cell carcinoma lines is a useful method for inducing cancer stem cells

  14. 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

    was enhanced, suggesting that hypoxia had been induced. Comparison of cancer drug resistance using cisplatin and doxorubicin in 3-D-cultured esophageal cancer cells showed that cancer drug resistance had increased. These results indicate that 3-D culture of esophageal squamous cell carcinoma lines is a useful method for inducing cancer stem cells.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Comparative evaluation of serum C-reactive protein (CRP) levels in the different histological subtypes of esophageal cancer (squamous cell carcinoma and adenocarcinoma of esophagus).

    Science.gov (United States)

    Lukaszewicz-Zając, Marta; Mroczko, Barbara; Kozłowski, Mirosław; Nikliński, Jacek; Laudański, Jerzy; Siewko, Maria; Szmitkowski, Maciej

    2012-02-01

    Elevated C-reactive protein (CRP) levels have been found in patients with several malignancies. The aim of the present study was to analyze the diagnostic and prognostic values of CRP levels measurement in esophageal cancer (EC) patients in relation to its different histological subtypes (squamous cell carcinoma-ESCC and adenocarcinoma-AC of esophagus) and compared them with classic tumor markers-carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag). The diagnostic sensitivity, specificity, and the areas under receiver operating characteristic curves (AUC) for all the proteins tested were defined. Serum CRP levels were statistically higher in EC, ESCC, and AC patients compared to healthy subjects and significantly increased in EC and ESCC patients with the presence of lymph node and distant metastases. The percentage of elevated CRP results in all the analyzed subgroups (EC, ESCC, and AC) was higher than CEA and SCC-Ag, similarly as AUC for CRP in comparison to SCC-Ag. Serum CRP level was a significant predictor of EC and ESCC patients' survival in univariate analysis. In conclusion, these results indicate that CRP can be used as an adjunct in evaluating the tumor markers-CEA and SCC-Ag and may improve the clinical diagnosis and follow-up of EC patients, especially for ESCC subgroup.

  1. Narrow-Band Imaging Magnifying Endoscopy versus Lugol Chromoendoscopy with Pink-Color Sign Assessment in the Diagnosis of Superficial Esophageal Squamous Neoplasms: A Randomised Noninferiority Trial

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    Kenichi Goda

    2015-01-01

    Full Text Available Previous studies have shown the high diagnostic accuracy of narrow-band imaging magnifying endoscopy (NBI-ME and Lugol chromoendoscopy with pink-color sign assessment (LCE-PS for superficial esophageal squamous cell carcinoma (SESCC. However, there has been no controlled trial comparing these two diagnostic techniques. We conducted a randomized noninferiority trial to compare the diagnostic accuracy of NBI-ME and LCE-PS. We recruited patients with, or with a history of, squamous cell carcinoma in the head and neck region or in the esophagus. They were randomly assigned to either NBI-ME or LCE-PS. When lesions > 5 mm in diameter were found as brownish areas on NBI or as Lugol-voiding lesions (LVL, they were evaluated to determine whether they are SESCC on the basis of the findings of NBI-ME or PS in the LVL. NBI-ME and LCE-PS were completed in 147 patients each. There was no significant difference in all diagnostic values between the two techniques. Compared with LCE-PS, NBI-ME showed a significantly shorter examination time but a larger number of misdiagnosed lesions especially in patients with many irregularly shaped multiform LVLs. Compared with LCE-PS, NBI-ME might be similarly accurate and less invasive, but less reliable in patients with many LVLs, in the diagnosis of SESCC.

  2. Nicotine activates YAP1 through nAChRs mediated signaling in esophageal squamous cell cancer (ESCC.

    Directory of Open Access Journals (Sweden)

    Yue Zhao

    Full Text Available Cigarette smoking is an established risk factor for esophageal cancers. Yes-associated protein 1 (YAP1, the key transcription factor of the mammalian Hippo pathway, has been reported to be an oncogenic factor for many cancers. In this study, we find nicotine administration can induce nuclear translocation and activation of YAP1 in ESCC. Consistently, we observed nuclear translocation and activation of YAP1 by knockdown of CHRNA3, which is a negative regulator of nicotine signaling in bronchial and esophageal cancer cells. Nicotine administration or CHRNA3 depletion substantially increased proliferation and migration in esophageal cancer cells. Interestingly, we find that YAP1 physically interacts with nAChRs, and nAChRs-signaling dissociates YAP1 from its negative regulatory complex composed with α-catenin, β-catenin and 14-3-3 in the cytoplasm, leading to upregulation and nuclear translocation of YAP1. This process likely requires PKC activation, as PKC specific inhibitor Enzastaurin can block nicotine induced YAP1 activation. In addition, we find nicotine signaling also inhibits the interaction of YAP1 with P63, which contributes to the inhibitory effect of nicotine on apoptosis. Using immunohistochemistry analysis we observed upregulation of YAP1 in a significant portion of esophageal cancer samples. Consistently, we have found a significant association between YAP1 upregulation and cigarette smoking in the clinical esophageal cancer samples. Together, these findings suggest that the nicotine activated nAChRs signaling pathway which further activates YAP1 plays an important role in the development of esophageal cancer, and this mechanism may be of a general significance for the carcinogenesis of smoking related cancers.

  3. 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

  4. 食管癌肿瘤条件培养新生血管形成机制的探讨%Angiogenesis mechanism of esophageal squamous cell cancer in different culture condition esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵晶; 刘丹; 刘明娜; 裴凤华; 迟宝荣

    2011-01-01

    OBJECTIVE: To investigate the roles of Survivin, Survivin-△Ex3 and VEGF in angiogenesis induced by esophageal squamous cell carcinoma (ESCC). METHODS: VEGF expression in conditioned medium (CM) was examined by ELISA. Expression levels of the Survivin and Survivin-△Ex3 in Human umbilical vein endo-thelial cells (HUVEC) which were cultured with CM from ESCC cell line (TE-5) were examined by RT-PCR. RESULTS: VEGF protein concentration in ESCC-derived CM was increased in time-dependent manner by ELISA, The expression level of Survivin in HUVEC increased significantly at 4 and 10 h(CM vs RPMI:4 h;1. 019 7±0. 058 8 vs 0. 658 8 ± 0. 043 7, P = 0. 000 5; 10 hs 0. 797 1 ± 0.074 4 vs 0.444 9±0. 041 2,P = 0. 001). But Survivin-AEx3 had no significant change in each group (CM vs RP-MI:4 h: 0. 423 7 ± 0. 087 0 vs 0. 294 0± 0. 043 1, P = 0.109 l;10 h:0.372 7±0.084 8 vs 0.226 4±0.009 2, P= 0.078 1). The expression level of VEGF decreased significantly at 4 h and 10 h, which has a very significant difference compared with the control group(CM vs RPMI: 4 h:0. 276 7±0. 065 8 vs 0. 977 8±0. 044 5,P=0. 000 0t 10 h: 0. 173 9 ± 0. 024 1 vs 0. 917 8± 0. 124 7, P = 0.004 8).CONCLUSION: The wild type Survivin but not Survivin-△Ex3 is related to angiogenesis in ESCC.%目的:探讨Survivin、Survivin-△Ex3及VEGF在食管癌细胞诱导血管形成中作用的相关性.方法:用食管鳞癌肿瘤条件培养基培养人脐静脉内皮细胞,用ELISA法检测肿瘤条件培养基中VEGF蛋白的表达情况.用RT-PCR法检测内皮细胞中Survivin、Survivin-△Ex3及VEGF的表达情况.结果:肿瘤条件培养基中VEGF蛋白表达随培养时间呈上升趋势.实验组人脐静脉内皮细胞中Survivin在更换肿瘤条件培养基后4及10 h时表达明显增加,与对照组比较差异有统计学意义(CMvsRPMI:4 h:1.019 7±0.058 8 vs 0.658 8±0.043 7,P=0.000 5;10 h:0.797 1±0.074 4 vs0.444 9±0.041 2,P=0.001 0),而Survivin-△Ex3在实验组和对照组间的表

  5. [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.

  6. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Montejo, Michael E.; Shrieve, Dennis C. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O. [Division of Otolaryngology-Head Neck Surgery, Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Agarwal, Neeraj [Department of Internal Medicine, Oncology Division, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Hitchcock, Ying J., E-mail: ying.hitchcock@hci.utah.edu [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States)

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  7. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States)

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  8. [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.

  9. [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

  10. Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India.

    Science.gov (United States)

    Makhdoomi, Muzamil Ashraf; Shah, Idrees Ayoub; Bhat, Gulzar Ahmad; Amin, Shajrul; Lone, Mohd Maqbool; Islami, Farhad; Dar, Nazir Ahmad

    2015-04-01

    Polymorphisms in glutathione-S-transferases (GSTs), the phase II xenobiotic detoxifying enzymes, have been associated with increased cancer risk. In this study, we assessed the association of functional polymorphisms in GSTM1 and GSTT1 with esophageal cancer in Kashmir, India, an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We analyzed genotypes of GSTM1 and GSTT1 using a multiplex PCR in 492 pairs of ESCC cases and individually matched controls. The associations between polymorphisms in these genes and ESCC risk were examined by conditional logistic regression models adjusted for multiple potential confounders. In addition, the interaction between these genes and several environmental exposures with regard to ESCC risk was assessed. Our results showed an association between the GSTT1 null genotype and ESCC risk (odds ratio (OR) = 1.58; 95% confidence interval (CI) 1.04-2.39). Although GSTM1 alone was not associated with ESCC risk, individuals with the GSTM1 (-)/GSTT1 (+) genotype showed an inverse relation with ESCC risk (OR = 0.55; 95% CI 0.32-0.93), compared to GSTM1 (+)/GSTT1 (+) individuals. We found a significant interaction between the GSTT1 and GSTM1 genotypes with regard to ESCC risk (P = 0.001); however, there were no interactions between environmental factors and GSTT1 and GSTM1 genotypes. This study indicates that GSTT1 null genotype is associated with ESCC risk in Kashmiri population. The association between GSTM1 and ESCC risk needs further investigations. Interactions of these genotypes with environmental exposures should be examined in multicentric studies with bigger sample sizes.

  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. Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition

    Institute of Scientific and Technical Information of China (English)

    Jia Nan; Wen Xiaoduo; Zhang Nan; Yang Yi; Zhang Liwei; Wang Xiaoling; Wang Na

    2014-01-01

    Background Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer.However,whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain.This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma (ESCC) cases with or without a positive family history of the cancer.Methods Age at onset and the percentage of multiple primary cancers were compared between ESCCs with (n=766) or without (n=1 776) a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.Results Overall,ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history (onset age 51.83 vs.53.49 years old,P <0.01; percent of multiple primary cancers 5.50% vs.1.70%,x2=25.42,P <0.01).Both the differences were evident in subgroup analyses,but did not correlate.While age at onset differed significantly by family history among the male,smoking,and drinking groups,the difference of multiple primary cancers was significant among the otherwise nonsmoking,nondrinking,and younger onset age groups.Conclusions Younger age of onset and multiple primary cancers associated with ESCCs with a positive,as opposed to a negative family history of the cancer,suggest a genetic predisposition.The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors,but multiple primary cancers may be related only to genetic predisposition.

  13. Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN. We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population. Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend = 0.046), particularly for non-oropharyngeal tumors (Ptrend = 0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR = 1.29, 95% CI = 1.01-1.64; AG/GG vs. AA: adjusted OR = 1.30, 95% CI = 1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR = 0.54, 95% CI = 0.34-0.86; TG/GG vs. TT: adjusted OR = 0.76, 95% CI = 0.61-0.95). Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers

  14. MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Yamashita Shunichi

    2011-03-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is often diagnosed at later stages until they are incurable. MicroRNA (miR is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2

  15. Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580 000 subjects within the Me-Can project

    International Nuclear Information System (INIS)

    Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study. The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox’s proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS). In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC. In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the

  16. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    Science.gov (United States)

    Souza, Rhonda F

    2016-01-01

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention. PMID:27331918

  17. 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.

  18. 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.

  19. 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.

  20. Esophageal microbiome in eosinophilic esophagitis.

    Directory of Open Access Journals (Sweden)

    J Kirk Harris

    Full Text Available The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis.In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD and normal mucosa using the Esophageal String Test (EST. Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease.Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects.Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

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

    Institute of Scientific and Technical Information of China (English)

    Ji-Ye An; Zong-Min Fan; Ze-Hao Zhuang; Yan-Ru Qin; Shan-Shan Gao; Ji-Lin Li; Li-Dong Wang

    2004-01-01

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

  3. Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.

    Science.gov (United States)

    Cai, Xianbin; Hu, Xi; Tan, Xiaojun; Cheng, Weijie; Wang, Qinjia; Chen, Xiaofeng; Guan, Yinghong; Chen, Chong; Jing, Xubin

    2015-01-01

    Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health and the current treatments for ESCC are frequently not effective. Recent epidemiological studies suggest that the anti-hyperglycemic agent metformin may reduce the risk of developing cancer, including ESCC, among diabetic patients. However, the antitumor effects of metformin on ESCC and the mechanisms underlying its cell cycle regulation remain elusive. The findings reported herein show that the anti-proliferative action of metformin on ESCC cell lines is partially mediated by AMPK. Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1. In vivo experiments further showed that metformin inhibited tumor growth in a ESCC xenograft model. Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo. In conclusion, metformin inhibits the growth of ESCC cells both in cell cultures and in an animal model. AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC. These findings indicate that metformin has the potential for use in the treatment of ESCC.

  4. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  5. The therapeutic response of CDDO-Me in the esophageal squamous cell carcinoma (ESCC) cells is mediated by CaMKIIα.

    Science.gov (United States)

    Wang, Yan-Yang; Zhou, Shun; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    CDDO-Me has exhibited a potent anticancer effect in human esophageal squamous cell carcinoma (ESCC) cells in our previous study, but the molecular interactome remains elusive. We applied the approach of stable-isotope labeling by amino acids in cell culture (SILAC) to assess the proteomic responses of CDDO-Me treatment in human ESCC Ec109 cells. The data were subsequently validated using Western blot assay. The results of our study revealed that CDDO-Me increased the expression level of 543 protein molecules, but decreased the expression level of 709 protein molecules in Ec109 cells. Among these modulated protein molecules, calcium/calmodulin-dependent protein kinase type II subunit α (CaMKIIα) was highly expressed in all tested ESCC cell lines, whereas its expression levels were substantially lower in normal control cell line. Its silencing by small interfering RNA inhibited CDDO-Me induced apoptosis and autophagy in ESCC cells. Collectively, these data demonstrate that the therapeutic response of CDDO-Me in the human ESCC cells is mediated by CaMKIIα.

  6. A dual mTORC1 and mTORC2 inhibitor shows antitumor activity in esophageal squamous cell carcinoma cells and sensitizes them to cisplatin.

    Science.gov (United States)

    Huang, Yu; Xi, Qingsong; Chen, Yu; Wang, Jing; Peng, Ping; Xia, Shu; Yu, Shiying

    2013-10-01

    The mammalian target of rapamycin (mTOR) signaling pathway is critical for the growth and proliferation of various malignant tumors, including esophageal squamous cell carcinoma (ESCC). Therefore, targeting of mTOR protein is a promising strategy for therapy in this disease. In the present study, we examined the antitumor effects of a specific mTOR kinase inhibitor, PP242, which blocks both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) pathways, in two ESCC cell lines: Eca-109 and TE-1. We showed that PP242, but not rapamycin, attenuated the activities of both mTORC1 and mTORC2 signaling in ESCC. PP242 inhibited 4E-binding protein-1 phosphorylation and abrogated mTORC1-dependent PI3K/Akt feedback activation. Significantly, PP242 effectively suppressed ESCC cell proliferation, induced apoptosis, and arrested the cell cycle. Furthermore, PP242 promoted cisplatin-induced apoptosis and enhanced the antitumor efficacy of cisplatin in ESCC cells, which was likely to be associated with inhibition of Akt activity. Our results show that simultaneous targeting of both mTORC1 and mTORC2 pathways leads to effective antitumor actions in ESCC, and strongly suggest that dual mTORC1/2 inhibitors should be developed as potential agents for the treatment of ESCC.

  7. Downregulation of retinoic acid receptor-β2expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Zhong-Min Liu; Fang Ding; Ming-Zhou Guo; Li-Yong Zhang; Min Wu; Zhi-Hua Liu

    2004-01-01

    AIM: To study the role of hypermethylation in the loss ofretinoic acid receptorβ2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS: The role of hypermethylation in RAR,β2 gene silencing in 6 ESCC cell lines was determined by methylationspecific PCR (MSP), and its methylation status was compared with RARβ2 mRNA expression by RT-PCR. The MSP results were confirmed by bisulfite sequencing of RARβ2promoter regions. RESULTS: Methylation was detected in 4 of the 6 cell lines, and the expression of RARβ2was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2was restored in one RARβ2-downregulated cell line with the partial demethylation of promoter region of RARβ after 5aza-2'-deoxycytidine (5-aza-dc) treatment.CONCLUSION: The methylation of the 5' region may play an important role in the downregulation of RARβ2 in someESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2expression in ESCC cell lines. This study may have clinical applications for treatment and prevention of ESCC.

  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. 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.

  10. 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.

  11. Radiation therapy for the treatment of feline advanced cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    The efficacy of radiation therapy for feline advanced cutaneous squamous cell carcinoma was evaluated. A full course radiation therapy protocol was applied to six cats showing single or multiple facial squamous cell carcinomas, in a total of seven histologically confirmed neoplastic lesions. Of the lesions, one was staged as T1, and six as T4 according to WHO staging system of epidermal tumors. The animals were submitted to twelve radiation fractions of 4 Gy each, on a Monday-Wednesday-Friday schedule, and the equipment used was an orthovoltage unit. Energy used was 120 kV, 15 mA and 2 mm aluminum filter. The cats were evaluated during the treatment and 30 and 60 days after the end of the radiation therapy. In this study, 87% of the lesions had complete remission and 13% partial remission to the treatment. Side effects were considered mild according to Veterinary Radiation Therapy Oncology Group Toxicity criteria, and included erythema, epilation and rhinitis. Radiation Therapy was considered safe for feline cutaneous squamous cell carcinoma, leading to mild side effects and can represent a good therapeutic option. (author)

  12. Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

    International Nuclear Information System (INIS)

    Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). Our results demonstrated that dietary and environmental exposures, some demographic

  13. Long-term outcome of irradiation with or without chemotherapy for esophageal squamous cell carcinoma: a final report on a prospective trial

    International Nuclear Information System (INIS)

    To investigate the long-term outcome of esophageal squamous cell carcinoma (SCC) treated by irradiation with or without concurrent chemotherapy. A prospective clinical trial was carried out from 1998 to 2000. One hundred and eleven patients were randomly enrolled to receive either late course accelerated hyperfractionated irradiation (LCAF) or LCAF with concurrent chemotherapy (LCAF + CT). For LCAF, 41.4 Gy in 23 fractions was first delivered at five fractions per week, followed by 27 Gy in 18 fractions at two 1.5 Gy fractions a day. Concurrent chemotherapy of cis-platinum and 5-fluorouracil was administered for four cycles. Overall survival (OS), locoregional recurrence and distant metastasis were observed. Late toxicity was scored by RTOG criteria, and quality of life (QOL) was also evaluated. The median follow-up time was 24 months for all patients and 138 months for 17 living patients. Median survival time was 25 months and 32 months in LCAF and LCAF + CT (p = 0.653), respectively. For an entire group of patients, overall survivals were 34%, 27% and 22%; locoregional recurrence rates were 30%, 36% and 41%; and distant metastasis rates were 26%, 28% and 29% at 5-yr, 8-yr and 10-yr, respectively. Incidences of ≥ Grade 3 late toxicity were 29% at 10-yr. There were no statistically significant differences between LCAF and LCAF + CT with respect to the parameters mentioned above. Cumulative incidence of late toxicities of ≥ Grade 3 increased sharply after the attained age of 70 years. Eighty-eight percent of patients lived with good KPS (≥ 90) and 94% could eat regular or soft diet. The long-term outcome of esophageal SCC patients who received LCAF or LCAF + CT was good. The locoregional and distant failures occurred more often in the first three years after treatment, but could continuously occur up to 10 years. The late toxicity was acceptable. Late toxicities ≥ Grade 3 were more likely to occur in elderly patients. QOL was good in living patients

  14. Prognostic and clinicopathological features of E-cadherin, α-catenin, β-catenin, γ-catenin and D1 cyclin expression in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-Cheng Lin; Ming-Yao Wu; De-Rui Li; Xian-Ying Wu; Rui-Ming Zheng

    2004-01-01

    AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis.METHODS: Expression of E-cadherin, α-catenin, β-catenin,γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis.RESULTS: The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5%and 53.2%, respectively. Cyclin D1 positive expression rate was 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x2 = 4.183 and x2 = 5.035, respectively, P<0.05),whereas the expression of E-cadherin was correlated only with the degree of differentiation (x2 = 5.769, P<0.05).Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and56% in E-cadherin preserved expression group and in reduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one,respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin(P<0.05).CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cydin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.

  15. Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

    Directory of Open Access Journals (Sweden)

    Gao Weimin

    2006-12-01

    Full Text Available Abstract Background Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC. Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. Methods A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX were assessed from genomic DNA using PCR based techniques. Results Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P GSTT1 null genotype was higher in cases (59.4% compared to controls (47.2% with an odds ratio (OR of 1.68 and 95% confidence interval (CI from 0.96 to 2.97 (P = 0.07, especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01. No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05. Conclusion Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian

  16. A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley

    Institute of Scientific and Technical Information of China (English)

    Imtiyaz Murtaza; Dhuha Mushtaq; Mushtaq A Margoob; Amit Dutt; Nisar Ahmad Wani; Ishfaq Ahmad; Mohan Lal Bhat

    2006-01-01

    AIM: To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India.METHODS: All cases (n = 51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient's age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS: Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P < 0.05) with familial history of cancer (CD = 58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable "Hakh" (CD = 19.5),red chillies (CD = 20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD = 1.1).CONCLUSION: Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea

  17. Nm23H1 mediates tumor invasion in esophageal squamous cell carcinoma by regulation of CLDN1 through the AKT signaling

    Science.gov (United States)

    Kuo, K-T; Chen, C-L; Chou, T-Y; Yeh, C-T; Lee, W-H; Wang, L-S

    2016-01-01

    Esophageal cancer is a lethal malignancy worldwide. Previously, low expression of metastasis suppressor Nm23H1 and tight junction (TJ) protein claudin-1 (CLDN1) have been known to correlate with poor prognosis in esophageal squamous cell carcinoma (ESCC). However, the molecular interaction between them has not been clarified. In the present study, we first examined the expression of Nm23H1 and CLDN1 in 74 surgical ESCC samples by immunohistochemistry (IHC) to verify their clinicopathologic significance. The biologic effects of Nm23H1 gene silencing or overexpression in ESCC cell lines were then studied by migration and invasion studies, and its regulation on CLDN1 expression was also investigated by western blot analysis. Moreover, the expression of Nm23H1 and CLDN1 at the same invasion front of ESCC tumors was verified by immunofluorescence. The results showed a significantly positive correlation between the expression of Nm23H1 and CLDN1 (γ=0.296, P=0.011) in surgical specimens, especially for the 34 tumors with lymph-node metastasis (γ=0.455, P=0.007). In ESCC cell lines, silencing of Nm23H1 expression markedly enhanced cell invasiveness, accompanied by increased Akt phosphorylation and decreased CLDN1 expression. Conversely, Nm23H1-expressed transfectants exhibited reduced invasiveness, decreased Akt phosphorylation and correspondingly increased CLDN1 expression. Regain of CLDN1 expression in ESCC cells significantly suppressed invasiveness, but did not influence the Akt phosphorylation. Moreover, treating Nm23H1-depleted cells with the AKT inhibitor MK2206 recovered CLDN1 expression, and diminished the invasiveness of ESCC cells. Finally, decreased expressions of both CLDN1 and E-cadherin were observed at the invasive front of the Nm23H1-negative tumors. Overall, our current study documented that reduced Nm23H1 expression activates the AKT signaling pathway, results in diminished CLDN1 expression and potentiates invasiveness of ESCC cells. Enhancement of Nm

  18. 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...

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

    Institute of Scientific and Technical Information of China (English)

    Ahmed Abbas; Karine Delvinquière; Mathilde Lechevrel; Pierre Lebailly; Pascal Gauduchon; Guy Launoy; Fran(c)ois Sichel

    2004-01-01

    AIM: To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (ADC) in a high risk area of northwest of France.METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP1A1 *2C and GSTP1 exon 7 Val alleles, GSTM1*2/*2and GSTT1*2/*2 null genotypes). A total of 79 esophageal cancer cases and 130 controls were recruited.RESULTS: GSTM1*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell carcinomas at a level close to statistical significance (OR = 1.83, 95% CI 0.88-3.83, P= 0.11; OR = 3.03, 95% CI 0.93-9.90, P= 0.07,respectively). For GSTP1 polymorphism, no difference was found between controls and cases, whatever their histological status. Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR = 13.31, 95% CI 1.66-106.92, P<0.01).CONCLUSION: In SCC, our results are consistent with the strong association of this kind of tumour with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses:(1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTT1; (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC,possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

  20. Genetic polymorphisms in cytochrome P4502E1,alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Guo; Qin Wang; Yan-Zhen Liu; Huei-Min Chen; Zhi Qi; Qing-Hong Guo

    2008-01-01

    AIM:To evaluate the association between genetic polymorphisms in CYP2E1,ALDH2 and ADHIB and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu province,in Chinese males.METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2EI*cl/*c2,ALDH2*I/*2 and ADHIB "1/'1genotypes).A total of 80 esophageal cancer cases and 480 controls were recruited.RESULTS:Compared with controls,cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%).Heavier alcohol consumption and alcohol drinking with > 30 drink-years increased the risk of ESCC,with ORs (95% CI)of 3.20 (1.32-9.65) and 1.68 (0.96-3.21).CYP2E1(*cl/*cl),ALDH2 ('1/'2) and ADHIB (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas,at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively).There were synergistic interactions among alcohol drinking and ALDH2,ADHIB and CYP2E1 genotypes.The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*I/*2 as well as ADHIB encoded by ADHIB "1/'1 and CYP2E1 encoded by CYP2E1 *cl/*cl was higher than that in the never/rare-to-light drinkers with an active ALDH2 ('1/'1 genotype)as well as ADHIB ('1/'2 + *2/*2) and CYP2E1 (*c1/*c2+ *c2/*c2) genotypes,with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68),27.12(8.52-70.19) and 7.64 (2.82-11.31) respectively.The risk of the ESCC in moderate-to-heavy drinkers with ALDH2('1/'2) combined theADHIB ('1/'1) genotype orALDH2('11"2) combined the CYP2E1 (*cl/*cl) genotype leads to synergistic interactions,higher than drinkers with ALDH2 (* 1/* 1) + ADHIB ('1/'2 + *2/*2),ALDH2 (* 1/* 1)+ CYP2E1 (*cl/*c2 + *c2/*c2) respectively,ORs (95%CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively.Individuals with the ADHIB combined the CYP2E1genotype

  1. Secondhand Smoking and the Risk of Esophageal Squamous Cell Carcinoma in a High Incidence Region, Kashmir, India: A Case-control-observational Study.

    Science.gov (United States)

    Rafiq, Rumaisa; Shah, Idrees Ayoub; Bhat, Gulzar Ahmad; Lone, Mohd Maqbool; Islami, Farhad; Boffetta, Paolo; Dar, Nazir Ahmad

    2016-01-01

    Studies have associated secondhand smoking (SHS) with cancers of the lung, larynx, and pharynx. Only a few studies have examined the association between SHS and esophageal squamous cell carcinoma (ESCC) and the findings are inconclusive. We aimed to investigate the association between SHS and risk of ESCC in a case-control study in Kashmir, where the incidence of ESCC is high. We recruited 703 histopathologically confirmed ESCC cases and 1664 hospital-based controls individually matched to the cases for age, sex, and district of residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression models. Among never-tobacco users, the ORs for the association between SHS and ESCC risk were above unity with ever exposure to SHS (OR = 1.32; 95% CI, 0.43-4.02) and exposure to SHS for > 14 h/wk (median value) (OR = 2.69; 95% CI, 0.75-20.65). In the analysis of data from all participants, the OR (95% CI) for the association between SHS and ESCC was (OR = 1.02; 95% CI, 0.53-1.93) for SHS ≤ 14 h/wk and (OR = 1.91; 95% CI, 0.75-4.89) for SHS >14 h/wk in the models adjusted for tobacco use and several other potential confounding factors. We found an indication of increased risk of ESCC associated with exposure to SHS. Studies with larger numbers of SHS-exposed never tobacco users are required to further examine this association.

  2. Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy

    International Nuclear Information System (INIS)

    To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of residual lymph node status on overall survival (OS) and progression-free survival (PFS). Among the originally analyzed 296 patients, 100 (33.7 %) patients had ypT0, including 78 patients (78 %) with ypT0N0, and 22 patients (22 %) with ypT0N1. The 5-year OS of the total patients was 42.4 %. Patients with ypT0N0 have significant improved 5-year OS and PFS than ypT0N1 patients (OS: 50.7 % vs 13.6 %, P = 0.004; PFS: 49.6 % vs 13.6 %, P = 0.003). In multivariate analysis, residual lymph node status was also an independent prognostic factors for OS (HR: 0.406, 95 % CI: 0.240–0.686, P = 0.001) and PFS (HR: 0.427, 95 % CI: 0.248–0.734, P = 0.002). Our results indicate that patients with ypT0N0 after preoperative radiotherapy had significantly better OS and PFS than patients with ypT0N1 in ESCC. Residual nodal metastasis of ESCC patients with pathological complete response of the primary tumor after neoadjuvant radiotherapy does influence prognosis

  3. Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    LU Tai-ying; LI Wen-cai; CHEN Ren-yin; FAN Qing-xia; WANG Liu-xing; WANG Rui-lin; LU Shi-xin; MENG Hui

    2011-01-01

    Background The potential application of retinoic acid receptor activators,such as all trans-retinoic acid (ATRA),for treating various cancers have been studied both pre-clinically and clinically.Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown.We have explored the anticancer effect of ATRA in ESCC,and in this study,the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line,EC9706,in nude mice.Methods The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice.Reverse transcription-polymerase chain reaction (RT-PCR),Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.Results Compared to the control group,the tumor inhibition rates in the low dose ATRA,high dose ATRA,and 5-FU groups were 83.21%,88.32%,91.02%,respectively.The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P <0.05).The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31,CD34,and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P <0.05).Conclusions ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice.These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction,which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.

  4. Nuclear Factor-κB Signaling Pathway Constitutively Activated in Esophageal Squamous Cell Carcinoma Cell Lines and Inhibition of Growth of Cells by Small Interfering RNA

    Institute of Scientific and Technical Information of China (English)

    Fang TIAN; Wei-Dong ZANG; Wei-Hong HOU; Hong-Tao LIU; Le-Xun XUE

    2006-01-01

    Although constitutive nuclear factor (NF)-κB activation has been reported in many human tumors, the role of the NF-κB pathway in esophageal squamous cell carcinoma (ESCC) has not been known.In this study, NF-κB pathway in two ESCC cell lines was investigated using immunocytochemistry, Western blot and reverse transcription-polymerase chain reaction. The activation of NF-κB DNA binding was determined by electrophoretic mobility-shift assay. RNA interference was used to specifically inhibit the expression of p65. Growth of cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.The results showed that p50, p65, Iκ Bα, p-Iκ Bα and Iκ B kinase β were expressed and mainly localized in the cytoplasm. Reverse transcription-polymerase chain reaction results showed the constitutive expressions of p50, p65 and Iκ Bα mRNA in the two ESCC cell lines. Furthermore, the nuclear extracts revealed that p50 and p65 translocated to the nucleus had DNA-binding activity. Finally, small interfering RNA of p65 decreased the expression of p65, and the viability of cells transfected with p65 small interfering RNA was significantly suppressed at the same concentration of 5-fluorouracil (P<0.05) compared to untransfected cells. The results of this study showed that there was the constitutively activated NF-κB signaling pathway in the ESCC cell lines. RNA interference targeting at p65 increased the sensitivity of the ESCC cell lines to 5-fluorouracil,suggesting that NF-κB might be a good target for cancer treatment.

  5. Overexpression of the DEC1 protein induces senescence in vitro and is related to better survival in esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Qing Xu

    Full Text Available Esophageal squamous cell carcinoma (ESCC is a leading cause of cancer-related death in China and has limited effective therapeutic options except for early surgery, since the underlying molecular mechanism driving its precursor lesions towards invasive ESCC is not fully understood. Cellular senescence is the state of the permanent growth arrest of a cell, and is considered as the initial barrier of tumor development. Human differentiated embryo chondrocyte expressed gene 1 (Dec1 is an important transcription factor that related to senescence. In this study, DEC1 immunohistochemical analysis was performed on tissue microarray blocks constructed from ESCC combined with adjacent precursor tissues of 241 patients. Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. In vitro, DEC1 overexpression induced cellular senescence, and it inhibited cell growth and colony formation in ESCC cell line EC9706. Fresh esophagectomy tissue sections from five ESCC patients were detected by immunohistochemistry of DEC1 and senescence-associated β-galactosidase (SA-β-Gal activity, and strongly positive expression of DEC1 was correlated to more senescent cells in these fresh tissue sections. Kaplan-Meier method analysis of the 241 patients revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with age, tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. These results suggest that DEC1 overexpression in precursor lesions of ESCC is a protective mechanism by inducing cellular senescence in ESCC initiation, and DEC1 may be a potential prognostic marker of ESCC.

  6. TIM-3 promotes the metastasis of esophageal squamous cell carcinoma by targeting epithelial-mesenchymal transition via the Akt/GSK-3β/Snail signaling pathway.

    Science.gov (United States)

    Shan, Baoen; Man, Hongwei; Liu, Junfeng; Wang, Ling; Zhu, Tienian; Ma, Ming; Xv, Zhili; Chen, Xinran; Yang, Xingxiao; Li, Pengfei

    2016-09-01

    T-cell immunoglobulin and mucin domain-con-taining protein-3 (TIM-3), a negative regulator of antitumor immune response, has been demonstrated to be involved in the onset and progression of several types of malignancies. The present study aimed to determine whether and how TIM‑3 plays such a role in esophageal squamous cell carcinoma (ESCC). TIM-3 expression was analyzed by immunohistochemistry and real‑time fluorescence quantitative PCR (qRT‑PCR) in ESCC and matched adjacent normal tissues. Functional experiments in vitro were performed to elucidate the effect of TIM‑3 knockdown on the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) in Eca109 and TE‑1 cell lines. Our data revealed that TIM‑3 expression was significantly elevated at both the mRNA and protein levels in ESCC tissues compared with the levels in the matched adjacent normal tissues (both Pdownregulation of matrix metalloproteinase (MMP)-9 and upregulation of tissue inhibitor of metalloproteinase (TIMP)-1, and with reversion of EMT, as reflected by higher levels of the epithelial marker E‑cadherin and lower levels of the mesenchymal markers N‑cadherin and vimentin. Further study found that TIM‑3 depletion suppressed the signaling pathway involving p‑Akt, p‑GSK‑3β and Snail. Taken together, these results suggest that TIM‑3 is a novel therapeutic target and prognostic biomarker for ESCC and promotes metastasis of ESCC by inducing EMT via, at least partially, the Akt/GSK-3β/Snail signaling pathway. PMID:27430162

  7. 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.)

  8. Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Ye Liu; Yong-Hong Li; Zhuo-Wei Liu; Zhi-Ling Zhang; Yun-Lin Ye; Kai Yao; Hui Han; Zi-Ke Qin; Fang-Jian Zhou

    2013-01-01

    The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on local y advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregional y advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overal survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potential y curative in locoregional y advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

  9. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Sanambar Sadighi

    2015-06-01

    Full Text Available To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years. Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%. No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014. Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

  10. Response evaluation after chemoradiotherapy for advanced staged oropharyngeal squamous cell carcinoma: a nationwide survey in the Netherlands

    NARCIS (Netherlands)

    Schouten, C.S.; Hoekstra, O.S.; Leemans, C.R.; Castelijns, J.A.; Bree, R. de

    2015-01-01

    Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response eval

  11. 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 ...

  12. 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

  13. Rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract: A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Moloy, P.J.; Moran, E.M.; Azawi, S. (Permanente Medical Group, Fresno, CA (USA))

    1991-01-01

    A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irradation were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study.

  14. Polymorphisms in tumor necrosis factor genes and susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high incidence region of North China

    Institute of Scientific and Technical Information of China (English)

    GUO Wei; WANG Na; LI Yan; ZHANG Jian-hui

    2005-01-01

    Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor (TNF) genes with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). Methods The TNF-α-308G/A and TNF-β+252G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, in 555 cancer patients (291 ESCC and 264 GCA) and 437 healthy controls in a high incidence region of North China. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4%,9.2% and 1.4% respectively, while frequencies of the TNF-β B1/B1, B1/B2 and B2/B2 genotypes were 12.6%,32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G/A and TNF-β+252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [the age and gender adjusted odds ratio (OR)=2.04 and 1.91, 95% confidence interval (CI)=1.04-4.43 and 1.14-2.60, respectively] and GCA (the age and gender adjusted OR=2.68 and 2.64, 95% CI=1.14-6.29 and 1.47-4.72, respectively) in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 1/1 genotypes (the age and gender adjusted OR=0.37 and 0.34, 95% CI=0.15-0.92 and 0.13-0.90, respectively).Conclusions Therefore, the TNF-α-308G/A and TNF-β+252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.

  15. Comparison of the effect of p65 siRNA and curcumin in promoting apoptosis in esophageal squamous cell carcinoma cells and in nude mice.

    Science.gov (United States)

    Tian, Fang; Zhang, Caifeng; Tian, Weihong; Jiang, Yanan; Zhang, Xiaoyan

    2012-07-01

    The activation of the NF-κB signaling pathway plays a critical role in carcinogenesis. The role of the NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. The objective was to detect whether p65siRNA and curcumin could promote ESCC cell apoptosis and increase the sensitivity of ESCC cells to chemotherapeutic drugs by inhibiting the NF-κB signaling pathway, and to compared these two treatments. In the present study, the status of the NF-κB pathway, in the two ESCC cell lines Eca109 and EC9706, was analyzed and the ability of p65 siRNA and curcumin alone or in combination with 5-FU to modulate this pathway in vitro and in vivo was investigated. The results showed that the NF-κB signaling pathway in the ESCC cell lines was constitutively activated. Both p65 siRNA and curcumin mediated suppression of activation of the NF-κB signaling pathway via inhibition of the expression of p65 or IκBα phosphorylation in ESCC cell lines. The cells treated with combination of p65 siRNA or curcumin and 5-FU revealed a lower cell viability and higher apoptosis compared to those treated with 5-FU alone. In a human ESCC xenograft model, p65 siRNA or curcumin and 5-FU alone reduced the tumor volume, respectively, but their combination had the strongest anticancer effects. Curcumin was more effective than p65 siRNA in vitro and in vivo. Overall, our results indicate that the constitutively activated NF-κB signaling pathway plays a crucial role in these two ESCC cell lines and both p65siRNA and curcumin can promote ESCC cell apoptosis and enhance the sensitivity to 5-FU through suppression of the NF-κB signaling pathway. It is still a long time before RNA interference will be used in the clinic. Therefore, curcumin is proved to be useful in the treatment of ESCC as it is a pharmacologically safe compound without side effects.

  16. Percutaneous endoscopic gastrostomy for nutritional palliation of upper esophageal cancer unsuitable for esophageal stenting

    Directory of Open Access Journals (Sweden)

    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

  17. Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors

    International Nuclear Information System (INIS)

    Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC). Using multiplex-fluorescence in situ hybridization (M-FISH) and oligo array-based comparative hybridization (array-CGH), we identified aberrations and breakpoints in six ESCC cell lines. Furthermore, we detected recurrent breakpoints in primary tumors by dual-color FISH. M-FISH and array-CGH results revealed complex numerical and structural aberrations. Frequent gains occurred at 3q26.33-qter, 5p14.1-p11, 7pter-p12.3, 8q24.13-q24.21, 9q31.1-qter, 11p13-p11, 11q11-q13.4, 17q23.3-qter, 18pter-p11, 19 and 20q13.32-qter. Losses were frequent at 18q21.1-qter. Breakpoints that clustered within 1 or 2 Mb were identified, including 9p21.3, 11q13.3-q13.4, 15q25.3 and 3q28. By dual-color FISH, we observed that several recurrent breakpoint regions in cell lines were also present in ESCC tumors. In particular, breakpoints clustered at 11q13.3-q13.4 were identified in 43.3% (58/134) of ESCC tumors. Both 11q13.3-q13.4 splitting and amplification were significantly correlated with lymph node metastasis (LNM) (P = 0.004 and 0.022) and advanced stages (P = 0.004 and 0.039). Multivariate logistic regression analysis revealed that only 11q13.3-q13.4 splitting was an independent predictor for LNM (P = 0.026). The combination of M-FISH and array-CGH helps produce more accurate karyotypes. Our data provide significant, detailed information for appropriate uses of these ESCC cell lines for cytogenetic and molecular biological studies. The aberrations and breakpoints detected in both the cell lines and primary tumors will contribute to identify affected genes involved in the development and progression of ESCC

  18. Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, M-T; Chen, G; An, S-J; Chen, Z-H; Huang, Z-M; Xiao, P; Ben, X-S; Xie, Z; Chen, S-L; Luo, D-L; Tang, J-M; Lin, J-Y; Zhang, X-C; Wu, Y-L

    2012-01-01

    CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell cycle, and related with the development of many cancers. However, the co-alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less understood. This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal tissues were detected using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Their prognosis significance was analyzed by Kaplan-Meier method. We found that 41% of the patients had CCND1 DNA amplification, which had a short survival time compared with the patients without CCND1 amplification (25.63 months vs. not reached, P=0.007). The patients with the co-alternation of CCND1(+) /pRb(-) /ppRb(+) protein expression levels have a poorer overall survival than the others (11.4 vs. 43.4 months, P=0.001). Cox regression analysis showed that the co-alternation of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent prognosis factors of patients with esophageal cancer. These findings suggested that CCND1 amplification and co-alternation of CCND1(+) /pRb(-) /ppRb(+) may play a crucial role in the prognostic evaluation of patients with esophageal cancer, and the patients with CCND1(+) /pRb(-) /ppRb(+) have the worst prognosis in all the patients. The results also indicated that the patients with CCND1 amplification or co-alternation of CyclinD1(+) /pRb(-) /ppRb(+) might be the preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the future.

  19. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Scheistroeen, M. (Norwegian Radium Hospital, Oslo (Norway)); Trope, C. (Norwegian Radium Hospital, Oslo (Norway))

    1993-01-01

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.).

  20. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    International Nuclear Information System (INIS)

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.)

  1. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  2. 光动力疗法治疗食管癌合并白色念珠菌感染%Photodynamic Therapy for Esophageal Squamous Cell Carcinoma Associated with Candida albicans Infection

    Institute of Scientific and Technical Information of China (English)

    毛永平; 邱海霞; 顾瑛; 王颖; 朱建国; 曾晶; 刘庆森; 杨云生

    2011-01-01

    目的 观察光动力疗法抗食管真菌感染的疗效.方法 临床及病理确诊为食管癌合并食管白色念珠菌感染的患者1例,静脉注射光敏剂PSD-007 5 mg/kg后6h,以波长630nm的半导体激光(激光功率密度150 mW/cm2)出光段为3 cm的柱状光纤分节段及分次进行照射.食管癌或食管癌合并白色念珠菌感染灶处,每光斑照射30 min;单纯白色念珠菌感染灶,每光斑照射15min.观察术中和术后不良反应发生情况,根据相应标准进行近期临床疗效评价.结果 该患者共进行了3次PDT治疗,其中距门齿21 ~24 cm的食管癌2次治疗后达到完全效应,伴发的白色念珠菌感染1次治疗后治愈;距门齿25 ~28 cm念珠菌性食管炎2次治疗后治愈;距门齿35~33、33~30 cm的食管癌分别经2次和3次治疗后达到明显效应.除距门齿21 ~ 24 cm的食管癌第2次PDT治疗病变完全消失后遗留少量瘢痕外,余区未发生瘢痕,狭窄、穿孔等不良反应.结论 光动力疗法不仅能有效控制进展期食管癌,还能有效治疗食管白色念珠菌感染,具有高选择性、安全、毒副作用小、可重复应用等优点,对食管真菌感染,尤是对食管真菌感染合并食管癌的患者是一种有希望的治疗方法.%Objective To observe the ability of photodynamic therapy to deal with Candida esophagitis.Methods One patient with esophageal squamous cell carcinoma associated with Candida albicans infection confirmed by endoscopy and histopathology was included in the study. PSD-007 at 5 mg/kg body mass was intravenously injected 6 h prior to laser irradiation. A semiconductor laser emitting at 630 run was used as light source. The power density of 150 mW/cm2 was used. To lesions of esophageal squamous cell carcinoma associated with C. Albicans infection or esophageal squamous cell carcinoma alone, the exposure time of30 min and a total light dose of 270 J/cm2 was used at one light spot. To lesion with Candida

  3. 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.

  4. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  5. 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

  6. Strategies to improve the outcome of esophagectomy for esophageal cancer

    NARCIS (Netherlands)

    Boone, J.

    2009-01-01

    Esophageal cancer is the 8th most common type of malignancy in the world. For the past decades the incidence of esophageal cancer has rapidly increased, particularly due to a rise in adenocarcinoma of the esophagus. Yet, worldwide the incidence of esophageal squamous cell carcinoma (ESCC) is highest

  7. Translational Research on Esophageal Cancer: From Cell Line to Clinic

    NARCIS (Netherlands)

    J.J. Boonstra (Jurjen)

    2011-01-01

    textabstractWorldwide esophageal cancer is a signifi cant and an increasing health problem. In 2005, there were 497,700 new cases, and the prevalence is expected to increase by approximately 140% by 2025. Esophageal squamous cell carcinoma (ESCC) accounts for most of the cases of esophageal cancer w

  8. Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

    Institute of Scientific and Technical Information of China (English)

    WEN Deng-gui; YANG Yi; WEN Xiao-duo; SHAN Bao-en

    2013-01-01

    Background In China,esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci,but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.Methods The percent of cases with a positive family history,median onset age,rate of multiple primary cancer,and male/female ratio associated with upper,middle,lower third ESCC and GCA were compared to reveal the proportion of familial cancer.The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases,e.g.with 42% of the males and 59% of the females.For upper,middle,lower third ESCC and GCA,the percent of cases with a positive family history decreased by 38.5%,26.3%,26.5%,and 11.2% in males (P <0.000) and 25.0%,22.3%,23.9%,and 9.8% in females (P <0.0001).Median onset age increased from 49,52,55,to 56 years old in males and from 50,53,55,to 56 years old in females (both P <0.0001) for upper,middle,lower third ESCC and GCA.Male/female ratio increased from 2.2,2.1,2.2,to 6.2:1 for upper,middle,lower third ESCC and GCA (P<0.0001).For upper,middle,lower third ESCC and GCA,the percent of multiple primary cancers decreased from 21.2%,2.3%,2.2%,to 1.5% in males and from 14.3%,2.4%,3.4%,to 3.1% in females.The preponderance of males,smoking,drinking,or onset-age ≥50 years was significantly higher in GCA than in ESCC,and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA,but not in ESCC,suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.Conclusions The proportion of familial cancer in upper gastrointestinal

  9. CDH1基因甲基化与食管鳞癌的关系%Relationship between CDH1 gene methylation and esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    李永丽; 张立玮

    2012-01-01

    目的 探对食管鳞癌组织中CDH1基因启动子区甲基化的表达状况及其与烟酒史、肿瘤家族史的关系.方法 应用甲基化特异性聚合酶链反应(MSP)法检测食管鳞癌中CDH1基因启动子区甲基化情况.结果 食管鳞癌、癌旁及正常组织CDH1基因的甲基化阳性率分别为51.6%(32/62)、22.6%(14/62)和0(0/18).癌与癌旁组织比较,甲基化阳性率差异有统计学意义(P<0.01);癌和正常组织比较,甲基化阳性率差异有统计学意义(x2=15.484,P<0.01);癌旁与正常组织间差异无统计学意义(x2 =3.487,P>0.05).食管鳞癌CDH1基因甲基化情况与其性别、年龄、烟酒史和上消化道肿瘤家族史比较差异均无统计学意义(均P >0.05).结论 CDH1基因启动子区甲基化与食管鳞癌发生关系密切,在食管鳞癌中是一常见的表观遗传学事件.CDH1基因甲基化可能是一个独立的危险因素.%Objective To study CDH1 gene promoter methylation status in tissues of esophageal squamous cell' carcinomas(ESCC) and its relationship with tobacco and alcohol history, family history of cancer. Methods CDHl gene promoter methylation in ESCC Was detected by methylation-specific polymerase chain reaction (MSP) and was analyzed statistically. Results CDH1 gene methylation positive rates in tumor tissues, adjacent and normal tissues of ESCC were 51. 6%(32/62) ,22. 6%(14/62) and 0(0/18) .respectively,the difference between cancer and adjacent tissue was significant ( P 0. 05). Compared CDHl gene methylation in ESCC with sex,age,tobacco and alcohol history,family history of upper gastrointestinal tumors, there were no statistical significance (all P > 0. 05). Conclusion CDHl gene promoter methylation is closely related to the occurrence of ESCC, and it is a common epigenetic event in ESCC. CDHl gene methylation may be an independent risk factor.

  10. The Changing Face of Esophageal Cancer

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    Melhado, Rachel E., E-mail: raye732001@yahoo.co.uk; Alderson, Derek; Tucker, Olga [Academic Department of Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham (United Kingdom)

    2010-06-28

    The two main histological esophageal cancer types, adenocarcinoma and squamous cell carcinoma, differ in incidence, geographic distribution, ethnic pattern and etiology. This article focuses on epidemiology with particular reference to geographic and temporal variations in incidence, along with a review of the evidence supporting environmental and genetic factors involved in esophageal carcinogenesis. Squamous cell carcinoma of the esophagus remains predominantly a disease of the developing world. In contrast, esophageal adenocarcinoma is mainly a disease of western developed societies, associated with obesity and gastro-esophageal reflux disease. There has been a dramatic increase in the incidence of adenocarcinoma in developed countries in parallel with migration of both esophageal and gastric adenocarcinomas towards the gastro-esophageal junction.

  11. N ek8在食管鳞癌中的表达及意义%Significance of Nek8 expression in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    郭亚平; 朱红; 付茂勇; 王朝莉; 李倩倩; 胡为民

    2015-01-01

    目的:探讨食管鳞癌组织和细胞系中Nek8的表达及其与食管鳞癌临床病理特征和术后生存的关系。方法采用RT‐PCR法检测食管鳞癌细胞系Eca109细胞、2例配对的食管鳞癌组织和癌旁黏膜上皮中Nek8 mRNA表达情况;应用免疫组织化学法检测Nek8蛋白在食管鳞癌组织芯片中的表达情况,并结合临床病理资料和生存率进行统计学分析。结果 Nek8 mRNA在Eca109细胞、2例食管鳞癌患者的癌组织均有表达,而癌旁食管黏膜上皮中均未见明显的表达。组织芯片结果示N ek8蛋白主要表达于细胞质,在78例配对的标本中,Nek8在食管鳞癌组织中的表达显著高于其在癌旁黏膜组织的表达(P=2.16E‐13)。其表达与肿瘤大小有关(P=0.008),而与性别、年龄、分化程度、浸润深度、淋巴结转移无关(P>0.05)。生存分析显示高表达和低表达Nek8的患者生存率差异无统计学意义(P>0.05)。结论 Nek8在食管鳞癌组织和细胞中表达上调,可能参与了食管鳞癌的发生、发展,可作为诊断的标志物和治疗的靶点。%Objective To investigate the expression of Nek8 in esophageal squamous cell carcinoma(ESCC) tissues and cell line , and to evaluate its correlation with the clinicopathological features of ESCC and the survival rate of ESCC patients after operation . Methods The expression of Nek8 mRNA in human ESCC Eca109 cell line and two pairs of ESCC tissues and adjacent normal e‐sophageal mucosal epithelium were detected by semi‐quantitative reverse transcription polymerase chain reaction (RT‐PCR) .Immu‐nohistochemistry and tissue microarray technique were used to examine the expression of Nek 8 protein in ESCC tissues and tumor‐adjacent tissues .The correlation between Nek8 expression and clinicopathological features of ESCC and survival rate of ESCC pa‐tients was then analyzed .Results The expression of Nek8 mRNA was

  12. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ross Zeitlin

    2015-04-01

    Full Text Available Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC. In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy.

  13. Personalized therapy in locally advanced head and neck squamous-cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sánchez-Escribano R

    2013-11-01

    Full Text Available Introduction: Locally advanced head and neck squamous cell carcinoma patients (LAHNSCC represents a truly heterogeneous population with differences in comorbidities, primary tumor location and etiology. These are key factors in optimal treatment selection. Material and methods: An extensive literature review was made in order to identify the most relevant factor in the therapeutic decision, with special interest in induction chemotherapy as the latest and most debatable option. Results: In the therapeutic decision we have to take into account factors related to the patient, age and performance status are the most important, and others related to the tumor as stage, site of origin and etiology, between this ones l, viral subtypes (EBV and HPV are becoming relevant in the later decades. Chemoradiotherapy is considered the gold standard treatment, supported by several randomized trials and metaanalysis. Induction chemotherapy is one of the later options appeared in the therapeutic arena, improving results in organ preservation and survival. Although a substantial increase in toxicities and lack of prospective comparisons with the standard concurrent chemoradioterapy, warrants a cautious use. Conclusions: Therapeutic choice in the LAHNSCC patient is a complex and multidimensional process, that should be carried in a specialized and multidisciplinary team that can assure the highest efficiency and security for the patient

  14. 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)

  15. miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis.

    Science.gov (United States)

    Zhang, Weiguo; Lei, Caipeng; Fan, Junli; Wang, Jing

    2016-08-12

    Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Cyclin D1 is overexpressed and plays an important role in the carcinogenesis of ESCC; however the mechanism of the deregulation of Cyclin D1 in ESCC remains to be determined. In the study, we found that miR-18a promotes the expression Cyclin D1 by targeting PTEN in eophageal squamous cell carcinoma TE13 and Eca109 cells. Transfection of miR-18a mimetics increased cyclin D1, while transfection of miR-18a antagomir decreased D1. Moreover, miR-18a-mediated upregulation of cyclin D1 was accompanied with downregulation of PTEN, which is a direct target of miR-18a, and increase of the phosphorylation of AKT and S6K1. In addition, pharmacologic inhibition of AKT or mTOR kinases abolished the increase of cyclinD1 by miR-18a, which was accompanied with decreased phosphorylation of RbS780 and inhibition of cell proliferation. Our results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. PMID:27291152

  16. 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

  17. 食管鳞状上皮低级别上皮内瘤变的内镜表现与食管癌形成关系分析%Pathological Esophageal Squamous Intraepithelial Neoplasia of Low-level and Effect Analysis of the Formation of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    谭莫伟; 张乐星; 黄小津

    2015-01-01

    Objective To explore the pathological esophageal squamous intraepithelial neoplasia of low-level and ef ect analysis of the formation of esophageal cancer. Methods Chose from May 2007 to May 2010, 41 cases of gastroscopy diagnosis of patients with esophageal squamous epithelium low level intraepithelial neoplasia. To fol ow-up of its research object, analyzes its neoplasia outcome and pathological manifestations. The fol ow-up of patients was stil at the termination of the esophageal squamous epithelium low level intraepithelial neoplasia or disappearance of low-level epithelial neoplasia in patients classified as stable lesion group, the patients at the end of fol ow-up for high-grade intraepithelial neoplasia or esophageal cancer patients classified as lesions progress group. Results Sharing at the end of the 10 patients were fol ow-up for high level intraepithelial neoplasia or esophageal cancer, 31 patients were stil low level intraepithelial neoplasia or neoplasia . Group of patients with lesions progress erosion and shal ow ulcer significantly higher proportions of stable lesion group ( < 0.05), pathological changes and stable group of patients is significantly higher proportions of erythema and uplift melee lesion group ( < 0.05). Lesions progress group in the scope of lesions acuity 2.0 cm and 2.0 ~ 2.0 cm range significantly higher proportions of stable lesion group ( <0.05), and a stable lesion group within the scope of lesions in the range 1.0 cm or less progress significantly higher proportions of lesion group ( <0.05).Conclusion Esophageal squamous epithelium low level intraepithelial neoplasia is closely related to the occur ence of esophageal cancer, is associated with esophageal gastroscope pathological classification and scope of lesions.%目的探讨食管鳞状上皮低级别上皮内瘤变的病理表现及食管癌形成作用分析。方法选择我院2007年5月~2011年5月胃镜检查确诊的41例食管鳞状上皮低级别上皮内瘤变

  18. Glucose-regulated protein 78 expression in human esophageal squamous cell carcinoma and its correlation with tumor biological behavior%人食管鳞状细胞癌组织中GRP78的表达及其与肿瘤生物学行为的关系

    Institute of Scientific and Technical Information of China (English)

    许鹏; 王丹云; 王宗明; 张志平; 沈令广; 杨长征

    2009-01-01

    Objective: To investigate the expression of glucose-regulated protein 78 in human esophageal squamous cell carcinoma and normal esophageal tissues, and to evaluate its correlation with clinical pathological characteristics of esophageal squamous cell carcinoma. Methods: Fifty-nine specimens of human esophageal squamous cell carcinoma and twenty adjacent normal specimens were collected from the patients who received operation for esophageal squamous cell carcinomas in our Hospital between Oct. 2007 and Nov. 2008. GRP78 mRNA and GRP78 protein expressions were examined by RT-PCR assay and Western blotting, respectively. The relationship between GRP78 expression with clinical parameters of patients, such as gender, length of tumor, tumor infiltration depth, tumor differentiation grade stage, and lymphatic metastasis, was analyzed. Results: GRP78 mRNA and GRP78 protein expression levels in human esophageal squamous cell carcinoma were significantly higher than those in the normal esophageal tissues (all P0.05). Conclusion: GRP78 participates in the development, progress of esophageal squamous cell carcinomas, and its expression is positively associated with the malignancy of carcinoma. GRP78 may be taken as a potential biomarker in evaluating the malignancy of esophageal squamous cell carcinoma.%目的:探讨葡萄糖调节蛋白78(glucose-regulated proteins 78,GRP78)在食管鳞状细胞癌组织及正常鳞状上皮组织中的表达情况,并分析其与临床病理特征的关系.方法: 取自2007年10月至2008年11月在山东大学附属济南中心医院胸外科手术切除的新鲜食管鳞状细胞癌标本59例及距癌组织5 cm以上的手术远端切缘的正常食管鳞状上皮组织20例,RT-PCR检测GRP78 mRNA的表达,应用Western blotting检测GRP78蛋白的表达,并从mRNA和蛋白水平分析GRP78的表达与患者性别、肿瘤长度、浸润深度、分化程度、病理分期及淋巴转移等临床病理特征之间的关系.结果:食

  19. 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.

  20. Combined Chemoradiotherapy vs Radiotherapy Alone for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hyeon Ju; Suh, Hyun Suk; Kim, Chul Soo; Kim, Re Hwe; Kim, Sung Rok [Inje University College of Medicine, Seoul (Korea, Republic of)

    1996-03-15

    Purpose : The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer provides anticipated cure rates of 10-65% depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Methods and Materials : From November 1983 to October 1994, 31 patients with Stage II and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone. and 15 patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy(median 7010 cGy). In combined group. 7 patients were treated with cis-platin plus 5-FU, 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient (66.6%) of the RT alone group and 14 patient (93.3%) of the chemoradiation group. There was no statistical difference in CR rate between the two groups. The overall survival rates at 5 years were 23.4% in the radiation alone group. 23.5% in the chemoradiation group. Disease-free survival rates at 3 year were 44.5% in the radiation alone group. 40% in the chemoradiation group. There was no statistical differences in overall survival rates and disease free survival rates between the two groups. Local recurrences occurred in 71.5% of the radiation alone group. 72.7% of the chemoradiation group and distant metastasis occurred in 14.4% of radiation alone group. 9.1% of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity. Conclusion : Total response rates in the combined chemotherapy and

  1. Establishment and characterization of esophageal squamous cell carcinoma cell line subpopulation with higher invasive ability%食管癌细胞株高侵袭力亚系的建立及其生物学特性研究

    Institute of Scientific and Technical Information of China (English)

    夏宇; 李秀娟; 张志强; 温浩; 胡翠梨

    2012-01-01

    OBJECTIVE: To establish a higher invasive ability cell line from esophageal squamous cell carcinoma cell line (ESCC). METHODS: Trans well invasion chamber was used to subdivide a human esophageal carcinoma cell line named Eca-109 to sublines. The cell morphology were compared by HE staining; Methyl thiazolyl tetrazolium (MTT) method were used to detect changes in cell proliferation; the alteration of the cell cycle was detected using flow cytometry (FCM); The expression of invasion-related MMP-2 and TIMP-2 protein were detected by westen bloting. RESULTS; An esophageal squamous cell carcinoma subline was established and named Eca-109 T4. There was no significant difference in cell morphology,MTT assay showed a strong proliferation of subline,and cell cycle showed proliferation index (PI) was 41. 0%,Which was higher than Eca-109; Westen bloting showed that the expression of MMP-2 protein increased (P = 0. 023); TIMP-2 protein expression also increased,but the difference was not statistically significant (P = 0. 392). CONCLUSION: The higher invasive ability of esophageal carcinoma cell line is obtained and may be used to further research works.%目的:建立具有不同转移潜能的高侵袭能力食管癌细胞株亚系并研究其生物特性.方法:利用Transwell侵袭小室从人食管鳞癌Eca-109细胞株筛选高侵袭能力食管癌亚系,HE染色比较细胞形态;四甲基偶氯唑蓝(MTT)法检测细胞增殖能力的变化;流式细胞术( FCM)检测细胞周期;蛋白质印迹法检测与侵袭能力相关基质金属蛋白酶-2(MMP-2)和金属蛋白醇组织抑制因子-2(TIMP-2)蛋白表达.结果:利用Transwell侵袭小室从食管癌Eca-109细胞株中筛选出高侵袭能力食管癌细胞株亚系,命名为Eca-109 T4.2个细胞系细胞形态没有明显差异.MTT法检测显示,亚系Eca-109 T4增殖能力强.细胞周期显示,增殖指数(PI)高,PI=41.0%,且MMP-2蛋白表达相比增高,P=0.023;TIMP-2蛋白表达相比增高,

  2. The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer

    OpenAIRE

    Wang, Yao-Ching; Hsieh, Te-Chun; Yu, Chun-Yen; Yen, Kuo-Yang; Chen, Shang-Wen; Yang, Shih-Neng; Chien, Chun-Ru; Hsu, Shih-Ming; Pan, Tinsu; Kao, Chia-Hung; Liang, Ji-An

    2012-01-01

    A combination of four-dimensional computed tomography with 18F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTVPET) was determined with...

  3. Research and application of tumor markers in esophageal squamous cell carcinoma%肿瘤标志物在食管鳞状细胞癌中的研究与应用

    Institute of Scientific and Technical Information of China (English)

    王皓; 钟理; 王建飞; 张小刚

    2009-01-01

    Esophageal squamous cell carcinoma (ESCC), the main type of esophageal cancer, is one of the most common gastrointestinal malignant cancers. Tumor markers detection are easy, economical, fast and non-invasive. Some tumor markers can be expressed before morphological changes occurred in tissues and organs; therefore, they can be used for the diagnosis of disease in the asymptomatic stage, thus making the research into tumor marker discovery even more meaningful. This paper summarizes several known tumor makers' expression detected in ESCC in recent years, and illustrates them from the aspects of genes, proteins, autoimmune antibodies, antigens and prognostic factors.%食管鳞状细胞癌作为食管癌的主要类型, 是人类最常见的消化系恶性肿瘤之一. 作为诊断手段之一的肿瘤标志物检测, 具有简便、经济、快速、无创的特点, 更重要的是一些标志物在组织器官发生形态学变化之前就有表达, 因此, 肿瘤标志物对食管癌的研究就更有意义.本文综述近几年来一些发现和检测到的肿瘤标志物在食管鳞状细胞癌中的差异表达, 分别从基因、蛋白、自身免疫抗体、抗原及预测因子角度总结介绍.

  4. miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression

    Science.gov (United States)

    JIANG, SEN; ZHAO, CHAO; YANG, XIAODI; LI, XIANGYANG; PAN, QING; HUANG, HAIJIN; WEN, XUYANG; SHAN, HUSHENG; LI, QIANWEN; DU, YUNXIANG; ZHAO, YAPING

    2016-01-01

    Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR-1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR-1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR-1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR-1 promoted cell proliferation and decreased apoptosis, suggesting that miR-1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR-1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR-1. miR-1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR-1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR-1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC. PMID:27247259

  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. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Khambati

    2016-07-01

    Full Text Available Condyloma acuminata (CA is a common sexually transmitted disease caused by Human Papilloma Virus (HPV infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  9. miR-130b在食管鳞癌中的表达及对食管鳞癌细胞增殖和迁移的影响%Expression of miR-130b in esophageal squamous cell carcinoma and effect of miR-130b transfection on cell proliferation and migration in an esophageal squamous cell carcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    郁婷婷; 李硕; 傅敏根; 曹日昇; 朱宏; 施瑞华

    2013-01-01

    目的:检测微小RNA-130b(miR-130b)在食管鳞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达并探讨其对ESCC细胞增殖、迁移的影响.方法:microRNA(miRNA)芯片筛选ESCC组织中异常表达的miRNAs,TaqMan MGB探针法定量PCR检测19例ESCC组织及配对癌旁组织标本中miR-130b的表达;通过脂质体转染模拟物miR-130bmimics(miR-130bm)促进ESCC细胞Ecal09中miR-130b的表达,转染抑制物miR-130b inhibitor(miR-130bi)抑制Ecal09细胞中miR-130b的表达;进一步采用CCK-8法和Transwell迁移实验检测ESCC细胞增殖、迁移的变化;生物学信息预测miR-130b的靶基因,双荧光素酶报告基因验证其靶向作用;采用SYBR Green定量PCR和Western blot检测靶基因mRNA和蛋白表达.结果:miR-130b在ESCC组织中的表达明显高于癌旁组织(P<0.01);转染miR-130bm可有效增加ESCC细胞Ecal09中miR-130b的表达,进而促进Ecal09细胞的增殖和迁移,平均迁移细胞数明显多于对照(112.9±2.4 vs 54.3±1.8,P<0.01);转染miR-130bi则降低细胞中miR-130b的表达;进而抑制细胞的增殖和迁移,平均迁移细胞数较对照明显减少(33.9±2.3 vs56.2±1.9,P<0.01).miR-130b可作用于PTEN3’非翻译区抑制其表达.miR-130b可负向调控PTEN蛋白表达,并促进Akt磷酸化,但对PTENmRNA表达无明显影响.结论:miR-130b在ESCC组织中表达上调,增加其表达促进ESCC细胞Eca109增殖和迁移,降低其表达则抑制Eca109细胞增殖和迁移;miR-130b可在转录后水平负向调控PTEN的表达并促进Akt磷酸化.提示miR-130b有望成为ESCC治疗的新靶点.%AIM:To detect the expression of microRNA 130b (miR-130b) in esophageal squamous cell carcinoma (ESCC) and explore its effects on the proliferation and migration of ESCC cells in vitro.METHODS:MicroRNA (miRNA) microarray was used to select dysregulated miRNAs in ESCC.The expression of miR-130b in ESCC tissue specimens and matched tumor-adjacent tissue specimens was

  10. 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。

  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. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Pranshu eBansal

    2016-05-01

    Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

  13. Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism.

    Science.gov (United States)

    Zhang, Hai-Feng; Alshareef, Abdulraheem; Wu, Chengsheng; Li, Shang; Jiao, Ji-Wei; Cao, Hui-Hui; Lai, Raymond; Xu, Li-Yan; Li, En-Min

    2015-10-01

    Our previous studies have shown that loss of miR-200b enhances the invasiveness of esophageal squamous cell carcinoma (ESCC) cells. However, whether the miR-200-ZEB1/2-E-cadherin regulatory cascade, a master regulator of epithelial-to-mesenchymal transition (EMT), is involved in the regulation of ESCC invasion remains elusive. Here, we show that miR-200b represses ESCC cell invasion in vivo without altering the expression of E-cadherin and vimentin, two surrogate markers of EMT. However, an inverse correlation was observed between the expression levels of miR-200b and ZEB1/2 in both ESCC cell lines (n = 7, P ESCC tumor samples (n = 88, P ESCC. We revealed that miR-200b suppresses the integrin β1-AKT pathway via targeting Kindlin-2 to mitigate ESCC cell invasiveness. In two independent cohorts of ESCC samples (n = 20 and n = 53, respectively), Kindlin-2 expression positively correlated with the activation status of both the integrin signaling pathway and the PI3K-AKT signaling pathway (both P ESCC.

  14. Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus. Long-term outcome

    Energy Technology Data Exchange (ETDEWEB)

    Ordu, Arif Deniz; Deymann, Lisa Felicia; Scherer, Vera; Combs, Stephanie E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Nieder, Carsten [University of Tromsoe, Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodoe (Norway); Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Geinitz, Hans [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Krankenhaus der Barmherzigen Schwestern Linz, Department of Radiation Oncology, Linz (Austria); Kup, Philipp Guenther [Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Fakhrian, Khashayar [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Sankt Josef Hospital Bochum, Bochum (Germany)

    2014-11-18

    The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universitaet Muenchen was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1-212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients' choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy. The median overall survival (OS) was 20 months (95 % confidence interval 17-23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0-1 vs. 2-3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis. Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general

  15. MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

    Directory of Open Access Journals (Sweden)

    Henríquez-Hernández Luis

    2012-08-01

    Full Text Available Abstract Objective To explore the role of Major Vault Protein (MVP in oral cavity squamous cell carcinoma patients. Subjects and Methods 131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8–2 Gy/fraction. MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. Results MVP expression was positive in 112 patients (85.5% and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein was related to insulin-like growth factor receptor-1 (IGF-1R expression (P = 0.014. Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B = 2.730, CI95% (1.302-5.724 and cause-specific survival (P = 0.014, Exp(B = 2.570, CI95% (1.215-5.437 in patients achieving tumour stages III-IV, in multivariate analysis. Conclusions MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.

  16. EGFR、Her-2、HIF-1α在食管鳞癌的表达及意义%Significance of EGFR, Her-2, and HIF-1α expression in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    石祥东; 孟令新; 丁兆军; 孙树艳; 梁粉花; 王刚平

    2014-01-01

    Objective To explore EGFR, Her-2, HIF-1 alpha expression in esophageal squamous cell carcinoma(ESCC) and investigate the relationship between clinical pathological features in esophageal squamous carcinoma and the correlation between the three index. Methods Immunohistochemical Envision two-steps method was applied to assay EGFR, Her-2, HIF-1 alpha expression in 80 cases specimens of ESCC and 40 cases of adjacent normal squamous epithelial tissues. Results HIF-1 alpha, EGFR and Her-2 in ESCC and adjacent normal squamous epithelial tissues positive expression rate were 62.5% vs. 0.0% (P=0.000), 67.5% vs. 12.5% (P=0.000), 7.5% vs. 0.0% (P=0.183) each other. The expression of HIF-1 alpha, Her-2, EGFR had correlation with tumor cell differentiation, TNM staging and lymph node metastasis, had nothing to do with gender, age. HIF-1 alpha expression in esophageal squamous carcinoma had positive correlation with EGFR and Her-2, correlation coefficient were 0.565(P=0.000) and 0.221 (P=0.039). However, EGFR had no correlation with Her-2, correlation coefficient was 0.198(P=0.079). Conclusions EGFR and HIF-1 alpha high expression may plays an important role in tumor genesis and development of ESCC, may be used as useful indicators for predicating tumor genesis, metastasis, prognosis and may be likely to become new target for targeted therapy of ESCC. Her-2 expression was low in ESCC, and may be not suitable for be targeted therapy targets.%目的:研究EGFR、Her-2和HIF-1α在食管鳞癌中的表达,探讨三者的表达与食管鳞癌临床病理学特征之间的关系及三者之间的相关性。方法应用免疫组化 Envision 二步法检测80例食管鳞癌的切除标本和40例正常鳞状上皮组织中EGFR、Her-2和HIF-1α的表达。结果 HIF-1α、EGFR、Her-2在食管鳞癌及癌旁正常鳞状上皮组织表达阳性率分别为62.5%vs.0.0%(P=0.000)、67.5%vs.12.5%(P=0.000)和7.5%vs.0.0%(P=0.183)。HIF-1α、Her-2、EGFR表达

  17. Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal squamous cell carcinoma: analysis of treatment results and prognostic factors

    International Nuclear Information System (INIS)

    Concurrent radiochemotherapy is a recommended treatment option for patients with locally advanced squamous cell head and neck carcinomas with recent data showing the most significant absolute overall and event-free survival benefit achieved in patients with oropharyngeal tumours. The aim of this study was to analyse the results of three-dimensional conformal radiotherapy given with concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma and to identify prognostic factors influencing outcomes of this patients category. Sixty-five patients with stage III or IV squamous cell carcinoma of the oropharynx who underwent concurrent radiochemotherapy between January 2005 and December 2010 were retrospectively analyzed. All patients received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m2) started at the first day of radiotherapy. Median age was 57 years (range, 36 to 69 years) and 59 (90.8%) patients were male. Complete composite response was achieved in 47 patients (72.3%). Local and/or regional recurrence was the most frequent treatment failure present in 19 out of 25 patients (76.0%). At a median follow-up of 14 months (range, 5 to 72 months), 2-year local relapse-free, regional relapse-free, locoregional relapse-free, disease-free, and overall survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively. On multivariate analysis the only significant factor for inferior regional relapse-free survival was the advanced N stage (p = 0.048). Higher overall stage was independent prognostic factor for poorer local relapse-free survival, locoregional relapse-free survival and disease-free survival (p = 0.022, p = 0.003 and p = 0.003, respectively). Pre-treatment haemoglobin concentration was an independent prognostic factor for local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, disease-free survival, and

  18. Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal squamous cell carcinoma: analysis of treatment results and prognostic factors

    Directory of Open Access Journals (Sweden)

    Krstevska Valentina

    2012-05-01

    Full Text Available Abstract Background Concurrent radiochemotherapy is a recommended treatment option for patients with locally advanced squamous cell head and neck carcinomas with recent data showing the most significant absolute overall and event-free survival benefit achieved in patients with oropharyngeal tumours. The aim of this study was to analyse the results of three-dimensional conformal radiotherapy given with concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma and to identify prognostic factors influencing outcomes of this patients category. Methods Sixty-five patients with stage III or IV squamous cell carcinoma of the oropharynx who underwent concurrent radiochemotherapy between January 2005 and December 2010 were retrospectively analyzed. All patients received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m2 started at the first day of radiotherapy. Results Median age was 57 years (range, 36 to 69 years and 59 (90.8% patients were male. Complete composite response was achieved in 47 patients (72.3%. Local and/or regional recurrence was the most frequent treatment failure present in 19 out of 25 patients (76.0%. At a median follow-up of 14 months (range, 5 to 72 months, 2-year local relapse-free, regional relapse-free, locoregional relapse-free, disease-free, and overall survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively. On multivariate analysis the only significant factor for inferior regional relapse-free survival was the advanced N stage (p = 0.048. Higher overall stage was independent prognostic factor for poorer local relapse-free survival, locoregional relapse-free survival and disease-free survival (p = 0.022, p = 0.003 and p = 0.003, respectively. Pre-treatment haemoglobin concentration was an independent prognostic factor for local relapse-free survival, regional relapse-free survival

  19. 人食管癌相关基因4在食管癌细胞系EC9706中表达缺失的机制%Mechanism of loss of human esophageal cancer-related gene 4 (ECRG4) gene expression in esophageal squamous cell carcinoma cell line EC9706

    Institute of Scientific and Technical Information of China (English)

    李林蔚; 余茜颖; 李晓燕; 郭黎平; 周云; 陆士新

    2011-01-01

    目的 探讨人食管癌相关基因4(ECRG4)在食管癌中表达缺失的机制.方法 采用聚 合酶链反应-单链构象多态(PCR-SSCP)和DNA测序的方法检测80对配对食管鳞状细胞癌(ESCC)肿瘤组织和癌旁正常上皮中ECRG4的外显子突变;采用DNA亚硫酸氧盐修饰和序列特异性聚合酶链反应(ssPCR)检测EC9706细胞系ECRG4基因启动子CpG岛甲基化状态;采用逆转录聚合酶链反应(RT-PCR)检测去甲基化药物5-氮杂-2-脱氧胞苷或三氧化二砷(As2O3)处理后ECRG4 mRNA的重新表达.结果 80对ESCC配对标本中,ECRG4的4个外显子编码区均未发现突变.EC9706细胞系ECRG4基因核心启动子区16个CpG岛中,有11个呈高甲基化状态,ECRG4 mRNA不表达.EC9706细胞处理前ECRG4 mRNA不表达,去甲基化药物处理后,ECRG4 mRNA均重新表达.结论 甲基化表观遗传学机制是导致ECRG4基因在食管癌细胞系EC9706中表达缺失的一个机制.%Objective To investigate the mechanism of loss of human esophageal cancer-related gene 4 (ECRG4) expression in esophageal squamous cell carcinoma (ESCC.) Methods PCR-SSCP and DNA sequencing analysis were used to detect the mutation of ECRG4 exons in esophageal cancer and matched adjacent normal tissues of 80 patients. DNA bisulfite-modifying ssPCR sequencing assay was used to examine the methylation status of ECRG4 promoter in human esophageal squamous cell carcinoma EC9706 cells. The re-expression of ECRG4 mRNA was examined by RT-PCR in EC9706 cells, after treatment with either demethylation drug 5-aza-2'-deoxycytidine or arsenic trioxide. Results No mutation in the four ECRG4 exons was found in all the ESCC and matched normal adjacent tissues. RT-PCR showed that 11 of 16 CpG islands of ECRG4 promoter were hypermethylated, while ECRG4 mRNA expression level was undetectable in the EC9706 cells. The ECRG4 mRNA was re-expressed after treatment with either demethylation drug 5-aza-2'-deoxycytidine or arsenic trioxide. Conclusion The

  20. Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Park, R.I.; Liberman, F.Z.; Lee, D.J.; Goldsmith, M.M.; Price, J.C. (Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD (United States))

    1991-04-01

    Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5-year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only.

  1. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    International Nuclear Information System (INIS)

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip® HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  2. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  3. 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

  4. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    2016-03-11

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  5. Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kaoru; Koeda, Keisuke; Sato, Nobuhiro [Iwate Medical Univ., Morioka (Japan). School of Medicine] [and others

    1999-06-01

    The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student`s T test: p<0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p<0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection. (author)

  6. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

    DEFF Research Database (Denmark)

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel;

    2015-01-01

    BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...

  7. Esophageal atresia

    Science.gov (United States)

    Esophageal atresia is a disorder of the digestive system in which the esophagus does not develop properly. The ... Esophageal atresia (EA) is a congenital defect. This means it occurs before birth. There are several types. In ...

  8. Esophageal Cancer

    Science.gov (United States)

    ... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...

  9. 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.

  10. 转录因子在食管鳞癌基因表达中的调控作用%Role of transcription factors in regulation of gene expression in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴耀松; 陈玉龙; 尹素改; 王慧慧

    2013-01-01

    目的:研究食管鳞癌(esophageal squamous cell carcinoma,ESCC)中转录因子的调控作用.方法:从GEO下载两个基因数据集,利用BRB-ArrayTool分析食管癌细胞和正常细胞之间差异基因表达.从差异表达基因中富集出转录因子,根据转录因子目的基因、结合蛋白和差异基因的相互作用来分析其调控作用.结果:根据463个差异表达基因富集了8个转录因子,差异基因中含此8个转录因子的110个调控基因,包括靶基因、和靶基因相互作用基因及其上游的酶基因.这些基因参与了许多的生物过程,如细胞周期、有丝分裂、细胞分离、细胞转移、DNA的损伤反应和DNA的修复.其中37个基因参与了KEGG信号通路,包括癌化途径、黏着斑、细胞周期、细胞外基质受体相互作用、小细胞肺癌、卵母细胞减数分裂、P53信号通路和脂肪酸代谢通路等.这110个基因和463个差异表达基因参与的信号通路没有明显的差异.这110个基因相互作用,形成有110个节点和316条边组成分子网路.结论:在ESCC中,8个转录因子通过调控其靶基因和相互作用基因而发挥重要作用,其调控基因组成一个复杂的相互作用分子网络.%AIM:To study the role of transcription factors (TFs) in regulation of gene expression in esophageal squamous cell cancer.METHODS:Two gene microarray data sets downloaded from the GEO BRB-ArrayTool were used to analyze differentially expressed genes between esophageal squamous cell cancer and normal esophageal tissue.TFs were enriched from differentially expressed genes,and the regulatory role of TFs was assessed by analyzing interactions among target genes,binding proteins and differentially expressed genes.RESULTS:Eight TFs were obtained from 463differentially expressed genes.There were 110genes that may be regulated by TFs,including target genes,genes encoding interaction proteins,and upstream enzyme genes.These genes participated in multiple

  11. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    Science.gov (United States)

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  12. Epidemiologic differences in esophageal cancer between Asian and Western populations

    Institute of Scientific and Technical Information of China (English)

    Han-Ze Zhang; Guang-Fu Jin; Hong-Bing Shen

    2012-01-01

    Esophageal cancer is a common cancer worldwide and has a poor prognosis.The incidence of esophageal squamous cell cancer has been decreasing,whereas the incidence of esophageal adenocarcinoma has been increasing rapidly,particularly in Western men.Squamous cell cancer continues to be the major type of esophageal cancer in Asia,and the main risk factors include tobacco smoking,alcohol consumption,hot beverage drinking,and poor nutrition.In contrast,esophageal adenocarcinoma predominately affects the whites,and the risk factors include smoking,obesity,and gastroesophageal reflux disease.In addition,Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds.However,comparison studies between these two populations are limited and need to be addressed in the near future.Ethnic differences should he taken into account in preventive and clinical practices.

  13. Clinical observation of the effect of radiotherapy combined with S-1 in advanced esophageal cancer%调强放疗同步替吉奥化疗中晚期食管癌的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    阿合力·那斯肉拉; 那·那芹; 阿衣古丽·哈热

    2014-01-01

    Objective To evaluate the efficacy and survival rate and side reaction of S-1 combined with con-current radiotherapy in the treatment of advanced esophageal cancer .Methods 66 patients with advanced squamous cell carcinoma of the esophagus were divided into two groups :the experimental group (38 cases) and the control group (28 cases) .The radiotherapy regimens was intensity modulated radiation therapy (IMRT) ,the radiotherapy dosage was 60 -66 Gy .Then we observed the therapeutic effect and side effect of the two groups after the treatment .Results The overall response rate (CR+PR) of the ex-perimental group and the control group were 89 4.% and 89 3.% respectively (P >0 0.5) .The one-year and two-year survival rates of S-1 chemoradiotherapy group and Fluorouracil chemoradiotherapy group were 86 1.% ,64 1.% and 76 9.% ,41 9.% ,and the difference was not statistically significant (P >0 0.5) .Serious side effects ,including marrow depression and radioactive esophagitis ,did not occur in both groups .Con-clusion The curative effect of concurrent radiochemotherapy in locally advanced esophageal cancer is better than that of radiotherapy only ,and will not elicit the serious adverse reaction .The short term cura-tive effect of S-1 and Fluorouracil in combination with radiotherapy is feasible for medium and terminal e-sophageal cancer ,and toxicity is tolerable .%目的:探讨替吉奥与单药氟尿嘧啶加同步放疗治疗中晚期食管癌的近期临床疗效。方法将66例中晚期食管癌患者随机分为两组,替吉奥胶囊口服+同步放疗组(试验组)38例,单药氟尿嘧啶静点+同步放疗组(对照组)28例,放疗方案均采用食管病灶区适形调强放射治疗(intensity modulated radiation therapy ),放疗剂量为60~66 Gy。观察两组临床疗效、生存情况及毒副反应。结果试验组和对照组的治疗有效率分别为894.%和893.%,差异无统计学意义(χ2=0.012, P =0

  14. Esophageal Cancer in Iran: A Review

    OpenAIRE

    Siavosh Nasseri-Moghaddam; Shahryar Semnani; Hajiamin Marjani; Alireza Sadjadi

    2010-01-01

    Esophageal cancer is the second and third most common malignancy in Iranian malesand females, respectively, claiming lives of approximately 5800 Iranians each year.Squamous cell carcinoma (SCC) is presently the most common type accounting forabout 90% of all esophageal cancers in Iran. Recent studies have shown that there isa gradual increase in the incidence of adenocarcinoma of the distal esophagus alongwith gastric cardia adenocarcinoma. Thirty-five years ago, the age standardizied rate (...

  15. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    International Nuclear Information System (INIS)

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% (α = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg2/day), cisplatin (15 mg/mg2/day), and paclitaxel (200 mg/mg2/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg2/day) with cisplatin (15 mg/mg2/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was ≥T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%–82%).

  16. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    Energy Technology Data Exchange (ETDEWEB)

    Swisher, Stephen G., E-mail: sswisher@mdanderson.org [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn A. [Headquarters, Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko U. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Wu, Tsung T. [Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Konski, Andre A. [Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Willett, Christopher G. [Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  17. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  18. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bujor, L.; Grillo, I.M.; Pimentel, N. [Hospital Santa Maria, Radioterapia, Lisboa (Portugal); Macor, C.; Catarina, M. [Hospital Santa Maria, ORL, Lisboa (Portugal); Ribeiro, L. [Hospital Santa Maria, Oncologia, Lisboa (Portugal)

    2009-10-15

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  19. Percutaneous endoscopic gastrostomy for nutritional palliation of upper esophageal cancer unsuitable for esophageal stenting

    OpenAIRE

    Ana Grilo; Carla Adriana Santos; Jorge Fonseca

    2012-01-01

    "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...

  20. 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.

  1. Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma

    OpenAIRE

    Zhong, Lai-ping; Zhang, Chen-Ping; Ren, Guo-xin; Guo, Wei; William, William N.; Hong, Christopher S.; Sun, Jian; ZHU, HAN-GUANG; Tu, Wen-yong; Li, Jiang; Cai, Yi-li; Yin, Qiu-ming; WANG, LI-ZHEN; Wang, Zhong-he; Hu, Yong-jie

    2015-01-01

    Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75m...

  2. The balance between 4-hydroxynonenal and intrinsic glutathione/glutathione S-transferase A4 system may be critical for the epidermal growth factor receptor phosphorylation of human esophageal squamous cell carcinomas.

    Science.gov (United States)

    Uno, Kaname; Kato, Katsuaki; Kusaka, Gen; Asano, Naoki; Iijima, Katsunori; Shimosegawa, Tooru

    2011-10-01

    Oxidative stress might participate in the carcinogenesis of human esophageal squamous cell carcinomas (hESCC). 4-Hydroxynonenal (HNE) is a major product of membrane lipid peroxidation with short life. It might act as an important mediator through the generation of adducts and activate epidermal growth factor receptor (EGFR) signaling. It is mainly trapped with glutathione (GSH) and catalyzed by glutathione S-transferases (GSTs). This study aimed to elucidate the possible participation of HNE, GSH/GST system, and EGFR signaling in hESCC development. Immunohistochemistry of HNE adducts, EGFR, and phosphorylated EGFR (pEGFR) was performed with hESCC specimens. The effect of HNE on the phosphorylation of EGFR and its downstream PhospholipaseCγ1 (PLCγ1) was investigated with KYSE30 cell-line. Pretreatment with GSH inducer N-acetylcysteine (NAC) or GSH inhibitor Buthionine sulfoximine (BSO) and mandatory transfection of hGSTA4 gene in KYSE30 were conducted to investigate the relationship between HNE and GSH/GST system. Immunoreactants of HNE adducts, EGFR, and pEGFR were increased in hESCC compared to non-cancerous epithelium with positive correlations. The treatment of HNE ligand-independently induced the phosphorylation of EGFR and PLCγ1 accompanying the diminishment of intracellular GSH level. NAC increased GSH contents but BSO decreased in dose-dependent manners. Reflecting changes in GSH, HNE-induced EGFR phosphorylation was suppressed by NAC, whereas it was promoted by BSO. Mandatory expression of hGSTA4 suppressed HNE-induced events. We first demonstrated that the ligand-independent activation of EGFR by the balance between the stimulation of HNE and the prevention of intrinsic GSH/GST system might participate in the development of hESCC.

  3. Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis.

    Science.gov (United States)

    Halec, Gordana; Schmitt, Markus; Egger, Sam; Abnet, Christian C; Babb, Chantal; Dawsey, Sanford M; Flechtenmacher, Christa; Gheit, Tarik; Hale, Martin; Holzinger, Dana; Malekzadeh, Reza; Taylor, Philip R; Tommasino, Massimo; Urban, Margaret I; Waterboer, Tim; Pawlita, Michael; Sitas, Freddy

    2016-07-01

    Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a) . Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis. PMID:26529033

  4. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Fang Tian; Tianli Fan; Yan Zhang; Yanan Jiang; Xiaoyan Zhang

    2012-01-01

    Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors,the role of NF-κB pathway in esophageal squamous ceil carcinoma (ESCC) remains illdefined.Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer.In this study,we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706,and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo.The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines.Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation,and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines.Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone.In a human ESCC xenograft model,curcumin or 5-FU alone reduced the tumor volume,but their combination had the strongest anticancer effects.Besides,curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo.Overall,our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes.

  5. MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Huang Sheng-Dong

    2012-08-01

    Full Text Available Abstract Background The enhancer of zeste homolog 2 (EZH2 was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC. On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC. Methods and results The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109 transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3’-UTR of EZH2. Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2. Conclusions These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein.

  6. Tumor recurrence and in-field control after multimodality treatment of locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Purpose: Neoadjuvant chemoradiotherapy is used prior to surgery in curative treatment of esophageal cancer (EC). We evaluated the in-field control of this multimodal treatment by extraction of radiation dose parameters and determination of the spatial relation between tumor recurrence location(s) and radiation target volume (RTV). Methods and materials: Treatment consisted of neoadjuvant chemotherapy (5-FU and cisplatin) and radiotherapy (36 Gy) followed by Ivor–Lewis esophagectomy. For patients with locoregional recurrence(s), image fusion was performed between radiotherapy planning CT and follow-up CT(s). A region-of-interest was contoured on the planning CT around each locoregional recurrence. Mean and maximum radiation doses were then extracted to classify recurrences as out-of-field, marginal or in-field. Results: Eighty patients were included. The median follow-up duration was 19 months. Fifteen of 95 locoregional recurrences were detected in the RTV. These in-field relapses occurred in only 6 patients (7.8%) on 12 different anatomical locations. None of the patients with in-field failure had a pCR and all had concurrent distant failure on multiple anatomical sites. Conclusion: Neoadjuvant chemoradiotherapy followed by Ivor–Lewis esophagectomy yields excellent in-field control, as only a clear minority (7.8%) of patients developed a relapse in the RTV. In-field recurrence is associated with widespread tumor dissemination and poor pathological response to neoadjuvant treatment

  7. Esophageal stenosis with esophageal atresia

    Energy Technology Data Exchange (ETDEWEB)

    Thomason, M.A.; Gay, B.B.

    1987-03-01

    Esophageal atresia with tracheosophageal fistula may be associated rarely with distal esophageal stenosis. Three patients are reported with this combination of esophageal anomalies. In addition the clinical and radiologic features of 24 patients previously reported in the literature are reviewed. Careful evaluation of the distal esophagus during postoperative contrast studies in patients with esophageal atresia should be obtained to exclude distal stenosis. The presence of unrecognized distal esophageal stenosis may lead to complications of postoperative anastomotic leaks, poor healing of the anastomosis, aspiration, and impaction of a solid food bolus proximal to the stenosis.

  8. Expessions of POKemon and P14ARF in esophageal squamous cell carcinoma tissue%食管鳞状细胞癌组织中POKemon和P14ARF蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    荣爱梅; 郭长青

    2011-01-01

    目的:研究食管鳞状细胞癌(ESCC)组织中POKemon和P14ARF蛋白的表达及意义。方法:采用免疫组化法检测88例ESCC及其中28例相应的癌旁正常食管黏膜组织中POKemon和P14ARF蛋白的表达。结果:ESCC组织中POKemon阳性表达率高于癌旁正常组织(X2=8.450,P<0.001),P14ARF阳性表达率低于癌旁组织(X2=15.042,P<0.001);POKemon蛋白阳性表达率与ESCC的TNM分期和淋巴结转移有关(P<0.05),而与性别、年龄、分化程度无关(P>0.05);P14ARF蛋白阳性表达率与ESCC的分化程度有关(P<0.05),而与性别、年龄、TNM分期、淋巴结转移无关(P>0.05);ESCC组织中POKemon和P14ARF的表达呈负相关(r=0.349,P<0.001)。结论:POKemon蛋白的过表达和P14ARF蛋白的低表达可能与ESCC的发生发展关系密切,2者有望成为ESCC临床诊断、基因治疗和判断预后的可靠指标。%Aim: To investigate the expressions of oncogene POKemon and anti-oncogene P14ARF in human esophage-al squamous cell carcinoma(ESCC) tissue. MethodS:The expressions of POKemon and P14ARF were detected by immuno-histochemical S-P method in 88 cases of primary ESCC and 28 cases of normal esophageal tissue. Results: The positive expression rate of POKemon in ESCC was obviously higher(X2 = 8.450,P 0.05). The positive rate of P14ARF was closely related with histological differentiation grade(P 0.05) . The expression of POKemon was negatively correlated with the expression of P14ARF ( rp = 0. 349 ,P < 0.001) in ESCC tissue. Conclusion: The over expression of POKemon and the loss expression of P14ARF maybe play important roles in the development of ESCC. POKemon 和 P14ARF may be considered as reliable markers for clinical diagnosis, gene therapy and clinical prognosis.

  9. 食管鳞癌恶性表型相关蛋白的蛋白质组学研究%Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    牛保华; 齐义军; 曹世华; 邱政夫; 马远方; 何庆瑜

    2009-01-01

    Objective:To identify differentially expressed proteins related with malignant transformation of esophageal squamous cell carcinoma (ESCC) using proteomic analysis. Methods:Two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization timE-of flight mass spectrometry (MALDI-TOF-MS) in combination with protein database searching were used to determine and identify differentially expressed proteins in esophageal cancer cell lines (EC1, EC18, and EC109) and immortal cell line (NECA-E6E7-hTERT). Western blotting and immunocytochemistry were used to verify the differential expression of annexin 2 in esophageal cancer cell lines and immortal cell line (NECA-E6E7-hTERT). Real-time fluorogentic quantitative PCR(RFQ-PCR) was performed to analyze the expression level of annexin A2 mRNA.Results: A total of 15 differentially expressed proteins were identified with more than 5 folds difference. Among them three proteins were down-regulated and 12 proteins were up-regulated. Western blotting and immunocytochemical analysis verified the down-regulation of annexin A2 protein in ESCC cell lines. However, differential expression pattern of annexin A2 mRNA was not consistant with its protein expression in ESCC cell lines and immortal cell line (NECA-E6E7-hTERT). Conclusion:The findings provide important clues for identifying the candidate biomarkers for high-risk population screening and early diagnosis of ESCC. Post-translative regulation/modification contributes to the down-regulation of annexin A2 protein.%目的:利用蛋白质组学技术探讨与人食管鳞癌细胞(esophageal squamous cell carcinoma, ESCC)恶性表型转化相关的差异表达的蛋白质谱.方法:采用二维双向电泳(two-dimensional electrophoresis, 2-DE)和基质辅助激光解吸电离飞行时间质谱(matrix assisted laser desorption ionisation timE-of-flight mass spectrometry, MALDI-TOF-MS)法鉴定人食管上皮永生化细胞株NECA-E6E7-hTERT和ESCC细胞株EC1

  10. Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    Fan, Katherine Y.; Gogineni, Hrishikesh; Zaboli, David; Lake, Spencer; Zahurak, Marianna L.; Best, Simon R.; Levine, Marshall A.; Tang, Mei; Zinreich, Eva S.; Saunders, John R.; Califano, Joseph A.; Blanco, Ray G.; Pai, Sara I.; Messing, Barbara; Ha, Patrick K.

    2013-01-01

    Purpose The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs. Methods We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m2/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months. Results Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1–2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11). Conclusions With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required. PMID:22290566

  11. Cutaneous Metastases From Esophageal Adenocarcinoma

    Science.gov (United States)

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou

    2015-01-01

    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  12. 人食管鳞癌细胞系RJEC-2的建立及其生物学特性分析%Establishment and biological characterization of human esophageal squamous cell carcinoma cell line RJEC-2

    Institute of Scientific and Technical Information of China (English)

    杨杰; 廖晓东; 闫铮; 张丽君; 叶清; 徐明; 黄雷

    2012-01-01

    目的:建立新的人食管鳞状细胞癌细胞系并分析其生物学特性,为食管癌分子机制和治疗干预的研究提供新的实验模型.方法:采用组织块培养法,从病人食管癌组织中分离纯化鳞状上皮癌细胞并建立细胞系.对细胞系的形态特点、细胞角蛋白表达、生长特征、细胞周期分布、细胞遗传特征和致瘤能力进行了研究分析.结果:建立了食管鳞状细胞癌细胞系RJEC-2,已在体外持续传代4个多月,传至46代,生长稳定;该细胞系具有鳞状上皮细胞的形态和特点:单层贴壁生长,免疫组化显示细胞角蛋白表达阳性,电镜下可见明显的胞质内张力纤维束和细胞间桥粒;群体倍增时间为46.5 h,细胞培养至90%汇合时,细胞周期分析显示C0/C1期平均占56.72%,S期平均占33.96%,G2/M期平均占9.32%;细胞染色体结构和数量异常,呈现肿瘤细胞特性;细胞呈克隆性生长,平板克隆平均形成率为13.93%,裸鼠移植瘤实验表明细胞具有致瘤能力,病理分析显示移植瘤与病人肿瘤病理形态特征相似,均为中、高分化鳞状细胞癌.结论:成功建立的人食管鳞癌细胞系RJEC-2,为食管癌发病机制和治疗方案的研究提供了新的研究实验模型.%Objective To establish a novel cell line of human esophageal squamous cell carcinoma (ESCC) and to investigate the biological characterization in pursuit of a new model for further studies on molecular mechanisms and therapeutic intervention. Methods Small tissue blocks taken from resected specimens of an ESCC patient were cultured, and squamous cell carcinoma cells were purified. Biological characters of the cell line were investigated, including morphology, cytokeratin expression, growth kinetic features, cell cycle, cytogenetic features and tumorigenicity. Results An ESCC cell line (RJEC-2) was established. It grew continuously in vitro for more than 4 months and 46 passages. This cell line presented

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

    Directory of Open Access Journals (Sweden)

    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

  14. Influence of Ionizing Radiation on Stromal-Epithelial Communication in Esophageal Carcinogenesis

    Science.gov (United States)

    Huff, Janice; Patel, Zarana; Grugan, Katharine; Rustgi, Anil; Cucinotta, Francis A.

    Esophageal cancer is the 6th leading cause of cancer death worldwide and is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. A connection with ionizing radiation exposure is revealed by the high excess relative risk for esophageal squamous cell carcinoma observed in the survivors of the atomic bomb detonations in Japan. Esophageal carcinomas are also seen as secondary malignancies in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely responsive to treatment. In normal epithelium, the stromal microenvironment is essential for the maintenance and modulation of cell growth and differentiation. Cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibrob-lasts (Okawa et al., Genes Dev. 2007. 21: 2788-2803). We examined how irradiation of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. These assays were conducted in modified Boyden chambers using conditioned media from irradiated fibroblasts. Our results using low LET gamma radiation showed a dose-dependent increase in migration of epithelial

  15. Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. Forty-one patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre- and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival. (author)

  16. Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

    International Nuclear Information System (INIS)

    Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. ‘DNA Replication, Recombination and Repair’ represented one of the most important mechanisms activated in non-responsive cervical tumors, and the ‘Role of BRCA1 in DNA Damage Response’ was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information

  17. Incompletely resected advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    From 1982-1988, 441 patients were treated at Virginia Medical College for AJC Stage III and IV squamous cell carcinoma of head and neck. On 84 patients is reported, whose tumors were incompletely resected based on histopathological margins of 1mm or less. Of the 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The 2 groups are comparable with respects to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24- 110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p=0.0006 and p=0.0003 levels, respectively, related to the surgery-alone-group. Patients in the first group also experienced a significantly improved adjusted and overall survival, p=0.005 and p=0.001, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage tumor after tumor recurrence. (author). 17 refs.; 5 figs.; 6 tabs

  18. 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].

  19. Early detection and determinants of esophageal cancer

    NARCIS (Netherlands)

    Bus, P.

    2014-01-01

    Barrett’s esophagus (BE) is a premalignant condition of the esophagus and characterized by the metaplastic replacement of esophageal squamous epithelium by specialized intestinal-type columnar epithelium. A BE diagnosis is based on endoscopy and histological examination of biopsies taken during endo

  20. Esophageal Inlet Patch

    Directory of Open Access Journals (Sweden)

    C. Behrens

    2011-01-01

    Full Text Available An inlet patch is a congenital anomaly consisting of ectopic gastric mucosa at or just distal to the upper esophageal sphincter. Most inlet patches are largely asymptomatic, but in problematic cases complications related to acid secretion such as esophagitis, ulcer, web and stricture may occur. The diagnosis of inlet patch is strongly suggested on barium swallow where the most common pattern consists of two small indentations on the wall of the esophagus. The diagnosis of inlet patch is confirmed via endoscopy with biopsy. At endoscopy, the lesion appears salmon-coloured and velvety and is easily distinguished from the normal grey-white squamous epithelium of the esophagus. The prominent margins correlate with the radiological findings of indentations and rim-like shadows on barium swallow. Histopathology provides the definitive diagnosis by demonstrating gastric mucosa adjacent to normal esophageal mucosa. No treatment is required for asymptomatic inlet patches. Symptomatic cases are treated with proton pump inhibitors to relieve symptoms related to acid secretion. Strictures and webs are treated with serial dilatation and should be biopsied to rule out malignancy.

  1. FEASIBILITY OF INDUCTION DOCETAXEL, CISPLATIN, 5-FLUOROURACIL, CETUXIMAB (TPF-C) FOLLOWED BY CONCURRENT CETUXIMAB RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA

    OpenAIRE

    Nikolaos eCharalambakis; Vassilis eKouloulias; Helena eVaja; Dimitrios ePectasides; Theodoros eRampias; Theofanis eEconomopoulos; Panagiotis eKatsaounis; Spiros eSiolos; Valentina eBartzi; Christos ePerisanidis; Konstantinos eLaschos; Pavlos eMaragoudakis; Konstantinos ePrikas; Nikolaos ePapadimitriou; Nikolaos ePapadogeorgakis

    2013-01-01

    Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutati...

  2. Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. Two induction courses of methotrexate (40 mg/m2/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m2/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m2/day) and 5-fluorouracil (400 mg/m2/day) on day 1. Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and concurrent chemoradiotherapy (CCRT), respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach. (author)

  3. Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Steevens, J.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2011-01-01

    Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric c

  4. 食管鳞癌细胞中五聚素3基因的表达及甲基化%Methylation and expression of pentraxin3 gene in human esophageal squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    王俊雄; 姜春燕; 李敏; 朱圣韬; 张澍田

    2012-01-01

    目的 研究食管鳞状细胞癌(ESCC)中五聚素3(PTX3)基因的表达以及基因启动子区甲基化状态对其表达的影响.方法 采用RT-PCR、甲基化特异性PCR(MSP)、亚硫酸氢盐测序等方法 对ESCC细胞进行检测PTX3基因mRNA的表达、基因启动子区甲基化状态.应用甲基转移酶抑制剂5-氮-2′-脱氧胞苷(5-Aza-DC)去甲基化处理对该基因表达的影响.结论 RT-PCR结果 显示PTX3 mRNA在细胞株TE-11、EC109、EC9706、KYSE30、KYSE510均不表达,在KYSE410,Het-1A细胞株中有PTX3 mRNA表达.MSP结果 显示TE-11、EC109、EC9706、KYSE30、KYSE510存在PTX3基因甲基化,而KYSE410,Het-1A细胞株中不存在PTX3基因甲基化.甲基化测序结果 进一步证实了MSP结果 结果 ,28个CpG位点中,TE-11、EC109、EC9706、KYSE30、KYSE510甲基化程度分别为64.3%,81.0%,94.5%,78.5%及81.0%,而KYSE410,Het-1A不存在甲基化.ESCC细胞株PTX3基因启动子处于异常的高甲基化状态,经5-Aza-DC处理后,高甲基化的PTX3基因启动子去甲基化,处理前PTX3基因启动子高甲基化的细胞株其mRNA均不表达,去甲基化处理后能重新激活该基因表达.结论 PTX3基因启动子高甲基化是PTX3表达失活的主要原因之一,PTX3基因启动子甲基化检测可作为ESCC的潜在肿瘤标志物之一.%Objective To investigate the methylation and expression of PTX3 gene in esophageal squamous cell carcinoma ( ESCC) cell lines. Methods Six ESCC cell lines ( EC109 , EC9706 , KYSE30 , KYSE410 , KYSE 510, TE-11)and one esophageal epithelial cell Het-1A were selected. RT-PCR and MSP were used to detect the mRNA expression and methylation status of PTX3 gene. The esophageal cancer cell lines were treated with 5-Aza-CdR, and the changes of PTX3 mRNA expression before and after 5-Aza-CdR treatment were tested. Results PTX3 transcript was silenced in 5ESCC cell lines ( TE11 , KYSE30, KYSE510 EC109 and EC9706 ) , but not in KYSE410 and immortalized normal esophageal

  5. Expression of giutathione s-transferase-πin human esophageal squamous cell carcinoma%谷胱甘肽硫转移酶π在人食管鳞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    目的研究谷胱甘肽硫转移酶-π(CST-π)在人食管鳞癌中的表达及其与食管鳞癌临床病理的相互关系。方法应用免疫组织化学方法和sandwich酶联免疫吸附测定法(enzyme linked immunosorbent assay, ELISA)对143例食鳞癌石蜡标本和43例食管鳞癌患者的术前及术后血清标本进行检测。结果 GST-π在人食管鳞癌石蜡标本和43例食管鳞癌患者的术前及术后血清标本异有极显著性(P〈0.01)。GST-π在高分化食管鳞癌中的表达显著高于其在低分公食管鳞癌中的表达(P〈0.05).GST-π在高分公食管鳞癌中的表达显著高天其在低分公食管鳞癌中的表达(P<0.05).食管鳞癌患者术前和术后血清CST-π含量平均值均显著高天正常人CST-π含量平均值,但两者差异无显著性(P<0.05).结论 GST-π含量平均值低于术前血清GST-π含量平均值,但两者差异著性(P<0.05).结论 GST-π是食管鳞癌的一个有应用价值的标志物,其与食管鳞癌的发生有关,可能是食管上皮癌变前的一个早期标志物.%Objective To evaluate the expression of glutathione S-transferase-π(GST-π)in human esophageal squamous cell carcinoma (ESGG)and ith correlation with the clinicopathological data,Methods Immuuohistochemical method(Labeled avidin biotin metod)and ELISAwere used to detect the expression of glu-tathione S-transferase-πin 143 cases of formalin fixed,paraffin embedded ESCC tissue sections. Serum GST-πwas determined before and after operation in 43 patients with ESCC. Resuits GST-πwas positively stained immunohistochemically in 58.7%(84/143)of ESGG and 79.6%(109/139)of surrounding noncancerous esophageal tissues(P<0.05).The expression level of GST-π was significantly higher in well differentiated than poorly differentiated carcinomas(P<0.05).No significant correlation was observed between CST-πLevels and lymph node metastasis,pathological staging or long term survival. The preoperative and

  6. IGHMBP2 overexpression promotes cell migration and invasion in esophageal squamous carcinoma%IGHMBP2过表达促进食管鳞癌细胞的侵袭和迁移

    Institute of Scientific and Technical Information of China (English)

    王春丽; 郝佳洁; 吴李飞; 潘蓓青; 徐昕; 蔡岩; 王明荣; 贾雪梅

    2015-01-01

    IGHMBP2(Immunoglobulin mu binding protein 2)基因编码一种解旋酶,参与DNA的复制和修复,并且作为转录调节因子在基因转录中发挥重要作用。IGHMBP2基因定位于11q13.2,该染色体区段在食管鳞癌中扩增频率较高。为了探讨IGHMBP2基因在食管鳞癌中的扩增情况及其在食管鳞癌中的作用,文章对本实验室前期报道的59例食管鳞癌原发肿瘤array-CGH数据进行分析,结果显示IGHMBP2基因扩增频率为28.9%(17/59)。进一步利用荧光原位杂交(FISH)和Western blot技术,发现食管鳞癌细胞系KYSE30、KYSE180、KYSE510和KYSE150中存在IGHMBP2基因扩增/增益以及蛋白高表达。敲降IGHMBP2后,KYSE30和KYSE150细胞的侵袭迁移能力明显降低(P<0.001),侵袭迁移相关蛋白E-cadherin的表达水平升高;敲降后转染IGHMBP2质粒,回复其蛋白表达后,细胞的侵袭迁移能力又得以恢复(P<0.01)。上述结果表明,IGHMBP2过表达可能通过降低E-cadherin的表达从而增强食管鳞癌细胞的侵袭迁移能力。%Immunoglobulin mu binding protein 2 (IGHMBP2) is located in 11q13.2, which is frequently amplified in esophageal squamous cell carcinoma (ESCC). IGHMBP2 encodes a helicase involved in DNA replication and re-pair. IGHMBP2 protein also regulates gene transcription. The present study aims to explore the amplification of IGHMBP2 and its potential role in ESCC. A further analysis of our previously reported array-CGH data showed that IGHMBP2 was amplified in 28.9% of primary ESCC tumors. Fluorescence in situ hybridization (FISH) and West-ern blot showed that IGHMBP2 was amplified and overexpressed in KYSE30, KYSE180, KYSE510 and KYSE150 esophageal cancer cell lines. Transwell assays demonstrated that knockdown of IGHMBP2 in KYSE30 and KYSE150 inhibited cell invasion and migration, and increased the expression levels of E-cadherin. When rescue plasmids ex-pressing IGHMBP2 were introduced, the abilities of cell

  7. Esophageal Atresia

    DEFF Research Database (Denmark)

    Pedersen, Rikke Neess; Markøw, Simone; Kruse-Andersen, Søren;

    2013-01-01

    Esophageal atresia (EA) is one of the most frequent congenital alimentary tract anomalies with a considerable morbidity throughout childhood. This study evaluates the gastroesophageal problems in 5-15year old children with EA and aims to identify factors predisposing to esophagitis in EA....

  8. 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.

    OpenAIRE

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

    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...

  9. Clinical significance of expression of OX40 and SLP-2 in esophageal squamous cell carcinoma%OX40和SLP-2在食管鳞癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    蒋冬; 李建生; 张金平; 李东颖; 刘艳红

    2013-01-01

    目的:研究OX40和SLP-2在食管鳞癌(esophageal squamous cell carcinoma,ESCC)中的表达情况,并探讨OX40和SLP-2与食管鳞癌患者临床病理特性的相关性.方法:(1)应用免疫组织化学法分别检测OX40和SLP-2在94例食管鳞癌癌组织、31例癌旁不典型增生组织及31例正常组织中的表达.应用SPSS17.0软件对数据进行统计分析.两样本的比较采用四格表资料的x2检验;OX40和SLP-2的相关性采用Spearman等级相关分析.检验水准α=0.05.结果:(1)免疫组织化学结果显示OX40和SLP-2在癌组织(54.3%、50.0%)及癌旁不典型增生组织中(54.8%、25.8%)的表达均明显高于正常组织(3.2%、6.5%)(x2=26.374,20.988,P<0.05),且OX40和SLP-2的表达与患者TNM分期及有无淋巴结转移相关;(2)OX40与SLP-2的表达具有相关性(r=0.363,P<0.05).结论:(1)OX40和SLP-2在食管鳞癌组织中高表达,可能参与食管鳞癌的发生发展和转移;(2)OX40和SLP-2的表达具有相关性.

  10. miR - 22 inhibits esophageal squamous cell carcinoma cell invasion and migration%miR -22抑制食管鳞状细胞癌细胞侵袭和转移

    Institute of Scientific and Technical Information of China (English)

    武圣达; 尉丁; 孔令敏

    2015-01-01

    目的:探讨微小 RNA -22(miR -22)对食管鳞状细胞癌细胞侵袭和转移的影响。方法:采用实时定量 RT - PCR 检测 miR -22在食管鳞状细胞癌细胞系中的表达。过表达 miR -22后应用 Transwell 小室、MTT增殖及划痕试验分析对食管鳞状细胞癌细胞侵袭和转移能力的影响。结果:在食管鳞状细胞癌细胞系中 miR-22的表达比正常对照明显降低。此外,过表达 miR -22可明显抑制食管鳞状细胞癌细胞系 Eca109和 TE-1细胞增殖、侵袭和转移能力。结论:miR -22作为肿瘤抑制小片段 RNA 可以抑制食管癌细胞的侵袭和转移。本研究有助于了解 miR -22在食管鳞状细胞癌中的功能,为食管鳞状细胞癌治疗提供新靶点。%Objective:To explore the effect of miR - 22 on the metastasis and invasion of esophageal squamous cell carcinoma(ESCC)cell line. Methods:The miR - 22 expression level was measured by real - time quantitative RT - PCR in ESCC cell lines. We performed the invasion assay,MTT proliferation assay and wound - healing assay to test the invasion and proliferation of ESCC cell after overexpression of miR - 22. Results:The expression of miR - 22 in ESCC cell lines were much lower than that in normal control. Moreover,transfection of miR - 22 expression plasmid could significantly inhibit the cell proliferation,migration and invasion in Eca109 and TE - 1 ESCC cell lines. Con-clusion:The tumor suppressor,miR - 22 could inhibit ESCC cell migration and invasion. Our findings contribute to the current understanding of the expression and function of miR - 22 in ESCC.

  11. 1H-NMR spectroscopic characteristics of serum from patients with esophageal squamous cell carcinoma%食管鳞癌患者血清核磁共振氢谱特征研究

    Institute of Scientific and Technical Information of China (English)

    姜玉章; 孙晓阳; 史昆波; 尹起范

    2011-01-01

    1H-nuclear magnetic resonance spectroscopy ( 1H-NMRs ) analysis was performed on serum specimens obtained from 60 preoperative patients with esophageal squamous cell carcinoma ( ESCC )and 30 healthy controls, and supernatant from 2 ESCC cell lines Eca-109 and TE-13.The characteristic fingerprint was profiled with 1H-NMRs data in healthy controls.Serum 1H-NMRs from 60 preoperative patients with ESCC were measured and compared with the 1H-NMRs from 30 healthy controls.We found some specific peaks in 1H-NMRs profile of serum specimens from ESCC patients, especially at 1.0-1.2 mg/L and 3.4 - 3.6 mg/L.The results were verified by the 1H-NMRs measurement on the supernatant from 2 ESCC cell lines Eca-109 and TE-3.Our results suggest that this two absorption peaks may be characteristic for ESCC and 1H-NMRs analysis on serum specimens may provide information for early diagnosis of ESCC.%运用核磁共振波谱仪测试30名正常人和60例术前食管鳞癌患者血清、2株食管鳞癌细胞株(Eca-109和TE-13)的细胞培养上清液的核磁共振氢谱(1H-NMR).利用1H-NMR分析软件构建了正常人血清1H-NMR图谱.将食管鳞癌患者与正常人的血清1H-NMR峰叠加处理进行比较发现,二者血清样品的波谱多处存在差异,尤其在1.0~1.2 mg/L和3.4~3.6 mg/L明显,推测可能为食管鳞癌血清的特征峰.2株食管鳞癌细胞株细胞培养上清液的1H-NMR也证实上述结果.提示借助特征峰检测,有助于食管鳞癌的早期诊断.

  12. Notch1调控Srcasm在人食管鳞状细胞癌TE1细胞株中的表达%Notch1 up-regulates srcasm expression in human esophageal squamous cell carcinoma TE1 cell line

    Institute of Scientific and Technical Information of China (English)

    齐宇; 李鑫

    2014-01-01

    Objective To study the Src-activating and signaling molecule (Srcasm) expression regulated by Notchl in human esophageal squamous cell carcinoma (ESCC) TE1 cell line.Methods We transfected pcDNA3.1-Srcasm plasmid DNA (2 μg),pcDNA3.1-Srcasm plasmid NDA (2 μg),double (pcDNA3.1-Notch1 plasmid DNA 1 μg and pcDNA3.1-Srcasm plasmid DNA 1 μg) and mock (2 μg) into TE1 cells and examined Notch1/Srcasm expression by using Western blotting.Results Notch1 increased the Srcasm protein expression in TE1 cells.Conclusion Notch1 may act as a positive regulator of Fyn in human ESCC,and play an important role in human ESCC progress.%目的 探讨人食管鳞状细胞癌中Notch1参与调节人食管鳞状细胞癌TE1细胞株中Srcasm负调控Src家族酪氨酸激酶Fyn的机制.方法 分别转染pcDNA3.1-Notch1质粒DNA(2 μg)、pcDNA3.1-Srcasm质粒DNA(2μg)、Double(pcDNA3.1-Notch1质粒DNA 1μg和pcDNA3.1-Srcasm质粒DNA 1 μg)、pcDNA3.1空载体(2μg)至人食管鳞状细胞癌TE1细胞株中,观察Notch1对Srcasm表达的影响.结果 pcDNA3.1-Notch1质粒DNA的转染,原来低表达Srcasm的TE1细胞株中,Srcasm蛋白的表达明显增高.结论 人食管鳞状细胞癌TE1细胞株中Notch1可能是Srcasm的上游信号分子.

  13. Effect of fentanyl on proliferation and apoptosis in esophageal squamous cell carcinoma cell line Eca109%芬太尼对食管鳞癌细胞株Eca109增殖及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    张明鑫; 张灵敏; 姚煜

    2015-01-01

    Objective:To investigate the effects of fentanyl on proliferation and apoptosis in esophageal squamous cell carcinoma cell line Eca109. Methods:Eca109 cells cultured to logarithmic phase were randomly treated with dif-ferent dose of fentanyl(0. 5,5,50,500ng/ml). MTT was applied to test the effect on cell proliferation and Annexin-V/PI assay was used to study its effect on apoptosis. Results:MTT test revealed that fentanly had no effect on prolifer-ation at 24h,but inhibited cell proliferation at 48h and 72h in a dose and time department manner. Annexin-V/PI as-say demonstrated that fentanly induced more early and late apoptosis in Eca109 cells with increased drug dose. Con-clusion:Fentanyl inhibited cell proliferation and induced apoptosis in ESCC cell line Eca109.%目的::探讨不同浓度的芬太尼对食管鳞癌细胞株Eca109增殖和凋亡的影响。方法:选用不同浓度的芬太尼(0.5、5、50、500ng/ml)干预细胞。采用四甲基偶氮唑蓝(MMT)法检测细胞增殖,流式细胞仪Annex-in V/PI 双染色法测定细胞凋亡。结果:各组芬太尼孵育Eca109细胞24h后,对细胞的增殖无明显影响;孵育48h后,与对照组相比,各浓度组均能显著抑制细胞的增殖(P<0.05),且呈浓度和时间依赖性。芬太尼孵育Eca109细胞48h,与对照组相比,各浓度组均能诱导早期凋亡和晚期凋亡,呈浓度依赖性(P<0.05)。结论:芬太尼可抑制食管鳞癌细胞株Eca109的增殖并诱导凋亡。

  14. Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes

    International Nuclear Information System (INIS)

    Saliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT). All patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006–2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed. 114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort. cSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients

  15. Concurrent chemoradiotherapy using cisplatin, tegafur, and leucovorin for advanced squamous cell carcinoma of the hypopharynx and oropharynx

    Directory of Open Access Journals (Sweden)

    Hung-Ming Wang

    2014-06-01

    Full Text Available Background: To evaluate the efficacy and adverse events of cisplatin, tegafur, and leucovorin concomitantly with radiotherapy for patients with advanced, non-metastatic squamous cell carcinoma (SCC of the oropharynx and hypopharynx. Methods: The PTL regimen consisted of cisplatin (P 50 mg/m 2 on day 1, oral tegafur (T 800 mg/day plus leucovorin (LV 60 mg/day on days 1 through 14. It was repeated every 2 weeks through the radiotherapy course. Conventional radiotherapy with 1.8-2.0 Gy/day, 5 days per week, was delivered in a total dose of between 70 and 72 Gy. Results: Sixty-five patients with stage III or IV of SCC of the head and neck were consecutively treated between May 2002 and November 2005. Forty-six (70.7% patients had complete response after concomitant chemoradiotherapy (CCRT. With a median follow-up of 54.0 months (range 1-103 months, the 5-year locoregional control, progression-free survival, and overall survival rates were 50.6%, 40.7%, and 59.7%, respectively. Three (4.6% patients had toxic death during treatment. Fifty-one (80.0% patients experienced grade 3-4 mucositis which occurred in about 35% of the CCRT duration. The functional preservation rate among post-CCRT complete responders was 93.5% (43/46. The median cisplatin accumulated dosage was 150 mg, and the rate of hearing impairment among the survivors was 7.8%. Conclusion: CCRT with outpatient-based PTL for advanced SCC of oropharynx and hypopharynx is feasible and has comparative efficacy and acceptable adverse events.

  16. Novel insights into esophageal diagnostic procedures

    DEFF Research Database (Denmark)

    Savarino, Edoardo; Ottonello, Andrea; Tolone, Salvatore;

    2016-01-01

    The 21st century offers new advances in diagnostic procedures and protocols in the management of esophageal diseases. This review highlights the most recent advances in esophageal diagnostic technologies, including clinical applications of novel endoscopic devices, such as ultrathin endoscopy and...

  17. Locally advanced oral cavity squamous cell carcinoma: Barriers related to effective treatment

    Directory of Open Access Journals (Sweden)

    K C Lakshmaiah

    2015-01-01

    Full Text Available Background: Oral cavity cancer is a significant health problem in India. Majority of patients present with locally advanced disease requiring multimodality treatment. Compliance to recommended treatment is an important factor affecting outcome. Aims: The aim was to evaluate the outcome of locally advanced oral cavity cancer patients with regards to treatment adherence and to assess reasons of noncompliance. Materials and Methods: This was a prospective observational study. We included patients referred to Department of Medical Oncology for induction chemotherapy in view of locally advanced oral cavity cancer. Results: Only 15 (26% patients completed planned treatment schedule. Their 1 year overall survival was 93%. The remaining 43 patients who received inadequate treatment had a dismal 21% 1 year overall survival. Illiteracy, poverty, long waiting list for surgery, prolonged delay for health scheme treatment plan approval and dissatisfaction with attitude of hospital staffs are major barriers related to effective treatment of these patients. Conclusions: A detailed discussion with patient and their relatives regarding recommended treatment, proper implementation of health schemes, increasing trained manpower to avoid long waiting list for surgery, provision of additional financial support for family member accompanying the patient and a sympathetic approach toward patients are needed to help these patients overcome the battle.

  18. Locally advanced esophageal adenocarcinoma: Response to neoadjuvant chemotherapy and survival predicted by {sup [18F]}FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kauppi, Juha T.; Salo, Jarmo A.; Sihvo, Eero I.; Raesaenen, Jari V. [Helsinki Univ. Central Hospital, Div. of General Thoracic and Esophageal Surgery, Dept. of Cardiothoracic Surgery, Helsinki Univ. Central Hospital, Helsinki (Finland)], Email: jarmo.salo@hus.fi; Oksala, Niku [Dept. of Vascular Surgery, Tampere Univ. Central Hospital, Tampere (Finland); Helin, Heikki [HUSLAB/Dept. of Pathology, Helsinki Univ. Central Hospital, Helsinki (Finland); Karhumaeki, Lauri [HUSLAB/Dept. of Clinical Physiology and Nuclear Medicine, Helsinki Univ. Central Hospital, Helsinki (Finland); Kemppainen, Jukka [PET-Center, Turku Univ., Turku (Finland)

    2012-05-15

    Background. {sup [18F]}fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography ({sup [18F]}FDG-PET/CT) is commonly used in staging of locally advanced esophageal cancer. Its predictive value for response to neoadjuvant therapy and survival after multimodality therapy is controversial. Methods. Sixty-six consecutive patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction underwent surgery after neoadjuvant chemotherapy. Staging was done prospectively with {sup [18F]}FDG-PET/CT, before and after completion of neoadjuvant therapy. Pre- and post-therapy maximal standardized uptake values for the primary tumor (SUV1 and SUV2) were determined, and their relative change (SUV{Delta}%) calculated. Percentage change in SUV1 was compared with histopathologic response (HPR, complete or subtotal histologic remission), disease-free- (DFS) and overall survival (OS). Results. Resection with negative margins was achieved in 60 patients. HPR rate was 14 of 66 (21.2%). Median follow-up was 16 months (range 4-72). For all patients, OS probability at three years was 59% and DFS 50%. In receiver operating characteristics (ROC) analysis, HPR was optimally predicted by a > 67% change in baseline maximal SUV (sensitivity 79% and specificity 75%). In univariate survival analysis (Cox regression proportional hazards), HPR associated with improved DFS (HR 0.208, p = 0.033) but not OS (HR 0.030, p = 0.101), SUV % > 67% associated with improved OS (HR 0.249, p = 0.027) and DFS (HR 0.383, p 0.040). In a multivariate model (adjusted by age, sex, and ASA score), neither HPR nor SUV{Delta}% > 67% was predictive of improved OS and DFS. However, SUV{Delta}% as a continuous variable was an independent predictor of OS (HR 0.966, p < 0.0001) or DFS (HR 0.973, p < 0.0001). Conclusion. Our results support previous results showing that {sup [18F]}FDG-PET/CT can distinguish a group of patients with worse prognosis after neoadjuvant chemotherapy in

  19. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study.

    Science.gov (United States)

    Li, Yu Hong; Qiu, Miao Zhen; Xu, Jian Ming; Sun, Guo Ping; Lu, Hui Shan; Liu, Yun Peng; Zhong, Mei Zuo; Zhang, He Long; Yu, Shi Ying; Li, Wei; Hu, Xiao Hua; Wang, Jie Jun; Cheng, Ying; Zhou, Jun Tian; Guo, Zeng Qing; Guan, Zhon Gzhen; Xu, Rui Hua

    2015-10-27

    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

  20. Expression and Clinical Significance of Pokemon and P14ARF in Esophageal Squamous Cell Cancer%Pokemon、P14ARF蛋白在食管鳞状细胞癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    张健; 王磊; 赵智宏; 王巨; 刘鑫远; 禹亮

    2012-01-01

    Objective: To investigate the correlation of the expression of Pokemon and P14ARF in esophageal squamous cell caci-noma (ESCC)tissues, and their values for determining the clinicopathological characteristics and prognosis of ESCC. Methods: Immuno histochemical SP staining was used to detect the expressions of pokemon and P14ARF proteins in 96 ESCC tumor tissues and 20 adjacent normal tissues. Their relationship with the pathological characteristics of ESCC was analyzed.The correlation of abnormal expressions of pokemon and P14ARF was analyzed.The effects of the expressions of the two proteins on the long-term prognosis of ESCC patients were observed based on the follow-up data. Results: In normal tissues there was no Pokemon expression but the positive rate of P14ARF expression was 90.0 %. In ESCC tissues, the positive rate of Pokemon and P14ARF protein were 75 % and 30.2 %,respectively. The expression of Pokemon had negative correlation with expression of P14ARF(r=-0.458,P=0.000). The expression of Pokemon and P14ARF were associated with TNM staging and lymph node metastasis(P<0.05). In Pokemon positive patients,the five-year survival rate was 20.8 %, which was significantly lower than that in Pokemon negative patients (P=0.004). In contrast,the five-year survival rate was 41.4 % in patients with positive expression of P14ARF, which was significantly higher than that in patients with negative expression of P14ARF (P=0.011). Conclusion: The over expression of Pokemon and the less expression of P14ARF maybe play important roles in the development of ESCC. Pokemon and P14ARF have a certain clinical significance for evaluating the prognosis of ESCC patients.%目的:探讨食管鳞癌(esophageal squamous cell cacinoma,ESCC)组织中Pokemon和P14ARF表达的关系及其对ESCC临床病理特征和预后的判定价值.方法:应用SP免疫组织化学方法检测Pokemon和P14ARF二种蛋白在96例ESCC组织及20例癌旁正常组织中的表达,分析它们与ESCC病

  1. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus

    NARCIS (Netherlands)

    J.J.G.H.M. Bergman; Y.M. Zhang; S. He; B. Weusten; L. Xue; D.E. Fleischer; N. Lu; S.M. Dawsey; G.Q. Wang

    2011-01-01

    Background: Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett's esophagus. Objective: To evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate-grade squamous intraepithelial neoplasia (MGIN) and high-grade squamous int

  2. MicroRNA-31在食管鳞状细胞癌中的表达及其与预后的关系%The expression of microRNA-31 in esophageal squamous cell carcinoma and its prognostic value

    Institute of Scientific and Technical Information of China (English)

    罗君; 凌志强; 彭兵锋; 袁嘉敏; 郑智国; 毛伟敏

    2013-01-01

    Background and purpose:It was reported that many microRNAs (miRNAs) have close relation with carcinomas. miR-31 (microRNA-31) shows abnormal change in numerous cancers. China is one of the most high-risk areas of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the expression of miR-31 in ESCC, and analyze the relationship of its expression with clinicopathological features and prognosis. Methods:The expression of miR-31 in KYSE410, EC1 and EC9706 cell lines, as well as 81 cases of ESCC tissues and adjacent normal esophageal tissues were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). The result was combined with clinical and follow-up data and statistical analysis was conducted. Results: MiR-31 was up-expression in 3 cell lines and 75.31% of the ESCC tissues. miR-31 up-expression was positively related to severer lymph node metastasis (P=0.043), deeper invasion of tumors (P=0.002) and advanced pathological stage (P=0.027). There was no relationship of miR-31 with other clinicopathological features (P>0.05). Furthermore, high expression of miR-31 was associated with poor progression-free survival (PFS) in 81 ESCC patients by Kaplan-Meier analysis (P=0.014) and by multivariate Cox analysis (P=0.021). Conclusion:Our results identiifed miR-31 may be a new diagnostic criteria and prognostic biomarker for ESCC.%背景与目的:研究发现,许多微小RNA(microRNAs,miRNAs)与恶性肿瘤密切相关,其中miR-31(microRNA-31)在许多肿瘤中呈异常改变。中国是食管鳞状上皮细胞癌(esophageal squamous cell carcinoma,ESCC)最高发的地区之一。本研究旨在调查miR-31在ESCC中的表达水平与临床病理学因素以及预后的关系。方法:采用实时反转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)技术检测食管癌细胞株KYSE410、EC1和EC9706,以及81例ESCC组织和癌旁正常组织中miR-31的表达水平。

  3. 河南汉族食管鳞癌与XPD基因多态性关系%Association of XPD gene polymorphisms with susceptibility of esophageal squamous cell carcinoma in Henan province

    Institute of Scientific and Technical Information of China (English)

    吴晓冰; 王鹏; 运玉霞; 王珂; 王龙智; 王凯娟; 张建营; 代丽萍

    2012-01-01

    目的 探讨着色性干皮病基因D( xeroderma pigmentosum group D,xPD)基因多态性与食管鳞癌的关系,为揭示食管癌病因及制定食管癌干预措施提供理论依据.方法 采用病例对照研究方法,选取郑州大学附属第一医院食管鳞癌患者235例,按性别与年龄1∶1匹配选取河南省新乡县健康人群235人作为对照,采用聚合酶链反应-限制性片段长度多态性方法,检测xPD312位点和751位点基因型,采用非条件Logistic回归进行多因素和交互作用分析.结果 与野生型GG比较,xPD312位点GA、AA和(GA +AA)基因型与食管鳞癌易感性无关,分别调整后OR=0.83(95%CI=0.05~ 13.55),OR=1.12(95% CI=0.06 ~19.47)和OR=1.35(95%CI=0.73~2.51):与野生型AA比较,xPD751位点AC、CC和(AC +CC)基因型与食管鳞癌易感性无关,分别调整后OR=1.21 (95% CI =0.80 ~1.83),OR=0.99(95%CI=0.42~2.31)和OR=1.17(95% CI=0.79~1.75);以GA作为对照单体型,GC、AA和AC单体型与食管鳞癌易感性无关,未发现两位点与吸烟或饮酒之间的交互作用.结论 xPD 312和xPD 751位点多态性可能与河南汉族人群食管鳞癌的发生无关,且与吸烟或饮酒不存在交互作用.%Objective To explore the association of two single nu