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Sample records for esophageal carcinoma cells

  1. Chemoprevention of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Stoner, Gary D.; Wang Lishu; Chen Tong

    2007-01-01

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC

  2. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

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    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  3. Human papilloma virus and esophageal squamous cell carcinoma.

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    Hayedeh Haeri

    2014-03-01

    Full Text Available Human papillomavirus (HPV has also been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in the substantial number of esophageal SCCs in our region is unlikely.

  4. Risk Factors for Esophageal Squamous Cell Carcinoma in a Kenyan ...

    African Journals Online (AJOL)

    Background: Esophageal squamous cell carcinoma (ESCC) is common in some parts of Kenya. Both the regional factors associated with ESCC in Kenya and geographic distribution has not been completely described. Methods: We analyzed the association of ESCC with smoking, khat chewing, alcohol, diet, ...

  5. Clinicopathologic Features of Submucosal Esophageal Squamous Cell Carcinoma.

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    Emi, Manabu; Hihara, Jun; Hamai, Yoichi; Furukawa, Takaoki; Ibuki, Yuta; Okada, Morihito

    2017-12-01

    The prognoses of submucosal esophageal squamous cell carcinoma patients vary. Patients with favorable prognoses may receive less invasive or nonsurgical interventions, whereas patients with poor prognoses or advanced esophageal cancer may require aggressive treatments. We sought to identify prognostic factors for patients with submucosal esophageal squamous cell carcinoma, focusing on lymph node metastasis and recurrence. We included 137 submucosal esophageal squamous cell carcinoma patients who had undergone transthoracic esophagectomy with systematic extended lymph node dissection. Submucosal tumors were classified as SM1, SM2, and SM3 according to the depth of invasion. Prognostic factors were determined by univariable and multivariable analyses. Lymph node metastasis was observed in 18.8%, 30.5%, and 50.0% of SM1, SM2, and SM3 cases, respectively. The overall 5-year recurrence rate was 21.9%; the rates for SM1, SM2, and SM3 tumors were 9.4%, 18.6%, and 34.8%, respectively. The SM1 tumors all recurred locoregionally; distant metastasis occurred in SM2 and SM3 cases. The 5-year overall survival rates were 83%, 77%, and 59% for SM1, SM2, and SM3 cases, respectively. On univariable analysis, lymph node metastasis, depth of submucosal invasion (SM3 versus SM1/2), and tumor location (upper thoracic versus mid/lower thoracic) were poor prognostic factors for overall survival. Multivariable Cox regression analyses identified depth of submucosal invasion (hazard ratio 2.51, 95% confidence interval: 1.37 to 4.61) and tumor location (hazard ratio 2.43, 95% confidence interval: 1.18 to 4.63) as preoperative prognostic factors. Tumor location (upper thoracic) and infiltration (SM3) are the worse prognostic factors of submucosal esophageal squamous cell carcinoma, but lymph node metastasis is not a predictor of poorer prognosis. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

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    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  7. Reevaluation of Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

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    Zheng, Yan; Li, Yin; Liu, Xianben; Sun, Haibo; Wang, Zongfei; Zhang, Ruixiang

    2015-01-01

    Abstract The effect of neoadjuvant chemotherapy on the survival of patients with thoracic esophageal squamous cell carcinomas (ESCCs) remains controversial. The optimal management strategy for resectable ESCCs varies regionally based on local randomized controlled trials. A systematic review and meta-analysis was conducted to re-evaluate this controversial issue. A systematic review of the Medline, Embase, and PubMed databases was carried out on data collected between August 1994 and August 2...

  8. Esophageal Squamous Cell Carcinoma Presenting with Streptococcus intermedius Cerebral Abscess

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    Rabih Nayfe

    2017-01-01

    Full Text Available Background. Cerebral abscess is caused by inoculation of an organism into the brain parenchyma from a site distant from the central nervous system. Streptococcus intermedius (S. intermedius is a commensal organism that is normally present in the aerodigestive tract and was reported to be the cause of brain abscesses after esophageal dilatation or upper endoscopy. Case Presentation. We report the case of a 53-year-old female who presented with hematemesis and melena followed by left-sided weakness. Initially, her hemiplegia was found to be secondary to a right thalamic brain abscess caused by S. intermedius. Investigations led to the diagnosis of a mid-esophageal squamous cell carcinoma. We hypothesize that the cause of the abscess with this bacterium that naturally resides in the digestive tract and oral cavity is secondary to hematogenous spread from breach in the mucosal integrity from ulceration due to the cancer. Conclusion. To our knowledge, our case is the first in the literature to describe a brain abscess caused by S. intermedius in association with a previously undiagnosed esophageal squamous cell carcinoma without any prior esophageal intervention.

  9. Radiation therapy in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Fietkau, R.; Grabenbauer, G.G.; Sauer, R.

    1994-01-01

    The records of 52 patients with inoperable but localized squamous cell carcinomas of the esophagus were reviewed to determine the influence of different treatment modalities on survival, dysphagia and sites of recurrence. 22 patients were treated by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU; 19 patients by radiotherapy alone; six patients by chemotherapy followed by irradiation and five patients by concurrent radio-chemotherapy with various drugs. External beam radiotherapy consisted of treating the primary lesion (mean dose 53 Gy) and the lymphatic areas (mean dose 31±26 Gy) at the rate of 2 Gy/day for five days/week. Additional intraluminal high-dose-rate radiotherapy was performed in 13 patients with single fractions of 6 Gy as a boost. Minimum follow-up was twelve months, median follow-up 4.3 years. For the whole population a remission rate of 65% (34/52 patients) was achieved (complete remission 18/52 patients=35%; partial remission 16/52 patients=31%). Relief of dysphagia accompanied tumor regression. Median survival was eleven months; three-year survival rate 23%; five-year survival rate 7.6%. The analysis of recurrence revealed a high rate of local failures (26/52 patients=50%) and distant metastases (9/52 patients=18%). Comparing the different modalities the best results were achieved by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU: Complete remission could be determined in 46% and median survival was 14.9 months. Additional intracavitary radiotherapy resulted in a slightly better local control rate (54% vs. 46%) and three-year-survival rate (30% vs. 20%) compared to external beam irradiation alone. (orig./MG) [de

  10. Photodynamic therapy in early esophageal squamous cell carcinoma

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    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

    1995-03-01

    From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

  11. 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.

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

    International Nuclear Information System (INIS)

    Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Peri, Suraj; Kumar, Ghantasala S. Sameer; Jacob, Harrys K.C.; Prasad, Thottethodi Subrahmanya Keshava; Mahmood, Riaz; Kumar, K. V. Veerendra; Kumar, M. Vijaya; Meltzer, Stephen J.; Montgomery, Elizabeth A.; Kumar, Rekha V.; Pandey, Akhilesh

    2010-01-01

    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

  13. Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

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    Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

    2017-07-01

    Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was

  14. RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

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    Zhang, Jinyao; Chen, Zhaoli; Tang, Zefang; Huang, Jianbing; Hu, Xueda; He, Jie

    2017-07-01

    In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

  15. [Impact of postoperative pathological features of esophageal squamous cell carcinoma on the prognosis].

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    Xu, Lei; Li, Yin; Sun, Haibo; Zheng, Yan; Wang, Zongfei; Chen, Xiankai

    2017-12-25

    Esophageal cancer is located in the 8th position of the incidence of malignant tumors and the 6th most common cause of cancer-related mortality in the world, while China has the highest incidence and mortality of esophageal cancer. Esophageal squamous cell carcinoma (ESCC), the predominant histologic type of esophageal cancer in China, accounts for about 90%. Despite recent improvement of surgical techniques and philosophy, however, the prognosis of ESCC patients treated with surgery is still poor, and 5-year survival remains unsatisfactorily low. So far, the pathogenesis of esophageal squamous cell carcinoma is still unclear, and effective prevention is also out of the question. To find the main factors affecting the prognosis of esophageal squamous cell carcinoma, and to improve the survival of patients, are the main directions of all scholars. Postoperative pathology of esophageal squamous cell carcinoma is considered to be one of the most important predictors of prognosis. Currently, the evaluation of postoperative esophageal prognosis mainly depends on TNM staging, but some criteria of its specific content and staging remains controversial. In this paper recent domestic and foreign related researches and clinical trials reports are collected, and the postoperative pathological features affecting esophageal squamous cell carcinoma prognosis were reviewed.

  16. [Epidemiology and risk factors of the esophageal squamous cell carcinoma].

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    Szumiło, Justyna

    2009-01-01

    Esophageal carcinoma is the eighth most common malignancy in the world. In most countries, including Poland, the squamous cell carcinoma is a predominant histological type. It is characterized by extreme diversity in geographical distribution and incidence. High incidence is noted in regions located along with so-called "Asian esophageal cancer belt" beginning from eastern Turkey through Caspian littoral countries, northern Afghanistan to Central and Eastern Asia, as well as in Japan, South Africa and some South American countries. In Western Europe the highest incidence is observed in France, Portugal and northern Italy. Poland belongs to low-incidence countries with the age-standardized annual incidence exceeding 4.5 and 0.7/100,000, for men and women respectively. Etiology of the cancer is multi-factorial. In western countries the most important risk factors are tobacco smoking and alcohol consumption, and to a lesser extent, an inappropriate diet. In other countries, a diet lacking of fresh vegetables and fruits with vitamin and mineral deficiency and high level of sodium chloride, carbohydrates and animal fats is a predominant factor. Furthermore, preserving and processing food which facilitates accumulation of carcinogens, special dietary habits and viral infections are also attributed to the development of cancer. More recently, the significance of genetically determined increased susceptibility of some individuals versus environmental factors has been stressed. Previous studies proved the relationship between cancer susceptibility and polymorphisms in genes encoding some important molecules engaged in carcinogens metabolism or DNA repair.

  17. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

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    Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

    2015-01-01

    A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  18. A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

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    Hui-Hui Cao

    Full Text Available Esophageal squamous cell carcinoma (ESCC has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR, phosphorylated Specificity protein 1 (p-Sp1, and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset and validated using an independent cohort of 185 specimens (validation dataset.The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001. Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset. Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

  19. Ultrasound-Guided Phrenic Nerve Block for Intractable Hiccups following Placement of Esophageal Stent for Esophageal Squamous Cell Carcinoma.

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    Arsanious, David; Khoury, Spiro; Martinez, Edgar; Nawras, Ali; Filatoff, Gregory; Ajabnoor, Hossam; Darr, Umar; Atallah, Joseph

    2016-05-01

    Hiccups are actions consisting of sudden contractions of the diaphragm and intercostals followed by a sudden inspiration and transient closure of the vocal cords. They are generally short lived and benign; however, in extreme and rare cases, such as esophageal carcinoma, they can become persistent or intractable, up to and involving significant pain, dramatically impacting the patient's quality of life. This case involves a 60-year-old man with a known history of squamous cell carcinoma of the esophagus. He was considered to have high surgical risk, and therefore he received palliative care through the use of fully covered metallic esophageal self-expandable stents due to a spontaneous perforated esophagus, after which he developed intractable hiccups and associated mediastinal pain. Conservative treatment, including baclofen, chlorpromazine, metoclopramide, and omeprazole, provided no relief for his symptoms. The patient was referred to pain management from gastroenterology for consultation on pain control. He ultimately received an ultrasound-guided left phrenic nerve block with bupivacaine and depomedrol, and 3 days later underwent the identical procedure on the right phrenic nerve. This led to complete resolution of his hiccups and associated mediastinal pain. At follow-up, 2 and 4 weeks after the left phrenic nerve block, the patient was found to maintain complete alleviation of the hiccups. Esophageal dilatation and/or phrenic or vagal afferent fiber irritation can be suspected in cases of intractable hiccups secondary to esophageal stenting. Regional anesthesia of the phrenic nerve through ultrasound guidance offers a long-term therapeutic option for intractable hiccups and associated mediastinal pain in selected patients with esophageal carcinoma after stent placement. Esophageal stent, esophageal stenting, intractable hiccups, intractable singultus, phrenic nerve block, phrenic nerve, ultrasound, palliative care, esophageal carcinoma.

  20. The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma.

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    Chen, Miao-Fen; Lee, Kuan-Der; Lu, Ming-Shian; Chen, Chih-Cheng; Hsieh, Ming-Ju; Liu, Yun-Hen; Lin, Paul-Yang; Chen, Wen-Cheng

    2009-03-01

    The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.

  1. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Zhu Weiguo; You Zhenbin; Li Tao; Yu Changhua; Tao Guangzhou; Hu Mingli; Chen Xiaofei

    2011-01-01

    The objective of this study was to investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma. In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P=0.01), locoregional progression (P=0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P=0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival. These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy. (author)

  2. Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal Squamous Cell Carcinoma.

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    Ji, Huaijun; Cao, Ming; Ren, Kunlun; Sun, Ningbo; Wang, Wei; Zhu, Qiang; Zang, Qi; Jiang, Zhongmin

    2017-01-01

    The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies. However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in esophageal squamous cell carcinoma are still unclear. In this study, we analyzed the expression levels of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89 esophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction analyses. We found that the expression of melanoma nuclear protein 18 in the carcinoma tissues was significantly lower than that in the noncancerous mucosal tissues ( P .05). B-cell-specific Moloney leukemia virus insert site 1 expression was strongly correlated with the degree of differentiation, clinical stage, and lymph node metastasis ( P .05). Moreover, there was a negative correlation between melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma ( P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 may play a crucial role in esophageal squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney leukemia virus insert site 1 may be a potential biomarker for diagnosis and prognosis of esophageal squamous cell carcinoma.

  3. Significance of Nuclear Accumulation of Foxo3a in Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Chen, M.-F.; Fang, F.-M.; Lu, C.-H.; Lu, M.-S.; Chen, W.-C.; Lee, K.-D.; Lin, P.-Y.

    2008-01-01

    Purpose: To investigate the value of Foxo3a in predicting the response to neoadjuvant treatment of, and prognosis for, esophageal squamous cell carcinoma. Methods and Materials: Immunohistochemical staining was performed in a retrospective series of 60 biopsied esophageal squamous cell carcinomas, and the correlation between nuclear accumulation of Foxo3a and clinicopathologic features was analyzed, including patient survival. In addition, in vitro biologic changes, radiosensitivity, and in vivo tumorigenicity of esophageal carcinoma cells after experimental manipulation of Foxo3a expression levels were determined. Results: Clinical findings point to a significant correlation between the nuclear accumulation of Foxo3a and the survival rate of esophageal cancer patients. In addition, Foxo3a is a significant predictor for the response to neoadjuvant therapy. In cell culture, irradiation and oxidative stress seemed to result in nuclear accumulation of Foxo3a. Down-regulation of Foxo3a significantly decreased radiosensitivity but had no obvious effect on tumor growth, as measured by a clonogenic assay in vitro and growth delay in vivo. Conclusions: Nuclear accumulation of Foxo3a in tumor cells was correlated with increased radiosensitivity and with improved patient survival. Thus, it is suggested that Foxo3a may be a potential marker for esophageal cancer

  4. [Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

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    Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

    2016-12-01

    Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

  5. Number of negative lymph nodes as a prognostic factor in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ma, Mingquan; Tang, Peng; Jiang, Hongjing; Gong, Lei; Duan, Xiaofeng; Shang, Xiaobin; Yu, Zhentao

    2017-10-01

    The aim of this study is to investigate the number of negative lymph nodes (NLNs) as a prognostic factor for survival in patients with resected esophageal squamous cell carcinoma. A total of 381 esophageal squamous cell carcinoma patients who had underwent surgical resection as the primary treatment was enrolled into this retrospective study. The impact of number of NLNs on patient's overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system. The number of NLNs was closely related to the overall survival, and the 5-year survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs ≤ 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of NLNs remained an independent prognostic factor (P = 0.002) as did the other current TNM factors. For subgroup analysis, the predictive value of number of NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2 disease or patients with N0 disease. The number of NLNs, which represents the extent of lymphadenectomy for esophageal squamous cell carcinoma, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-positive disease and advanced T-stage tumor. © 2016 John Wiley & Sons Australia, Ltd.

  6. Cost-effectiveness of cetuximab for advanced esophageal squamous cell carcinoma

    NARCIS (Netherlands)

    V.T. Janmaat (Vincent T.); M.J. Bruno (Marco); S. Polinder (Suzanne); S. Lorenzen (Sylvie); F. Lordick (Florian); M.P. Peppelenbosch (Maikel); M.C.W. Spaander (Manon)

    2016-01-01

    textabstractBackground Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in

  7. High endothelin-converting enzyme-1 expression independently predicts poor survival of patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Ching-Fang; Lee, Ching-Tai; Kuo, Yao-Hung; Chen, Tzu-Haw; Chang, Chi-Yang; Chang, I-Wei; Wang, Wen-Lun

    2017-09-01

    Patients with esophageal squamous cell carcinoma have poor survival and high recurrence rate, thus an effective prognostic biomarker is needed. Endothelin-converting enzyme-1 is responsible for biosynthesis of endothelin-1, which promotes growth and invasion of human cancers. The role of endothelin-converting enzyme-1 in esophageal squamous cell carcinoma is still unknown. Therefore, this study investigated the significance of endothelin-converting enzyme-1 expression in esophageal squamous cell carcinoma clinically. We enrolled patients with esophageal squamous cell carcinoma who provided pretreated tumor tissues. Tumor endothelin-converting enzyme-1 expression was evaluated by immunohistochemistry and was defined as either low or high expression. Then we evaluated whether tumor endothelin-converting enzyme-1 expression had any association with clinicopathological findings or predicted survival of patients with esophageal squamous cell carcinoma. Overall, 54 of 99 patients with esophageal squamous cell carcinoma had high tumor endothelin-converting enzyme-1 expression, which was significantly associated with lymph node metastasis ( p = 0.04). In addition, tumor endothelin-converting enzyme-1 expression independently predicted survival of patients with esophageal squamous cell carcinoma, and the 5-year survival was poorer in patients with high tumor endothelin-converting enzyme-1 expression ( p = 0.016). Among patients with locally advanced and potentially resectable esophageal squamous cell carcinoma (stage II and III), 5-year survival was poorer with high tumor endothelin-converting enzyme-1 expression ( p = 0.003). High tumor endothelin-converting enzyme-1 expression also significantly predicted poorer survival of patients in this population. In patients with esophageal squamous cell carcinoma, high tumor endothelin-converting enzyme-1 expression might indicate high tumor invasive property. Therefore, tumor endothelin-converting enzyme-1 expression

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

    Science.gov (United States)

    Noori, Sadat; Monabati, Ahmad; Ghaderi, Abbasali

    2012-01-01

    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. PMID:23115442

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

    Directory of Open Access Journals (Sweden)

    Sadat Noori

    2012-06-01

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

  10. Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

    Science.gov (United States)

    Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

    2016-01-15

    The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Measuring telomere length for the early detection of precursor lesions of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Lin, Shih-Wen; Wang, Guo-Qing; Wei, Wen-Qiang; Lu, Ning; Taylor, Philip R; Qiao, You-Lin; Dawsey, Sanford M; Abnet, Christian C; Freedman, Neal D; Murphy, Gwen; Risques, Rosana; Prunkard, Donna; Rabinovitch, Peter; Pan, Qin-Jing; Roth, Mark J

    2013-01-01

    Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Esophageal balloon cytology successfully retrieves exfoliated and scraped superficial esophageal epithelial cells, but cytologic reading of these cells has poor sensitivity and specificity for detecting esophageal squamous dysplasia (ESD), the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring telomere length, a marker for chromosomal instability, may improve the utility of balloon cytology for detecting ESD and early ESCC. We examined balloon cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high-grade) and 92 age- and sex-matched normal controls from an esophageal cancer early detection screening study. All subjects also underwent endoscopy and biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the balloon cytology cells, and telomere length was measured by quantitative PCR. A receiver operating characteristic (ROC) curve was plotted for telomere length as a diagnostic marker for high-grade dysplasia. Telomere lengths were comparable among the low- and high-grade dysplasia cases and controls, with means of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for telomere length as a diagnostic marker for high-grade dysplasia. Further adjustment for subject characteristics, including sex, age, smoking, drinking, hypertension, and body mass index did not improve the use of telomere length as a marker for ESD. Telomere length of esophageal balloon cytology cells was not associated with ESCC precursor lesions. Therefore, telomere length shows little promise as an early detection marker for ESCC in esophageal balloon samples

  12. 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.

  13. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  14. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    International Nuclear Information System (INIS)

    He, Wei; Wang, Zhihui; Wang, Qi; Fan, Qingxia; Shou, Chengcao; Wang, Junsheng; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

    2009-01-01

    HIWI, the human homologue of Piwi family, is present in CD34 + hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development

  15. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    Directory of Open Access Journals (Sweden)

    Shou Chengcao

    2009-12-01

    Full Text Available Abstract Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5% cases, 16 (10.5% cases were negative in both nuclei and cytoplasm. 86 (56.2% were strongly positive in cytoplasm, while 49 (32.0% were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011, T stage (P = 0.035, and clinic outcome (P Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development.

  16. Distinct effects of EGFR inhibitors on epithelial- and mesenchymal-like esophageal squamous cell carcinoma cells.

    Science.gov (United States)

    Yoshioka, Masahiro; Ohashi, Shinya; Ida, Tomomi; Nakai, Yukie; Kikuchi, Osamu; Amanuma, Yusuke; Matsubara, Junichi; Yamada, Atsushi; Miyamoto, Shin'ichi; Natsuizaka, Mitsuteru; Nakagawa, Hiroshi; Chiba, Tsutomu; Seno, Hiroshi; Muto, Manabu

    2017-08-01

    Epidermal growth factor receptor (EGFR) plays a pivotal role in the pathophysiology of esophageal squamous cell carcinoma (ESCC). However, the clinical effects of EGFR inhibitors on ESCC are controversial. This study sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors in ESCC cells. Immortalized-human esophageal epithelial cells (EPC2-hTERT), transformed-human esophageal epithelial cells (T-Epi and T-Mes), and ESCC cells (TE-1, TE-5, TE-8, TE-11, TE-11R, and HCE4) were treated with the EGFR inhibitors erlotinib or cetuximab. Inhibitory effects on cell growth were assessed by cell counting or cell-cycle analysis. The expression levels of genes and proteins such as involucrin and cytokeratin13 (a squamous differentiation marker), E-cadherin, and vimentin were evaluated by real-time polymerase chain reaction or western blotting. To examine whether mesenchymal phenotype influenced the effects of EGFR inhibitors, we treated T-Epi cells with TGF-β1 to establish a mesenchymal phenotype (mesenchymal T-Epi cells). We then compared the effects of EGFR inhibitors on parental T-Epi cells and mesenchymal T-Epi cells. TE-8 (mesenchymal-like ESCC cells)- or TE-11R (epithelial-like ESCC cells)-derived xenograft tumors in mice were treated with cetuximab, and the antitumor effects of EGFR inhibitors were evaluated. Cells were classified as epithelial-like or mesenchymal-like phenotypes, determined by the expression levels of E-cadherin and vimentin. Both erlotinib and cetuximab reduced cell growth and the ratio of cells in cell-cycle S phase in epithelial-like but not mesenchymal-like cells. Additionally, EGFR inhibitors induced squamous cell differentiation (defined as increased expression of involucrin and cytokeratin13) in epithelial-like but not mesenchymal-like cells. We found that EGFR inhibitors did not suppress the phosphorylation of EGFR in mesenchymal-like cells, while EGFR dephosphorylation was observed after treatment with EGFR

  17. Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients.

    Science.gov (United States)

    Chen, C-Y; Hsieh, V C-R; Chang, C-H; Chen, P-R; Liang, W-M; Pan, S-C; Shieh, S-H

    2017-10-01

    This study aims to investigate the effects of treatments on the quality of life for patients with esophageal squamous cell carcinoma patients diagnosed at early and late stages. From a medical center in central Taiwan, patients who had been diagnosed with esophageal squamous cell carcinoma from February 2007 and March 2011 were recruited. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Oesophageal 18 (QLQ-OES18), quality of life scores for 105 esophageal squamous cell carcinoma patients were obtained and assessed. Multivariate analysis was performed on the quality of life scores after stratification by cancer stage. Among early-stage esophageal squamous cell carcinoma patients, those received only surgery (S-only) performed better in physical and social functioning compared with patients who underwent surgery and concurrent chemoradiotherapy (S+CCRT) (β = 9.0, P = 0.03; β = 12.1, P = 0.04, respectively). For those that received only concurrent chemoradiotherapy (CCRT-only), they performed worse in role and emotional functioning relative to S+CCRT patients (β = -17.2, P = 0.02; β = -15.7, P = 0.05, respectively). Among late-stage patients, CCRT-only treatment gave insignificantly better global health status and functional scale scores and less severe symptoms compared to the S+CCRT option. Better functional scores and less aggravated symptoms are observed in early-stage esophageal squamous cell carcinoma patients who received surgery-only treatment relative to those that underwent both surgery and chemoradiotherapy. For late-stage esophageal cancer patients, the measured difference of quality of life is not significant between CCRT-only and S+CCRT treatments. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  19. Synchronous advanced gastric adenocarcinoma and advanced esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Fernando Augusto Mardiros Herbella

    2002-01-01

    Full Text Available CONTEXT: Synchronous associations of esophageal and gastric cancers are not a common finding, especially with differing histological types and both tumors in advanced forms. A case with such an association is presented, in which an unusual therapy was proposed: palliative gastrectomy and esophageal intubation. CASE REPORT: A 75-year-old white man was referred to our service complaining of malaise and weight loss for one year and dysphagia and vomiting for 2 months. The patient had sought out medical consultation as a result of the latter two complaints.

  20. A prediction model for lymph node metastasis in T1 esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Jie; Chen, Qi-Xun; Shen, Di-Jian; Zhao, Qiang

    2018-04-01

    Endoscopic resection is widely used for the treatment of T1 esophageal cancer, but it cannot be used to treat lymph node metastasis (LNM). This study aimed to develop a prediction model for LNM in patients with T1 esophageal squamous cell carcinoma. A prospectively maintained database of all patients who underwent surgery for esophageal cancer between January 2002 and June 2010 was retrospectively reviewed, and patients with T1 squamous cell carcinoma were included in this study. Correlations between LNM and clinicopathological variables were evaluated using univariable and multivariable logistic regression analyses. The penalized maximum likelihood method was used to estimate regression coefficients. A prediction model was developed and internally validated using a bootstrap resampling method. Model performance was evaluated in terms of calibration, discrimination, and clinical usefulness. A total of 240 patients (197 male, 43 female) with a mean age of 57.9 years (standard deviation ± 8.3 years) were included in the analysis. The incidence of LNM was 16.3%. The prediction model consisted of four variables: grade, T1 stage, tumor location and tumor length. The model showed good calibration and good discrimination with a C-index of 0.787 (95% confidence interval [CI], 0.711-0.863). After internal validation, the optimism-corrected C-index was 0.762 (95% CI, 0.686-0.838). Decision curve analysis demonstrated that the prediction model was clinically useful. Our prediction model can facilitate individualized prediction of LNM in patients with T1 esophageal squamous cell carcinoma. This model can aid surgical decision making in patients who have undergone endoscopic resection. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  1. A case of esophageal so-called carcinosarcoma, which proliferated after radiochemotherapy against squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sasaki, Shozo; Kurosaka, Yoshiyuki; Funaki, Kohziro; Michiwa, Yoshio; Takegawa, Shigeru; Kiriyama, Masato; Kawashima, Atsuhiro; Kojima, Yasuhiko

    2007-01-01

    A 89-year-old woman undergoing fibroptic esophagoscopy elsewhere for dysphagia was found to have an esophageal tumor and was referred to our hospital. Upper gastrointestinal endoscopy showed a type 1 esophageal tumor about 3 cm in diameter in the lower thoracic esophagus pathologically diagnosed as moderately differentiated squamous cell carcinoma from the biopsy specimen. CT and MRI showed metastasis in the right lymph node of cardia. Although we advised an esophagectomy, she did not agree to it due to her high age, so we treated her with radiochemotherapy. She underwent radiotherapy (54 Gy) and chemotherapy (cisplatin and 5-fluorouracil (FU)) concurrently. It was effective and the tumor almost disappeared and the biopsy specimen showed few viable cells. After 12 months, the tumor recurred and the pathological diagnosis was so-called carcinosarcoma. She died 14 months after treatment and pathological autopsy showed the tumor of the esophagus to be so-called carcinosarcoma, but metastasized tissue consisted of squamous cell carcinoma and did not have a sarcoma component. We concluded that metaplastic change of squamous carcinoma cells into spindle cells, occurred due to radiochemotherapy and the tumor recurred as so-called carcinosarcoma. (author)

  2. Postoperative radiation in esophageal squamous cell carcinoma and target volume delineation

    Directory of Open Access Journals (Sweden)

    Zhu Y

    2016-07-01

    Full Text Available Yingming Zhu,* Minghuan Li,* Li Kong, Jinming Yu Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Esophageal cancer is the sixth leading cause of cancer death worldwide, and patients who are treated with surgery alone, without neoadjuvant therapies, experience frequent relapses. Whether postoperative therapies could reduce the recurrence or improve overall survival is still controversial for these patients. The purpose of our review is to figure out the value of postoperative adjuvant therapy and address the disputes about target volume delineation according to published data. Based on the evidence of increased morbidity and disadvantages on patient survival caused by postoperative chemotherapy or radiotherapy (RT alone provided by studies in the early 1990s, the use of postoperative adjuvant therapies in cases of esophageal squamous cell carcinoma has diminished substantially and has been replaced gradually by neoadjuvant chemoradiation. With advances in surgery and RT, accumulating evidence has recently rekindled interest in the delivery of postoperative RT or chemoradiotherapy in patients with stage T3/T4 or N1 (lymph node positive carcinomas after radical surgery. However, due to complications with the standard radiation field, a nonconforming modified field has been adopted in most studies. Therefore, we analyze different field applications and provide suggestions on the optimization of the radiation field based on the major sites of relapse and the surgical non-clearance area. For upper and middle thoracic esophageal carcinomas, the bilateral supraclavicular and superior mediastinal areas remain common sites of recurrence and should be encompassed within the clinical target volume. In contrast, a consensus has yet to be reached regarding lower thoracic esophageal carcinomas; the

  3. Inhibition of DNA synthesis and radiosensitization effects of thalidomide on esophageal carcinoma TE1 cells

    International Nuclear Information System (INIS)

    Yu Jingping; Sun Suping; Sun Zhiqiang; Sun Meiling; Liu Fenju

    2010-01-01

    Objective: To explore the radiosensitization effect of thalidomide combined with X-ray on esophageal carcinoma TE1 cells. Methods: Cell scratch assay was used to detect the inhibition ability of different concentration of Thalidomide on cell invasion and metastasis. H 3 -TdR incorporation assay was used to investigate the inhibition of DNA synthesis in TE1 cells by treated with Thalidomide singly or combination with X-rays. The colony formation assay was used to analyze the radiosensitization of Thalidomide effect on TE1 cells. Results: Thalidomide had obvious inhibition effect on TE1 cell metastasis, DNA synthesis and colony formation, which were correlated with drug concentration. The values D 0 , D q and SF 2 in TE1 cells were gradually decreased with thalidomide concentration increased. When the concentration of thalidomide was 100μg/ml, the SER D 0 and SER D 0 and SER D q were (1.4±0.2) and (1.5±0.1), respectively, While the concentration of thalidomide was 150 μg/ml, the SER D 0 and SER D q were (1.5±0.2) and (1.8±0.2), respectively. Conclusions: Thalidomide could inhibit TE1 cell invasion, metastasis, DNA synthesis, and significantly enhance the radiosensitizing effect on esophageal carcinoma TE1 cells. (authors)

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

    Science.gov (United States)

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

    2002-01-01

    AIM: To Quantitatively analyze the nitri oxide (NO) and Ca2+ in apoptosis of esophageal carcinoma cells induced by arsenic trioxide (As2O3). METHODS: The cell line SHEEC1, a malignant esophageal epithelial cell induced by HPV in synergy with TPA in our laboratory, was cultured in a serum-free medium and treated with As2O3. Before and after administration of As2O3, NO production in cultured medium was detected quantitatively using the Griess Colorimetric method. Intracellular Ca2+ was labeled by using the fluorescent dye Fluo3-AM and detected under confocal laser scanning microscope (CLSM), which was able to acquire data in real-time enabling Ca2+ dynamics of individual cells in vitro. The apoptotic cells were examined under electron microscopy. RESULTS: Intracellular concentration of Ca2+ increased from 1.00 units to 1.09-1.38 units of fluorescent intensity at As2O3 treatment and NO products subsequently released from As2O3-treated cells increased from 0.98-1.00 × 10-2 μmol·L-1 up to 1.48-1.52 × 10-2 μmol·L-1 and maintained in a high level continuously. Finally apoptosis of cells occurred, chromatin being agglutinated, cells shrunk, nuclei became round and mitochondria swelled. CONCLUSION: Ca2+ and NO increased with cell damage and apoptosis in cells treated by As2O3. The Ca2+ is an initial messenger to the apoptotic pathway. To investigate Ca2+ and NO will be a new direction for studying the apoptotic signaling messenger of the esophageal carcinoma cells induced by As2O3. PMID:11833068

  5. Status of epigenetic chromatin modification enzymes and esophageal squamous cell carcinoma risk in northeast Indian population.

    Science.gov (United States)

    Singh, Virendra; Singh, Laishram C; Singh, Avninder P; Sharma, Jagannath; Borthakur, Bibhuti B; Debnath, Arundhati; Rai, Avdhesh K; Phukan, Rup K; Mahanta, Jagadish; Kataki, Amal C; Kapur, Sujala; Saxena, Sunita

    2015-01-01

    Esophageal cancer incidence is reported in high frequency in northeast India. The etiology is different from other population at India due to wide variations in dietary habits or nutritional factors, tobacco/betel quid chewing and alcohol habits. Since DNA methylation, histone modification and miRNA-mediated epigenetic processes alter the gene expression, the involvement of these processes might be useful to find out epigenetic markers of esophageal cancer risk in northeast Indian population. The present investigation was aimed to carryout differential expression profiling of chromatin modification enzymes in tumor and normal tissue collected from esophageal squamous cell carcinoma (ESCC) patients. Differential mRNA expression profiling and their validation was done by quantitative real time PCR and tissue microarray respectively. Univariate and multiple logistic regression analysis were used to analyze the epidemiological data. mRNA expression data was analyzed by Student t-test. Fisher exact test was used for tissue microarray data analysis. Higher expression of enzymes regulating methylation (DOT1L and PRMT1) and acetylation (KAT7, KAT8, KAT2A and KAT6A) of histone was found associated with ESCC risk. Tissue microarray done in independent cohort of 75 patients revealed higher nuclear protein expression of KAT8 and PRMT1 in tumor similar to mRNA expression. Expression status of PRMT1 and KAT8 was found declined as we move from low grade to high grade tumor. Betel nut chewing, alcohol drinking and dried fish intake were significantly associated with increased risk of esophageal cancer among the study subject. Study suggests the association of PRMT1 and KAT8 with esophageal cancer risk and its involvement in the transition process of low to high grade tumor formation. The study exposes the differential status of chromatin modification enzymes between tumor and normal tissue and points out that relaxed state of chromatin facilitates more transcriptionally active

  6. Study on relationship between apoptosis-related genes and radiosensitivity of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Li Huixiang; Wang Yaohe; Shi Yonggang; Gao Dongling; Zhang Yunhan

    2000-01-01

    Objective: To observing the relationship between apoptosis-related genes bcl-2,c-myc, p53 and the radiosensitivity of esophageal squamous cell carcinoma. Methods: The expression levels of bcl-2, c-myc and p53 genes in 57 biopsy samples from patients of esophageal squamous cell carcinoma were detected with the LSAB immunohistochemistry method. All the patients were treated with radiotherapy. The radiotherapeutic effect in these patients was observed and the relation between gene expression and radiosensitivity was analyzed. Results: Compared with the bcl-2-negative group, the radiosensitivity of bcl-2-positive one was lower(P<0.01). The radiosensitivity of p53-positive group was slightly lower than that of the p53-negative one (P<0.05). The c-myc protein expression was not related to radiosensitivity. Conclusion: Detection and comprehensive analysis of bcl-2, c-myc and p53 protein expressions are useful in forecasting the radiotherapeutic effect on squamous cell carcinoma of esophagus

  7. Preoperative serum lipids as prognostic predictors in esophageal squamous cell carcinoma patients with esophagectomy.

    Science.gov (United States)

    Chen, Pengxiang; Han, Lihui; Wang, Cong; Jia, Yibin; Song, Qingxu; Wang, Jianbo; Guan, Shanghui; Tan, Bingxu; Liu, Bowen; Jia, Wenqiao; Cui, Jianfeng; Zhou, Wei; Cheng, Yufeng

    2017-06-20

    This study was to evaluate the prognostic significance of serum lipids in esophageal squamous cell carcinoma patients who underwent esophagectomy. Preoperative serum lipids were collected from 214 patients who were diagnosed with esophageal squamous cell carcinoma. All of the patients received esophagectomy in Qilu Hospital of Shandong University from January 2007 to December 2008. The records and data were analyzed retrospectively. We found that low total cholesterol (for T stage, p = 0.006; for TNM stage, p = 0.039) and low-density lipoprotein cholesterol (for T stage, p = 0.031; for TNM stage, p = 0.035) were associated with advanced T stage and TNM stage. Kaplan-Meier survival analysis indicated that low total cholesterol and low-density lipoprotein cholesterol were associated with shorter disease-free survival(for total cholesterol, p = 0.045; for low-density lipoprotein cholesterol, p squamous cell carcinoma patients who underwent esophagectomy. LHR can serve as a promising serum lipids-based prognostic indicator.

  8. Polycyclic Aromatic Hydrocarbons and Esophageal Squamous Cell Carcinoma-A Review

    Science.gov (United States)

    Roshandel, Gholamreza; Semnani, Shahryar; Malekzadeh, Reza; Dawsey, Sanford M.

    2018-01-01

    Esophageal cancer (EC) is the 8th most common cancer and the 6th most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC. PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC. Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas. PMID:23102250

  9. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

    International Nuclear Information System (INIS)

    Xie, J.J.; Xu, L.Y.; Zhang, H.H.; Cai, W.J.; Mai, R.Q.; Xie, Y.M.; Yang, Z.M.; Niu, Y.D.; Shen, Z.Y.; Li, E.M.

    2005-01-01

    Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility in various transformed cells. The overexpression of fascin in esophageal squamous cell carcinoma (ESCC) has been described only recently, but the roles and mechanism still remained unclear. Here, by using RNA interference (RNAi), we have stably silenced the expression of the fascin in EC109 cells, an ESCC cell line. Down-regulation of fascin resulted in a suppression of cell proliferation and as well as a decrease in cell invasiveness. Furthermore, we revealed that fascin might have functions in regulating tumor growth in vivo. The effect of fascin on cell invasiveness correlated with the activation of matrix metalloproteases such as MMP-2 and MMP-9. We examined that fascin down-expression also led to a decrease of c-erbB-2 and β-catenin at the protein level. These results suggested that fascin might play crucial roles in regulating neoplasm progression of ESCC

  10. Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence

    Science.gov (United States)

    Cimperman, Katherine A.; Haas, Sarah R.; Guasch, Geraldine; Waclaw, Ronald R.; Komurov, Kakajan; Lane, Adam; Wikenheiser-Brokamp, Kathryn A.

    2018-01-01

    Esophageal cancer occurs as either squamous cell carcinoma (ESCC) or adenocarcinoma. ESCCs comprise almost 90% of cases worldwide, and recur with a less than 15% five-year survival rate despite available treatments. The identification of new ESCC drivers and therapeutic targets is critical for improving outcomes. Here we report that expression of the human DEK oncogene is strongly upregulated in esophageal SCC based on data in the cancer genome atlas (TCGA). DEK is a chromatin-associated protein with important roles in several nuclear processes including gene transcription, epigenetics, and DNA repair. Our previous data have utilized a murine knockout model to demonstrate that Dek expression is required for oral and esophageal SCC growth. Also, DEK overexpression in human keratinocytes, the cell of origin for SCC, was sufficient to cause hyperplasia in 3D organotypic raft cultures that mimic human skin, thus linking high DEK expression in keratinocytes to oncogenic phenotypes. However, the role of DEK over-expression in ESCC development remains unknown in human cells or genetic mouse models. To define the consequences of Dek overexpression in vivo, we generated and validated a tetracycline responsive Dek transgenic mouse model referred to as Bi-L-Dek. Dek overexpression was induced in the basal keratinocytes of stratified squamous epithelium by crossing Bi-L-Dek mice to keratin 5 tetracycline transactivator (K5-tTA) mice. Conditional transgene expression was validated in the resulting Bi-L-Dek_K5-tTA mice and was suppressed with doxycycline treatment in the tetracycline-off system. The mice were subjected to an established HNSCC and esophageal carcinogenesis protocol using the chemical carcinogen 4-nitroquinoline 1-oxide (4NQO). Dek overexpression stimulated gross esophageal tumor development, when compared to doxycycline treated control mice. Furthermore, high Dek expression caused a trend toward esophageal hyperplasia in 4NQO treated mice. Taken together, these

  11. 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...... tissue (e.g. CYP2C8, CYP3A4, CYP3A5, and CYP2E1) between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus....

  12. Isolated Nasal Tip Metastasis from Esophageal Squamous Cell Carcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Georg J. Ledderose

    2015-01-01

    Full Text Available Objectives. Cutaneous metastases can be the first sign of a malignant disease and have an unfavorable prognostic significance. The external nose is rarely affected. The uncommon clinical presentation of these cutaneous metastases may lead to the wrong diagnosis and treatment. Methods. We present the case of a 59-year-old patient with a small indolent tumor on the tip of the nose that turned out to be the first sign of an extended esophageal cancer. Conclusion. The differential diagnosis of tumors of the facial skin and the nasal tip includes metastases from an unknown primary tumor. In rare cases, squamous cell carcinoma of the esophagus needs to be considered.

  13. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

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    A. Casini

    2011-09-01

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

  14. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Casini, Alessandro; Tschanz, Elisabeth; Dietrich, Pierre-Yves; Nendaz, Mathieu

    2011-01-01

    Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus b...

  15. Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    He, Xiaoyan; Zhang, Zhimei; Li, Ming; Li, Shuo; Ren, Lihua; Zhu, Hong; Xiao, Bin; Shi, Ruihua

    2015-01-01

    Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3′ untranslated region (3′-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2. The online version of this article (doi:10.1186/s12885-015-1581-6) contains supplementary material, which is available to authorized users

  16. Transcription factor AP-1 in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection

    International Nuclear Information System (INIS)

    Hussain, Showket; Bharti, Alok C; Salam, Irfana; Bhat, Mohammad Akbar; Mir, Mohammad Muzaffar; Hedau, Suresh; Siddiqi, Mushtaq A; Basir, Seemi Farhat; Das, Bhudev C

    2009-01-01

    Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high-risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection. Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively. A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues. Differential AP-1 binding activity and expression of its specific proteins between HPV - positive and HPV - negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis

  17. 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.

  18. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Raissouni Soundouss

    2012-08-01

    Full Text Available Abstract Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  19. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

    Science.gov (United States)

    Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

    2012-08-09

    Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  20. [The molecular mechanisms of curcuma wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells in vitro].

    Science.gov (United States)

    Jing, Zhao; Zou, Hai-Zhou; Xu, Fang

    2012-09-01

    To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells. The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence. 100 microL RMPI-1640 culture medium containing 0.1% DMSO was added in Group 1 as the control group. 100 microL 25, 50, and 100 mg/L Curcuma Wenyujin extract complete culture medium was respectively added in the rest 3 groups as the low, middle, and high dose Curcuma Wenyujin extract groups. The effects of different doses of Curcuma Wenyujin extract (25, 50, and 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro were analyzed by MTT assay. The gene expression profile was identified by cDNA microarrays in esophageal carcinoma TE-1 cells exposed to Curcuma Wenyujin extract for 48 h. The differential expression genes were further analyzed by Gene Ontology function analysis. Compared with the control group, MTT results showed that Curcuma Wenyujin extract significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (PCurcuma Wenyujin extract could inhibit the growth of human esophageal carcinoma cell line TE-1 in vitro. The molecular mechanisms might be associated with regulating genes expressions at multi-levels.

  1. Preoperative chemoradiotherapy for stage 2 or 3 esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kawai, Takaharu; Kochi, Mitsugu; Fujii, Masashi

    2016-01-01

    The goal of this retrospective study was to investigate the efficacy and safety of preoperative chemoradiotherapy (NACR) in patients with Stage 2 or Stage 3 esophageal squamous cell carcinoma (SCC). Between 2004 and 2014, a total of 86 patients underwent surgical resection in conjunction with NACR for esophageal SCC at our institute. Thirty-one patients (36.0%) had Stage 2 disease and 55 patients (64.0%) had Stage 3 disease. The median age was 64 (43-81) years. A total of 78 patients received the full NACR regimen. The most common major Grade 3 hematologic toxic effects of NACR were leukopenia and neutropenia (48 cases), while the most common major Grade 3 non-hematologic toxic effect was anorexia (12 cases). One patient died in the hospital and no patients died within 30 days after surgery. A pathological complete response was achieved in 23 cases. Pathological staging (number of cases) was Stage 0 (23), Stage 1 (8), Stage 2 (28), Stage 3 (25), and Stage 4 (2). The 5-year overall survival rate (OS) was 51.0%, and was 83.2% in Stage 2 patients and 29.9% in Stage 3 patients. Preoperative NACR is safe and may improve OS and down-staging rates in patients with esophageal SCC. (author)

  2. Essential role of STX6 in esophageal squamous cell carcinoma growth and migration

    Energy Technology Data Exchange (ETDEWEB)

    Du, Jin [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028 (China); Liu, Xiang [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Wu, Yanhu, E-mail: wuyanhu@njmu.edu.cn [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Zhu, Jinfu; Tang, Yihu [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China)

    2016-03-25

    Abnormalities in endosomes, or dysregulation in their trafficking, play an important role directly in many diseases including oncogenesis. Syntaxin-6 (STX6) is involved in diverse cellular functions in a variety of cell types and has been shown to regulate many intracellular membrane trafficking events such as endocytosis, recycling and anterograde and retrograde trafficking. However, its expression pattern and biological functions in esophageal squamous cell carcinoma (ESCC) remained unknown. Here, we have found that the expression of STX6 was up-regulated in ESCC samples, its expression was significantly correlated with tumor size, histological differentiation, lymph node metastasis and depth. On one hand, STX6 silencing inhibited ESCC cells viability and proliferation in a p53-dependent manner. On the other hand, STX6 effect integrin trafficking and regulate ESCC cells migration. Taken together, our study revealed the oncogenic roles of STX6 in the progression of ESCC, and it might be a valuable target for ESCC therapy.

  3. Alteration in gene expression profile and oncogenicity of esophageal squamous cell carcinoma by RIZ1 upregulation.

    Science.gov (United States)

    Dong, Shang-Wen; Li, Dong; Xu, Cong; Sun, Pei; Wang, Yuan-Guo; Zhang, Peng

    2013-10-07

    To investigate the effect of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) upregulation in gene expression profile and oncogenicity of human esophageal squamous cell carcinoma (ESCC) cell line TE13. TE13 cells were transfected with pcDNA3.1(+)/RIZ1 and pcDNA3.1(+). Changes in gene expression profile were screened and the microarray results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Nude mice were inoculated with TE13 cells to establish ESCC xenografts. After two weeks, the inoculated mice were randomly divided into three groups. Tumors were injected with normal saline, transfection reagent pcDNA3.1(+) and transfection reagent pcDNA3.1(+)/RIZ1, respectively. Tumor development was quantified, and changes in gene expression of RIZ1 transfected tumors were detected by RT-PCR and Western blotting. DNA microarray data showed that RIZ1 transfection induced widespread changes in gene expression profile of cell line TE13, with 960 genes upregulated and 1163 downregulated. Treatment of tumor xenografts with RIZ1 recombinant plasmid significantly inhibited tumor growth, decreased tumor size, and increased expression of RIZ1 mRNA compared to control groups. The changes in gene expression profile were also observed in vivo after RIZ1 transfection. Most of the differentially expressed genes were associated with cell development, supervision of viral replication, lymphocyte costimulatory and immune system development in esophageal cells. RIZ1 gene may be involved in multiple cancer pathways, such as cytokine receptor interaction and transforming growth factor beta signaling. The development and progression of esophageal cancer are related to the inactivation of RIZ1. Virus infection may also be an important factor.

  4. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ 2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (POverexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients.

  5. Study on chemotherapeutic sensitizing effect of nimotuzumab on different human esophageal squamous carcinoma cells.

    Science.gov (United States)

    Yang, Xiaoyu; Ji, Yinghua; Kang, Xiaochun; Chen, Meiling; Kou, Weizheng; Jin, Cailing; Lu, Ping

    2016-02-01

    Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5-fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1 or EC9706 cells. The cell killing effect of the combined use of h-R3 with DDP and 5-FU showed no obvious

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

    Directory of Open Access Journals (Sweden)

    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

  7. Hot food and beverage consumption and the risk of esophageal squamous cell carcinoma: A case-control study in a northwest area in China.

    Science.gov (United States)

    Tai, Wei-Ping; Nie, Guo-Ji; Chen, Meng-Jie; Yaz, Tajigul Yiminni; Guli, Arzi; Wuxur, Arzigul; Huang, Qing-Qing; Lin, Zhi-Gang; Wu, Jing

    2017-12-01

    This study was trying to investigate the association of hot food and beverage consumption and the risk of esophageal squamous cell carcinoma in Hotan, a northwest area of China with high risk of esophageal squmous cell carcinoma. A population-based case-control study was designed. For the study, 167 patients diagnosed with esophageal squamous cell carcinoma were selected from Hotan during 2014 to 2015, and 167 community-based controls were selected from the same area, matched with age and sex. Information involved of temperature of food and beverage intake was obtained by face-to-face interview. Logistic regression analyses were performed to investigate the association between temperature of food and beverage intake and the risk of esophageal squamous cell carcinoma. The temperature of the food and beverage consumed by the esophageal squamous cell carcinoma patients was significantly higher than the controls. High temperature of tea, water, and food intake significantly increased the risk of esophageal squamous cell carcinoma by more than 2-fold, with adjusted odds ratio 2.23 (1.45-2.90), 2.13 (1.53-2.66), and 2.98 (1.89-4.12). Intake of food and beverage with high temperature was positively associated with the incidence of esophageal squamous cell carcinoma in Northwestern China. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  8. Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

    NARCIS (Netherlands)

    Wang, X.; Niu, H.; Fan, Q.; Lu, P.; Ma, C.; Liu, W.; Liu, Y.; Li, W.; Hu, S.; Ling, Y.; Guo, L.; Ying, J.; Huang, J.

    2016-01-01

    This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ

  9. Inflammation-based prognostic score and number of lymph node metastases are independent prognostic factors in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Kaneko, Susumu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

    2010-08-01

    Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, is useful for postoperative prognosis of esophageal squamous cell carcinoma. GPS was calculated on the basis of admission data as follows: patients with elevated C-reactive protein level (>10 mg/l) and hypoalbuminemia (l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0. A new scoring system was constructed using independent prognostic variables and was evaluated on whether it could be used to dictate the choice of clinical options. 65 patients with esophageal squamous cell carcinoma were enrolled. GPS and the number of lymph node metastases were found to be independent prognostic variables. The scoring system comprising GPS and the number of lymph node metastases was found to be effective in the prediction of a long-term outcome (p GPS may be useful for postoperative prognosis of patients with esophageal squamous cell carcinoma. GPS and the number of lymph node metastases could be used to identify a subgroup of patients with esophageal squamous cell carcinoma who are eligible for radical resection but show poor prognosis.

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

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    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

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

    International Nuclear Information System (INIS)

    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

  12. Secondary Prevention of Esophageal Squamous Cell Carcinoma in Areas Where Smoking, Alcohol, and Betel Quid Chewing are Prevalent

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    Chen-Shuan Chung

    2010-06-01

    Full Text Available Esophageal cancer is ranked as the sixth most common cause of cancer death worldwide and has a substantial effect on public health. In contrast to adenocarcinoma arising from Barrett's esophagus in Western countries, the major disease phenotype in the Asia-Pacific region is esophageal squamous cell carcinoma which is attributed to the prevalence of smoking, alcohol, and betel quid chewing. Despite a multidisciplinary approach to treating esophageal cancer, the outcome remains poor. Moreover, field cancerization reveals that esophageal squamous cell carcinoma is closely linked with the development of head and neck cancers that further sub-optimize the treatment of patients. Therefore, preventive strategies are of paramount importance to improve the prognosis of this dismal disease. Since obstacles exist for primary prevention via risk factor elimination, the current rationale for esophageal cancer prevention is to identify high-risk groups at earlier stages of the disease, and encourage them to get a confirmatory diagnosis, prompt treatment, and intensive surveillance for secondary prevention. Novel biomarkers for identifying specific at-risk populations are under extensive investigation. Advances in image-enhanced endoscopy do not just substantially improve our ability to identify small precancerous or cancerous foci, but can also accurately predict their invasiveness. Research input from the basic sciences should be translated into preventive measures in order to decrease the disease burden of esophageal cancer.

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

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    Zhang B

    2016-06-01

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

  14. Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients

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    Lin, De-Chen; Wang, Ming-Rong; Koeffler, H. Phillip

    2018-01-01

    Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. The exomes of more than 600 ESCCs have been sequenced in the past 4 years, and numerous key aberrations have been identified. Recently, researchers reported both inter- and intratumor heterogeneity. Although these are interesting observations, their clinical implications are unclear due to the limited number of samples profiled. Epigenomic alterations, such as changes in DNA methylation, histone acetylation, and RNA editing, also have been observed in ESCCs. However, it is not clear what proportion of ESCC cells carry these epigenomic aberrations or how they contribute to tumor development. We review the genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes. We discuss their clinical implications and future research directions. PMID:28757263

  15. KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression.

    Science.gov (United States)

    Fujita, Yuji; Masuda, Kiyoshi; Hamada, Junichi; Shoda, Katsutoshi; Naruto, Takuya; Hamada, Satoshi; Miyakami, Yuko; Kohmoto, Tomohiro; Watanabe, Miki; Takahashi, Rizu; Tange, Shoichiro; Saito, Masako; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Tangoku, Akira; Otsuji, Eigo; Imoto, Issei

    2017-11-24

    KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.

  16. Integrated Analysis of Long Noncoding RNA and Coding RNA Expression in Esophageal Squamous Cell Carcinoma

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    Wei Cao

    2013-01-01

    Full Text Available Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC. We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

  17. Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma.

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    Zhao-Ting Yang

    Full Text Available Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC.In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs were also determined.Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001. Tenascin-C expression in ESCC stromal fibroblasts was associated with patient's age, tumor (pT stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM population, cancer recurrence, and hypoxia inducible factor1α (HIF1α expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS and disease-free survival (DFS. In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα, PDGFR

  18. Population attributable fraction of Esophageal squamous cell carcinoma due to smoking and alcohol in Uganda

    International Nuclear Information System (INIS)

    Okello, Samson; Churchill, Cristina; Owori, Rogers; Nasasira, Benson; Tumuhimbise, Christine; Abonga, Charles Lagoro; Mutiibwa, David; Christiani, David C.; Corey, Kathleen E.

    2016-01-01

    Despite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown. We conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy. Our study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40–64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively. In this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown

  19. ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil

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    Francisco TUSTUMI

    Full Text Available ABSTRACT Background Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. Objective This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. Methods The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil quaternary oncology institute were retrospectively reviewed. Results Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. Conclusion Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure.

  20. ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil.

    Science.gov (United States)

    Tustumi, Francisco; Takeda, Flavio Roberto; Kimura, Cintia Mayumi Sakurai; Sallum, Rubens Antônio Aissar; Ribeiro, Ulysses; Cecconello, Ivan

    2016-01-01

    Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil) quaternary oncology institute were retrospectively reviewed. Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure.

  1. Genetic variations in MTHFR and esophageal squamous cell carcinoma susceptibility in Chinese Han population.

    Science.gov (United States)

    Tang, Weifeng; Zhang, Sheng; Qiu, Hao; Wang, Lixin; Sun, Bin; Yin, Jun; Gu, Haiyong

    2014-05-01

    Esophageal cancer is the sixth most common cancer worldwide. Esophageal squamous cell carcinoma (ESCC) is a fatal malignancy associated with low 5-year survival rate. The aim of this study was to assess the association between methylenetetrahydrofolate reductase (MTHFR) tagging single nucleotide polymorphisms (SNPs) rs1801133 C>T, rs3753584 A>G, rs4845882 G>A, rs4846048 A>G and rs9651118 T>C genotypes and ESCC susceptibility in a hospital-based case-control study. We conducted genotyping analyses for these five SNPs with 629 ESCC cases and 686 controls in a Chinese Han population. Ligation detection reaction method was used to identify genotypes of these MTHFR SNPs. Our results demonstrated that MTHFR rs1801133 C>T was associated with the risk of ESCC; however, MTHFR rs4845882 G>A and rs4846048 A>G SNPs were associated with the decreased risk of ESCC, and MTHFR rs3753584 A>G and rs9651118 T>C SNPs were not associated with ESCC risk. Our findings suggests that MTHFR rs1801133 C>T, rs4845882 G>A and rs4846048 A>G SNPs may be genetic modifiers for developing ESCC in Chinese Han population.

  2. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  3. Prognostic significance of Glasgow prognostic score in patients undergoing esophagectomy for esophageal squamous cell carcinoma.

    Science.gov (United States)

    Feng, Ji-Feng; Zhao, Qiang; Chen, Qi-Xun

    2014-01-01

    Recent studies have revealed that Glasgow prognostic score (GPS), an inflammation-based prognostic score, is inversely related to prognosis in a variety of cancers; high levels of GPS is associated with poor prognosis. However, few studies regarding GPS in esophageal cancer (EC) are available. The aim of this study was to determine whether the GPS is useful for predicting cancer-specific survival (CSS) of patients for esophageal squamous cell carcinoma (ESCC). The GPS was calculated on the basis of admission data as follows: Patients with elevated C-reactive protein (CRP) level (>10 mg/L) and hypoalbuminemia (L) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0, respectively. Our study showed that GPS was associated with tumor size, depth of invasion, and nodal metastasis (PGPS0, GPS1, and GPS2 were 60.8%, 34.7% and 10.7%, respectively (PGPS was a significant predictor of CSS. GPS1-2 had a hazard ratio (HR) of 2.399 [95% confidence interval (CI): 1.805-3.190] for 1-year CSS (PGPS is associated with tumor progression. GPS can be considered as an independent prognostic factor in patients who underwent esophagectomy for ESCC.

  4. Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas

    Science.gov (United States)

    Li, Yaqing; Li, Xiaoran; Kan, Quancheng; Zhang, Mingzhi; Li, Xiaoli; Xu, Ruiping; Wang, Junsheng; Yu, Dandan; Goscinski, Mariusz Adam; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

    2017-01-01

    Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas. PMID:27911865

  5. Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

    Science.gov (United States)

    Shin, Hae Jin; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Kim, Seok Hyun; Lee, Byung Seok; Kim, Ju Seok; Yun, Gee Young

    2017-12-01

    The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P squamous cell carcinoma treated with definitive CRT, the serum albumin level squamous cell carcinoma treated with definitive CRT is a significant prognostic factor. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Chen, Jenny Ling-Yu; Chen, Jo-Pai; Huang, Yu-Sen; Tsai, Yuan-Chun; Tsai, Ming-Hsien; Jaw, Fu-Shan; Cheng, Jason Chia-Hsien; Kuo, Sung-Hsin; Shieh, Ming-Jium

    2016-01-01

    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.) [de

  7. Azoxystrobin Induces Apoptosis of Human Esophageal Squamous Cell Carcinoma KYSE-150 Cells through Triggering of the Mitochondrial Pathway

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    Xiao-ke Shi

    2017-05-01

    Full Text Available Recent studies indicate that mitochondrial pathways of apoptosis are potential chemotherapeutic target for the treatment of esophageal cancer. Azoxystrobin (AZOX, a methoxyacrylate derived from the naturally occurring strobilurins, is a known fungicide acting as a ubiquinol oxidation (Qo inhibitor of mitochondrial respiratory complex III. In this study, the effects of AZOX on human esophageal squamous cell carcinoma KYSE-150 cells were examined and the underlying mechanisms were investigated. AZOX exhibited inhibitory effects on the proliferation of KYSE-150 cells with inhibitory concentration 50% (IC50 of 2.42 μg/ml by 48 h treatment. Flow cytometry assessment revealed that the inhibitory effect of AZOX on KYSE-150 cell proliferation occurred with cell cycle arrest at S phase and increased cell apoptosis in time-dependent and dose-dependent manners. Cleaved poly ADP ribose polymerase (PARP, caspase-3 and caspase-9 were increased significantly by AZOX. It is worth noted that the Bcl-2/Bax ratios were decreased because of the down-regulated Bcl-2 and up-regulated Bax expression level. Meanwhile, the cytochrome c release was increased by AZOX in KYSE-150 cells. AZOX-induced cytochrome c expression and caspase-3 activation was significantly blocked by Bax Channel Blocker. Intragastric administration of AZOX effectively decreased the tumor size generated by subcutaneous inoculation of KYSE-150 cells in nude mice. Consistently, decreased Bcl-2 expression, increased cytochrome c and PARP level, and activated caspase-3 and caspase-9 were observed in the tumor samples. These results indicate that AZOX can effectively induce esophageal cancer cell apoptosis through the mitochondrial pathways of apoptosis, suggesting AZOX or its derivatives may be developed as potential chemotherapeutic agents for the treatment of esophageal cancer.

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

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    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.

  9. Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Liu, Wan-li; Li, Man-zhi; Song, Li-bing; Zeng, Mu-sheng; Guo, Xian-zhi; Zhang, Lan-jun; Wang, Jun-ye; Zhang, Ge; Guan, Su; Chen, Yu-min; Kong, Qing-li; Xu, Li-hua

    2010-01-01

    Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. The objective of this study was to determine the level of Bmi-1 expression or its autoantibodies in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic data. We first examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and Western blot analysis. We then analyzed Bmi-1 protein expression in 171 clinicopathologically characterized ESCC cases by immunohistochemistry. In addition, we detected its autoantibodies in sera of patients with ESCC by ELISA. We found that Bmi-1 expression was higher in the immortalized cells, cancer cell lines and most cancer tissue than in non-tumorous control tissue at both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3% (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells. There was a significant difference of Bmi-1 expression in patients categorized according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate analysis suggested that Bmi-1 expression was an independent prognostic marker for ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1 antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were significant. Our results suggest that Bmi-1 protein is a valuable marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from patients with ESCC may have clinical utility in esophageal cancer diagnosis

  10. Synchronous Supraglottic and Esophageal Squamous Cell Carcinomas Treated with a Monoisocentric Hybrid Intensity-Modulated Radiation Technique

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    Christian L. Barney

    2018-01-01

    Full Text Available Risk factors for squamous cell carcinomas (SCCs of the head and neck (HN and esophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT is standard care for locally advanced HNSCC and is a preferred option for inoperable esophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous supraglottic and esophageal SCC primary tumors, highlighting treatment with a monoisocentric hybrid radiation technique and normal tissue toxicity considerations.

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

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

    2012-08-24

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

  12. Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells.

    Science.gov (United States)

    Chen, Chuangui; Ma, Zhao; Zhang, Hongdian; Liu, Xiaoqiong; Yu, Zhentao

    2017-07-11

    BACKGROUND The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively. RESULTS The sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase. CONCLUSIONS KLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC.

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

    Directory of Open Access Journals (Sweden)

    Myoung Sook Kim

    2010-02-01

    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.

  14. Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

    2018-02-14

    Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (levels has potential diagnostic and prognostic value for ESCC patients.

  15. Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Qing; Ma, Chenming; Kemmner, Wolfgang

    2013-01-01

    We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n = 10) and normal esophageal squamous tissue (n = 18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n = 71) consisting of esophageal squamous cell carcinoma (n = 25), normal esophagus (n = 11), esophageal adenocarcinoma (n = 13), gastric adenocarcinoma (n = 15) and colorectal cancers (n = 7). In order to understand WDR66’s functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. High WDR66 expression was significantly associated with poor overall survival (P = 0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P = 0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. WDR66 might be a useful biomarker for risk

  16. Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Sugawara, Kotaro; Yamashita, Hiroharu; Uemura, Yukari; Mitsui, Takashi; Yagi, Koichi; Nishida, Masato; Aikou, Susumu; Mori, Kazuhiko; Nomura, Sachiyo; Seto, Yasuyuki

    2017-10-01

    The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate

  17. CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells.

    Science.gov (United States)

    Xia, Lijie; Wu, Yanling; Kang, Su; Ma, Ji; Yang, Jianhua; Zhang, Fuchun

    2014-10-01

    Antimicrobial peptides exist in the non-specific immune system of organism and participate in the innate host defense of each species. CecropinXJ, a cationic antimicrobial peptide, possesses potent anticancer activity and acts preferentially on cancer cells instead of normal cells, but the mechanism of cancer cell death induced by cecropinXJ remains largely unknown. This study was performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on human esophageal carcinoma cell line Eca109 using scanning electron microscopy observation, fluorescence imaging, cell migration and invasion assays, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The electronic microscope and fluorescence imaging observation suggested that cecropinXJ could result in morphological changes and induce damage to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell migration and invasion assays demonstrated that cecropinXJ could inhibit migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed that there was obvious correlation between microtubule depolymerization and actin polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause decreased expression of α-actin, β-actin, γ-actin, α-tubulin, and β-tubulin genes in concentration- and time-dependent manners. In summary, this study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through inducing the cytoskeleton destruction and regulating the expression of cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect is instrumental in our understanding of the detailed action of antimicrobial peptides in human cancer cells and cecropinXJ might be a potential therapeutic agent for the treatment of cancer in the future. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology

  18. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China

    OpenAIRE

    Chen, Xingdong; Winckler, Bj?rn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of eac...

  19. [Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

    Science.gov (United States)

    Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

    2018-01-23

    Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

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

    International Nuclear Information System (INIS)

    Islamian, Jalil Pirayesh; Mohammadi, Mohsen; Baradaran, Behzad

    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 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

  1. MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma

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    Meng, Xiangrui, E-mail: xiangruimengzz@163.com [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China); Chen, Xiaoqi [Department of Digestion and Oncology, The First Affiliated Hospital of Henan Uninversity of TCM, 19 Renmin Road, Zhengzhou 450000, Henan Province (China); Lu, Peng [Department of Gastrointestinal Surgery, The People' s Hospital of Zhengzhou, 33 Huanghe Road, Zhengzhou 450000, Henan Province (China); Ma, Wang; Yue, Dongli; Song, Lijie; Fan, Qingxia [Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450000, Henan Province (China)

    2016-05-13

    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in the gastrointestinal tract. Emerging studies have indicated that microRNAs (miRNAs) are strongly implicated in the development and progression of ESCC. Here, we focused on the function and the underlying molecular mechanism of miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510 cells markedly suppressed cell proliferation and cell migration, and induced cell apoptosis. Furthermore, laminin α1 (LAMA1) expression was frequently positive in ESCC tissues and inversely correlated with miR-202 expression. Then we demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and inhibited its protein expression. Additionally, LAMA1 overexpression rescued the proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202 also inhibited the protein expression of p-FAK and p-Akt, which were all reversed by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may function as a novel tumor suppressor in ESCC by repressing cell proliferation and migration, and its biological effects may attribute the inhibition of LAMA1-mediated FAK-PI3K-Akt signaling. - Highlights: • Expression of miR-202 was decreased in ESCC tissues and cell lines. • MiR-202 overexpression inhibited ESCC cell growth and induced apoptosis. • MiR-202 directly targeted LAMA1 in ESCC. • The LAMA1-FAK-PI3K signaling mediated the suppressive role of miR-202.

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

    Directory of Open Access Journals (Sweden)

    Cong Wang

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

  3. A Rare Case of Metastasis to the Thyroid Gland from Renal Clear Cell Carcinoma 11 Years after Nephrectomy and Concurrent Primary Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mohammad Saud Khan

    2018-01-01

    Full Text Available Renal cell carcinoma is known to cause metastasis to unusual sites, which can be both synchronous or metachronous. Thyroid gland is a rare site for metastasis, but when it occurs, renal cell carcinoma is the most common primary neoplasm. We report the case of a 81-year-old female patient who had a significant medical history of right clear cell renal carcinoma with adrenal metastasis. She underwent right radical nephrectomy and adrenalectomy followed by radiofrequency ablation of left adrenal metastasis and systemic chemotherapy with sunitinib. Eleven years later, she presented with dysphagia and was found to have distal esophageal adenocarcinoma. On imaging, there was incidental detection of a left renal mass lesion and a right thyroid nodule, which on histopathology and immunohistochemistry were confirmed to be clear cell carcinoma of renal origin.

  4. Treatment Outcomes and Prognostic Factors After Recurrence of Esophageal Squamous Cell carcinoma.

    Science.gov (United States)

    Hamai, Yoichi; Hihara, Jun; Emi, Manabu; Furukawa, Takaoki; Ibuki, Yuta; Yamakita, Ichiko; Kurokawa, Tomoaki; Okada, Morihito

    2017-12-29

    The evaluation of treatment outcomes and detection of prognostic factors after recurrence are very important for tailoring optimal therapies for individual patients with recurrent esophageal cancer. We reviewed 133 patients in whom esophageal squamous cell carcinoma (ESCC) recurred after curative surgery, and assessed recurrence patterns, treatment outcomes and prognostic factors. Recurrence in 57 (42.9%), 54 (40.6%) and 22 (16.5%) patients was locoregional, distant and combined, respectively. The median amounts of elapsed time until recurrence and median survival after recurrence for all patients were 9.1 and 8.3 months, respectively. Univariate and multivariate analyses selected time to recurrence (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.999; p = 0.04), recurrence location (locoregional vs. distant: HR, 1.63; 95% CI, 1.03-2.61; p = 0.04), number of organs with recurrence (1 vs. 3: HR, 3.49; 95% CI, 1.23-9.87; p = 0.02) and treatment after recurrence (best supportive care, [BSC] vs. chemotherapy [CT] or radiation therapy [RT]: HR, 0.37; 95% CI, 0.15-0.94; p = 0.04; BSC vs. CT and RT: HR, 0.50; 95% CI, 0.26-0.94; p = 0.03; BSC vs. HR, 0.47; 95% CI, 0.25-0.88; p = 0.02) as independent factors for survival after recurrence. Seventeen (12.8%) patients who had localized lymph node recurrence and lung oligometastasis and received multidisciplinary therapy after recurrence survived for >3 years thereafter. Despite the poor survival of patients with ESCC and early or distant recurrence or recurrence in ≥3 recurrent organs, appropriate multimodal therapies should be tailored for individual patients with recurrent ESCC.

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

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

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

  6. 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.

  7. Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma

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    Yang WJ

    2018-03-01

    Full Text Available Wenjing Yang, Yan Qu, Bingxu Tan, Yibin Jia, Nana Wang, Peng Hu*, Jianbo Wang* Department of Radiation, Qilu Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: IκB kinase epsilon (IKBKE; IKKε, a member of the nuclear factor-κB kinase inhibitor family, is upregulated in several human cancers, including breast cancer, prostate cancer, and ovarian cancer. Esophageal squamous cell carcinoma (ESCC is one of the most common and most aggressively malignant cancers with dismal prognosis. However, the state of IKBKE expression in ESCC is still unknown and its potential value remains unexplored.Patients and methods: IKBKE protein expression was evaluated by immunohistochemistry in 118 paraffin specimens of ESCC treated by curative surgery. All patients were regularly followed up by telephone over 3 years after surgery. The chi-square test, Kaplan–Meier method, and Cox proportional hazard regression model were used to analyze the relationship of IKBKE expression, clinicopathological characteristics, and prognostic value for ESCC.Results: IKBKE expression was 61.9% (73/118 in paraffin-embedded archived ESCC. Its expression was significantly associated with tumor differentiation grade (p=0.045 and advanced TNM (pathologic tumor node metastasis stages (p=0.023. In univariate analysis, IKBKE expression was closely associated with decreased 3-year disease-free survival (HR 1.804, 95% CI 1.076–3.027; p=0.023 and overall survival (HR 2.118, 95% CI 1.189–3.773; p=0.009. Meanwhile, in multivariate analysis it was identified as an independent prognostic factor for 3-year disease-free survival (HR 1.777, 95% CI 1.034–3.054; p=0.037 and overall survival (HR 2.078, 95% CI 1.138–3.796; p=0.017.Conclusion: Our data indicated for the first time that IKKε expression is a highly recurrent event in ESCC and could play a pivotal role in the evaluation of prognosis. IKBKE upregulation is

  8. Effect of suicidal gene combined with irradiation on esophageal carcinoma cell line

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    Pan Jianji; Wang Jiezhong; Zheng Tianrong; Zheng Qiuhong

    2005-01-01

    Objective: As generally known that non-cytotoxic pro-drag can be transformed into cytotoxic drug by suicide gene, this work is to investigate the effect of Coli cytosine deaminase/5-fluorocytosine suicide gene (CD/5-FC) used alone or combined with irradiation in esophageal carcinoma cell line(EC). Methods: CD gene was amplified from Coli DNA genome library with PCR technique, with the eukaryotic vector pcDNA3.1-CD then constructed. ECl09 cells were transfected with pcDNA3.1-CD by liposome method. The cytotoxic effect, bystander effect and radiosensitization effect of CD/5-FC in ECl09 was analyzed. Results: The transfection of CD gene into ECl09 and its transcription was confirmed by RT-PCR method. In vitro, 5-FC showed significantly cytotoxic effect on the EPC cell transfected with CD gene. After adding 5-FC , the survival rate of cultured cell containing 5 % transfect CD gene cell was 41.8 % ± 14.2% while that in the control group was 94.6 ± 4.3 %, (t=3.14, P < 0.05). The survival rate of cultured cell containing 10% transfected CD gene cell was 37.8 ± 4.4% compared to 95.6% ± 5.4% in the control group, (t=9.75, P<0.01). CD/5-FC showed significant radiosen-sitization effect, the survival fraction of CD transfected cell was much lower in 5-FC combined with irradiation, when compared with 5-FC alone and radiotherapy alone group together, (F=11.50, P < 0.01 ). When it was compared with 5-FC alone group and irradiation alone group separately, the difference was also significant( F=4.11, P < 0.05 and F10.53, P < 0.01, respectively). Conclusions: Suicide gene CD/5-FC shows conspicuous by-stander effect and radiosensitization effect. (authors)

  9. Significance of lymph node capsular invasion in esophageal squamous cell carcinoma.

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    Sakai, Makoto; Suzuki, Shigemasa; Sano, Akihiko; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kuwano, Hiroyuki

    2012-06-01

    Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

  10. MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

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    Sun, Jiangtao; Song, Kaifang; Feng, Xiaoshan, E-mail: xiaoshan.feng@aol.com; Gao, Shegan

    2016-04-29

    Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independent prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated

  11. Pattern of relapse in surgical treated patients with thoracic esophageal squamous cell carcinoma and its possible impact on target delineation for postoperative radiotherapy

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    Cai Wenjie; Xin Peiling

    2010-01-01

    Objective: To provide a reference for determination of the postoperative radiotherapy target volume for thoracic esophageal squamous cell carcinoma. Background data: The irradiation target volume is important for effective postoperative treatment of thoracic esophageal squamous cell carcinoma. Methods: One hundred forty patients with recurrent or metastatic thoracic esophageal squamous cell carcinoma who had been treated with radical surgery but not with postoperative radiotherapy were enrolled in this study. The information of locoregional recurrence and distant metastasis for these patients was analyzed. Results: The median time to progression in the 140 patients with recurrence or metastasis was 18.3 months (range 15.4-21.1 months). Anastomotic recurrence accounted for 13.6% of treatment failures. The supraclavicular and station 1-5 and 7 lymph nodes had high metastasis rates for esophageal squamous cell carcinomas in all locations. The order from highest to lowest metastasis rate for the station 3 and 4 lymph nodes was middle, upper and lower thoracic esophageal regions and the order for upper abdominal lymph nodes was lower, middle, and upper thoracic esophageal regions. Locoregional recurrence was the most common type of recurrence. Conclusions: For upper and middle thoracic esophageal squamous cell carcinomas, the anastomosis, supraclavicular, and station 1-5 and 7 lymph nodes should be delineated as the postoperative prophylactic irradiation target volume with upper abdominal lymph nodes excluded; for lower thoracic esophageal squamous cell carcinomas, anastomosis, supraclavicular, station 1-5 and 7 lymph nodes and upper abdominal lymph nodes should be delineated as the postoperative prophylactic irradiation target volume.

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

    Science.gov (United States)

    2012-01-01

    Background Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. Methods We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. Results The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0

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

    International Nuclear Information System (INIS)

    Li, Shau-Hsuan; Huang, Yung-Cheng; Huang, Wan-Ting; Lin, Wei-Che; Liu, Chien-Ting; Tien, Wan-Yu; Lu, Hung-I

    2012-01-01

    Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.003, univariately) and overall survival (P = 0

  14. Carcinostatic effects of platinum nanocolloid combined with gamma irradiation on human esophageal squamous cell carcinoma.

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    Li, Qiang; Tanaka, Yoshiharu; Saitoh, Yasukazu; Tanaka, Hiroshi; Miwa, Nobuhiko

    2015-04-15

    To explore the carcinostatic effects of platinum nanocolloid (Pt-nc) combined with gamma rays on human esophageal squamous cell carcinoma (ESCC). ESCC-derived KYSE-70 cells were treated with various concentrations of Pt-nc and/or gamma irradiation, and subsequently cultured in phenol red free DMEM with 10% FBS for 48 h. The proliferative status of the KYSE-70 cells was evaluated using trypan blue dye exclusion and WST-8 assays. Cellular and nucleic morphological aspects were evaluated using crystal violet and Hoechst 33342 stainings, respectively. Radiosensitivity was quantified by a cell viability assay, and the activated form of caspase-3, a characteristic apoptosis-related protein, was detected by Western blotting. Although single treatment with either Pt-nc or gamma irradiation could slightly inhibit the growth of the KYSE-70 cells, their combination exerted remarkable carcinostatic effects in a manner dependent on either Pt-nc concentrations or gamma ray doses, compared with the effect of each treatment alone (pirradiated with gamma rays, were shown to undergo distinct apoptotic morphological changes. The carcinostatic effect of gamma rays at 7 Gy without Pt-nc was approximately equal to that when 3-Gy irradiation was combined with 100 ppm Pt-nc or that 5-Gy irradiation was combined with 50 ppm Pt-nc. Pt-nc in combination with gamma rays may exert a cooperative effect through platinum- or gamma ray-induced apoptosis resulting in the inhibition of growth of cancer cells, while concurrently enabling the lowering of the radiative dose. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

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    Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

    2017-06-19

    Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

  16. [Inhibitory effect of 17-AAG combined with paclitaxel on proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro].

    Science.gov (United States)

    Chen, Size; Chen, Xuemei; Li, Yuqi; Yang, Shu; Mo, Xianyi; Zhang, Fan; Mo, Kailan; Ding, Ying

    2015-06-01

    To investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro. Eca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry. Compared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5 µmol/L PTX and 0.625 µmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (PAAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone. 17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.

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

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    Luo J

    2014-09-01

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

  18. SIRT1 overexpression is an independent prognosticator for patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ma, Ming-Chun; Chiu, Tai-Jan; Lu, Hung-I; Huang, Wan-Ting; Lo, Chien-Ming; Tien, Wan-Yu; Lan, Ya-Chun; Chen, Yen-Yang; Chen, Chang-Han; Li, Shau-Hsuan

    2018-04-10

    Sirtuin 1 (SIRT1) regulates DNA repair and metabolism by deacetylating target proteins. SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the prognostic role of SIRT1 in patients with esophageal squamous cell carcinoma (ESCC) and evaluate the effect of SIRT1 inhibitor in vitro. The expression of SIRT1 was evaluated immunohistochemically in 155 surgically resected ESCC and the staining results were evaluated semiquantitatively by the Immunoreactive Scoring System. The clinical features and treatment outcome were analyzed. The effect of SIRT1 inhibitor, SIRT 1 inhibitor IV, (S)-35, was investigated in vitro on ESCC cell lines. The expression of SIRT1 on ESCC did not correlate with age, gender, tumor location, stage, T classification, N classification, surgical margin or histology. Univariate analysis showed that SIRT1 overexpression was associated with inferior overall survival (P = 0.004) and disease-free survival (P = 0.004). In multivariate comparison, SIRT1 overexpression remained independently associated with worse overall survival (P = 0.009, hazard ratio = 1.776) and disease-free survival (P = 0.017, hazard ratio = 1.642). In cell lines, SIRT1 inhibitor inhibited ESCC growth. Our study suggests that SIRT1 overexpression is an independent prognosticator for patients with ESCC and the SIRT1 inhibitor suppressed cell proliferation of ESCC cell lines. Our findings suggest that inhibition of SIRT1 signaling may be a promising novel target for ESCC.

  19. PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shi, Guo-Zhen; Yuan, Yang; Jiang, Guo-Jun; Ge, Zhi-Jun; Zhou, Jian; Gong, De-Jun; Tao, Jing; Tan, Yong-Fei; Huang, Sheng-Dong

    2012-01-01

    Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). The expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay. We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines. Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC

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

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    Peng-Cheng Chen

    2016-01-01

    Full Text Available 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 ratio (PLR (>150 were defined as I3. Patients with two, one, or no abnormal value were defined as I2, I1, or I0, respectively. The prognostic factors were evaluated by univariate and multivariate analyses. Results. There were 112 patients for I0, 97 patients for I1, 66 patients for I2, and 48 patients for I3, respectively. The 5-year cancer-specific survival (CSS in patients with I0, I1, I2, and I3 was 50.0%, 30.9%, 18.2%, and 8.3%, respectively (I0 versus I1, P=0.002; I1 versus I2, P=0.012; I2 versus I3, P=0.020. Multivariate analyses revealed that I stage was an independent prognostic factor in patients with resectable ESCC (P<0.001. Conclusion. The inflammation-based stage (I stage is a novel and useful predictive factor for CSS in patients with resectable ESCC.

  1. Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

    Science.gov (United States)

    Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

    2016-10-01

    We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

  2. Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

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    Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

    2017-04-01

    The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

  3. 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. © 2016 WILEY PERIODICALS, INC.

  4. 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. © 2013 Japanese Cancer Association.

  5. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Fujiwara, Daisuke; Kato, Kazunori; Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki

    2013-01-01

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  6. 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 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.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%.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.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.

  7. Evaluation on prognosis of esophageal squamous cell carcinoma patients after three-dimensional conformal radiotherapy with different clinical stage system

    International Nuclear Information System (INIS)

    Wang Yuxiang; Zhu Shuchai; Qiu Rong; Liu Zhikun; Shen Wenbin

    2011-01-01

    Objective: To evaluate the prognostic significance of 3 clinical stage system in 3-dimensional conformal radiotherapy (3DCRT) for esophageal squamous cell carcinoma. Methods: From January 2004 to August 2007, 179 cases of esophageal squamous cell carcinoma were treated with 3DCRT. Before radiation, each patient was staged with UICC 2003 TNM stage, stage of Chinese esophageal cancer cooperation group (cooperation group' stage), and Zhu's clinical stage respectively. Concordance of each clinical stage and prognosis was analyzed with SPSS 11.5. Results In 179 cases of esophageal cancer, Concordance was better in T stage (Kappa = 0.271) than in TNM stage (Kappa = 0.167) between cooperation group' stage and Zhu's stage. Among them, 98 cases was staged with UICC stage, concordance of T stage was better between UICC-T and cooperation group' T stage (Kappa =0.261) than between UICCT and Zhu's T stage (Kappa = 0.045) ;concordance of TNM stage was better between UICC-TNM and Zhu's TNM stage (Kappa = 0.597) than between UICC-TNM and cooperation group' TNM stage (Kappa =0.299). With multivariate analysis, T (χ 2 value is 11.58, 26.00 and 51.05, all P 2 value is 15.28, 16.10 and 16.10, all P 2 value is 5.59, 27.78 and 27.78, all P 2 value is 15.77, 34, 35 and 51.10, all P 1 - T 3 was difficult to definite and the prognosis was not significantly different in T 1 - T 3 stage. Conclusions: In this study, 3 kinds of clinical stage could evaluate prognosis of esophageal cancer after radiotherapy; cooperation group' stage and Zhu's stage need further application, with further accuracy needed. (authors)

  8. Esophageal Large-Cell Neuroendocrine Carcinoma with Inconsistent Response to Treatment in the Primary and Metastatic Lesions

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    Takashi Tomiyama

    2018-05-01

    Full Text Available Esophageal large-cell neuroendocrine carcinoma (NEC is a rare malignant tumor that is characterized by high-grade malignancy and a poor prognosis. However, the rarity of esophageal NEC has prevented the development of an established treatment, and no reports have described a discrepancy in the effectiveness of cisplatin plus irinotecan between primary and metastatic lesions. A 43-year-old Japanese man was referred to our hospital with refractory epigastralgia. A previous gastrointestinal endoscopy had revealed a 50-mm type 2 tumor in the abdominal esophagus. The pathological findings indicated poorly differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a metastatic liver tumor. One cycle of fluorouracil and cisplatin was not effective, and endoscopy was repeatedly performed. The pathological findings indicated a large-cell malignant tumor with tumor cells that were positive for CD56, synaptophysin, and Ki-67 (> 80%. Based on a diagnosis of esophageal large-cell NEC with a metastatic liver tumor, the patient received cisplatin plus irinotecan biweekly. After 4 months, computed tomography revealed marked shrinkage of the metastatic tumor, but the patient complained of dysphagia. Endoscopy revealed enlargement of the primary tumor, which was then treated using radiotherapy plus fluorouracil and cisplatin. The primary tumor subsequently shrank, and the patient’s symptoms were relieved, but the metastatic tumor grew. Thus, chemoradiotherapy could be an option for managing a primary esophageal large-cell NEC that does not respond to chemotherapy alone. However, the possibility of an inconsistent response to therapy in primary and metastatic lesions should be considered.

  9. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

    Science.gov (United States)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  10. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

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

    Science.gov (United States)

    Dąbrowski, Andrzej; Kwaśniewski, Wojciech; Skoczylas, Tomasz; Bednarek, Wiesława; Kuźma, Dorota; Goździcka-Józefiak, Anna

    2012-10-28

    To assess the prevalence of human papilloma virus (HPV) in esophageal squamous cell carcinoma (ESCC) in the south-eastern region of Poland. The study population consisted of 56 ESCC patients and 35 controls. The controls were patients referred to our department due to other non-esophageal 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. 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 prevalence of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7 (42

  12. An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma.

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    Genta Sawada

    Full Text Available Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC. Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes.We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.

  13. Human papillomavirus 16 infection predicts poor outcome in patients with esophageal squamous cell carcinoma

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    Xi R

    2015-03-01

    Full Text Available Ruxing Xi,1 Xiaozhi Zhang,1 Xin Chen,1 Shupei Pan,1 Beina Hui,1 Li Zhang,1 Shenbo Fu,1 Xiaolong Li,2 Xuanwei Zhang,1 Tuotuo Gong,1 Jia Guo,1 Shaomin Che1 1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiao Tong University, 2Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, People’s Republic of China Background: Previous studies indicate that human papillomavirus 16 (HPV16 infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC. We aim to detect the influence of HPV16 infection on ESCC patient prognosis. Patients and methods: Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR, and phosphatidylinositol 3-kinase (PI3K was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People’s Republic of China. Results: HPV16 E6 expression was significantly higher in the ESCC group (P<0.05. HPV16 E6 expression was significantly higher in men than in women (P<0.05. p75NTR expression was higher in those aged >56 years (P<0.05. PI3K expression was higher in those with a more advanced histopathological grade (P<0.05. There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001 and between p75NTR and PI3K expression (r=0.364, P<0.001. In 100 evaluable patients, the 5-year overall survival (OS rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05, 5-year OS (P<0.05, and progression-free survival (P<0.05. Conclusion: HPV16 infection likely contributes to the etiology of ESCC patients in Shaan Xi, People’s Republic of China. HPV16 infection status and PI3K expression levels could be useful for predicting prognosis in patients with ESCC. Keywords: low-affinity p75

  14. 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

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

    KAUST Repository

    Essack, Magbubah; MacPherson, Cameron Ross; Schmeier, Sebastian; Bajic, Vladimir B.

    2012-01-01

    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

  16. Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Huang, Sheng-Dong; Yuan, Yang; Liu, Xiao-Hong; Gong, De-Jun; Bai, Chen-Guang; Wang, Feng; Luo, Jun-Hui; Xu, Zhi-Yun

    2009-01-01

    p75 NTR has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75 NTR in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75 NTR+ cells. p75 NTR expression in ESCC was assessed by immunohistochemistry. p75 NTR+ and p75 NTR- cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75 NTR+ and p75 NTR- cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, 64 copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75 NTR+ cells. In ESCC specimens, p75 NTR was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75 NTR+ cells was 1.6%–3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75 NTR+ cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75 NTR+ cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75 NTR+ cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, β1-integrin and β4-integrin, were lower in p75 NTR+ cells. In addition, p75 NTR+ cells generated both p75 NTR+ and p75 NTR- cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75 NTR+ cells were found to be more resistant to DDP and exhibited lower 64 copper accumulation than p75 NTR- cells. Our results demonstrated that p75 NTR+ cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75 NTR+ cells may probably be attributable to

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

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    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

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

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    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.

  19. Unilateral cervical nodal metastasis is an independent prognostic factor for esophageal squamous cell carcinoma patients undergoing chemoradiotherapy: a retrospective study.

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    Peng Zhang

    Full Text Available To determine the prognostic significance of unilateral cervical lymph nodal metastasis (CLNM in patients with inoperable thoracic esophageal squamous cell carcinoma (SCC and to identify significant prognostic factors in these patients.This retrospective study involved 395 patients with inoperable esophageal SCC treated with concurrent chemoradiotherapy. The patients were classified into three groups according to their cervical lymph node status: group A, no evidence of CLNM; group B, unilateral CLNM; group C, other distant metastases. Overall survival (OS and progression-free survival (PFS were calculated. Significant prognostic factors were identified using univariate and multivariate analyses.The 3-year OS rates in groups A, B and C were 46.7%, 33.5% and 8.3%, respectively (p<0.001, log-rank test. The corresponding PFS rates were 40.7%, 26.4% and 4.7% (p<0.001, log-rank test. Group B had a similar prognosis to that of group A and better 3-year OS (p = 0.009 and PFS (p = 0.006 rates than those of group C. Multivariate analysis demonstrated that T stage, chemotherapy regimen and cervical lymph node involvement were independent prognostic factors affecting OS and PFS.Compared to other distant metastases, unilateral CLNM is associated with longer OS in esophageal SCC and should be regarded as a regional disease. Sex, T stage, concurrent chemotherapy modality and cervical lymph node involvement are independent predictors of survival in esophageal SCC.

  20. Effect of VEGF-C siRNA and endostatin on ring formation and proliferation of esophageal squamous cell carcinoma lymphatic endothelial cells

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    Zheng YP

    2016-10-01

    Full Text Available Yuping Zheng,1–3,* Miaomiao Sun,4,* Jinyan Chen,1,2 Lulu He,1,2 Na Zhao,1,2 Kuisheng Chen1,2 1Pathology Department, The First Affiliated Hospital of Zhengzhou University, 2Henan Key Laboratory of Tumor Pathology, 3Pathology Department, The Second Hospital of Shandong University, Jinan, 4Pathology Department, Henan Tumor Hospital, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells.Materials and methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8 assay was employed to detect cell proliferation.Results: The negative group’s three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups. Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells. Keywords: esophageal squamous carcinoma cells, esophageal cancer-associated lymphatic endothelial cells, VEGF-C, ring formation, proliferation

  1. The expression of podoplanin protein is a diagnostic marker to distinguish the early infiltration of esophageal squamous cell carcinoma.

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    Chen, Guangyong; Xu, Rui; Yue, Bing; Mei, Xue; Li, Peng; Zhou, Xiaoge; Huang, Shoufang; Gong, Liping; Zhang, Shutian

    2017-03-21

    The esophageal squamous cell carcinoma (ESCC) is usually develped from low-grade intraepithelial neoplasia (LGIEN) and high-grade intraepithelial neoplasia (HGIEN) to infiltrative squamous cell carcinoma. Till now, it remains hard to screen for infiltration at earlier stages, especially the differentiation between HGEIN and early infiltrative carcinoma. The purpose of this study is to determine a role of podoplanin in differentiating between HGEIN and early infiltrative squamous cell carcinoma. Totally 133 patients pathologically diagnosed with early ESCC and/or precancerous lesions were enrolled.The EnVision two-step IHC staining technique was applied using the monoclonal mouse anti-human Podoplanin antibody (clone number: D2-40). The expressions of PDPN protein on the basal layer of squamous epithelium lesions could be divided into three different patterns: complete type, incomplete (non-continuous) type, or missing type. A diagnosis of HGEIN can be made if the basal layer showed non-continuous or complete expression of PDPN and a diagnosis of early infiltration can be made if the expression of PDPN is completely missing. Our study confirmed that PDPN was a potential biomarker to identify the presence of early infiltrative squamous cell carcinoma.

  2. Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab

    International Nuclear Information System (INIS)

    Jing Zhao; Gong Ling; Xie Congying; Zhang Li; Su Huafang; Deng Xia; Wu Shixiu

    2009-01-01

    Background and purpose: The purpose of our study is to examine the capacity of cetuximab to reverse radiation resistance and investigate molecular mechanisms in human radiation-resistant esophageal carcinoma cell line KYSE-150R. Materials and methods: The radioresistant cell line KYSE-150R was established by using fractionated irradiation (FIR). The KYSE-150R cell line was exposed to radiation, treatment with cetuximab, and combined treatment. Cell cycle distribution and apoptosis were analyzed using flow cytometry. Radiation survival was analyzed using clonogenic assays. RT 2 profiler TM PCR array was performed to analyze EGF/PDGF signaling pathway genes. Results: The established esophageal carcinoma cell line KYSE-150R showed higher radioresistance than parental cell line. Cetuximab could reverse the radiation resistance of KYSE-150R cells. Cell cycle analysis showed that combination with radiation and cetuximab resulted in the accumulation of cells in G1 and G2/M phases, with the reduction of cells within the S phase. Cetuximab enhanced the apoptosis induced by radiation. RT 2 profiler TM array showed that some intracellular signaling genes deriving from EGF/PDGF signaling pathway regulated by cetuximab. Conclusions: Irradiation combined with EGFR blocked by cetuximab may reverse the resistance to radiation in radioresistant esophageal carcinoma cell. The mechanisms may include cell cycle perturbation and enhancement of radiation-induced apoptosis. Further studies are needed to evaluate the role of cetuximab in combination with radiotherapy in the management of esophageal carcinoma.

  3. The prognostic effect of perineural invasion in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Chen, Jie-Wei; Cai, Mu-Yan; Xie, Jing-Dun; Ling, Yi-Hong; Li, Peng; Yan, Shu-Mei; Xi, Shao-Yan; Luo, Rong-Zhen; Yun, Jing-Ping; Xie, Dan

    2014-01-01

    Perineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance in esophageal squamous cell carcinoma (ESCC) remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes. We retrospectively evaluated the PNI of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. The resulting data were analyzed using Spearman’s rank correlation, the Kaplan-Meier method, Cox proportional hazards regression modeling and Harrell’s concordance index (C-index). PNI was identified in 209 of the 433 (47.7%) cases of ESCC. The correlation analysis demonstrated that PNI in ESCC was significantly correlated with tumor differentiation, infiltration depth, pN classification and stage (P < 0.05). The five-year overall survival rate was 0.570 for PNI-negative tumors versus 0.326 for PNI-positive tumors. Patients with PNI-negative tumors exhibited a 1.7-fold increase in five-year recurrence-free survival compared with patients with PNI-positive tumors (0.531 v 0.305, respectively; P < 0.0001). In the subset of patients with node-negative disease, PNI was evaluated as a prognostic predictor as well (P < 0.05). In the multivariate analysis, PNI was an independent prognostic factor for overall survival (P = 0.027). The C-index estimate for the combined model (PNI, gender and pN status) was a significant improvement on the C-index estimate of the clinicopathologic model alone (0.739 v 0.706, respectively). PNI can function as an independent prognostic factor of outcomes in ESCC patients, and the PNI status in primary ESCC specimens should be considered for therapy stratification

  4. Smoking affects treatment outcome in patients with resected esophageal squamous cell carcinoma who received chemotherapy.

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    Yuzhen Zheng

    Full Text Available Cigarette smoking is reported to decrease survival and induce chemotherapy resistance in patients with various cancers. However, the impact of cigarette smoking on patients with esophageal squamous cell carcinoma (ESCC remains unknown.A total of 1,084 ESCC patients were retrospectively enrolled from a southern Chinese institution. Patients were divided into two groups according to their treatment modalities: the SC group (surgery with chemotherapy (n = 306 and the S group (surgery without chemotherapy (n = 778. Smoking status was quantified as smoking history (non-smoker, ex-smoker, and current smoker and cumulative smoking (0, between 0 and 20, and greater than 20 pack-years. The association between cigarette smoking and overall survival (OS was evaluated using the Kaplan-Meier method and univariate/multivariate regression analysis.Among 1,084 patients, 702 (64.8% reported a cigarette smoking history, and the 5-year OS for non-smokers and smokers was 45.8% and 37.3%, respectively. In the SC group, compared with non-smoker, the adjusted HRs of ex-smoker and current smoker were 1.540 (95% CI, 1.1-2.2 and 2.110 (95% CI, 1.4-3.1, respectively; there is a correlative trend of decreased OS with increased cigarette smoking (Ptrend = 0.001. These associations were insignificant in the S group. In subgroup analysis of the SC group, the lower OS conferred by smoking was not significantly modified by age, gender, body mass index, alcohol drinking, or chemotherapy method (chemotherapy and chemoradiotherapy.Our results suggest that smoking may affect treatment outcome in patients with resected ESCC who received chemotherapy.

  5. Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

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    Li, Duo-Jie; Li, Hong-Wei; He, Bin; Wang, Geng-Ming; Cai, Han-Fei; Duan, Shi-Miao; Liu, Jing-Jing; Zhang, Ya-Jun; Cui, Zhen; Jiang, Hao

    2016-01-01

    To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

  6. 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.

  7. Plasma Riboflavin Level is Associated with Risk, Relapse, and Survival of Esophageal Squamous Cell Carcinoma.

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    Li, Shan-Shan; Xu, Yi-Wei; Wu, Jian-Yi; Tan, Hua-Zhen; Wu, Zhi-Yong; Xue, Yu-Jie; Zhang, Jian-Jun; Li, En-Min; Xu, Li-Yan

    2017-01-01

    Riboflavin is an essential micronutrient for normal cellular activity, and deficiency may result in disease, such as cancer. We performed a case-control study to explore the association of riboflavin levels with risk and prognosis of esophageal squamous cell carcinoma (ESCC). Plasma riboflavin levels, as measured by enzyme-linked immunosorbent assay (ELISA), in ESCC patients were significantly lower than in those of healthy controls (7.04 ± 6.34 ng/ml vs. 9.32 ± 12.40 ng/ml; P riboflavin level and risk of ESCC (odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, P =  0.02). The 5-year relapse-free and overall survival rates were significantly lower when riboflavin levels were ≤0.8 ng/ml than >0.8 ng/ml (relapse-free survival rate: 29.4% vs. 54.8%; overall survival rate: 28.6% vs. 55.6%). Plasma riboflavin level was an independent protective factor for both relapse-free (hazard ratio (HR) = 0.325, 95% CI = 0.161-0.657, P = 0.002) and overall survival of ESCC patients (HR = 0.382, 95% CI = 0.190-0.768, P = 0.007). In conclusion, plasma riboflavin levels are significantly related to risk and prognosis of ESCC patients, suggesting that moderate supplementation of riboflavin will decrease risk and prevent recurrence of ESCC and also improve prognosis of ESCC patients.

  8. Elevated levels of serum amyloid A indicate poor prognosis in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Jun-Ye; Zheng, Yu-Zhen; Yang, Juan; Lin, Yue-Hao; Dai, Shu-Qin; Zhang, Ge; Liu, Wan-Li

    2012-01-01

    Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC). SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann–Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox’s proportional hazards model. SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls (13.88 ± 15.19 mg/L vs. 2.26 ± 1.66 mg/L, P < 0.001). Elevation of SAA levels (≥ 8.0 mg/L) was observed in 54.5% (91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001), histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of SAA (≥ 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001). An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC

  9. Overall Survival of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Nimotuzumab in the Real World.

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    Saumell, Yaimarelis; Sanchez, Lizet; González, Sandra; Ortiz, Ramón; Medina, Edadny; Galán, Yaima; Lage, Agustin

    2017-12-01

    Despite improvements in surgical techniques and treatments introduced into clinical practice, the overall survival of patients with esophageal squamous cell carcinoma remains low. Several epidermal growth factor receptor inhibitors are being evaluated in the context of clinical trials, but there is little evidence of effectiveness in real-world conditions. This study aimed at assessing the effectiveness of nimotuzumab combined with onco-specific treatment in Cuban real-life patients with locally advanced or metastatic esophageal squamous cell carcinoma. A comparative and retrospective effectiveness study was performed. The 93 patients treated with nimotuzumab were matched, with use of propensity score matching, with patients who received a diagnosis of locally advanced or metastatic squamous cell carcinoma of the esophagus in three Cuban provinces reported between 2011 and 2015 to the National Cancer Registry. The Kaplan-Meier method was used to estimate event-time distributions. Log-rank statistics were used for comparisons of overall survival between groups. A two-component mixture model assuming a Weibull distribution was fitted to assess the effect of nimotuzumab on short-term and long-term survival populations. There was an increase in median overall survival in patients treated with nimotuzumab (11.9 months versus 6.5 months without treatment) and an increase in the 1-year survival rate (54.0% versus 21.9% without treatment). The 2-year survival rates were 21.1% for patients treated with nimotuzumab and 0% in the untreated cohort. There were statistically significant differences in survival between groups treated and not treated with nimotuzumab, both in the short-term survival population (6.0 months vs 4.0 months, p = 0.009) and in the long-term survival population (18.0 months vs 11.0 months, p = 0.001). Our study shows that nimotuzumab treatment concurrent with chemoradiotherapy increases the survival of real-world patients with locally advanced

  10. Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

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    Ran Liu

    Full Text Available Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

  11. The application value of diffusion-weighted magnetic resonance imaging in gross tumor volume delineation of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hou Dongliang; Shi Gaofeng; Gao Xianshu

    2012-01-01

    Objective: To analyze the application value of diffusion-weighted magnetic resonance imaging (DWMRI) in gross tumor volume (GTV) delineation of esophageal squamous cell carcinoma (SCC). Methods: Twenty-nine patients with esophageal SCC treated with radical surgery were analyzed. Routine CT scan, MRI T 2 -weighted and DWMRI were employed before surgery; diffusion-sensitive gradient b-values were taken 400, 600 and 800 s/mm 2 . GTVs were delineated using CT, MRI T 2 -weighted images and DWMRI under different b-value images. The length of GTVs measured under different images was compared with the pathological length and confirm the most accurate imaging condition. Use radiotherapy planning system to fuse DWMRI images and CT images to investigate the possibility of delineate GTVs on fused images. Results: The difference of GTV length value between CT, T 2 WI images and specimen was 3.36 mm and 2.84 mm. When b =400,600 and 800 s/mm 2 , the difference between GTV length value on the DWMRI images and on specimen was 0.47 mm, -0.47 mm and - 1.53 mm; the correlation coefficient of the measuring esophageal lengths on DWMRI images and the pathological lengths was 0.928, 0.927 and 0.938. DWMRI images and CT images could fuse accurately on radiotherapy planning system. GTV margin could.show clearly on fused images. Conclusions: DWMRI images can display the esophageal carcinoma lengths and margin accurately. When DWMRI images fused with CT images, GTV margin could show clearly,it can be used to delineate GTV accurately. (authors)

  12. Experimental immunotargeting therapy for esophageal squamous cell carcinoma using anti-human esophageal monoclonal antibody KIS1

    International Nuclear Information System (INIS)

    Fujii, Teruhiko; Yamana, Hideaki; Higaki, Kensaku; Fujita, Hiromasa; Shirouzu, Kazuo; Morimatsu, Minoru

    1997-01-01

    In recent years, several MoAbs with high specificity to tumor associated antigens, have been produced and investigated for diagnosis and immunotherapy of tumors. We produced murine MoAb KIS1 against human squamous cell carcinoma of the esophagus, and we evaluated it and its F (ab') 2 fragment for experimental radioimmunotherapy (RIT), RIT combined with hyperthermia (HT) and KIS1-vindesine (VDS) conjugate using tumor bearing nude mice. KIS1 has been shown to react specifically with an antigen of human squamous cell carcinoma. Scintigraphy produced high quality tumor images on 3 days following the injection of 131 I-KIS1F (ab') 2 . By 14 days following injection, tumor bearing mice treated with RIT+HT group showed significant tumor growth inhibition about 1.5, 2.1 and 1.7 times greater than that of the KIS1-VDS group, 131 I-intact KIS1 group and 131 I-KIS1F (ab') 2 group. These results suggest that RIT combined with hyperthermia may be clinically useful for tumor targeting therapy for squamous cell carcinoma of the esophagus. (author)

  13. Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma

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    Kewei Ren

    2016-12-01

    Full Text Available Recent studies have shown that long noncoding RNAs (lncRNAs play pivotal roles in the initiation and progression of cancer, including esophageal squamous cell carcinoma (ESCC. The lncRNA HOX transcript antisense RNA (HOTAIR was reported to be dysregulated and correlated with the progression of ESCC. However, the biological role and the underlying mechanism of HOTAIR in the development of ESCC remain unclear. Herein, we found that HOTAIR was aberrantly upregulated in ESCC cells and that HOTAIR depletion inhibited proliferation and led to G1 cell cycle arrest in ESCC cells. Besides, we found that HOTAIR acted as an endogenous sponge to downregulate miR-1 expression by directly binding to miR-1. Furthermore, HOTAIR overturned the effect of miR-1 on the proliferation and cell cycle profile in ESCC cells, which involved the derepression of cyclin D1 (CCND1 expression, a target of miR-1. Taken together, our study elucidated a novel HOTAIR /miR-1/CCND1 regulatory axis in which HOTAIR acted as a competing endogenous RNA by sponging miR-1 and upregulated CCND1 expression, thereby facilitating the tumorigenesis of ESCC. Investigation of this lncRNA/miRNA/mRNA pathway may contribute to a better understanding of ESCC pathogenesis and facilitate the development of lncRNA-directed therapy against this disease.

  14. Radiation therapy for esophageal carcinoma

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    Chatani, Masashi; Matayoshi, Yoshinobu; Masaki, Norie

    1992-01-01

    From 1977 through 1989, 149 patients with esophageal carcinoma were treated with external irradiation (EI) with or without high-dose rate intraluminal irradiation (HDRII) using remote afterloading system. Concerning complete response group EI alone showed higher local control rate than EI + HDRII, especially in ulcerative type. Another problem is the EI field. Fourteen of 22 patients who were salvaged by surgery due to local recurrence after EI showed marginal or out-field metastasis of the lymph node. These preliminary results suggest that HDRII is not effective for the local control of the ulcerative lesion as a boost therapy, EI should be given for the entire regional lymph nodes. (author)

  15. MMP-9, uPA and uPAR proteins expression and its prognostic significance in esophageal squamous cell carcinoma treated by radiotherapy

    International Nuclear Information System (INIS)

    Zhu Shuchai; Wang Yafei; Su Jingwei; Wang Yuxiang; Shen Wenbin; Li Juan

    2008-01-01

    Objective: To explore the the prognostic significance of MMP-9, uPA and uPAR protein expression and its relationship with clinical-pathologic factors in esophageal squamous cell carcinoma treated by radiotherapy. Methods: MMP-9, uPA and uPAR protein expression was measured in 59 esophageal carcinomas and 41 peri-carcinoma tissues with immunohistochemistry. The relationship between the protein expression and the clinical-pathological parameters was analyzed, and the prognostic factors in esophageal squamous cell carcinoma treated by radiotherapy alone was evaluated. Results: The rates of positive expression of MMP-9, uPA and uPAR were 85%, 76% and 78% in esophageal carcinoma and 39%, 49% and 44% in peri-carcinoma tissues (χ 2 =22.54, 8.04 and 12.18; P=0.000,0.005 and 0.000). The rates of positive expression of MMP-9 was 79% and 100% when the depth of tumor invasion was ≤2 cm and >2 cm(P= 0.048), respectively. The expression of uPA was significantly correlated with the status of fat interspace between the esophageal lesion and the vertebra in CT scanning image. When the fat interspace existed and disappeared, the rates of strong positive expression was 44% and 70%, respectively (χ 2 =4.21, P=0.040). The positive expression rate of uPA was significantly correlated with distant metastasis, which was 100% in patients with distant metastasis and 68.89% in those without distant metastasis(χ 2 =4.12, P=0.042). The positive expression rate of MMP-9, uPA and uPAR did not affect the prognosis and the short-term result of esophageal carcinoma treated by radiotherapy alone. Conclusions: The protein expression of MMP-9, uPA and uPAR may correlate with local infiltration and distant metastasis in esophageal squamous cell carcinoma. Protein expression may not influence the prognosis of esophageal carcinoma treated by radio therapy, though long time followed-up is still needed. (authors)

  16. 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.

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    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.

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

    International Nuclear Information System (INIS)

    Wang, Chia-Chun; Cheng, Jason Chia-Hsien; Tsai, Chiao-Ling; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Hsieh, Min-Shu; Chang, Yih-Leong; Hsu, Feng-Ming

    2015-01-01

    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

  18. Long-term outcomes of minimally invasive Ivor Lewis esophagostomy for esophageal squamous cell carcinoma: Compared with open approach.

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    Zhang, Zhenghua; Xu, Meiqing; Guo, Mingfa; Liu, Xuegang

    2017-09-01

    To investigate the safety and long-term efficacy of combined thoraco-laparoscopic minimally invasive Ivor Lewis esophagostomy(MI-ILE) in the treatment of esophageal squamous cell carcinoma. The clinical data of patients with esophageal squamous cell carcinoma who underwent Ivor Lewis esophagostomy of esophageal cancer from October 2011 to June 2013 were retrospectively analyzed. Of which 90 patients received MI-ILE, 95 patients underwent open Ivor Lewis esophagostomy (O-ILE). The clinicopathological features, intraoperative records and incidences of postoperative complications of the two groups were compared with t-test and χ2 test. The primary end point of the study was 3-year disease-free survival (DFS) and 3-year overall survival (OS) was a secondary end point. There were no statistically significant differences in gender, age, preoperative comorbidities, American Society of Anesthesiologists score and position of the tumor between the two groups. There was also no significant difference in clinicopathological characteristics, operation time, length of tumor resection margin and number of resected lymph nodes between the two groups (P > 0.05). In MI-ILE group, the blood loss was lower than in the O-ILE group [(159.1 + 97.4) ml vs. (191.7 + 141.9) ml, t = 1.811, P = 1.811]and the postoperative hospital stay was shorter [(11.5 + 4.5) d vs. (13.9 + 6.2) d, t = 2.944, P = 0.004]. There was no significant difference in the incidences of perioperative mortality and major morbidities (P > 0.05). Minor complications including incision infection rate (1.1% vs 8.4%, χ2 = 3.873, P = 0.049) and pulmonary infection incidence (3.3% vs 11.57%, χ2 = 4.492, P = 0.034) is lower in MIILE group. There was no significant difference in 3-year disease-free survival (DFS) and 3-year overall survival (OS) between the two groups. MI-ILE is a technically safe and feasible approach for esophageal squamous cell carcinoma treatment. The oncologic outcomes of MI

  19. The influence of circumferential resection margin status on loco-regional recurrence in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Park, Hae Jin; Kim, Hak Jae; Chie, Eui Kyu; Kang, Chang Hyun; Kim, Young Tae

    2013-06-01

    To analyze treatment outcomes and patterns of recurrence, and to examine the impact of adjuvant postoperative radiotherapy (PORT) after esophagectomy in esophageal squamous cell carcinoma (SqCC) regarding the status of circumferential resection margin (CRM). We performed a retrospective review of esophageal cancer patients operated in Seoul National University Hospital between 2003 and 2010. Pathologically proven T3 SqCC patients with written reports mentioning the status of CRM were selected. Fifty-nine out of 71 patients (83.1%) had CRM+. Twenty-eight patients had radiotherapy in CRM+ and CRM-, respectively. The median follow-up period was 17.1 months (range: 5.2-63.1). Median survival and 2-year overall survival were 13.8 months and 41.9% in CRM+, and 27.3 months and 74.1% in CRM-, respectively. Loco-regional relapse-free survival (LRRFS) rate at 2 years was 33.6% and 74.1% in each groups (P = 0.029). Loco-regional recurrence was the major pattern of failure in CRM+. PORT did not improve LRRFS. The esophageal SqCC patients with CRM+ after resection showed worse LRRFS. This finding validated the prognostic value of CRM status. Nevertheless, we failed to demonstrate the benefits of adjuvant PORT in CRM+. This might suggest the necessity of neoadjuvant therapy to decrease the CRM+ rate after esophagectomy. Copyright © 2012 Wiley Periodicals, Inc.

  20. Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Lei, Zhijin; Tian, Dongping; Zhang, Chong; Zhao, Shukun; Su, Min

    2016-01-01

    Chaoshan region, a littoral area of Guangdong province in southern China, has a high incidence of esophageal squamous cell carcinoma (ESCC). At present, the prognosis of ESCC is still very poor, therefore, there is urgent need to seek valuable molecular biomarker for prognostic evaluation to guide clinical treatment. GPX2, a selenoprotein, was exclusively expressed in gastrointestinal tract and has an anti-oxidative damage and anti-tumour effect in the progress of tumourigenesis. We collected 161 ESCC patients samples, among which 83 patients were followed up. We employed immunochemistry analysis, western blotting and quantitative real-time PCR for measuring the expression of GPX2 within ESCC samples. We analysed the relationship between the expression of GPX2 and clinicopathological parameters of 161 patients with ESCC by Chi-square or Fisher’s exact test. The survival analysis of GPX2 expression within ESCC tissues was evaluated by the Kaplan-Meier method and Cox-regression. A significant higher expression level of GPX2 was detected in tumour tissues compared to that in non-tumour tissues (P < 0.001). Moreover, GPX2 expression has statistically significant difference in the tumour histological grade of ESCC (P < 0.001), while there was no statistically significant difference in age, sex, tumour size, tumour location, gross morphology and clinical TNM stages (P > 0.05). Meanwhile, the expression of GPX2 protein was obviously down-regulated within poorly differentiated ESCC. Last, survival analysis revealed that tumour histological grade and clinical TNM stages, both of the clinical pathological parameters of ESCC, were associated with the prognosis of patients with ESCC (respectively, P = 0.009, HR (95 % CI) = 1.885 (1.212 ~ 2.932); P = 0.007, HR (95 % CI) = 2.046 (1.318 ~ 3.177)). More importantly, loss expression of GPX2 protein predicted poor prognosis in patients with ESCC (P < 0.001, HR (95 % CI) = 5.700 (2.337 ~ 13.907)). Collectively, these results

  1. Glasgow Prognostic Score as a Prognostic Clinical Marker in T4 Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Ohira, Masaichi; Kubo, Naoshi; Masuda, Go; Yamashita, Yoshito; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-09-01

    Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented. This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP >10 mg/l or albumin l, or CRP >10 mg/l and albumin l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses. Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, pGPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Extent of postoperative prophylactic radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Lu Jincheng; Tao Hua; Zha Wenwu; Xu Kangxiong

    2007-01-01

    Objective: To determine the extent of postoperative prophylactic radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma. Should the entire mediastinum (M), bilateral supraclavicular areas(S) and the left gastric area(L) be all included in the irradiation field. Methods The clinical data of 204 such patients treated from 1996 through 1999 were retrospectively reviewed. They were classified into four groups: group A, 26 patients given irradiation to the mediastinum M alone; group B, 139 patients given irradiation to the mediastinum and bilateral supraclavicular areas M + S; group C, 10 patients irradiation to the mediastinum plus left gastric area M + L; and group D, 29 patients irradiation to all these three areas ( M + S + L). The overall and disease-free survival rates were calculated using the Kaplan- Meier method and comparison of these groups was done with the Logrank test. Prognostic variables were entered into a Cox regression model controlling the age, gender, length, site, pT, pN, and treatment received. Results: The 1-, 3- and 5-year overall and disease-free survival rates of all 204 patients were 83.8%, 53.2%, 34.1% and 77.8%, 51.6%, 33.8% , respectively. The 5-year disease-free survival rates for patients in group A, group B, group C, and group D were 36.3%, 30.7%, 40.0% and 43.6% (χ 2 = 3.05, P=0.385), respectively. Multivariate analysis showed that the pT and pN were independent risk factors for disease-free survival rate, whereas treatment arm gave no significant difference (χ 2 =2.77, P=0.096). None of the 43 patents without irradiation to the L had abdominal lymph node metastasis from lesions in the upper and upper-middle third (located middle third but invasion to the upper third) thoracic esophagus. The data of supraclavicular lymph node metastasis between patients with and without irradiation showed that S in lesion in the lower and middle-lower third (located middle third but invasion to the lower third) thoracic

  3. Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Gonzaga, Isabela Martins; Andreollo, Nelson Adami; Simão, Tatiana Almeida de; Pinto, Luis Felipe Ribeiro; Soares-Lima, Sheila Coelho; Santos, Paulo Thiago Souza de; Blanco, Tania Cristina Moita; Reis, Bruno Souza Bianchi de; Quintella, Danielle Carvalho; Oliveira, Ivanir Martins de; Faria, Paulo Antonio Silvestre de; Kruel, Cleber Dario Pinto

    2012-01-01

    Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this

  4. Receptor interactive protein kinase 3 promotes Cisplatin-triggered necrosis in apoptosis-resistant esophageal squamous cell carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available Cisplatin-based chemotherapy is currently the standard treatment for locally advanced esophageal cancer. Cisplatin has been shown to induce both apoptosis and necrosis in cancer cells, but the mechanism by which programmed necrosis is induced remains unknown. In this study, we provide evidence that cisplatin induces necrotic cell death in apoptosis-resistant esophageal cancer cells. This cell death is dependent on RIPK3 and on necrosome formation via autocrine production of TNFα. More importantly, we demonstrate that RIPK3 is necessary for cisplatin-induced killing of esophageal cancer cells because inhibition of RIPK1 activity by necrostatin or knockdown of RIPK3 significantly attenuates necrosis and leads to cisplatin resistance. Moreover, microarray analysis confirmed an anti-apoptotic molecular expression pattern in esophageal cancer cells in response to cisplatin. Taken together, our data indicate that RIPK3 and autocrine production of TNFα contribute to cisplatin sensitivity by initiating necrosis when the apoptotic pathway is suppressed or absent in esophageal cancer cells. These data provide new insight into the molecular mechanisms underlying cisplatin-induced necrosis and suggest that RIPK3 is a potential marker for predicting cisplatin sensitivity in apoptosis-resistant and advanced esophageal cancer.

  5. Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

    NARCIS (Netherlands)

    Huang, J.; Fan, Q.; Lu, P.; Ying, J.; Ma, C.; Liu, W.; Liu, Y.; Tan, F.; Sun, Y

    2016-01-01

    INTRODUCTION: Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR

  6. Adherence to Mediterranean-style dietary pattern and risk of esophageal squamous cell carcinoma: a case-control study in Iran

    Science.gov (United States)

    The benefit of adherence to a Mediterranean-style dietary pattern in relation to the risk of esophageal squamous cell carcinoma (ESCC) has not been investigated among non-Mediterranean high-risk populations. The objective of the present study was to examine the association of compliance with the Med...

  7. 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)

    Hou, Dong-Liang; Shi, Gao-Feng; Gao, Xian-Shu; Asaumi, Junichi; Li, Xue-Ying; Liu, Hui; Yao, Chen; Chang, Joe Y

    2013-01-01

    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/mm 2 . 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/mm 2 , 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

  8. Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Xu, Youtao; Wang, Jie; Qiu, Mantang; Xu, Lei; Li, Ming; Jiang, Feng; Yin, Rong; Xu, Lin

    2015-03-01

    Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. The prognosis of ESCC remains poor; thus, it is still necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Some lncRNAs, such as HOTAIR and POU3F3, were reported to play important roles in ESCC. Here, we characterized the expression profile of taurine-upregulated gene 1 (TUG1), a lncRNA recruiting and binding to polycomb repressive complex 2 (PRC2), in ESCC. In a cohort of 62 patients, TUG1 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues, and high expression level of TUG1 was associated with family history and upper segment of esophageal cancer (p TUG1 via siRNA inhibited the proliferation and migration of ESCC cells and blocked the progression of cell cycle. Therefore, our study indicates that TUG1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC.

  9. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    OpenAIRE

    Xiang Yuan; Xinshuai Wang; Bianli Gu; Yingjian Ma; Yiwen Liu; Man Sun; Jinyu Kong; Wei Sun; Huizhi Wang; Fuyou Zhou; Shegan Gao

    2017-01-01

    Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing t...

  10. 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

    . In the 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 the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells...

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

    Directory of Open Access Journals (Sweden)

    Pimenta Amadeu P. A.

    1997-01-01

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

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

    International Nuclear Information System (INIS)

    Zhang Wencheng; Wang Qifeng; Xiao Zefen; Yang Longhai; Liu Xiangyang

    2012-01-01

    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 (χ 2 =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 N 0 patients (28.7%: 10.6%, χ 2 =9.94, P =0.001), and so did in middle thoracic esophageal cancer (20.0%: 5.6%, χ 2 =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%, χ 2 =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

  14. Sitting time and occupational and recreational physical activity in relation to the risk of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chen P

    2017-09-01

    Full Text Available Pengxiang Chen,1 Qingxu Song,1 Jie Han,2 Huapu Xu,3 Tong Chen,4 Jiaqi Xu,5 Yufeng Cheng1 1Department of Radiation Oncology, Qilu Hospital of Shandong University, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, 3Department of Oncology, Pingyi Hospital of Traditional Chinese Medicine, Pingyi, 4Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 5Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Backgrounds: Sitting time and physical activity are associated with cancer risk; however, their roles in the development of esophageal squamous cell carcinoma (ESCC are inconclusive. This study aimed to investigate the effects of total sitting time, occupational activity time (OAT, and recreational activity time (RAT on ESCC risk. Methods: Five hundred fifty-seven ESCC patients and 543 healthy controls matched by sex and age were recruited for this study. Conditional logistic regression was performed to obtain odds ratios (ORs and 95% confidence intervals (CIs. Results: Longer total sitting time (adjusted OR [AOR] 2.54, 95% CI 1.58–4.09 and longer OAT (AOR 2.90, 95% CI 2.11–3.99 were associated with higher ESCC risk, while longer RAT (AOR 0.27, 95% CI 0.19–0.38 could reduce ESCC risk. When the body mass index was incorporated into the multivariable models, the results changed slightly. In risk estimation according to sex, the same trends were observed in both men and women. Furthermore, longer RAT could completely or partially diminish the impacts of longer sitting time and OAT on increasing ESCC risk.Conclusion: Long sitting time and long OAT can increase the risk of ESCC, while long RAT is significantly associated with decreased ESCC risk. Keywords: esophageal squamous cell carcinoma, sitting time, physical activity, cancer epidemiology

  15. 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.

  16. Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

    Science.gov (United States)

    Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

    2016-05-01

    Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture

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

    Directory of Open Access Journals (Sweden)

    Shi Y

    2013-05-01

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

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

    International Nuclear Information System (INIS)

    Endo, K.; Kohnoe, S.; Toh, Y.; Haraguchi, M.; Okamura, T.; Nishiyama, K.; Baba, H.; Maehara, Y.

    2005-01-01

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

  19. Esophageal squamous cell carcinoma presenting as submucosal lesion with repeatedly negative endoscopic biopsies

    Directory of Open Access Journals (Sweden)

    Narendra S Choudhary

    2016-01-01

    Full Text Available A 74-year-old male presented with dysphagia for 2 months. Computed tomography revealed irregular wall thickening of the esophagus at T3 to T5 level. He underwent gastroscopy which revealed a submucosal bulge with normal mucosa at 25 cm from incisors. Repeated biopsies were taken, all were negative for malignancy. The patient underwent endoscopic ultrasound, and fine-needle aspiration was taken which was suggestive for squamous cell carcinoma.

  20. DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zou, Shitao; Shang, Zeng-Fu; Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

    2016-05-31

    DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

  1. 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

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

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    Dong, Wenjie, E-mail: dongwenjie200581@126.com [Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University (China); Shen, Ruizhe; Cheng, Shidan [Department of Gastroenterology, Rui-jin Hospital, Shanghai Jiao Tong University, Shanghai (China)

    2014-10-31

    Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

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

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    Li, Minghuan; Zhang, Xiaoli; Zhao, Fen; Luo, Yijun; Kong, Li; Yu, Jinming

    2016-02-05

    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.

  4. Analysis of failure patterns in patients with resectable esophageal squamous cell carcinoma receiving chemoradiotherapy

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    Wen-Bin Shen

    2016-01-01

    Conclusion: The incidence of locoregional recurrence and distant metastasis in patients with upper thoracic esophageal cancer was lower than those who had middle thoracic and lower thoracic esophageal cancer. The incidence of locoregional recurrence and distant metastasis in patients who achieved complete response after treatment was low.

  5. Targeting c-Myc: JQ1 as a promising option for c-Myc-amplified esophageal squamous cell carcinoma.

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    Wang, Jingyuan; Liu, Zhentao; Wang, Ziqi; Wang, Shubin; Chen, Zuhua; Li, Zhongwu; Zhang, Mengqi; Zou, Jianling; Dong, Bin; Gao, Jing; Shen, Lin

    2018-04-10

    c-Myc amplification-induced cell cycle dysregulation is a common cause for esophageal squamous cell carcinoma (ESCC), but no approved targeted drug is available so far. The bromodomain inhibitor JQ1, which targets c-Myc, exerts anti-tumor activity in multiple cancers. However, the role of JQ1 in ESCC remains unknown. In this study, we reported that JQ1 had potent anti-proliferative effects on ESCC cells in both time- and dose-dependent manners by inducing cell cycle arrest at G1 phase, cell apoptosis, and the mesenchymal-epithelial transition. Follow-up studies revealed that both c-Myc/cyclin/Rb and PI3K/AKT signaling pathways were inactivated by JQ1, as indicated by the downregulation of c-Myc, cyclin A/E, and phosphorylated Rb, AKT and S6. Tumor suppression induced by JQ1 in c-Myc amplified or highly expressed xenografts was higher than that in xenografts with low expression, suggesting its potential role in prediction. In conclusion, targeting c-Myc by JQ1 could cause significant tumor suppression in ESCC both in vitro and in vivo. Also, c-Myc amplification or high expression might serve as a potential biomarker and provide a promising therapeutic option for ESCC. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Esophageal perforation during or after conformal radiotherapy for esophageal carcinoma

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    Chen Haiyan; Ma Xiumei; Ye Ming; Hou Yanli; Xie Huaying; Bai Yongrui

    2014-01-01

    The aim of this study was to analyze the risk factors and prognosis for patients with esophageal perforation occurring during or after radiotherapy for esophageal carcinoma. We retrospectively analyzed 322 patients with esophageal carcinoma. These patients received radiotherapy for unresectable esophageal tumors, residual tumors after operation, or local recurrence. Of these, 12 had radiotherapy to the esophagus before being admitted, 68 patients had concurrent chemoradiotherapy (CRT), and 18 patients had esophageal perforation after RT (5.8%). Covered self-expandable metallic stents were placed in 11 patients. Two patients continued RT after stenting and control of infection; one of these suffered a new perforation, and the other had a massive hemorrhage. The median overall survival was 2 months (0-3 months) compared with 17 months in the non-perforation group. In univariate analysis, the Karnofsky performance status (KPS) being ≤ 70, age younger than 60, T4 stage, a second course of radiotherapy to the esophagus, extracapsular lymph nodes (LN) involving the esophagus, a total dose > 100 Gy (biologically effective dose -10 ), and CRT were risk factors for perforation. In multivariate analysis, age younger than 60, extracapsular LN involving the esophagus, T4 stage, and a second course of radiotherapy to the esophagus were risk factors. In conclusion, patients with T4 stage, extracapsular LN involving the esophagus, and those receiving a second course of RT should be given particular care to avoid perforation. The prognosis after perforation was poor. (author)

  7. The diagnostic value of long non-coding RNA MIR31HG and its role in esophageal squamous cell carcinoma.

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    Sun, Kaiyan; Zhao, Xinwei; Wan, Junhu; Yang, Lijun; Chu, Jie; Dong, Shuling; Yin, Huiqing; Ming, Liang; He, Fucheng

    2018-06-01

    This study aimed to assess plasma lncRNA microRNA-31 hist gene (MIR31HG) as a novel diagnostic and therapeutic biomarker for esophageal squamous cell carcinoma (ESCC) and to investigate its role in ESCC. The expression of MIR31HG, Furin and MMP1 was examined via quantitative real-time polymerase chain reaction. MIR31HG expression between plasma and ESCC tissues was compared using Pearson correlation analysis; furthermore, the association between Furin/MMP1 levels and MIR31HG levels in ESCC tissues was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma MIR31HG. A WST-1 assay was performed to assess cell proliferation. The migratability and invasiveness of cells was determined via Transwell assays. MIR31HG was significantly upregulated in ESCC tissues and plasma (P occurance. Furthermore, knockdown of MIR31HG suppressed the capacity for proliferation, migration, and invasion of ESCC cells (P < 0.01). In addition, silencing of MIR31HG inhibited the expression of Furin and MMP1 in EC9706 and EC1 and the level of Furin/MMP1 in ESCC tissues displayed a significant positive correlation with MIR31HG (P < 0.01). MIR31HG can be used as a novel potential diagnostic biomarker and a potential therapeutic target for ESCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Decreased expression of CIAPIN1 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma.

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    Zheng, Xiushan; Zhao, Yunping; Wang, Xin; Li, Yunming; Wang, Ruwen; Jiang, Yaoguang; Gong, Taiqian; Li, Mengbin; Sun, Li; Hong, Liu; Li, Xiaohua; Liang, Jie; Luo, Guanhong; Jin, Bin; Yang, Jianjun; Zhang, Hongwei; Fan, Daiming

    2010-12-01

    CIAPIN1, a newly identified antiapoptotic molecule, is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway in the mouse Ba/F3 pro-B cell line. Neither CIAPIN1 expression nor its clinical significance has been previously examined in esophageal squamous cell carcinoma (ESCC), and the present immunohistochemical analysis is the first study on CIAPIN1 distribution in ESCC. To investigate the relationships between the expression of CIAPIN1 and clinicopathological characteristics of ESCC, and evaluate the relationship between the expression of this gene and prognosis in ESCC patients. The expression of CIAPIN1 was investigated in 112 surgically resected specimens of ESCC by immunohistochemistry using a specific monoclonal antibody. The relations of CIAPIN1 expression with clinicopathological characteristics and the postoperative survival rate were statistically analyzed. We found that the expression of CIAPIN1 was statistically correlated with the degree of differentiation, depth of invasion, and lymph node metastasis of ESCC. Consistently, the survival rates of patients with CIAPIN1-negative tumors tended to be statistically lower than those with CIAPIN1-positive tumors. However, no significant difference was observed between CIAPIN1 expression and the patient age, sex, tumor location, and distant metastasis. Furthermore, multivariate analysis was performed by using Cox's proportional hazards model, and the results showed that lymph node metastases and CIAPIN1 expression were two independent prognostic factors. CIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a valuable prognostic indicator in ESCC. Finally, functional enhancement of CIAPIN1 might lead to a novel strategy for the treatment of SCC in the esophagus.

  9. Salvage lymphadenectomy of the right recurrent nerve node with tracheal involvement after definitive chemoradiation therapy for esophageal squamous cell carcinoma. Report of two cases

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    Doki, Yuichiro; Yasuda, Takushi; Miyata, Hiroshi

    2007-01-01

    Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma. (author)

  10. Role of Brg1 in progression of esophageal squamous cell carcinoma

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    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.

  11. 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.

  12. The Combination of Platelet Count and Neutrophil Lymphocyte Ratio Is a Predictive Factor in Patients with Esophageal Squamous Cell Carcinoma

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    Ji-Feng Feng

    2014-10-01

    Full Text Available OBJECTIVE: The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR in patients with esophageal squamous cell carcinoma (ESCC were investigated and compared. METHODS: This retrospective study included 375 patients who underwent esophagectomy for ESCC. The cancer-specific survival (CSS was calculated by the Kaplan-Meier method, and the difference was assessed by the log-rank test. The GPS was calculated as follows: patients with elevated C-reactive protein (>10 mg/l and hypoalbuminemia (300 × 109/l and neutrophil lymphocyte ratio (>3 were assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP-NLR1 or COP-NLR0, respectively. RESULTS: The 5-year CSS in patients with GPS0, 1, and 2 was 50.0%, 27.0%, and 12.5%, respectively (P < .001. The 5-year CSS in patients with COP-NLR0, 1, and 2 was 51.8%, 27.0%, and 11.6%, respectively (P < .001. Multivariate analysis showed that both GPS (P = .003 and COP-NLR (P = .003 were significant predictors in such patients. In addition, our study demonstrated a similar hazard ratio (HR between COP-NLR and GPS (HR = 1.394 vs HR = 1.367. CONCLUSIONS: COP-NLR is an independent predictive factor in patients with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.

  13. 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.

  14. The combination of platelet count and neutrophil lymphocyte ratio is a predictive factor in patients with esophageal squamous cell carcinoma.

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    Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun

    2014-10-01

    The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS) and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with esophageal squamous cell carcinoma (ESCC) were investigated and compared. This retrospective study included 375 patients who underwent esophagectomy for ESCC. The cancer-specific survival (CSS) was calculated by the Kaplan-Meier method, and the difference was assessed by the log-rank test. The GPS was calculated as follows: patients with elevated C-reactive protein (> 10 mg/l) and hypoalbuminemia (l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0, respectively. The COP-NLR was calculated as follows: patients with elevated platelet count (> 300 × 10(9)/l) and neutrophil lymphocyte ratio (> 3) were assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP-NLR1 or COP-NLR0, respectively. The 5-year CSS in patients with GPS0, 1, and 2 was 50.0%, 27.0%, and 12.5%, respectively (P GPS (P = .003) and COP-NLR (P = .003) were significant predictors in such patients. In addition, our study demonstrated a similar hazard ratio (HR) between COP-NLR and GPS (HR = 1.394 vs HR = 1.367). COP-NLR is an independent predictive factor in patients with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.

  15. Prognostic impact of body mass index stratified by smoking status in patients with esophageal squamous cell carcinoma

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    Sun P

    2016-10-01

    Full Text Available Peng Sun,1,2,* Fei Zhang,1,2,* Cui Chen,3,* Chao Ren,1,2 Xi-Wen Bi,1,2 Hang Yang,1,2 Xin An,1,2 Feng-Hua Wang,1,2 Wen-Qi Jiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 3Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: As smoking affects the body mass index (BMI and causes the risk of esophageal squamous cell carcinoma (ESCC, the prognostic impact of BMI in ESCC could be stratified by smoking status. We investigated the true prognostic effect of BMI and its potential modification by smoking status in ESCC. Methods: We retrospectively analyzed 459 patients who underwent curative treatment at a single institution between January 2007 and December 2010. BMI was calculated using the measured height and weight before surgery. Chi-square test was used to evaluate the relationships between smoking status and other clinicopathological variables. The Cox proportional hazard models were used for univariate and multivariate analyses of variables related to overall survival. Results: BMI <18.5 kg/m2 was a significantly independent predictor of poor survival in the overall population and never smokers after adjusting for covariates, but not in ever smokers. Among never smokers, underweight patients (BMI <18.5 kg/m2 had a 2.218 times greater risk of mortality than non-underweight (BMI =18.5 kg/m2 patients (P=0.015. Among ever smokers, BMI <18 kg/m2 increased the risk of mortality to 1.656 (P=0.019, compared to those having BMI =18 kg/m2. Conclusion: Our study is likely the first to show that the prognostic effect of BMI was substantial in ESCC, even after stratifying by smoking status. Furthermore, the risk of death due to low BMI would be significantly increased in never smokers. We believe that

  16. High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

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    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.

  17. Retrospective analysis of outcome differences in preoperative concurrent chemoradiation with or without elective nodal irradiation for esophageal squamous cell carcinoma.

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    Hsu, Feng-Ming; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh; Lee, Yung-Chie; Chia-Hsien Cheng, Jason

    2011-11-15

    To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor

  18. Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

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    Hsu, Feng-Ming [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China)

    2011-11-15

    Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal

  19. Macronutrients, vitamins and minerals intake and risk of esophageal squamous cell carcinoma: a case-control study in Iran

    Science.gov (United States)

    2011-01-01

    Background Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC. Methods In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education. Results ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed. Conclusion This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as

  20. Safety and efficacy of endoscopic submucosal dissection using IT knife nano with clip traction method for early esophageal squamous cell carcinoma.

    Science.gov (United States)

    Kitagawa, Yoshiyasu; Suzuki, Takuto; Hara, Taro; Yamaguchi, Taketo

    2018-01-01

    Although endoscopic submucosal dissection (ESD) is an accepted and established treatment for early esophageal squamous cell carcinoma (EESCC), it is technically difficult, time consuming, and less safe than endoscopic mucosal resection. To perform ESD safely and more efficiently, we proposed a new technique of esophageal ESD using an IT knife nano with the clip traction method. This study aimed to evaluate the efficacy and safety of ESD using this new technique. We retrospectively reviewed all consecutive cases of esophageal ESD performed using an IT knife nano with the clip traction method at our hospital between March 2013 and January 2017. Therapeutic efficacy and safety were also assessed. A total of 103 patients underwent esophageal ESD using the IT knife nano with the clip traction method. In all cases, we performed en bloc resection. Complete resection was achieved in 100 cases (97.1%). The median operating time was 40 (range 13-230) min. No cases of perforation or delayed bleeding occurred. Although two cases (2.0%) of mediastinal emphysema occurred without visible perforation at endoscopy, all were successfully managed conservatively. The new technique of esophageal ESD using the IT knife nano with the clip traction method appears to be feasible, effective, and safe for EESCC treatment.

  1. Early esophageal carcinoma treated with intracavitary irradiation

    International Nuclear Information System (INIS)

    Hishikawa, Y.; Tanaka, S.; Miura, T.

    1985-01-01

    Five patients with early esophageal carcinoma were treated by 6-12 Gy of intracavitary irradiation following 50-60 Gy of external irradiation as a boost therapy. Surgery was not performed in these cases. None of the patients had local recurrence after radiation therapy, as demonstrated by esophagography and endoscopy. Three patients have been alive for 1-3 years 10 months. Esophageal ulceration induced by intracavitary irradiation has occurred in three of the five patients; however, intracavitary irradiation is still a beneficial treatment because of its efficacy in controlling local lesions and because radiation ulceration can eventually be cured. Intracavitary irradiation is recommended to follow external irradiation as a boost therapy for the treatment of early esophageal carcinoma

  2. esophageal carcinoma complicating achalasia, 25 years post

    African Journals Online (AJOL)

    mine

    Some degree of stasis usually persists despite adequate treatment and relief of symptoms. Complications or recurrent symptoms include dysphagia, esophageal reflux, stricture and carcinoma. 5. This case report suggests that long term surveillance of the patient with achalasia is essential even after successful treatment.

  3. High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Lin; Wang, Wenchao; Li, Guoli; Sun, Canlin; Ren, Zhenqin; Sheng, Haihui; Gao, Hengjun; Wang, Chaofu; Yu, Hong

    2016-08-01

    Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance. The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed. The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors. Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC.

  4. Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Xi; Niu, Haitao; Fan, Qingxia; Lu, Ping; Ma, Changwu; Liu, Wei; Liu, Ying; Li, Weiwei; Hu, Shaoxuan; Ling, Yun; Guo, Lei; Ying, Jianming; Huang, Jing

    2016-04-26

    This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (picotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

  5. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

    Science.gov (United States)

    Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (PPCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

  6. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

    Science.gov (United States)

    Zhan, Qimin; Hu, Zhibin; He, Zhonghu; Jia, Weihua; Zhou, Yifeng; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Zhao, Xue-Ke; Gao, She-Gan; Yuan, Zhi-Qing; Zhou, Fu-You; Fan, Zong-Min; Cui, Ji-Li; Lin, Hong-Li; Han, Xue-Na; Li, Bei; Chen, Xi; Dawsey, Sanford M.; Liao, Linda; Lee, Maxwell P.; Ding, Ti; Qiao, You-Lin; Liu, Zhihua; Liu, Yu; Yu, Dianke; Chang, Jiang; Wei, Lixuan; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Han, Jing-Jing; Zhou, Sheng-Li; Zhang, Peng; Zhang, Dong-Yun; Yuan, Yuan; Huang, Ying; Liu, Chunling; Zhai, Kan; Qiao, Yan; Jin, Guangfu; Guo, Chuanhai; Fu, Jianhua; Miao, Xiaoping; Lu, Changdong; Yang, Haijun; Wang, Chaoyu; Wheeler, William A.; Gail, Mitchell; Yeager, Meredith; Yuenger, Jeff; Guo, Er-Tao; Li, Ai-Li; Zhang, Wei; Li, Xue-Min; Sun, Liang-Dan; Ma, Bao-Gen; Li, Yan; Tang, Sa; Peng, Xiu-Qing; Liu, Jing; Hutchinson, Amy; Jacobs, Kevin; Giffen, Carol; Burdette, Laurie; Fraumeni, Joseph F.; Shen, Hongbing; Ke, Yang; Zeng, Yixin; Wu, Tangchun; Kraft, Peter; Chung, Charles C.; Tucker, Margaret A.; Hou, Zhi-Chao; Liu, Ya-Li; Hu, Yan-Long; Liu, Yu; Wang, Li; Yuan, Guo; Chen, Li-Sha; Liu, Xiao; Ma, Teng; Meng, Hui; Sun, Li; Li, Xin-Min; Li, Xiu-Min; Ku, Jian-Wei; Zhou, Ying-Fa; Yang, Liu-Qin; Wang, Zhou; Li, Yin; Qige, Qirenwang; Yang, Wen-Jun; Lei, Guang-Yan; Chen, Long-Qi; Li, En-Min; Yuan, Ling; Yue, Wen-Bin; Wang, Ran; Wang, Lu-Wen; Fan, Xue-Ping; Zhu, Fang-Heng; Zhao, Wei-Xing; Mao, Yi-Min; Zhang, Mei; Xing, Guo-Lan; Li, Ji-Lin; Han, Min; Ren, Jing-Li; Liu, Bin; Ren, Shu-Wei; Kong, Qing-Peng; Li, Feng; Sheyhidin, Ilyar; Wei, Wu; Zhang, Yan-Rui; Feng, Chang-Wei; Wang, Jin; Yang, Yu-Hua; Hao, Hong-Zhang; Bao, Qi-De; Liu, Bao-Chi; Wu, Ai-Qun; Xie, Dong; Yang, Wan-Cai; Wang, Liang; Zhao, Xiao-Hang; Chen, Shu-Qing; Hong, Jun-Yan; Zhang, Xue-Jun; Freedman, Neal D; Goldstein, Alisa M.; Lin, Dongxin; Taylor, Philip R.; Wang, Li-Dong; Chanock, Stephen J.

    2014-01-01

    We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region. PMID:25129146

  7. Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhu, Jing; Ling, Yang; Xu, Yun; Lu, Mingzhu; Liu, Yongping; Zhang, Changsong

    2017-01-01

    The present study aimed to investigate the association between the methylation status of the reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene and its mRNA expression levels in patients with esophageal squamous cell carcinoma (ESCC). The methylation status of RECK was analyzed by methylation-specific polymerase chain reaction (PCR), and RECK mRNA expression levels were analyzed by quantitative PCR, in 310 paired ESCC tissues. The mean RECK methylation index (MI) was 0.65 in ESCCs and 0.49 in non-tumor samples. There was a significant association between RECK methylation and the American Joint Committee on Cancer stage and lymph node metastasis in ESCC (P0.16; mean-∆∆Cq=−2.85) compared with those with hypomethylation of the RECK gene (∆MI ≤0.16; mean-∆∆Ct=−0.83), and there was a significant difference in the mRNA expression levels of RECK between those with N0–1 and N2–3 lymph node metastasis (P<0.0001). A significant correlation was observed between RECK mRNA expression levels, the MI of RECK and poor postoperative survival (P=0.0003; P<0.0001). The results of the present study suggested that promoter hypermethylation may be an important factor for loss of RECK mRNA expression and may be an indicator of poor survival in ESCC. PMID:28454343

  8. SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Yin, Y [Shandong Cancer Hospital, Jinan, Shandong (China)

    2014-06-01

    Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters were derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.

  9. Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Hamada, Junichi; Shoda, Katsutoshi; Masuda, Kiyoshi; Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei

    2016-03-29

    T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.

  10. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  11. Determination of the Physical Status (Episomal/Integral of HPV by qPCR in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fariborz Soheili

    2017-03-01

    Full Text Available Background: In cervical cancer, the carcinogenic mechanism of human papillomavirus (HPV occurs through the integration of viral DNA into the host genome. This process initiates with a disruption in the E2 open reading frame (ORF of the viral genome. Disruption of E2 ORF results in an increased expression of the viral oncoproteins, E6 and E7, by removal of E2 suppression effect on their promoters. E6 and E7 interfere with the normal cell cycle by degrading the p53 and pRb tumor suppressor proteins, respectively. Objectives: The objective of this study was to determine the physical status (episomal/integral of HPV genome in esophageal squamous cell carcinoma (ESCC. Materials and Methods: The rate of copy numbers of E2 and E6 genes in HPV-18 and HPV-16 positive samples were analyzed by quantitative polymerase chain reaction (qPCR in order to assess the physical status (episomal/integral of HPV. DNA extracts from HeLa cell line were used as the positive control. Results: The E2 gene was detected in 1 sample, co-infected with HPV-16 and HPV-18. While, E6 gene was detected in all 11 HPV positive samples. The qPCR analysis showed the presence of integrated form of viral DNA in all HPV positive samples and only 1 mixed episomal-integrated form was detected. Conclusion: The presence of integrated forms of high risk HPV-16 and HPV-18 genomes might reflect a crucial process towards malignant transformation of ESCC.

  12. Analysis for prognostic factors of radiotherapy for esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nakano, Takashi; Ito, Jun; Ito, Ichiro; Yamanaka, Mikio; Suto, Hisao; Mitsuhashi, Norio; Niibe, Hideo

    1984-01-01

    Two hundred and fifty patients with squamous cell carcinoma of the esophagus were treated at our department from 1969 to 1981 with radiotherapy involving radiation alone and pre-and/or post-operative radiotherapy. For 167 patients receiving radiotherapy alone, 144 were inoperable cases and only 60 patients could be radically treated. The others were palliative treated patients because of the locally advanced state or distant metastases or severe complications. For 83 patients receiving pre-and/or post-operative radiotherapy, 62 were radically treated. Results of radiotherapy were analyzed to elucidate factors responsible for these prognosis. Relative 5 years survival rates for radically treated patients were 26% in radiotherapy alone and 20% in pre-and/or post-operative radiotherapy respectively. In radiotherapy alone, quite a good prognoses could be obtained in the patients with tumors less than 5cm at radiografical finding (42% for 5 yrs), with tumors located in Ei, Ea esophagus (40%), with tumors of serrative and tumorous X-P types (48%, 43%, respectively) and with good radiation response at the end of radiotherapy (54%). From the analysis of 12 patients surviving more than 5 years from onset of treatment, not only tumor size less than 5cm but also radiation response was major factor responsible for the prognosis. It might be important to treat patients precisely according to their own clinical characteristics and considering tumor host relationship. (author)

  13. Effect of radiotherapy on serum SCC, CEA, CRFRA21-1, TAG72, CA199 and lymphocyte subsets in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sha Sha

    2016-09-01

    Full Text Available 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.

  14. 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.

  15. Complex Epigenetic Regulation of Chemotherapy Resistance and Biology in Esophageal Squamous Cell Carcinoma via MicroRNAs

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    Kirsten Lindner

    2018-02-01

    Full Text Available Background: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC. We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology. Methods: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, hsa-miR-130a-3p, hsa-miR-1226-3p, and hsa-miR-148a-3p. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed in six ESCC cell lines. Target analyses were performed using Western blotting and luciferase techniques. Results: MiR-130a-3p sensitized cells towards cisplatin in 100% of cell lines, miR-148a-3p in 83%, miR-125a-5p in 67%, miR-1226-3p in 50% (p ≤ 0.04. MiR-130a-3p sensitized 83% of cell lines towards 5-FU, miR-148a-3p/miR-125a-5p/miR-1226-3p only 33% (p ≤ 0.015. Several resistance-relevant pathways seem to be targeted on various levels. Bcl-2 was confirmed as a direct target of miR-130a-3p and miR-148a-3p, and p53 as a target of miR-125a-5p. All microRNAs decreased migration and adhesion, except miR-130a-3p, and increased apoptosis. Simultaneous manipulation of two microRNAs exhibited additive sensitizing effects towards cisplatin in 50% (miR-125a-5p/miR-148a-3p, and 75% (miR-148a-3p/miR-130a-3p of cell lines (p ≤ 0.006. Conclusion: Our data present strong evidence that specific microRNA signatures are responsible for drug resistance and aggressiveness of ESCC. Final functional readout of these complex processes appears to be more important than single microRNA-target interactions.

  16. Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling

    Directory of Open Access Journals (Sweden)

    Yan J

    2018-06-01

    Full Text Available Jie Yan,1,2 Pan Du,3 Yongxu Jia,2 Zhiwei Chang,2 Silin Gan,4 Xiaohan Xu,5 Yaohe Wang,3 Yanru Qin,2 Quancheng Kan1 1Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 3National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Zhengzhou University, Zhengzhou, China; 4Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 5Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Introduction: Minichromosome maintenance 10 (MCM10 is deregulated in several malignancies including cervical cancer and urothelial carcinoma. However, the expression and biologic role of MCM10 in esophageal squamous cell carcinoma (ESCC is still unknown. Methods: In this study, we performed immunohistochemistry and real-time polymerase chain reaction (PCR analysis to examine the expression of MCM10 in ESCC and adjacent normal esophageal tissues. The associations of MCM10 expression with clinicopathologic parameters of ESCC were analyzed. Ablation of MCM10 through the CRISPR/Cas9 technology was conducted and its impact on ESCC cell growth and migration was investigated. Results: The mRNA and protein expression levels of MCM10 were significantly greater in ESCC than in normal tissues (P<0.001. The expression of MCM10 was significantly associated with age at diagnosis (P=0.033, but not with gender, differentiation grade, invasion status, or tumor–node–metastasis (TNM stage. Knockout of MCM10 significantly suppressed the proliferation, colony formation, and migration capacity of EC109 ESCC cells, compared to control cells harboring wild-type MCM10. Mechanistically, MCM10 depletion markedly reduced the phosphorylation of Akt. Overexpression of constitutively active Akt

  17. [Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

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    Wang, Yi-Min; Guo, Wei; Zhang, Xiu-Feng; Li, Yan; Wang, Na; Ge, Hui; Wei, Li-Zhen; Wen, Deng-Gui; Zhang, Jian-Hui

    2006-03-01

    Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model. Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, Pnon-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89). SHMT1 1420C/T genotype could significantly reduce susceptibilities to ESCC and GCA among individuals from high risk areas in Hebei Province of China.

  18. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

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    Xingdong Chen

    Full Text Available Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC. We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001. Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

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

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    Jian Zhang

    Full Text Available BACKGROUND: Accumulated evidences demonstrated that single nucleotide polymorphisms (SNPs in mRNA 3'-untranslated region (3'-UTR may impact microRNAs (miRNAs-mediated expression regulation of oncogenes and tumor suppressors. There is a TNFAIP2 3'-UTR rs8126 T>C genetic variant which has been proved to be associated with head and neck cancer susceptibility. This SNP could disturb binding of miR-184 with TNFAIP2 mRNA and influence TNFAIP2 regulation. However, it is still unclear how this polymorphism is involved in development of esophageal squamous cell carcinoma (ESCC. Therefore, we hypothesized that the functional TNFAIP2 rs8126 SNP may affect TNFAIP2 expression and, thus, ESCC risk. METHODS: We investigated the association between the TNFAIP2 rs8126 variant and ESCC risk as well as the functional relevance on TNFAIP2 expression in vivo. Genotypes were determined in a case-control set consisted of 588 ESCC patients and 600 controls. The allele-specific regulation on TNFAIP2 expression by the rs8126 SNP was examined in normal and cancerous tissue specimens of esophagus. RESULTS: We found that individuals carrying the rs8126 CC or CT genotype had an OR of 1.89 (95%CI  = 1.23-2.85, P = 0.003 or 1.38 (95%CI  = 1.05-1.73, P = 0.017 for developing ESCC in Chinese compared with individual carrying the TT genotype. Carriers of the rs8126 CC and CT genotypes had significantly lower TNFAIP2 mRNA levels than those with the TT genotypes in normal esophagus tissues (P<0.05. CONCLUSIONS: Our data demonstrate that functional TNFAIP2 rs8126 genetic variant is a ESCC susceptibility SNP. These results support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of cancer risk.

  20. Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma.

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    Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Tanaka, Hozumi; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

    2008-11-01

    Recent studies have revealed that Glasgow prognostic score (GPS), an inflammation-based prognostic score, is associated with poor outcome in a variety of tumors. However, few studies have investigated whether GPS measured prior to neoadjuvant chemoradiotherapy (nCRT) is useful for postoperative prognosis of patients with advanced esophageal squamous cell carcinoma (ESCC). GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminaemia (L) were allocated a GPS score of 2. Patients in whom only 1 of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. All patients underwent radical en-bloc resection 3-4 weeks after nCRT. A total of 48 patients with clinical TNM stage II/III were enrolled. Univariate analyses revealed that there were significant differences in cancer-specific survival in relation to grade of response to nCRT (P = .004), lymph node status (P = .0065), lymphatic invasion (P = .0002), venous invasion (P = .0001), pathological TNM classification (P = .015), and GPS (P GPS classification showed a close relationship with lymphatic invasion, venous invasion, and number of lymph node (P = .0292, .0473, and .0485, respectively). GPS was found to be the only independent predictor of cancer-specific survival (odds ratio, 0.17; 95% confidence interval, 0.06-0.52; P = .0019). GPS, measured prior to nCRT, is an independent novel predictor of postoperative outcome in patients with advanced ESCC.

  1. Imaging modalities for staging esophageal carcinoma

    International Nuclear Information System (INIS)

    Mattioli, S.; Pezzi, A.; Brusori, S.; Brusori, G.; Di Simone, M.P.; Gozzetti, G.; Gigli, F.

    1991-01-01

    Forty-four patients affected with thoracic esophageal carcinoma underwent preoperative CT to evaluate the value of this method in both staging and assessing the resectability of esophageal tumors. The authors compared the CTfindings with intraoperative macroscopei ones, pathologic, and bronchoscopic results in mid-high neoplasms. CT staging criteria were drawn from a careful review of literature and from personal experience. thirty-nine patients were submitted to surgery, and esophagectomy was possible in 34 of them. CT diagnostic accuracy was higher in proximal esophageal tumors than in sub-bronchial ones; as for the surgical choice, CT provided fundamental guidelines,especially if the choice was a blunt esophagectomy where it is important to exclude tumoral involvement of the airways (accuracy: 82.6%) or of the aorta (accuracy: 89.7%). CT staging accuracy was limited by the low sensitivity of the method in detecting lymphatic ( local: 66.6%, distant: 64.2%) and hepatic metastates. Combined thoraco-abdominal CT, tracheo-bronchoscopy and liver US, besides MR imgaging and endoscopic US, allow a better preoperative evaluation of esophageal carcinomas

  2. Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

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    Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

    2013-01-01

    5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

  3. Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma.

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    Yokoyama, Akira; Kato, Hoichi; Yokoyama, Tetsuji; Tsujinaka, Toshimasa; Muto, Manabu; Omori, Tai; Haneda, Tatsumasa; Kumagai, Yoshiya; Igaki, Hiroyasu; Yokoyama, Masako; Watanabe, Hiroshi; Fukuda, Haruhiko; Yoshimizu, Haruko

    2002-11-01

    The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-2 (ADH2), ADH3, and glutathione S-transferase M1 (GSTM1) influence the metabolism of alcohol and other carcinogens. The ALDH2*1/2*2 genotype, which encodes inactive ALDH2, and ADH2*1/2*1, which encodes the low-activity form of ADH2, enhance the risk for esophageal cancer in East Asian alcoholics. This case-control study of whether the enzyme-related vulnerability for esophageal cancer can be extended to a general population involved 234 Japanese men with esophageal squamous cell carcinoma and 634 cancer-free Japanese men who received annual health checkups. The GSTM1 genotype was not associated with the risk for this cancer. Light drinkers (1-8.9 units/week) with ALDH2*1/2*2 had an esophageal cancer risk 5.82 times that of light drinkers with ALDH2*1/2*1 (reference category), and their risk was similar to that of moderate drinkers (9-17.9 units/week) with ALDH2*1/2*1 (odds ratio = 5.58). The risk for moderate drinkers with ALDH2*1/2*2 (OR = 55.84) exceeded that for heavy drinkers (18+ units/week) with ALDH2*1/2*1 (OR = 10.38). Similar increased risks were observed for those with ADH2*1/2*1. A multiple logistic model including ALDH2, ADH2, and ADH3 genotypes showed that the ADH3 genotype does not significantly affect the risk for esophageal cancer. For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11. In comparison with the estimated population-attributable risks for preference for strong alcoholic beverages (30.7%), smoking (53.6%) and for lower intake of green and yellow vegetables (25.7%) and fruit (37.6%), an extraordinarily high proportion of the excessive risk for esophageal cancer in the Japanese males can be attributed to drinking (90.9%), particularly drinking by persons with inactive heterozygous ALDH

  4. Expressions of HPV 16-E6 in Esophageal Carcinoma and its Clinical Significance

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    Xing Zhao

    2015-07-01

    Full Text Available Background and Objective: The role of (Human Papilloma Virus HPV in cancer of certain anatomical location, such as cervix, has been widely recognized. The present study was conducted to explore the association between HPV 16-E6 protein and esophageal squamous cell carcinoma. Methods: SP immunohistochemical method was used to examine the expression of HPV 16-E6 in 50 cases of esophageal squamous cell carcinoma, 10 cases of normal esophageal squamous cell and 10 cases of adjacent tissue. Results: The expression of HPV 16-E6 was significantly higher in esophageal carcinoma than in normal esophageal mucosa and in adjacent tissue. The expressions of HPV 16-E6 had significant correlation with invasive depth (P<0.05, but not with patient age, lymph node metastasis, tumor size (P>0.05. Conclusion: HPV 16-E6 can promote the growth and metastasis of esophageal squamous cell carcinoma and can be a prognostic factor of esophageal squamous cell carcinoma.DOI: http://dx.doi.org/10.3126/jcmsn.v10i4.12970 JCMS Nepal 2014; 10(4:1-5 

  5. Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma

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    Zhang, Hao; Lin, Wan; Kannan, Kalpana; Luo, Liming; Li, Jing; Chao, Pei-Wen; Wang, Yan; Chen, Yu-Ping; Gu, Jiang; Yen, Laising

    2013-01-01

    It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10, as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response. PMID:24243830

  6. The Glasgow Prognostic Score. An useful tool to predict survival in patients with advanced esophageal squamous cell carcinoma.

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    Henry, Maria Aparecida Coelho de Arruda; Lerco, Mauro Masson; de Oliveira, Walmar Kerche; Guerra, Anderson Roberto; Rodrigues, Maria Aparecida Marchesan

    2015-08-01

    To evaluate the usefulness of the Glasgow Prognostic Score (GPS) in patients with esophageal carcinoma (EC). A total of 50 patients with EC were analyzed for GPS, nutritional and clinicopathologic parameters. Patients with CRP ≤ 1.0mg/L and albumin ≥ 3.5mg/L were considered as GPS = 0. Patients with only CRP increased or albumin decreased were classified as GPS = 1 and patients with CRP > 1.0mg/L and albumin L were considered as GPS = 2. GPS of 0, 1 and 2 were observed in seven, 23 and 20 patients, respectively. A significant inverse relationship was observed between GPS scores and the survival rate. The survival rate was greatest in patients with GPS = 0 and significantly higher than those from patients with GPS = 1 and GPS = 2. Minimum 12-month survival was observed in 71% patients with GPS = 0 and in 30% patients with GPS = 1. None of the patients with GPS = 2 survived for 12 months. A significant relationship between CRP or albumin individually and the survival rate was observed. No significant relationship among nutritional, clinic pathological parameters and survival was found. Glasgow Prognostic Score is an useful tool to predict survival in patients with esophageal carcinoma.

  7. Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia.

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    Yamasaki, Yuki; Tsukada, Tomoya; Aoki, Tatsuya; Haba, Yusuke; Hirano, Katsuhisa; Watanabe, Toshifumi; Kaji, Masahide; Shimizu, Koichi

    2017-01-01

    We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a "0-IIb+IIa" lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage.

  8. Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia

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    Yuki Yamasaki

    2017-01-01

    Full Text Available We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a “0-IIb+IIa” lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage.

  9. Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

    International Nuclear Information System (INIS)

    Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

    2001-01-01

    We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

  10. Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma?

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    Tanoglu A

    2014-03-01

    Full Text Available Alpaslan Tanoglu,1 Ergenekon Karagoz,2 Nurettin Yiyit,3 Ufuk Berber4 1Department of Gastroenterology, 2Department of Infectious Diseases and Clinical Microbiology, 3Department of Thoracic Surgery, 4Department of Pathology, GATA Haydarpasa Training Hospital, Uskudar, TurkeyWe read with interest the recent article entitled "Combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma" by Feng et al.1 In their study, authors aimed to investigate the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Finally, they concluded that combination of NLR and PLR is a useful predictor of postoperative survival in patients with ESCC and combination of these parameters is superior to NLR or PLR as a predictive factor in patients with ESCC. We would like to thank the authors for their contribution.View original paper by Feng and colleagues.

  11. The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients.

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    Zhou, Ya-Xing; Zhou, Ke-Ming; Liu, Qian; Wang, Hui; Wang, Wen; Shi, Yi; Ma, Yu-Qing

    2018-04-09

    Glucose transporter type 1 (Glut1) plays a crucial role in cancer-specific metabolism. We explored the expression of Glut1 and c-myc, the relationship between them and the effect of Glut1, c-myc on prognosis in esophageal squamous cell carcinoma. Immunohistochemistry was used to examine the expression of Glut1 and c-myc. χ 2 test analyzes the relationship between c-myc, Glut1 and pathological parameters. Spearman correlation analyzes the relationship between c-myc and Glut1. Survival analysis was used to investigate the effect of Glut1 and c-myc on prognosis. Glut1 positivity was associated with tumor size (p C-myc positivity was associated with tumor location (p = 0.015), depth of invasion (p = 0.022) and lymph node metastasis (p = 0.035). There was a positive correlation between c-myc and Glut1 (r = 0.321). Patients with Glut1 c-myc co-expression had poorer prognosis. Inhibiting Glut1 c-myc co-expression may improve the prognosis of esophageal squamous cell carcinoma.

  12. Areca nut is associated with younger age of diagnosis, poor chemoradiotherapy response, and shorter overall survival in esophageal squamous cell carcinoma.

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    Chang-Han Chen

    Full Text Available Areca nut chewing is carcinogenic to humans. However, little is known about the impact of areca nut chewing on esophageal squamous cell carcinoma (ESCC.We retrospectively reviewed 286 ESCC patients who received surgery or preoperative chemoradiotherapy followed by surgery at our institution. Background characteristics including areca nut chewing history were analyzed. The 4-nitroquinoline 1-oxide (4-NQO-induced murine ESCC model was used to test the impact of arecoline, a main constituent of areca nut, on ESCC.Compared to patients without areca nut chewing history, patients with areca nut chewing history had overall a younger age of onset (Mean age: 56.75 versus 52.68 yrs, P<0.001 and significantly worse overall survival than those without areca nut chewing history (P = 0.026. Among patients who received surgery, the overall survival rates were not significantly different between those with or without areca nut chewing history. Among patients who received preoperative chemoradiotherapy followed by surgery, those with areca nut chewing history had a significantly lower pathologic complete response rate (P = 0.002 and lower overall survival rate (P = 0.002 than those without. In the murine ESCC model, the incidence of esophageal invasive squamous cell carcinoma was 40% in mice exposed to concomitant 4-NQO and arecoline treatment for 8 weeks and 6% in mice exposed to 4-NQO only for 8 weeks (P = 0.037.Our results indicate that areca nut chewing history is significantly associated with younger age of onset, poor response to chemoradiotherapy, and shorter overall survival in ESCC patients. Arecoline, a main constituent of areca nut, accelerates esophageal tumorigenesis in the 4-NQO-induced murine ESCC model.

  13. The value of the combination of hemoglobin, albumin, lymphocyte and platelet in predicting platinum-based chemoradiotherapy response in male patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Cong, Lihong; Hu, Likuan

    2017-05-01

    The predictive value of HALP in esophageal cancer is currently unclear. We aimed to evaluate the value of HALP in predicting platinum-based definitive chemoradiotherapy response in male patients with esophageal squamous cell carcinoma. Data from all newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) were collected from January 1, 2010 to December 31, 2014 in Qilu Hospital. The treatment protocol was definitive chemoradiotherapy consisting of docetaxel plus cisplatin or carboplatin. The response assessment of the definitive chemoradiotherapy was based on computed tomography (CT) and barium meal test results. A total of 39 patients were included in the present study. The median value of HALP was 48.34. The chemoradiotherapy response rate of patients in the low HALP value group was 35%, compared with 78.95% of patients in the high HALP group (P=0.010). Additionally, the median progression-free survival in the 2 patient groups was significantly different (10.7 vs. 24.7m, P=0.041). In the multivariate analysis, patients with HALP higher than 48.34 had longer progression-free survival than patients with HALP of 48.34 or less (HR 2.745; 95% CI, 1.176-6.408; P=0.020). However, there was no significant difference for overall survival between the high HALP group and low HALP group. Our data suggested that pretreatment HALP could predict the platinum-based chemoradiotherapy response of tumors and progression free survival in male patients with ESCC. Therefore, HALP could be used in routine clinical practice to guide the therapeutic strategies for individual treatment in patients with ESCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Vascular density of superficial esophageal squamous cell carcinoma determined by direct observation of resected specimen using narrow band imaging with magnifying endoscopy.

    Science.gov (United States)

    Kikuchi, D; Iizuka, T; Hoteya, S; Nomura, K; Kuribayashi, Y; Toba, T; Tanaka, M; Yamashita, S; Furuhata, T; Matsui, A; Mitani, T; Inoshita, N; Kaise, M

    2017-11-01

    Observation of the microvasculature using narrow band imaging (NBI) with magnifying endoscopy is useful for diagnosing superficial squamous cell carcinoma. Increased vascular density is indicative of cancer, but not many studies have reported differences between cancerous and noncancerous areas based on an objective comparison. We observed specimens of endoscopic submucosal dissection (ESD) using NBI magnification, and determined the vascular density of cancerous and noncancerous areas. A total of 25 lesions of esophageal squamous cell carcinoma that were dissected en bloc by ESD between July 2013 and December 2013 were subjected to NBI magnification. We constructed a device that holds an endoscope and precisely controls the movement along the vertical axis in order to observe submerged specimens by NBI magnification. NBI image files of both cancerous (pathologically determined invasion depth, m1/2) and surrounding noncancerous areas were created and subjected to vascular density assessment by two endoscopists who were blinded to clinical information. The invasion depth was m1/2 in 20, m3/sm1 in four and sm2 in one esophageal cancer lesion. Mean vascular density was significantly increased in cancerous areas (37.6 ± 16.3 vessels/mm2) compared with noncancerous areas (17.6 ± 10.0 vessels/mm2) (P squamous cell carcinoma. The rates of agreement between vascular density values determined by two independent operators were high. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

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    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

  16. Esophageal stenosis after radiation for laryngeal carcinoma

    International Nuclear Information System (INIS)

    Takeuchi, Kazuhiko; Majima, Yuichi; Nomoto, Yoshito; Okamoto, Yasunori; Sakakura, Yasuo

    1995-01-01

    A 57-year-old female received radiation with 60 Gy, delivered by Cobalt 60 unit for laryngeal carcinoma in 1989. Several months later she complained of dyspnea, and fiberscopic observation revealed fixation of bilateral vocal cords and a swelling of bilateral arytenoid portions. In 1990, she developed difficulty swallowing. Further examinations showed that the cervical esophagus was extremely narrowed but no malignancy was found either in the larynx or in the esophagus. We suspected that the esophageal stenosis was caused by post-radiation fibrosis. (author)

  17. Esophageal stenosis after radiation for laryngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Kazuhiko; Majima, Yuichi; Nomoto, Yoshito; Okamoto, Yasunori; Sakakura, Yasuo [Mie Univ., Tsu (Japan). School of Medicine

    1995-10-01

    A 57-year-old female received radiation with 60 Gy, delivered by Cobalt 60 unit for laryngeal carcinoma in 1989. Several months later she complained of dyspnea, and fiberscopic observation revealed fixation of bilateral vocal cords and a swelling of bilateral arytenoid portions. In 1990, she developed difficulty swallowing. Further examinations showed that the cervical esophagus was extremely narrowed but no malignancy was found either in the larynx or in the esophagus. We suspected that the esophageal stenosis was caused by post-radiation fibrosis. (author).

  18. Esophageal bypass for the treatment of bronchoesophageal fistula in a case of squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Uchibori, Ken; Suhara, Kozo; Chiba, Sahoko; Tsuchiya, Kimitake; Fujie, Toshihide; Tamaoka, Meiyo; Sakashita, Hiroyuki; Inase, Naohiko

    2013-01-01

    Bronchoesophageal fistula in lung cancer is very rare. While these cases usually receive an implanted expandable stent in the esophagus or trachea, no standard therapeutic strategy has been developed. Our patient was a 63-year-old woman who had visited a local clinic because of productive cough. Lung cancer was suspected from her chest CT findings and an additional work-up with bronchoscopy and sputum cytology revealed squamous cell cancer of the lung. She also had obstructive pneumonia caused by a severe stricture from the trachea to the left main bronchus. Radiochemotherapy was begun for treatment of the obstruction by the tumor, with concurrent administration of antibiotics. In spite of apparent improvement of the disease by the fifth week of treatment, a large bronchoesophageal fistula appeared at the inlet of the left main bronchus. Stent implantation was judged contraindicated for either the trachea or the esophagus, because of the large size of the fistula. We performed an esophageal bypass procedure in an attempt to restore her dysphagia She regained oral intake ability and she required no antibiotic administration for pneumonia after the procedure. We performed an esophageal bypass for the treatment of a bronchoesophageal fistula that had occurred during radiochemotherapy for lung cancer. The procedure was successful and the patient regained the ability to eat from the mouth. The esophageal bypass procedure might be a viable choice of treatment for tracheo- or bronchoesophageal fistula in lung cancer patients. (author)

  19. Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression.

    Science.gov (United States)

    Feng, Feiyue; Qiu, Bin; Zang, Ruochuan; Song, Peng; Gao, Shugeng

    2017-04-25

    Natural antisense transcripts (NATs) as one of the most diverse classes of long noncoding RNAs (lncRNAs), have been demonstrated involved in fundamental biological processes in human. Here, we reported that human prohibitin gene pseudogene 1 (PHBP1) was upregulated in ESCC, and increased PHBP1 expression in ESCC was associated with clinical advanced stage. Functional experiments showed that PHBP1 knockdown inhibited ESCC cells proliferation, colony formation and xenograft tumor growth in vitro and in vivo by causing cell-cycle arrest at the G1-G0 phase. Mechanisms analysis revealed that PHBP1 transcript as an antisense transcript of PHB is partially complementary to PHB mRNA and formed an RNA-RNA hybrid with PHB, consequently inducing an increase of PHB expression at both the mRNA and protein levels. Furthermore, PHBP1 expression is strongly correlated with PHB expression in ESCC tissues. Collectively, this study elucidates an important role of PHBP1 in promoting ESCC partly via increasing PHB expression.

  20. Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

    International Nuclear Information System (INIS)

    Lee, Su Jin; Kim, Sungmin; Kim, Moonjin; Lee, Jeeyun; Park, Yeon Hee; Im, Young-Hyuck; Park, Se Hoon

    2015-01-01

    The aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma. Patients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000 mg/m 2 twice daily + D1 cisplatin 75 mg/m 2 , every 3 weeks) or the CP arm (D1–14 capecitabine 1000 mg/m 2 twice daily + D1, 8 paclitaxel 80 mg/m 2 , every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life. A total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0–6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9–8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2–11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4–17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms. Both CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma

  1. A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

    Science.gov (United States)

    Wang, Di; Yang, Xin-lu; Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

    2016-04-05

    The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.

  2. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  3. Expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma and their correlations.

    Science.gov (United States)

    Ping, Fu-Min; Liu, Gui-Jing; Liu, Zhi-Jun; Li, Hai-Bin; Zhai, Jian-Wen; Li, Shu-Xia; Liu, Yue-Mei; Li, Bao-Wei; Wei, Hong

    2015-01-01

    To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (PkB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (PkB p65 in ESCC tissues (PkB p65.

  4. 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.

  5. Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia

    OpenAIRE

    Yamasaki, Yuki; Tsukada, Tomoya; Aoki, Tatsuya; Haba, Yusuke; Hirano, Katsuhisa; Watanabe, Toshifumi; Kaji, Masahide; Shimizu, Koichi

    2017-01-01

    We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a “0-IIb+IIa” lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped ...

  6. Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma.

    Science.gov (United States)

    Fatima, Sarwat; Chui, Chung H; Tang, Wing K; Hui, Kin S; Au, Ho W; Li, Wing Y; Wong, Mei M; Cheung, Filly; Tsao, S W; Lam, King Y; Beh, Philip S L; Wong, John; Law, Simon; Srivastava, Gopesh; Ho, Kwok P; Chan, Albert S C; Tang, Johnny C O

    2006-01-01

    Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to delta catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming

  7. 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)

    Bao, Yong; Rong, TieHua; Li, Qun; Liu, Hui; Liu, ShiLiang; Zhou, QiChao; Cai, PeiQiang; Anfossi, Simone; Li, QiaoQiao; Hu, YongHong; Liu, MengZhong; Fu, JianHua

    2013-01-01

    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

  8. Occurrence and clinical features of brain metastasis after chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Kanemoto, Ayae; Hashimoto, Takayuki; Harada, Hideyuki; Asakura, Hirofumi; Ogawa, Hirofumi; Furutani, Kazuhisa; Boku, Narikazu; Nakasu, Yoko; Nishimura, Tetsuo

    2011-01-01

    Brain metastasis from esophageal carcinoma has been considered rare and survival following esophageal carcinoma with distant metastasis is poor. The purpose of this report was to clarify cumulative incidence and risk factors for brain metastasis after chemoradiotherapy for esophageal carcinoma, and to consider recommended treatments for brain metastasis from esophageal carcinoma. We reviewed 391 patients treated with chemoradiotherapy. Median age was 65 years. Clinical stages were I, II, III, and IV in 32, 47, 150, and 162 patients, respectively. Brain imaging was performed usually when patients revealed neurological symptoms. The 3-year cumulative incidence of brain metastasis after chemoradiotherapy was 6.6%. There were 4 patients with single metastasis and 8 with multiple metastases. Initial clinical stages were II, III, and IV in 1, 2, and 9 patients, respectively. Histology included squamous cell carcinoma in 10 patients and others in 2 patients. Univariate analysis demonstrated M factor, distant lymph node relapse, and recurrent lung and liver metastasis as significant risk factors of brain metastasis (P<0.05). Median survival time after diagnosis of brain metastasis was 2.1 months. Brain metastasis was not directly related to cause of mortality. The causes were extracranial tumor deterioration in 8 patients and infection in 4 patients. Brain metastasis may increase in the future with improving survival from esophageal carcinoma. However, considering the poor survival after diagnosis of brain metastasis, short-term palliative therapy for brain metastasis appears preferable to vigorous long-term therapy. (author)

  9. Serum levels of chemical elements in esophageal squamous cell carcinoma in Anyang, China: a case-control study based on machine learning methods.

    Science.gov (United States)

    Lin, Tong; Liu, Tiebing; Lin, Yucheng; Zhang, Chaoting; Yan, Lailai; Chen, Zhongxue; He, Zhonghu; Wang, Jingyu

    2017-09-24

    Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal carcinoma with extremely aggressive nature and low survival rate. The risk factors for ESCC in the high-incidence areas of China remain unclear. We used machine learning methods to investigate whether there was an association between the alterations of serum levels of certain chemical elements and ESCC. Primary healthcare unit in Anyang city, Henan Province of China. 100 patients with ESCC and 100 healthy controls matched for age, sex and region were included. Primary outcome was the classification accuracy. Secondary outcome was the p Value of the t-test or rank-sum test. Both traditional statistical methods of t-test and rank-sum test and fashionable machine learning approaches were employed. Random Forest achieves the best accuracy of 98.38% on the original feature vectors (without dimensionality reduction), and support vector machine outperforms other classifiers by yielding accuracy of 96.56% on embedding spaces (with dimensionality reduction). All six classifiers can achieve accuracies more than 90% based on the single most important element Sr. The other two elements with distinctive difference are S and P, providing accuracies around 80%. More than half of chemical elements were found to be significantly different between patients with ESCC and the controls. These results suggest clear differences between patients with ESCC and controls, implying some potential promising applications in diagnosis, prognosis, pharmacy and nutrition of ESCC. However, the results should be interpreted with caution due to the retrospective design nature, limited sample size and the lack of several potential confounding factors (including obesity, nutritional status, and fruit and vegetable consumption and potential regional carcinogen contacts). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted

  10. Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression.

    Science.gov (United States)

    Zhang, Jianguo; Zhu, Junya; Yang, Lei; Guan, Chengqi; Ni, Runzhou; Wang, Yuchan; Ji, Lili; Tian, Ye

    2015-09-01

    CtBP2, as a transcriptional corepressor of epithelial-specific genes, has been reported to promote tumor due to upregulating epithelial-mesenchymal transition (EMT) in cancer cells. CtBP2 was also demonstrated to contribute to the proliferation of esophageal squamous cell carcinoma (ESCC) cells through a negative transcriptional regulation of p16(INK4A). In this study, for the first time, we reported that CtBP2 expression, along with CCNH/CDK7, was higher in ESCC tissues with lymph node metastases than in those without lymph node metastases. Moreover, both CtBP2 and CCNH/CDK7 were positively correlated with E-cadherin, tumor grade, and tumor metastasis. However, the concrete mechanism of CtBP2's role in enhancing ESCC migration remains incompletely understood. We confirmed that CCNH/CDK7 could directly interact with CtBP2 in ESCC cells in vivo and in vitro. Furthermore, our data demonstrate for the first time that CtBP2 enhanced the migration of ESCC cells in a CCNH/CDK7-dependent manner. Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of ESCC.

  11. [Esophagobronchial fistula and empyema resulting from esophageal carcinoma].

    Science.gov (United States)

    Hippo, Y; Kawana, A; Yoshizawa, A; Koshino, T; Toyota, E; Kobayashi, N; Kobori, O; Arai, T; Kudo, K; Kabe, J

    1997-05-01

    A 59-year-old woman was admitted to the hospital with a one-month history of hemoptysis, generalized fatigue, and a high fever. A chest X-ray film obtained on admission showed a massive right-sided pleural effusion. Examination of an aspirate showed a high level of amylase, and bacteria that were the same as oral bacteria. Closed drainage yielded ichorous pus and food residues, which led us to the diagnosis of empyema caused by esophageal perforation. Esophagography and fiberoptic esophagoscopy revealed that an esophagobronchial fistula related to an advanced esophageal carcinoma had caused the empyema. Surgical resection was done, and the patient was alive at the time of this writing, 7 months after she was first treated. Esophageal carcinoma is sometimes accompanied by esophagobronchial fistula. Patients with this condition usually have severe respiratory symptoms; those presenting with empyema are rare. Esophageal carcinoma must be carefully ruled out as the cause of empyema.

  12. Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shigeoka, Manabu; Urakawa, Naoki; Nishio, Mari; Takase, Nobuhisa; Utsunomiya, Soken; Akiyama, Hiroaki; Kakeji, Yoshihiro; Komori, Takahide; Koma, Yu-ichiro; Yokozaki, Hiroshi

    2015-01-01

    Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment

  13. Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Muto, Manabu; Ohtsu, Atsushi; Boku, Narikazu; Yoshida, Shigeaki [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East; Miyata, Yoshinori; Shioyama, Yasukazu

    2001-06-01

    Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 deg C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications. (author)

  14. Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy

    International Nuclear Information System (INIS)

    Muto, Manabu; Ohtsu, Atsushi; Boku, Narikazu; Yoshida, Shigeaki; Miyata, Yoshinori; Shioyama, Yasukazu

    2001-01-01

    Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 deg C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications. (author)

  15. Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma--a retrospective analysis.

    Science.gov (United States)

    Yamashita, Hideomi; Okuma, Kae; Wakui, Reiko; Kobayashi-Shibata, Shino; Ohtomo, Kuni; Nakagawa, Keiichi

    2011-02-01

    To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy. One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume. All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local=20 and distant=20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  17. Merkel Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  18. Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis.

    Science.gov (United States)

    Tustumi, F; Bernardo, W M; da Rocha, J R M; Szachnowicz, S; Seguro, F C; Bianchi, E T; Sallum, R A A; Cecconello, I

    2017-10-01

    Achalasia of the cardia is associated with an increased risk of esophageal carcinoma. The real burden of achalasia at the malignancy genesis is still a controversial issue. Therefore, there are no generally accepted recommendations on follow-up evaluation for achalasia patients. This study aims to estimate the risk of esophageal adenocarcinoma and squamous cell carcinoma in achalasia patients. We searched for association between carcinoma and esophageal achalasia in databases up to January 2017 to perform a systematic review and meta-analysis. A total of 1,046 studies were identified from search strategy, of which 40 were selected for meta-analysis. A cumulative number of 11,978 esophageal achalasia patients were evaluated. The incidence of squamous cell carcinoma was 312.4 (StDev 429.16) cases per 100,000 patient-years at risk. The incidence of adenocarcinoma was 21.23 (StDev 31.6) cases per 100,000 patient-years at risk. The prevalence for esophageal carcinoma was 28 carcinoma cases in 1,000 esophageal achalasia patients (CI 95% 2, 39). The prevalence for squamous cell carcinoma was 26 cases in 1,000 achalasia patients (CI 95% 18, 39) and for adenocarcinoma was 4 cases in 1,000 achalasia patients (CI 95% 3, 6).The absolute risk increase for squamous cell carcinoma was 308.1 and for adenocarcinoma was 18.03 cases per 100,000 patients per year. To the best of our knowledge, this is the first meta-analysis estimating the burden of achalasia as an esophageal cancer risk factor. The high increased risk rate for cancer in achalasia patients points to a strict endoscopic surveillance for these patients. Also, the increased risk for developing adenocarcinoma in achalasia patients suggests fundoplication after myotomy, to avoid esophageal reflux and Barret esophagus, a known risk factor for adenocarcinoma. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please

  19. Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

    Science.gov (United States)

    LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

    2010-01-01

    The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

  20. Dietary patterns and the risk of esophageal squamous cell carcinoma: A population-based case-control study in a rural population.

    Science.gov (United States)

    Liu, Xudong; Wang, Xiaorong; Lin, Sihao; Lao, Xiangqian; Zhao, Jin; Song, Qingkun; Su, Xuefen; Tak-Sun Yu, Ignatius

    2017-02-01

    Few studies were available in exploring the roles of dietary patterns in the development of esophageal cancer, especially in China. This study aimed to investigate the roles of dietary patterns in the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese rural population. A population-based cases-control study was designed and conducted in Yanting County, Sichuan Province of China during two years (between June 2011 and May 2013). A total of 942 pairs of ESCC cases and controls were recruited. A food frequency questionnaire was adopted to collect information of dietary consumption. Dietary patterns were extracted by using principle component and factor analysis based on 24 dietary groups. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by using logistic regression model, with adjustment for possible confounding variables. Four major dietary patterns were identified, which were labeled as "prudent", "vegetable and fruits", "processed food" and "alcohol drinking". In comparison of the highest with the lowest quartiles of pattern scores, the processed food pattern (OR: 2.84, 95% CI: 2.13-3.80) and alcohol drinking pattern (OR: 2.69, 95% CI: 1.95-3.71) were significantly associated with an increased risk of ESCC, while the vegetable and fruit pattern (OR: 0.70, 95% CI: 0.53-0.92) was associated with reduced risk by 30%. The prudent pattern was associated with a reduced risk by 33% (OR: 0.67, 95% CI: 0.50-0.88) in a multivariate logistic regression model, but no statistical significance was reached in a composite model. The results suggest an important role of dietary patterns in ESCC. Diets rich in vegetables and fruits may decrease the risk of ESCC, whereas diets rich in processed food and drinking alcohol may increase the risk. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  1. HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case–control study

    International Nuclear Information System (INIS)

    Kayamba, Violet; Bateman, Allen C; Asombang, Akwi W; Shibemba, Aaron; Zyambo, Kanekwa; Banda, Themba; Soko, Rose; Kelly, Paul

    2015-01-01

    There is emerging evidence that esophageal cancer occurs in younger adults in sub-Saharan Africa than in Europe or North America. The burden of human immunodeficiency virus (HIV) is also high in this region. We postulated that HIV and human papillomavirus (HPV) infections might contribute to esophageal squamous cell carcinoma (OSCC) risk. This was a case–control study based at the University Teaching Hospital in Lusaka, Zambia. Cases were patients with confirmed OSCC and controls had completely normal upper endoscopic evaluations. A total of 222 patients were included to analyze the influence of HIV infection; of these, 100 patients were used to analyze the influence of HPV infection, alcohol, smoking, and exposure to wood smoke. The presence of HIV infection was determined using antibody kits, and HPV infection was detected by polymerase chain reaction. HIV infection on its own conferred increased risk of developing OSCC (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.0–5.1; P = 0.03). The OR was stronger when only people under 60 years were included (OR 4.3; 95% CI 1.5–13.2; P = 0.003). Cooking with charcoal or firewood, and cigarette smoking, both increased the odds of developing OSCC ([OR 3.5; 95% CI 1.4–9.3; P = 0.004] and [OR 9.1; 95% CI 3.0–30.4; P < 0.001], respectively). There was no significant difference in HPV detection or alcohol intake between cases and controls. We conclude that HIV infection and exposure to domestic and cigarette smoke are risk factors for OSCC, and HPV immunization unlikely to reduce OSCC incidence in Zambia

  2. Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Feng JF

    2013-11-01

    Full Text Available Ji-Feng Feng,1 Ying Huang,2 Jin-Shi Liu1 1Department of Thoracic Surgery, 2Department of Operating Theatre, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Background: Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various types of cancers. This study investigated the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, collectively named the CNP, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Materials and methods: The CNP was calculated on the basis of data obtained on the day of admission: patients with both elevated NLR (>3.45 and PLR (>166.5 were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. Results: The CNP was associated with tumor length (P<0.001, differentiation (P=0.021, depth of invasion (P<0.001, and nodal metastasis (P<0.001. No significant differences were found between the CNP and morbidity. However, significant differences were found between the CNP and mortality (P<0.001. The overall survival in the CNP 0, CNP 1, and CNP 2 groups were 63.4%, 50.0%, and 20.2%, respectively (CNP 0 versus CNP 1, P=0.014; CNP 1 versus CNP 2, P<0.001. Multivariate analyses showed that CNP was a significant predictor of overall survival. CNP 1–2 had a hazard ratio (HR of 1.964 (95% confidence interval [CI]: 1.371–2.814, P<0.001 for overall survival. CNP (HR =1.964, P<0.001 is superior to NLR (HR =1.310, P=0.053 or PLR (HR =1.751, P<0.001 as a predictive factor. Conclusion: The CNP is considered a useful predictor of postoperative survival in patients with ESCC. The CNP is superior to NLR or PLR as a predictive factor in patients with ESCC. Keywords: esophageal squamous cell carcinoma (ESCC, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, overall survival

  3. 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)

    Ma, Hongxia; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, Qingyi

    2011-01-01

    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 (P trend = 0.046), particularly for non-oropharyngeal tumors (P trend = 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

  4. Combined heavy smoking and drinking predicts overall but not disease-free survival after curative resection of locoregional esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sun P

    2016-07-01

    Full Text Available Peng Sun,1,2,* Cui Chen,3,* Fei Zhang,1,2,* Hang Yang,1,2 Xi-Wen Bi,1,2 Xin An,1,2 Feng-Hua Wang,1,2 Wen-Qi Jiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 3Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The prognostic impact of smoking and drinking on esophageal squamous cell carcinoma (ESCC was scarcely discussed. We investigated the prognostic value of smoking and drinking and their relationships with clinicopathological characteristics in a large cohort of patients with locoregional ESCC.Patients and methods: We retrospectively analyzed 488 patients who underwent curative treatment at a single institution between January 2007 and December 2008. A chi-square test was used to evaluate the relationships between smoking and drinking and clinicopathological variables, the Kaplan–Meier method was used for 5-year overall survival (OS and disease-free survival, and Cox proportional hazards models were applied for univariate and multivariate analyses of variables with respect to OS and disease-free survival.Results: Heavy smokers were more likely to have advanced Tumor-Node-Metastases (TNM stage and higher neutrophil/lymphocyte ratio at diagnosis (P<0.05. Drinkers were more likely to have advanced TNM stage, to present with a larger tumor, and to undergo multidisciplinary treatment (P<0.05. For patients who used neither heavy tobacco nor alcohol, used either tobacco or alcohol, and used both, the 5-year OS rates and OS times were 57.4%, 46.4%, and 39.1% (P<0.05 and not reached, 55.2 months, and 41.2 months (P<0.05, respectively. On multivariate analysis, patients who both heavily smoked and drank had 1.392 times the risk of dying during follow-up compared with

  5. Phosphorylation of ETS-1 is a critical event in DNA polymerase iota-induced invasion and metastasis of esophageal squamous cell carcinoma.

    Science.gov (United States)

    He, Chao; Wu, Shuhua; Gao, Aidi; Su, Ye; Min, Han; Shang, Zeng-Fu; Wu, Jinchang; Yang, Li; Ding, Wei-Qun; Zhou, Jundong

    2017-12-01

    An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that downregulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells. Kaplan-Meier analysis, based on 93 clinical tissue samples, revealed that ETS-1 phosphorylation at threonine-38 is associated with poor prognosis of ESCC patients. The present study thus demonstrates that phosphorylation of ETS-1 is a critical event in the Pol ι-induced invasion and metastasis of ESCC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. 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)

    Lindkvist, Björn; Nagel, Gabriele; Jonsson, Håkan; Selmer, Randi; Ulmer, Hanno; Tretli, Steinar; Stattin, Pär; Manjer, Jonas; Johansen, Dorthe; Stocks, Tanja; Concin, Hans; Bjørge, Tone; Almquist, Martin; Häggström, Christel; Engeland, Anders; Hallmans, Göran

    2014-01-01

    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

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

    International Nuclear Information System (INIS)

    Andolfo, Immacolata; Orditura, Michele; Ciardiello, Fortunato; De Vita, Fernando; Zollo, Massimo; Petrosino, Giuseppe; Vecchione, Loredana; De Antonellis, Pasqualino; Capasso, Mario; Montanaro, Donatella; Gemei, Marica; Troncone, Giancarlo; Iolascon, Achille

    2011-01-01

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

  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. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

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    Xiang Yuan

    2017-11-01

    Full Text Available Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC. We further define the molecular circuits that govern these processes by showing that SET modulated DOCK7/RAC1 and cofilin signaling events. Moreover, a detailed analysis of the spatial distribution of RAC1 and cofilin allowed us to decipher the synergistical contributions of the two in coordinating the advancing dynamics by measuring architectures, polarities, and cytoskeletal organizations of the lamellipodia leading edges. In further investigations in vivo, we identified their unique role at multiple levels of the invasive cascade for SET cell and indicate the necessity for their functional balance to enable efficient invasion as well. Additionally, SET epigenetically repressed miR-30c expression by deacetylating histones H2B and H4 on its promoter, which was functionally important for the biological effects of SET in our cell-context. Finally, we corroborated our findings in vivo by evaluating the clinical relevance of SET signaling in the metastatic burden in mice and a large series of patients with ESCC at diagnosis, observing it's significance in predicting metastasis formation. Our findings uncovered a novel signaling network initiated by SET that epigenetically modulated ESCC properties and suggest that targeting the regulatory axis might be a promising strategy to inhibit migration and metastasis.

  10. A decision tree-based combination of ezrin-interacting proteins to estimate the prognostic risk of patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    He, Jian-Zhong; Wu, Zhi-Yong; Wang, Shao-Hong; Ji, Xia; Yang, Cui-Xia; Xu, Xiu-E; Liao, Lian-Di; Wu, Jian-Yi; Li, En-Min; Zhang, Kai; Xu, Li-Yan

    2017-08-01

    Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Socioeconomic status is inversely associated with esophageal squamous cell carcinoma risk: results from a population-based case-control study in China

    Science.gov (United States)

    Suo, Chen; Yuan, Ziyu; Cheng, Hongwei; Zhang, Yuechan; Jin, Li; Lu, Ming; Chen, Xingdong; Ye, Weimin

    2018-01-01

    Socioeconomic status (SES) is suspected to influence the risk of esophageal squamous-cell carcinoma (ESCC) in China, however, the evidence is still inconclusive and the selection of SES indicators remains inconsistent. In current study, we examined the association between SES and risk of ESCC based on a population-based case-control study in Taixing, China, with 1298 histopathology-confirmed cases and 1900 controls recruited between October 2010 and September 2013. Data on SES indicators was collected using a structured questionnaire. We constructed a composite wealth score based on the ownership of a series of household appliances and other variables by using multiple correspondence analysis (MCA). We used unconditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of ESCC in association with SES indicators. SES was inversely associated with ESCC risk in current study. Higher education (secondary high school or above vs illiteracy, OR=0.60, 95%CI, 0.41-0.87), larger house area per person (>70 vs 5 years also had a lower ESCC risk. Whereas physical labor (very active vs sedentary, OR=1.69, 95%CI, 1.27-2.26) and larger families (≥6 vs <3 in household, OR=1.63, 95%CI, 1.30-2.03) increased the risk of ESCC. These findings confirm the strong inverse association between SES and ESCC risk. Future studies are needed to verify these findings and identify contributing factors underlying the observed associations. PMID:29467939

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

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    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.

  13. Prognostic value of TP53 transcriptional activity on p21 and bax in patients with esophageal squamous cell carcinomas treated by definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Michel, Pierre; Magois, Karine; Robert, Valerie; Chiron, Anne; Lepessot, Florence; Bodenant, Corinne; Roque, Isabelle; Seng, Sok H.; Frebourg, Thierry; Paillot, Bernard

    2002-01-01

    Purpose: The aim of this study was to evaluate biologic factors on survival and clinical response after definitive concomitant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods and Materials: TP53 protein hyperexpression (immunochemistry [IHC]) and functional assay (FA) of TP53, measuring the ability of TP53 to transactivate p21 and bax reporter systems, were performed in patients with ESCC treated by CRT. The impact of parameters studied on survival and clinical response to CRT was assessed. Results: Thirty-eight patients with ESCC were included. TP53 alterations were detected in 84.2% of cases with FA. All TP53 mutations abolished the transactivation of p21 and bax reporter systems. After CRT, complete response rate was 55.3%. The median survival of the population was 17.5 months. Serum albumin (p=0.002), weight loss <10% (p=0.005), and response to treatment (p<0.001) were significantly linked with survival. TP53 alteration in FA was not significantly predictive of response to CRT (p=0.132) nor survival (p=0.154). Conclusions: Our results suggest that wild-type TP53 in ESCC could be associated with good response to definitive CRT. However, the small rate of ESCC with wild-type TP53 suggests that systematic determination of TP53 status is not appropriate for the management of the ESCC population

  14. Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trail

    International Nuclear Information System (INIS)

    Meng, Xue; Wang, Jianhua; Sun, Xindong; Wang, Lvhua; Ye, Ming; Feng, Pingbo; Zhu, Guangying; Lu, You; Han, Chun; Zhu, Shuchai; Liao, Zhongxing; Yu, Jinming

    2013-01-01

    Background and purpose: This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). Material and methods: Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400 mg/m 2 loading dose on day 1; and on day 1 of the 2nd–7th weeks: cetuximab 250 mg/m 2 , paclitaxel 45 mg/m 2 , and cisplatin 20 mg/m 2 , concurrent with 59.4 Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status. Results: Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples. Conclusions: Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate

  15. Low EphA7 Expression Correlated with Lymph Node Metastasis and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Bai, Yu-Qin; Zhang, Jun-Yi; Bai, Chun-Ying; Xu, Xiu-E; Wu, Jian-Yi; Chen, Bo; Wu, Zhi-Yong; Wang, Shao-Hong; Shen, Jian; Shen, Jin-Hui; Yao, Xiao-Dong; Gao, Lian-Zhu; Wu, Bao; Gu, Hong-Li; Liu, Xiao-Hui; Li, Xin; Li, En-Min; Xu, Li-Yan

    2015-01-01

    As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression

  16. Albert-Lembert versus hybrid-layered suture in hand sewn end-to-end cervical esophagogastric anastomosis after esophageal squamous cell carcinoma resection.

    Science.gov (United States)

    Feng, Fan; Sun, Li; Xu, Guanghui; Hong, Liu; Yang, Jianjun; Cai, Lei; Li, Guocai; Guo, Man; Lian, Xiao; Zhang, Hongwei

    2015-11-01

    Hand sewn cervical esophagogastric anastomosis (CEGA) is regarded as preferred technique by surgeons after esophagectomy. However, considering the anastomotic leakage and stricture, the optimal technique for performing this anastomosis is still under debate. Between November 2010 and September 2012, 230 patients who underwent esophagectomy with hand sewn end-to-end (ETE) CEGA for esophageal squamous cell carcinoma (ESCC) were analyzed retrospectively, including 111 patients underwent Albert-Lembert suture anastomosis and 119 patients underwent hybrid-layered suture anastomosis. Anastomosis construction time was recorded during operation. Anastomotic leakage was recorded through upper gastrointestinal water-soluble contrast examination. Anastomotic stricture was recorded during follow up. The hybrid-layered suture was faster than Albert-Lembert suture (29.40±1.24 min vs. 33.83±1.41 min, P=0.02). The overall anastomotic leak rate was 7.82%, the leak rate in hybrid-layered suture group was significantly lower than that in Albert-Lembert suture group (3.36% vs. 12.61%, P=0.01). The overall anastomotic stricture rate was 9.13%, the stricture rate in hybrid-layered suture group was significantly lower than that in Albert-Lembert suture group (5.04% vs. 13.51%, P=0.04). Hand sewn ETE CEGA with hybrid-layered suture is associated with lower anastomotic leakage and stricture rate compared to hand sewn ETE CEGA with Albert-Lembert suture.

  17. Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance

    International Nuclear Information System (INIS)

    Bai, Bing; Ma, Wei; Wang, Kai; Ha, Sita; Wang, Jian-Bo; Tan, Bing-Xu; Wang, Na-Na; Yang, Sheng-Si; Jia, Yi-Bin; Cheng, Yu-Feng

    2013-01-01

    This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P<0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Although univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients

  18. Large body size and sedentary lifestyle during childhood and early adulthood and esophageal squamous cell carcinoma in a high-risk population.

    Science.gov (United States)

    Etemadi, A; Golozar, A; Kamangar, F; Freedman, N D; Shakeri, R; Matthews, C; Islami, F; Boffetta, P; Brennan, P; Abnet, C C; Malekzadeh, R; Dawsey, S M

    2012-06-01

    Little is known about the association of obesity and physical activity at young ages with subsequent risk of esophageal squamous cell carcinoma (ESCC). Between 2003 and 2007, we conducted a case-control study in a high-risk population in northeastern Iran. Three hundred ESCC cases and 571 matched controls were recruited. Each individual was shown a standard pictogram, to report body size at ages 15 and 30. Demographic and health-related information, including physical activity at these ages was also collected. In the fully adjusted models, very obese body size (last two pictograms) at age 15 [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.7] and age 30 (OR 3.1; 95% CI 1.1-8.5) were associated with ESCC in women, but not in men. Sedentary work at age 15 (OR 3.3, 95% CI 1.3-8.3) and 30 (OR 18.2, 95% CI 3.9-86.2) were also associated with ESCC risk in women only. The increased risk in women at age 15 remained high after later reduction in body size, while women who became very obese only at age 30 did not show a significantly increased risk. These results highlight the importance of early lifestyle modifications in the context of cancer prevention, particularly in women.

  19. A variable structure fuzzy neural network model of squamous dysplasia and esophageal squamous cell carcinoma based on a global chaotic optimization algorithm.

    Science.gov (United States)

    Moghtadaei, Motahareh; Hashemi Golpayegani, Mohammad Reza; Malekzadeh, Reza

    2013-02-07

    Identification of squamous dysplasia and esophageal squamous cell carcinoma (ESCC) is of great importance in prevention of cancer incidence. Computer aided algorithms can be very useful for identification of people with higher risks of squamous dysplasia, and ESCC. Such method can limit the clinical screenings to people with higher risks. Different regression methods have been used to predict ESCC and dysplasia. In this paper, a Fuzzy Neural Network (FNN) model is selected for ESCC and dysplasia prediction. The inputs to the classifier are the risk factors. Since the relation between risk factors in the tumor system has a complex nonlinear behavior, in comparison to most of ordinary data, the cost function of its model can have more local optimums. Thus the need for global optimization methods is more highlighted. The proposed method in this paper is a Chaotic Optimization Algorithm (COA) proceeding by the common Error Back Propagation (EBP) local method. Since the model has many parameters, we use a strategy to reduce the dependency among parameters caused by the chaotic series generator. This dependency was not considered in the previous COA methods. The algorithm is compared with logistic regression model as the latest successful methods of ESCC and dysplasia prediction. The results represent a more precise prediction with less mean and variance of error. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. EVALUATION OF LYMPHATIC SPREAD, VISCERAL METASTASIS AND TUMORAL LOCAL INVASION IN ESOPHAGEAL CARCINOMAS.

    Science.gov (United States)

    Tustumi, Francisco; Kimura, Cintia Mayumi Sakurai; Takeda, Flavio Roberto; Sallum, Rubens Antônio Aissar; Ribeiro-Junior, Ulysses; Cecconello, Ivan

    2016-01-01

    Knowing esophageal tumors behavior in relationship to lymph node involvement, distant metastases and local tumor invasion is of paramount importance for the best esophageal tumors management. To describe lymph node involvement, distant metastases, and local tumor invasion in esophageal carcinoma, according to tumor topography and histology. A total of 444 patients with esophageal squamous cell carcinoma and 105 adenocarcinoma were retrospectively analyzed. They were divided into four groups: adenocarcinoma and squamous cell carcinoma in the three esophageal segments: cervical, middle, and distal. They were compared based on their CT scans at the time of the diagnosis. Nodal metastasis showed great relationship with of primary tumor site. Lymph nodes of hepatogastric, perigastric and peripancreatic ligaments were mainly affected in distal tumors. Periaortic, interaortocaval and portocaval nodes were more commonly found in distal squamous carcinoma; subcarinal, paratracheal and subaortic nodes in middle; neck chains were more affected in cervical squamous carcinoma. Adenocarcinoma had a higher frequency of peritoneal involvement (11.8%) and liver (24.5%) than squamous cell carcinoma. Considering the local tumor invasion, the more cranial neoplasia, more common squamous invasion of airways, reaching 64.7% in the incidence of cervical tumors. Middle esophageal tumors invade more often aorta (27.6%) and distal esophageal tumors, the pericardium and the right atrium (10.4%). Esophageal adenocarcinoma and squamous cell carcinoma in different topographies present peculiarities in lymph node involvement, distant metastasis and local tumor invasion. These differences must be taken into account in esophageal cancer patients' care. Conhecer o comportamento das neoplasias esofágicas em relação à disseminação linfonodal, distribuição de metástases e invasão local do tumor, pode auxiliar o manejo dos pacientes. Descrever o envolvimento linfonodal, disseminação metast

  1. LincRNA-ROR promotes metastasis and invasion of esophageal squamous cell carcinoma by regulating miR-145/FSCN1

    Directory of Open Access Journals (Sweden)

    Shang M

    2018-01-01

    Full Text Available Muhe Shang, Xianghu Wang, Ying Zhang, Zhikui Gao, Tian Wang, Ran Liu Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China Background and objective: In an attempt to discover a new biomarker for early diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC, the regulation mechanism of large intergenic non-coding RNA–regulator of reprogramming (lincRNA-ROR as a microRNA (miRNA sponge was studied.Patients and methods: ROR expression in 91 pairs of ESCC tissue samples and matched adjacent tissues was quantified with real-time fluorescent quantitative polymerase chain reaction (qRT-PCR. The ROR–miRNA–mRNA regulatory network was built with 161 esophageal cancer (EC tissues and 11 adjacent tumor tissues from The Cancer Genome Atlas (TCGA database. A total of 96 cases of ESCC from TCGA database were collected for analysis on survival rates. The regulatory relationship between ROR, miR-145 and FSCN1 was verified in ESCC cells via qRT-PCR, dual luciferase reporter (DLR assay, RNA immunoprecipitation (RIP and Western blotting. The transwell method was used to detect cell migration and invasion.Results: ROR expression in ESCC tumor tissues was significantly higher than in the adjacent tissues, p<0.001. The survival rate of ESCC patients with high ROR expression levels was lower than that of patients with low ROR expression levels (p<0.001. ROR overexpression could downregulate miR-145 by up to 50% was proven by RIP, DLR assay, and qRT-PCR. Two effective binding sites of ROR to miR-145 were verified by DLR assay. One of the sites has never been cited in the literature. The Western blotting results showed that FSCN1 was a downstream target of ROR/miR-145 (p<0.05. Transwell assays were used to show that overexpression of ROR enhanced migration and invasion behavior of ESCC and miR-145 hindered these effects.Conclusion: ROR acted as a competitive

  2. MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

    2016-10-23

    BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (Ptissues was than in normal adjacent esophageal tissues (Ptissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

  3. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  4. Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

    2017-05-01

    Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic

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

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    Zhang, Weiguo, E-mail: weiguozhangHU@gmail.com; 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 Rb−S780 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. - Highlights: • miR-18a promotes the proliferation of ESCC cells. • miR-18a increase cyclin D1 expression in ESCC cells. • miR-18a directly targets PTEN in ESCC cells. • Inhibition of AKT-mTOR prevents miR-18a-induced cyclin D1 in ESCC cells. • miR-18a antagomir sensitizes ESCC cells to cisplatin.

  6. 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

  7. 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)

    Wang, Zemin; Wang, Jia-Sheng; Tang, Lili; Sun, Guiju; Tang, Yuntian; Xie, Yin; Wang, Shaokang; Hu, Xu; Gao, Weimin; Cox, Stephen B

    2006-01-01

    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

  8. Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

    Science.gov (United States)

    Huang, Jing; Fan, Qingxia; Lu, Ping; Ying, Jianming; Ma, Changwu; Liu, Wei; Liu, Ying; Tan, Fenlai; Sun, Yan

    2016-06-01

    Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification. For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee. Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%). Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  9. Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

    2017-08-14

    The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

  10. A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Lu; Wang, Cong; Wang, Jiangfeng; Huang, Xiaochen; Cheng, Yufeng

    2017-10-01

    A novel systemic immune-inflammation index (SII) based on platelet (P), neutrophil (N), and lymphocyte (L) counts has been reported to be associated with clinical outcomes in several solid tumors. We aimed to investigate its prognostic value in esophageal squamous cell carcinoma (ESCC) and the potential relationship with quality of life (QOL). A total of 280 ESCC patients who underwent esophagectomy were enrolled. SII (SII = P × N/L) was calculated on the basis of data obtained within 1 week before surgery. An optimal cut-off value stratified patients into high (≥560) and low (<560) preoperative SII groups. The widely used EORTC QLQ-C30 and QLQ-OES18 were utilized to assess QOL at cancer diagnosis and 36 months after surgery. Generalized estimating equations (GEEs) were used to evaluate the association of SII with QOL. Kaplan-Meier method and Cox proportional regression were used to analyze the prognostic value of SII. Kaplan-Meier analyses revealed that higher SII correlated significantly with poorer overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001) in patients with ESCC. Multivariate analysis identified SII as an independent prognostic factor for OS (p < 0.001; HR 2.578; 95% CI 1.625-4.088) and DFS (p < 0.001; HR 2.699; 95% CI 1.726-4.223). In addition, patients with high SII exhibited notably deteriorating QOL (p < 0.05). The preoperative SII is a promising biomarker for predicting survival and QOL of patients with ESCC. It may help to identify the high-risk patients for treatment strategy decisions.

  11. SU-E-T-119: Analysis the Efficacy of Different Radiotherapy Methods and Failure Mode in No-Metastasis Esophageal Squamous Cell Carcinoma

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    Yankun, C; Zhihui, T; Runxiao, L; Shen, W [The Forth Hospital of Hebei Medical University, Shijiangzhuang, Hebei (China)

    2015-06-15

    Purpose: To evaluate the curative effect of radio (chemo) therapy and mode of treatment failure in no-metastasis and lesion length ≤ 5.0cm esophageal squamous cell carcinoma (ESCC). Methods: There were 158 eligible patients were retrospectively analyzed, to analysis the curative effect of radio (chemo) therapy, prognosis factors, toxicity and prognostic index model. Results: To all patients the 1, 3, 5 overall survival rate were 83.54%, 52.53%, 32.58%, the local recurrence rate were 15.08%, 33.60% and 38.14%; distant metastasis rate were 10.64%, 25.21% and 36.06%; tumor specific survival rate were 76.64%, 54.07% and 44.51%. Multivariate analysis showed that patients with ECOG grade (χ2=13.945, P=0.000), short-term effect (χ2=19.360, P=0.000) and different radiotherapy methods (χ2=9.866, P=0.002) as the independent prognostic factors. Prognostic index model showed that the survival rate was significantly higher in the lower value of PI group than in the larger value of PI group (χ2=49.19, P=0.0000). In our whole group, there were simple locoregional recurrence (LR) 40 cases (25.3%), simple Distant metastasis (DM) 31 cases (19.6%), LR and DM in 14 cases (8.9%) after treatment. The chi-square test showed that there were no significant difference in the incidence of Elective Nodal Irradiation (ENI )and Involved Field Irradiation (IFI) patients with LR and DM ( χ2=2.363, 2.950, P=0.124, 0.085). Conclusion: Radio (chemo) therapy has a good curative effect in no-metastasis and lesion length ≤ 5.0cm ESCC patients.

  12. Polymorphisms of transforming growth factor beta 1 (RS#1800468 and RS#1800471) and esophageal squamous cell carcinoma among Zhuangese population, China.

    Science.gov (United States)

    Tang, Ren-Guang; Huang, Yong-Zhi; Yao, Li-Min; Xiao, Jian; Lu, Chuan; Yu, Qian

    2013-01-01

    Epidemiological evidence has shown two polymorphisms (namely RS#1800468G>A and RS#1800471G>C) of transforming growth factor-beta 1 (TGF-β1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-β1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-β1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-β1 RS#1800471G>C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran.

    Science.gov (United States)

    Golozar, Asieh; Etemadi, Arash; Kamangar, Farin; Fazeltabar Malekshah, Akbar; Islami, Farhad; Nasrollahzadeh, Dariush; Abedi-Ardekani, Behnoosh; Khoshnia, Masoud; Pourshams, Akram; Semnani, Shahriar; Marjani, Haji Amin; Shakeri, Ramin; Sotoudeh, Masoud; Brennan, Paul; Taylor, Philip; Boffetta, Paolo; Abnet, Christian; Dawsey, Sanford; Malekzadeh, Reza

    2016-03-01

    Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders.

  14. Poor oral health is associated with an increased risk of esophageal squamous cell carcinoma - a population-based case-control study in China.

    Science.gov (United States)

    Chen, Xingdong; Yuan, Ziyu; Lu, Ming; Zhang, Yuechan; Jin, Li; Ye, Weimin

    2017-02-01

    To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene. © 2016 UICC.

  15. Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in association with the prognosis of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Lu, Cheng; Xie, Hui; Wang, Fengliang; Shen, Hongbing; Wang, Jianming

    2011-01-01

    Folic acid may affect the development of human cancers. However, few studies have evaluated the consumption of diet folate in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). One hundred and twenty five ESCC patients underwent esophagectomy between January 2005 and March 2006 in the Yangzhong People's Hospital were recruited and followed up. The effects of diet folate, aberrant DNA methylation of selected genes and methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphisms on the prognosis of ESCC were evaluated by using Cox proportional hazard regression models. Our analysis showed an inverse association between diet folate intake and the risk of death after esophagectomy. The median survival time was 3.06 years for low or moderate folate consumption and over 4.59 years for high folate consumption. After adjusting for potential confounders, the hazard ratios (95% confidence interval) [HRs (95% CI)] were 0.72 (0.36-1.46) for moderate and 0.39 (0.20-0.78) for high folate intake, respectively (P for trend = 0.007). This preventive effect was more evident in patients carrying MTHFR 677CC genotype. No significant relation was observed between aberrant DNA methylation of P16, MGMT and hMLH1 gene, as well as MTHFR C677T genetic polymorphisms and the prognosis of ESCC. Our research indicated that diet folate intake may have benefits on the prognosis of ESCC after esophagectomy. From a practical viewpoint, the findings of our study help to establish practical intervention and surveillance strategies for managements of ESCC patients and can finally decrease the disease burden

  16. Esophageal carcinoma. From the viewpoint of surgery

    International Nuclear Information System (INIS)

    Kawano, Tatsuyuki; Nakajima, Yasuaki; Suzuki, Tomoyoshi

    2007-01-01

    Therapeutic performance of the esophageal cancer has improved rapidly. Now in the decision of therapeutic strategy not only life prognosis but also treatments-related morbidity and late term quality of life should be considered. The most important factor of the improvement of esophageal cancer treatment is a progress in early detection of esophageal cancers and active use of treatment methods such as endoscopic mucosal resection. In addition, the role of radiotherapy and chemotherapy has improved as an arm of multidisciplinary therapy, and the establishment of chemoradiotherapy as one of the standard therapy for esophageal cancer is also very important. This shows that surgical and non-surgical approach has been getting more interactive and the relationship to one another should always be considered. Surgical therapy is very effective in patients with localized esophageal tumor and the patient's satisfaction is high. However, many problems are remained, and the improvement of diagnosis for metastasis and lessening surgical invasiveness and early/late complications are expected. Moreover, the chemoradiotherapy as an esophagus preserving method will establish more important standpoint and the salvage surgery will be applied more actively. On the other hand, a new strategy such as chemoradiotherapy immediate after esophagectomy for the patients with possible residual tumor for improving therapeutic results may be considered under the status of reliable surgical procedures. (author)

  17. Significance of microscopic extention from 1162 esophageal carcinoma specimens

    International Nuclear Information System (INIS)

    Wang Jun; Zhu Shuchai; Han Chun; Zhang Xin; Xiao Aiqin; Ma Guoxin

    2007-01-01

    Objective: To examine the subclinical microscopic tumor extention along the long axis in 1162 specimens of esophageal carcinoma so as to help define the clinical target volume(CTV) according to the degree of microscopic extention(ME) for radiotherapy for esophageal carcinoma. Methods: 1162 resected esophageal carcinoma specimens originally located in the neck and thorax were studied with special reference to the correlation between upper and lower resection length from the tumor and positive microscopic margin. Another 52 resected esophageal carcinoma specimens were made into pathological giant sections: the actual resection length of upper and para-esophageal normal tissues was compared with that of the lower nor- mal tissues from the tumor, there by, the ratio of shrinkage was obtained and compared. Results: After fixation, microscopic positive margin ratio of the upper resection border in length ≤0.5 cm group was higher than that in length > 0.5 cm group (16.4% vs 4.1%, P=0.000). Microscopic positive margin ratio of the lower resection border in length ≤1.5 cm group was higher than that in length > 1.5 cm group( 8.1% vs 0.4%, P = 0.000). This showed that the positive margin ratio of the upper border was higher than that of the lower border in resection length > 1.5 cm group(3.5% vs 0.4%, P=0. 000). The actual length of upper and lower normal esophageal tissue after having been made into pathological giant sections in 52 patients, was 30% ± 14% and 44% ± 19% of that measured in the operation. Conclusions: Considering the shrinkage of the normal esophagus during fixation, a CTV margin of 2.0 cm along the upper long axis and 3.5 cm along the lower long axis should be chosen for radiotherapy for esophageal carcinoma, according to the ratio of shrinkage. Ascending invasion proportion is higher than the descending invasion in that tumor. (authors)

  18. Late Toxicity After Definitive Concurrent Chemoradiotherapy for Thoracic Esophageal Carcinoma

    International Nuclear Information System (INIS)

    Morota, Madoka; Gomi, Kotaro; Kozuka, Takuyo; Chin, Keisho; Matsuura, Masaaki; Oguchi, Masahiko; Ito, Hisao; Yamashita, Takashi

    2009-01-01

    Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

  19. The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous cell carcinoma cell lines via the Akt/XIAP pathway.

    Science.gov (United States)

    Ui, Takashi; Morishima, Kazue; Saito, Shin; Sakuma, Yuji; Fujii, Hirofumi; Hosoya, Yoshinori; Ishikawa, Shumpei; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro; Yasuda, Yoshikazu

    2014-02-01

    Although cisplatin (CDDP) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC), acquired chemoresistance remains a major problem. Combination therapy may represent one strategy to overcome this resistance. Heat shock protein 90 (HSP90) is known to be overexpressed in several types of cancer cells, and its inhibition by small molecules, either alone or in combination, has shown promise in the treatment of solid malignancies. In the present study, we evaluated the synergistic effects of combining CDDP with the HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) on two CDDP-resistant human esophageal squamous cancer cell lines, KYSE30 and KYSE150. The results obtained demonstrated the synergistic inhibitory effects of CDDP and 17-AAG on the growth of KYSE30 and KYSE150 cells. Cell growth and cell number were more effectively reduced by the combined treatment with CDDP and 17-AAG than by the treatment with either CDDP or 17-AAG alone. Western blotting revealed that the combined action of CDDP and 17-AAG cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, which demonstrated that the reduction in both cell growth and cell number was mediated by apoptosis. Time-course experiments showed that reduction in X-linked inhibitor of apoptosis protein (XIAP) and phosphorylated Akt were concomitant with apoptosis. The results of the present study demonstrate that 17-AAG synergizes with CDDP and induces apoptosis in CDDP-resistant ESCC cell lines, and also that modulation of the Akt/XIAP pathway may underlie this synergistic effect. Combination therapy with CDDP and an HSP90 inhibitor may represent a promising strategy to overcome CDDP resistance in ESCC.

  20. Esophageal carcinoma: surgery, radiotherapy, and chemotherapy

    NARCIS (Netherlands)

    van Lanschot, J. Jan B.; Aleman, Berthe M. P.; Richel, Dick J.

    2002-01-01

    Several new developments in the potentially curative therapy of esophageal cancer have drawn attention over the past year. There is a potential benefit of centralization of esophagectomies in dedicated centers. Early mucosal lesions are increasingly treated by local ablative therapy. Tumors invading

  1. Identification of the Key Genes and Pathways in Esophageal Carcinoma.

    Science.gov (United States)

    Su, Peng; Wen, Shiwang; Zhang, Yuefeng; Li, Yong; Xu, Yanzhao; Zhu, Yonggang; Lv, Huilai; Zhang, Fan; Wang, Mingbo; Tian, Ziqiang

    2016-01-01

    Objective . Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods . 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results . A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion . The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

  2. Identification of the Key Genes and Pathways in Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Peng Su

    2016-01-01

    Full Text Available Objective. Esophageal carcinoma (EC is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs were screened by bioinformatics analysis. Gene Ontology (GO enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment, and protein-protein interaction (PPI network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

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

    International Nuclear Information System (INIS)

    Inoue, Kazumasa

    1977-01-01

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

  4. Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Li Z

    2017-06-01

    Full Text Available Zhen Li,1 Qianlan Yao,1 Songjian Zhao,1 Yin Wang,2,3 Yixue Li,1,4 Zhen Wang4 1School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 2Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 3Collaborative Innovation Center for Genetics and Development, Fudan University, 4Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Esophageal squamous cell carcinoma (ESCC is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2 might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5

  5. Descending thoracic aorta dissection associated with esophageal carcinoma

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    Kaushik Saha

    2013-01-01

    Full Text Available The association of aortic dissection with a malignancy is a rare finding and previous reports are usually those of primary aortic sarcomas. A 45-year-old male presented to us with chest pain and dysphagia for 1 month with a background history of obstructive airway disease and uncontrolled hypertension. In this report we present a case of typical descending aorta dissection with associated esophageal carcinoma.

  6. Curability of esophageal carcinoma treated with irradiation

    International Nuclear Information System (INIS)

    Yamada, Shogo; Takai, Yoshihiro; Nemoto, Kenji; Kakuto, Yoshihisa; Ogawa, Yoshihiro; Hoshi, Akihiko; Sakamoto, Kiyohiko

    1994-01-01

    The curability of 168 squamous cell carcinomas of the esophagus treated with more than 60 Gy of irradiation between 1980 and 1987 were discussed. There were 49 autopsied cases. The curability rat was calculated after the conversion of 13 local free or 46 metastasis free patients who had not undergone autopsy into unknown cases in each analysis. Disease free, local free, and metastasis free rates were 11.2, 20.0, and 26.0%, respectively. The curability rate was higher in the superficial type cancer and stage I cases. The local control rate and the metastasis free rate were extremely poor in the infiltrative type cancer. The actuarial survival rate of overall patients was 31.5% at one year, 11.3% at three years, and 7.1% at five years. Reconstructed survival rates: disease free, local free, and metastasis free survival rates, indicated that the survival rates of overall patients might be improved by decreasing the number of intercurrent death in stage I and by elevating the ratio of the local control in stages II and III. The disease free survival rate of cases treated with low dose rate telecobalt therapy as a boost was better than that of the conventionally fractionated irradiation alone cases in stages II and III. (author)

  7. Simultaneous radio-chemotherapy in esophageal carcinoma

    International Nuclear Information System (INIS)

    Tosch, U.; Wendt, T.G.; Rohloff, R.; Willich, N.

    1988-01-01

    Between 1983 and 1986, 41 patients with a squamous cell carcinoma of the esophagus without hematogenic metastases were treated with a combination of radio- and chemotherapy preoperatively. Treatment consisted of mitomycin C (10 mg/sqm/day 1) and continuous infusion of 5 fluorouracil (1000 mg/sqm/day - day 1 to 4) with a maximum of 1500 mg per day. On day 2 radiotherapy was started. After the administration of 36 Gy all patients were restaged. Nine patients were referred to surgery. In 13 cases surgery was refused, because of inoperability, due to local or distant metastases. In these patients radiotherapy was continued up to 50 to 60 Gy for palliation. Although the disease was confined to the esophagus no surgery was performed in 19 patients, because of age, enhanced risk of anaesthesia or refusal by the patient. These patients were treated with radiotherapy alone (60 Gy) with curative intention. 32 patients treated without surgery were followed up. For the patients treated with curative intent, the one year survival rate was 62%, the two year survival rate was 42%. Compared to a group treated in 1970 to 1982 with the same dosage of irradiation without the combination of chemotherapy the median survival could be raized from nine to 24 months, the two year survival rate improved from 18% to 42%. Patients treated for palliation only did not survive the first year after therapy. (orig.) [de

  8. Three-dimensional positron emission tomography image texture analysis of esophageal squamous cell carcinoma: relationship between tumor 18F-fluorodeoxyglucose uptake heterogeneity, maximum standardized uptake value, and tumor stage.

    Science.gov (United States)

    Dong, Xinzhe; Xing, Ligang; Wu, Peipei; Fu, Zheng; Wan, Honglin; Li, Dengwang; Yin, Yong; Sun, Xiaorong; Yu, Jinming

    2013-01-01

    To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, Pheterogeneity and the commonly used simplistic parameter of SUV and tumor stage. Our findings suggest a complementary role of these parameters in the staging and prognosis of esophageal squamous cell carcinoma.

  9. The build oxygenation T{sub 2}{sup *} values of resectable esophageal squamous cell carcinomas as measured by 3T magnetic resonance imaging: Association with tumor stage

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yu Lian; Zhang, Xiao Ming; Huang, Yu Cheng; Chen, Tian Wu; Chen, Yan Il; Chen, Fan; Zeng, Nan Lin; Li, Rui [Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong (China); Yang, Zhi Gang [Dept. of Radiology, West China Hospital of Sichuan University, Chengdu (China); Hu, Jiani [Dept. of Radiology, Wayne State University, Detroit (United States)

    2017-08-01

    To explore the association between the blood oxygenation T{sub 2}{sup *} values of resectable esophageal squamous cell carcinomas (ESCCs) and tumor stages. This study included 48 ESCC patients and 20 healthy participants who had undergone esophageal T{sub 2}{sup *} -weighted imaging to obtain T{sub 2}{sup *} values of the tumors and normal esophagus. ESCC patients underwent surgical resections less than one week after imaging. Statistical analyses were performed to identify the association between T{sub 2}{sup *} values of ESCCs and tumor stages. One-way ANOVA and Student-Newman-Keuls tests revealed that the T{sub 2}{sup *} value could differentiate stage T1 ESCCs (17.7 ± 3.3 ms) from stage T2 and T3 tumors (24.6 ± 2.7 ms and 27.8 ± 5.6 ms, respectively; all ps < 0.001). Receiver operating curve (ROC) analysis showed the suitable cutoff T{sub 2}{sup *} value of 21.3 ms for either differentiation. The former statistical tests demonstrated that the T{sub 2}{sup *} value could not differentiate between stages T2 and T3 (24.6 ± 2.7 ms vs. 27.8 ± 5.6 ms, respectively, p > 0.05) or between N stages (N1 vs. N2 vs. N3: 24.7 ± 6.9 ms vs. 25.4 ± 4.5 ms vs. 26.8 ± 3.9 ms, respectively; all ps > 0.05). The former tests illustrated that the T{sub 2}{sup *} value could differentiate anatomic stages I and II (18.8 ± 4.8 ms and 26.9 ± 5.9 ms, respectively) or stages I and III (27.3 ± 3.6 ms). ROC analysis depicted the same cutoff T{sub 2}{sup *} value of 21.3 ms for either differentiation. In addition, the Student's t test revealed that the T{sub 2}{sup *} value could determine grouped T stages (T0 vs. T1–3: 17.0 ± 2.9 ms vs. 25.2 ± 6.2 ms; T0–1 vs. T2–3: 17.3 ± 3.0 ms vs. 27.1 ± 5.3 ms; and T0–2 vs. T3: 18.8 ± 4.2 ms vs. 27.8 ± 5.6 ms, all ps < 0.001). ROC analysis indicated that the T{sub 2}{sup *} value could detect ESCCs (cutoff, 20 ms), and discriminate between stages T0–1 and T2–3 (cutoff, 21.3 ms) and between T0–2 and T3 (cutoff, 20.4 ms

  10. Ultrastructural changes of human esophageal carcinoma induced by preoperative treatments with bleomycin and/or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kohro, T. (Niigata Univ. (Japan). School of Medicine)

    1982-01-01

    In the present study, 44 cases of esophageal carcinoma were electron-microscopically examined. Nuclear bodies of various types observed in carcinoma cells or in normal mucosa of the esophagus treated by bleomycin and radiation, single or combined (BLM/R), were classified into seven types. Types A and B were observed in carcinoma cells of both conditions of untreated or treated with BLM/R. Types C, D and E were specific findings in squamous carcinoma cells after BLM/R treatment. Types F and G were considered to be far advanced in terms of other nuclear bodies and were observed in strongly affected carcinoma cells. These nucleolar changes were considered to be specific alterations induced by BLM in esophageal carcinoma cells. The appearance of various nuclear bodies and a series of nucleolar segregation after BLM/R treatments were confirmed as well in metastatic lesions of abdominal lymph nodes that may be affected only with minimal or disregardable scattered radiation, if any, giving no sifnificant influence to cell activity. This fact has suggested that types C, D and E nuclear bodies and nucleolar segregation are changes specific to BLM/R treatments, some solely to BLM. Other nuclear changes consisted in the appearance of fibrillar structures of three different types that were considered to have been produced by disturbed ribosomal activity in the nuclei. On the basis of results in the present study, BLM apparently showed serious evidence of remarkable influences or effects, although not constantly and generally available, on certain squamous carcinoma cells of the esophagus. Some of the evidence was represented by nucleolar segregation and characteristic nuclear bodies of different types, particularly of types C, D and E.

  11. 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)

    Sato-Kuwabara, Yukie; Neves, José I; Fregnani, José HTG; Sallum, Rubens A; Soares, Fernando A

    2009-01-01

    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

  12. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

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    Lee Jang-Ming

    2009-05-01

    Full Text Available Abstract Background Overexpression of Cyclooxygenase-2 (COX-2 was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC. One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP, H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9. COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3. The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5. Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9, and the effect was observed to be enhanced for the lower third ESCC

  13. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study.

    Science.gov (United States)

    Hu, Huang-Ming; Kuo, Chao-Hung; Lee, Chien-Hung; Wu, I-Chen; Lee, Ka-Wo; Lee, Jang-Ming; Goan, Yih-Gang; Chou, Shah-Hwa; Kao, Ein-Long; Wu, Ming-Tsang; Wu, Deng-Chyang

    2009-05-23

    Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 - 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 - 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 - 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 - 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 - 0.47, p for

  14. Computed tomography in the staging of esophageal carcinoma

    International Nuclear Information System (INIS)

    Han, Kyung Min; Lee, Jong Tae; Yoo, Hyung Sik

    1986-01-01

    Computed Tomography (CT) was found to be highly accurate in predicting tumor size and assessing invasion of the surrounding structures and distant metastasis. Also CT played an important role for determination of operability of esophageal carcinoma. The CT findings with barium esophagogram in 21 patients with histologically proven esophageal carcinoma were reviewed from Feb. 1985 to Feb. 1986 at the department of Radiology, Yonsei University, College of Medicine. The results were as follows: 1. Number of patients in each stages were: 2 in stage 1, 6 in stage 2, 4 in stage 3, and 9 in stage 4. 2. Paek age distribution was in tis 6th decades as 9 patients (42.9%). Overall mean age was 60.8 years. Number of male patients were 19 and 2 of female. 3. Histologic types of esophageal carcinoma were 19 cases of epidermoid (90.5%) and 2 cases of adenocarcinoma (9.5%). 4. The tumor location was 1 case in upper, 14 cases (66.7%) in middle and 6 cases in lower one-third. 5. Various types of esophageal carcinoma were as follows: 3 cases of fungating, 4 cases of infiltrating, 5 cases of ulcerofungating, and 9 cases of ulceroinfiltrating type. 6. Average length of involvement in each stages were 4 cm in stage 1, 5.5 cm in stage 2, 8.8 cm stage 3, and 8.3 cm in stage 4. The involved length was longer in advanced cases. In 11 cases (52.4%), the involved length was between 4 and 8 cm. 7. Angle of periaortic fat plane obliteration of the aortic circumference were as follows: Below 45 (7 cases 33.3%), 45-90 (3 cases 14.3%), over 90 (11 cases, 52.4%). 8. Method of treatment of esophageal carcinoma were as follows: Only radiotherapy in 11 cases (52.4%), radiotherapy with operation in 5 cases, only operation on 1 case, and no treatment in 4 cases. 9. Distant metastatic sites were: brain in 1, pericardium in 5, liver in 5, trachea in 2, bronchus in 9, and distant lymph node in 5 cases.

  15. Esophageal carcinoma extending into the spinal canal - case report and review of the literature

    International Nuclear Information System (INIS)

    Urban, Linei A.B.D.; Rogacheski, Enio; Ledesma, Jorge A.; Zaparolli, Mauricio; Duarte, Maria Cecilia B.; Sakamoto, Danielle G.

    2002-01-01

    The authors report the case of a 62-year-old male with a 4 month history of weight loss and a 2 day complaint of weakness and paraesthesia on the lower limbs. A computed tomography myelogram revealed a mass in the posterior mediastinum associated with destruction of the vertebral body, spinal canal extension and irregular esophageal wall thickening. The patient was later submitted to a barium esophagogram that showed an irregular filling defect. A biopsy confirmed the presence of a squamous cell carcinoma. This is the first report in the Latin-American literature (Lilacs) of a patient with an esophageal carcinoma with spinal canal extension and spinal cord compression syndrome at initial presentation. (author)

  16. Oral alimentation following intubation for esophageal carcinoma.

    Science.gov (United States)

    Haffejee, A A; Angorn, I B

    1977-01-01

    The nutritional status of 15 patients suffering from unresectable carcinoma of the midthoracic esophagus was evaluated before and after palliative pulsion intubation. All patients showed evidence of protein-calorie malnutrition, prior to intubation. Oral alimentation using a formulated hospital ward diet with an elemental dietary supplement reversed the nutritional deficit. A mean daily positive nitrogen balance of seven grams was achieved three weeks following intubation. No episode of tube blockage was observed and the elemental diet supplement was well tolerated. PMID:74985

  17. Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells.

    Science.gov (United States)

    Wang, Xinyu; Ren, Yanli; Wang, Zhiqiong; Xiong, Xiangyu; Han, Sichong; Pan, Wenting; Chen, Hongwei; Zhou, Liqing; Zhou, Changchun; Yuan, Qipeng; Yang, Ming

    2015-12-21

    5S rRNA plays an important part in ribosome biology and is over-expression in multiple cancers. In this study, we found that 5S rRNA is a direct target of miR-150 and miR-383 in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-150 and miR-383 inhibited ESCC cell proliferation in vitro and in vivo. Moreover, 5S rRNA silencing by miR-150 and miR-383 might intensify rpL11-c-Myc interaction, which attenuated role of c-Myc as an oncogenic transcriptional factor and dysregulation of multiple c-Myc target genes. Taken together, our results highlight the involvement of miRNAs in ribosomal regulation during tumorigenesis. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. A case of likely radiation-induced synchronous esophageal and skin carcinoma following post-operative radiation for breast cancer

    International Nuclear Information System (INIS)

    Kanogawa, Naoya; Shimada, Hideaki; Kainuma, Osamu; Cho, Akihiro; Yamamoto, Hiroshi; Itami, Makiko; Nagata, Matsuo

    2009-01-01

    A 71-year-old woman was admitted in January 2008 with on upper thoracic esophageal squamous cell carcinoma and a right chest wall skin tumor. When she was 32 years old, she had a radical mastectomy for right breast cancer and received postoperative radiation. Due to the presence of lung adhesions, trans-thoracic esophagectomy could not be done; thus, a blunt dissection was performed. She was discharged on the 19 th postoperative day. On pathology, a pT2N0M0 (pStage II) esophageal tumor was diagnosed. A resection of her skin tumor underwent 79 days after the esophageal surgery; on pathology, the skin tumor was diagnosed as a basal cell carcinoma. Since the esophageal tumor and the skin tumor occurred in the same area that had received radiation therapy, these tumors were diagnosed as being radiation-induced secondary tumors. In the English language medical literature, several reports of radiation-induced esophageal cancer occurring as a second cancer after radiotherapy for breast cancer have been published. Radiation-induced esophageal cancer rates may increase in Japan given the number of women who previously received radiotherapy for breast cancer. (author)

  19. Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

    Science.gov (United States)

    Matsuda, S; Tsubosa, Y; Sato, H; Takebayashi, K; Kawamorita, K; Mori, K; Niihara, M; Tsushima, T; Yokota, T; Onozawa, Y; Yasui, H; Takeuchi, H; Kitagawa, Y

    2017-02-01

    Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5

  20. Treatment of loco-recurrence after resection of esophageal carcinoma

    International Nuclear Information System (INIS)

    Zhang Yaohong; Tang Xijun; Tao Ruikang; Liu Jianhe

    2003-01-01

    Objective: To analyze the optimum method of radiotherapy for loco-regional recurrence in 45 patients after surgery for esophageal carcinoma. Methods: From June 1993 to June 1999, 45 such patients were treated by radiotherapy. Eleven patients had recurrent lesions in the supraclavicular region, 23 in the mediastinum, 5 in both mediastinum plus supraclavicular area and 6 in mediastinum plus anastomotic orifice. A total dose of 50-80 Gy was given. Nineteen patients received FP (5-Fu+DDP) chemotherapy after radiotherapy. Results: The medium survival was 12 months and the 1-, 2- and 3-year survival rates were 51.1%, 26.7% and 11.1%. For those who received R+C and R only, the 3-year survival rates were 21.1% and 3.9%, showing a conspicuous raise in the survival although P>0.05. Multi-variate analysis showed that post-surgical staging (P=0.023) and radiotherapy (P=0.002) were closely related to prognosis. Conclusion: Among the various methods of treating loco-regional recurrence after surgery of esophageal carcinoma, commonly yielding poor results, radiotherapy is still the method of choice. A total dose of >60 Gy is able to effect a good loco-regional control as well as a good result

  1. Intraoperative radiotherapy in the management of esophageal and gastro-esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Suh, David; Ahmad, Neelofur; Huq, M Saiful; Mohiuddin, Mohammed; Cohn, Herbert; Barbot, Donna; Rosato, Francis

    1995-07-01

    Purpose: Patients with esophageal and gastro-esophageal junction (GEJ) carcinomas suffer a high rates of local regional failure following conventional therapies. This report describes a unique institutional experience with the use of intraoperative radiation therapy (IORT) in the multimodality management of these tumors. Methods and Materials: From January, 1989 through August, 1994, 22 patients with distal esophageal(n=8) or GEJ junction carcinomas (n=14) underwent surgery followed by IORT to the tumor bed. Two patients died perioperatively of complications unrelated to the IORT and were excluded from the study. In the remaining 20 patients, IORT doses ranged from 12 to 20 Gy (median 15 Gy). The electron energies ranged from 4 to 22 MeV (median 6 MeV). Ten patients received no further radiation therapy (IORT only group), and ten patients received adjuvant external beam radiation (IORT + EB group) ranging from 39.6 to 60.8 Gy (median 45.0 Gy) in standard fractionation. 5-FU-based chemotherapy was administered to 15 patients either pre- or postoperatively. Follow-up ranged from 4 to 62 months (median 10 months). Results: The overall median survival time (MST) was 10 months. The overall 2-year actuarial survival rate was 25%. Distant metastasis developed in (9(20)) patients. The results by treatment subgroups are listed below. There was 1 local failure each in the IORT only group and the IORT+EB group. There were no perioperative complications related to IORT. The average length of hospital stay did not appear different than that of patients not receiving IORT. Conclusions: This is the first North American series describing the use of IORT after resection of esophageal/GEJ carcinomas. The use of IORT in our study did not increase perioperative morbidity over that reported for patients undergoing surgery alone. The addition of EBRT was associated with a longer median survival time although not with improved long-term survival when compared to the outcome of patients

  2. A combined radiation and platinum chemotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Takamura, Akio; Saito, Hiroya; Sakurai, Yasuo; Horio, Keiji; Mizoe, Junetsu.

    1993-01-01

    The prognosis of the patients with advanced esophageal carcinoma treated by definitive radiotherapy is still dismal with a reported 5-year survival rate of 5-10% in most series. Since 1986, combined radiotherapy with chemotherapy using platinum analogue was initiated at Asahikawa and Obihiro Kosei Hospitals in order to improve local-regional control and the survival of the patients. From 1980 to 1992, 81 patients with unresectable esophageal carcinoma were treated with radiotherapy. Since April 1986, 37 out of the 81 patients received both radiotherapy and chemotherapy with platinum. Platinum was used during the course of radiotherapy. The method of administration of platinum was as follows; Cisplatin intravenously (50 mg, weekly, total 200 mg) in 9 patients, Carboplatin intravenously (100-150 mg, weekly, total 400-900 mg) in 11 patients and Cisplatin intraarterially (100 mg, at a 3-4 week interval, total 100-300 mg) in 17 patients. These 37 patients (Group A) were compared to 44 patients treated by radiotherapy alone (Group B) with respect to initial response and survival rate. Response was defined according to the guidelines recommended by Japanese Society for Esophageal Diseases. Response rates were 59.1% (19 CR and 7 PR) in Group B and 70.3% (7 CR and 19 PR) in Group A. Primary relapse-free rates were 36.4% in Group B and 37.8% in Group A. The cumulative survival at 3 years were 11.7% in Group B and 10.6% in Group A. Enhancement of side effects by chemotherapy was minimal and acceptable. Improvement of local-regional control and survival was not obvious by adding a concomitant platinum-chemotherapy. A definite conclusion, however, could not be drawn because of the retrospective, non-controlled nature of this study. Introduction of more intensive, multiple agents chemotherapy seems necessary if one aims at improving the results. (author)

  3. Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.

    Science.gov (United States)

    Li, Shuying; Shen, Haie; Li, Ji; Hou, Xiaoli; Zhang, Ke; Li, Jintao

    2018-03-01

    To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection. Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients. Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC). A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.

  4. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  5. Expressão imuno-histoquímica das metaloproteinases 2 e 9 não está associada à progressão do carcinoma de células escamosas de esôfago Metalloproteinases 2 and 9 immunohistochemistry expression is not associated to esophageal squamous cell carcinoma progression

    Directory of Open Access Journals (Sweden)

    Izabella Paz Danezi Felin

    2009-08-01

    Full Text Available INTRODUÇÃO: O carcinoma de células escamosas do esôfago está entre os tipos mais agressivos de câncer e de pior prognóstico. As metaloproteinases de matriz (MMPs, especialmente as MMP-2 e MMP-9, vêm sendo utilizadas para avaliação prognóstica do câncer, associadas a invasão, tamanho e crescimento tumoral. OBJETIVO: O presente estudo visa investigar as expressões imuno-histoquímicas de MMP-2 e MMP-9, avaliando se existe correlação entre sua expressão e o estadiamento tumoral, invasão vascular, invasão local (pT e diferenciação tumoral no carcinoma de células escamosas de esôfago. MATERIAL E MÉTODO: Foi realizado um estudo retrospectivo utilizando 31 blocos de parafina contendo tumores de carcinoma escamoso esofágico, obtidas por esofagectomias realizadas entre 1998 e 2003, no Hospital Universitário de Santa Maria (HUSM. Os cortes histológicos foram submetidos à reação imuno-histoquímica, com sistema de amplificação por polímero não-biotinilado Novolink para detecção de MMP-2 e MMP-9. RESULTADOS: A avaliação da MMP-2 apresentou positividade fraca em apenas cinco casos, não demonstrando correlação com as variáveis estudadas. Também não foram observadas associações significativas entre as variáveis do estudo e o grau de expressão imuno-histoquímica da MMP-9. CONCLUSÃO: A expressão imuno-histoquímica das MMP-2 e MMP-9 não parece ser influenciada pelos parâmetros investigados. Nesse sentido, estudos adicionais são necessários para melhor compreensão de sua associação aos fatores prognósticos do carcinoma de células escamosas de esôfago.INTRODUCTION: Esophageal squamous cell carcinoma is an aggressive malignant neoplasia with poor prognosis. The expression of matrix metalloproteinases (MMPs, mainly 2 and 9, has been used for the prognostic evaluation of cancer in association with tumor invasion, size and tumoral growth analysis. OBJECTIVE: The aim of the present study was to investigate

  6. Analysis of locally controlled esophageal carcinomas treated with radiotherapy

    International Nuclear Information System (INIS)

    Gotoh, Yasuo; Yamada, Shogo; Takai, Yoshihiro; Nemoto, Kenji; Ogawa, Yoshihiro; Hoshi, Akihiko; Ariga, Hisanori; Sakamoto, Kiyohiko

    1996-01-01

    Of 227 esophageal carcinomas treated with a radiation dose of 60 Gy or more, 100 patients had no tumor or ulceration (with or without stenosis) of the esophagus after irradiation. We analyzed local control factors of these 100 patients to determine the need for further treatment. The cumulative local control rate at five years was 40% in all cases, 37% in 21 cases without any stenosis of the esophagus and 40% in 79 cases with stenosis. The presence of stenosis of the esophagus after irradiation was not a critical factor in predicting final local control. Local recurrence of tumors with findings of Borrmann III or Borrmann IV by the pretreatment esophageal barium study, tumors controlled after a total dose of more than 80 Gy, tumors without low dose rate telecobalt therapy (LDRT: 1 Gy/hour, 5 to 7 Gy/day, a total dose of 12 to 15 Gy) as boost therapy, and apparently controlled tumors with a stenotic ratio of 60% or more or with 5 cm or more length of stenosis of the esophagus after irradiation was significantly higher than that of the others (p<0.05). Multivariate analysis revealed that findings of pretreatment barium study, total dose, with or without LDRT, and length of stenosis of the esophagus after irradiation were significantly important factors in local control. Members of the high risk group of apparently controlled tumors should undertake surgical treatment or further intensive chemotherapy. (author)

  7. Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis

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    Minami Hitomi

    2013-01-01

    Full Text Available Abstract Background Per oral endoscopic myotomy (POEM has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. Methods This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. Results POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p Conclusions POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.

  8. Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis.

    Science.gov (United States)

    Minami, Hitomi; Yamaguchi, Naoyuki; Matsushima, Kayoko; Akazawa, Yuko; Ohnita, Ken; Takeshima, Fuminao; Nakayama, Toshiyuki; Hayashi, Tomayoshi; Inoue, Haruhiro; Nakao, Kazuhiko; Isomoto, Hajime

    2013-01-30

    Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, ptreatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.

  9. Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells.

    Science.gov (United States)

    Lin, Meng-Liang; Lu, Yao-Cheng; Chen, Hung-Yi; Lee, Chuan-Chun; Chung, Jing-Gung; Chen, Shih-Shun

    2014-05-01

    Stromal cell-derived factor-1α (SDF-1α) is a ligand for C-X-C chemokine receptor type 4 (CXCR4), which contributes to the metastasis of cancer cells by promoting cell migration. Here, we show that the SDF-1α/CXCR4 axis can significantly increase invasion of esophageal carcinoma (EC) cells. We accomplished this by examining the effects of CXCR4 knockdown as well as treatment with a CXCR4-neutralizing antibody and the CXCR4-specific inhibitor AMD3100. Curcumin suppressed SDF-1α-induced cell invasion and matrix metalloproteinase-2 (MMP-2) promoter activity, cell surface localization of CXCR4 at lipid rafts, and lipid raft-associated ras-related C3 botulinum toxin substrate 1 (Rac1)/phosphatidylinositol 3-kinase (PI3K) p85α/Akt signaling. Curcumin inhibited SDF-1α-induced cell invasion by suppressing the Rac1-PI3K signaling complex at lipid rafts but did not abrogate lipid raft formation. We further demonstrate that the attenuation of lipid raft-associated Rac1 activity by curcumin was critical for the inhibition of SDF-1α-induced PI3K/Akt/NF-κB activation, cell surface localization of CXCR4 at lipid rafts, MMP-2 promoter activity, and cell invasion. Collectively, our results indicate that curcumin inhibits SDF-1α-induced EC cell invasion by suppressing the formation of the lipid raft-associated Rac1-PI3K-Akt signaling complex, the localization of CXCR4 with lipid rafts at the cell surface, and MMP-2 promoter activity, likely through the inhibition of Rac1 activity. © 2012 Wiley Periodicals, Inc.

  10. Esophageal Cancer—Patient Version

    Science.gov (United States)

    The most common types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. These forms of esophageal cancer develop in some parts of the esophagus and are driven by genetic changes. Start here to find information on esophageal cancer treatment, causes and prevention, screening, research, and statistics.

  11. Late course accelerated fractionation in radiotherapy of esophageal carcinoma

    International Nuclear Information System (INIS)

    Shi, X.-H.; Yao, W.; Liu, T.

    1999-01-01

    Purpose: To evaluate the efficacy of adding accelerated fractionation after completing two thirds of routine fractionated radiotherapy in esophageal carcinoma.Methods and materials: From April 1988 to April 1990, 85 patients with histologically confirmed carcinoma of the esophagus were randomized into two groups. (1) The conventional fractionation (CF) group, received 1.8 Gy per day five times a week to a total dose of 68.4 Gy in 7-8 weeks, and (2) the late course accelerated hyperfractionated (LCAF) group which received the same schedule as the CF group during the first two thirds of the course of radiotherapy to a dose of 41.4 Gy/23 fx/4 to 5 weeks. This was then followed by accelerated hyperfractionation using reduced fields. In the LCAF portion of the radiotherapeutic course, the irradiation schedule was changed to 1.5 Gy twice a day, with an interval of 4 h between fractions, to a dose of 27 Gy/18 fx. Thus the total dose was also 68.4 Gy, the same as the CF group, but the course of radiotherapy was shorter, being only 6.4 weeks. The same Cobalt 60 teletherapy unit was used to treat all the cases.Results: The 5 year actuarial survival and disease-free survival rates in the LCAF group were 34% and 42%, as compared to 15% and 15% respectively in the CF group, all statistically significant. Better local control was seen in the LCAF group than in the CF group, the 5 year control rates being 55% versus 21% (P=0.003). The acute reactions were increased but acceptable in the LCAF patients, the radiation treatments could be completed without any breaks. The late reactions as observed after 5 years were not increased in comparison with the CF patients.Conclusions: The results from this study show that the late course accelerated hyperfractionated radiotherapy regime can improve results in esophageal carcinoma, with acceptable acute reactions as compared to conventional radiotherapy. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

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

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-09-01

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

  13. The implantation of esophageal stent with radioactive 125I particles for advanced esophageal carcinomas: observation of therapeutic results

    International Nuclear Information System (INIS)

    Zhao Peng; Cui Hongkai; Yang Ruimin; Zhang Xizhong

    2011-01-01

    Objective: To investigate the therapeutic effect of the implantation of esophageal stent with radioactive 125 I particles in treating advanced esophageal carcinomas in aged patients. Methods: During the period from Sep. 2009 to Dec. 2010, implantation of esophageal stent was used to treat 43 aged patients with advanced esophageal cancer. Based on the patient's free will, the patients were divided into study group (n=18) receiving stent with 125 I particles and control group (n=25) receiving ordinary stent without 125 I particles. No significant difference in the age, the lesion length, the degree of stenosis and the disease stage existed between the study group and the control group. The technical success rate, the remission rate of dysphagia, the occurrence of complications and the mean survival time were calculated and analyzed. The results were compared between the two groups. Results: The technical success rate was 100% in both groups. The short-term remission rate of dysphagia was also 100% in both groups. The mean survival time in the study group and in the control group was 9.8 months and 4.8 months respectively, the difference between the two groups was statistically significant (P 0.05). Conclusion: This results of study indicate that for the treatment of advanced esophageal carcinomas the implantation of esophageal stent with radioactive 125 I particles can surely and markedly prolong the patient's survival time and relive the symptom of dysphagia. This technique is safe, feasible and effective in clinical practice. The use of the stent with radioactive 125 I particles is superior to the use of the traditional stent in treating patients with advanced esophageal cancer. (authors)

  14. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna

    2008-01-01

    BACKGROUND: 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...

  15. 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

  16. An analysis of autopsied esophageal carcinomas treated with irradiation

    International Nuclear Information System (INIS)

    Yamada, Shogo; Kakuto, Yoshihisa; Sakamoto, Kiyohiko

    1994-01-01

    Ninety-one fresh autopsied esophageal carcinomas treated with a radiation dose of more than 40 Gy were analyzed, because no primary tumor with under 40 Gy was controlled. There were no residual tumors in 6.6% of the patients. Radiation controlled 28.6% of the locoregional tumors. The local control rate was higher in patients with a tumor length under 5 cm. Metastasis was detected in 76.9% of all the patients. Twenty patients (22.0%) had no primary tumor but metastases. The most common sites of metastasis were the lymph node, lung and liver. Multivariate analysis indicated that the primary tumor control correlated directly with the survival period. Some patients with a primary tumor which was easy to control developed lung metastasis more often. Liver metastasis was found more frequently in patients where the primary tumor was located in the lower portion of the esophagus. Patients with a tumor length of more than 10 cm had neck or mediastinal lymph node involvement more often; neck or mediastinal lymph node metastases were not always fatal immediately. Perforations into other organs were observed in 41.8% of the patients. Younger patients, patients with the tumor located in the upper portion of the esophagus, and patients with T4 tumor have a significantly higher risk of perforation. In such a patient, the total radiation dose should be reduced to less than 70 Gy. Nine patients (9.9%) had double cancers. (author)

  17. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  18. Expressão de p53, p16 E COX-2 em carcinoma escamoso de esôfago e associação histopatológica p53, p16 E COX-2 expression in esophageal squamous cell carcinoma and histopathological association

    Directory of Open Access Journals (Sweden)

    Izabella Paz Danezi Felin

    2008-12-01

    and COX-2 proteins and cancer esophageal prognosis has been suggested. AIMS: To Investigate whether the expression of p53, p16 and COX-2 proteins are associated to tumor staging. METHODS: For this purpose we proceeded immunohistochemistry assays and TMN in 31 esophageal tumor and normal tissue samples. The p53 nuclear expression was considered positive when it appears in 10.00% or more cells. COX-2 expression was scored according to intensity in three scores (1+, 2+, 3+. RESULTS: On the tumor samples the results presented 48.38% positivity for p53, 16.12% for p16 and 100% with 1+, 2+ or 3+ scores for COX-2. However, when we investigated whether the expression of p53, p16 and COX-2 proteins are related to tumor staging, only COX-2 expression, score 3+, had shown statistical significant association. CONCLUSION: Therefore, in the present study we could see positive correlation between COX-2 protein and high grade tumor as well as advanced tumor staging in esophageal carcinoma.

  19. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  20. Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

    Science.gov (United States)

    Strasser, Daniel S; Seger, Shanon; Bussmann, Christian; Pierlot, Gabin M; Groenen, Peter M A; Stalder, Anna K; Straumann, Alex

    2018-05-17

    Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease characterized clinically by symptoms of esophageal dysfunction and histopathologically by a prominent eosinophilic inflammation. Despite eosinophils having histologically a pre-dominant position, their role in the immunopathogenesis of the disease is still questionable. Several other inflammatory cells are involved and may play a critical role as well. The purpose of this study was to characterize the mast cell infiltration, and to correlate it with clinical state of EoE. Using immunohistochemistry and quantitative morphometry, we extensively investigated eosinophils and mast cells in esophageal biopsies from patients with active EoE and from patients with EoE in remission, and compared the findings with healthy individuals. In EoE, epithelium and lamina propria were similarly infiltrated with eosinophils. In contrast, mast cells infiltration was limited to the epithelium, displaying a localized immune response. Interestingly, whereas epithelial mast cells and eosinophils were high in active EoE, some patients in remission e.g. normalized epithelial eosinophils, showed remaining high numbers of mast cells. Patient clustering supported 2 groups of patients in clinical remission, differentiating based on presence or absence of epithelial mast cells. Active EoE is characterized - in addition to the well-known tissue eosinophilia by a marked epithelium-restricted mast cell infiltration. Of interest, in a subgroup of patients, mast cell infiltration persisted despite clinical remission. To elucidate the clinical consequence of persistent epithelial mast cells infiltration further studies are required following patients in clinical remission longitudinally. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. 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...

  2. Effect of different ways of intraoperative lymph node dissection on prognosis of patients with thoracic mid-upper esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhi Huang

    2016-02-01

    Full Text Available Objective: To analyze the effect of different ways of intraoperative lymph node dissection on prognosis of patients with thoracic mid-upper esophageal carcinoma. Methods: 106 cases of patients with thoracic mid-upper esophageal carcinoma were selected and according to different ways of lymph node dissection, divided into three-field group who received three-field lymph node dissection and two-field group who received two-field lymph node dissection, then serum lactate dehydrogenase (LDH, nitric oxide (NO, nitric oxide synthase (NOS and carcinoembryonic antigen (CEA as well as soluble interleukin-2 receptor (SIL- 2R, keratinized protein fragment 19 (Cyfra21-1 and squamous cell carcinoma antigen (SCC levels of two groups were compared, and postoperative follow-up was carried out to record disease-free survival rate and overall survival rate. Results: In three-field group, postoperative average serum LDH levels of patients with thoracic upper esophageal carcinoma and thoracic mid esophageal carcinoma were lower than LDH values of corresponding patients in two-field group (P<0.05; postoperative serum NO value of three-field group was higher than that of two-field group, and NOS, CEA and SIL-2R values were lower than those of two-field group (P<0.05; postoperative serum Cyfra21-1 and SCC values of three-field group were lower than those of two-field group (P<0.05; postoperative disease-free survival rate during the followup period of three-field group was higher than that of two-field group, and overall survival rate at corresponding points in time was also higher than that of two-field group (P<0.05. Conclusion: After patients with thoracic mid-upper esophageal carcinoma receive three-field lymph node dissection, levels of serum indexes with poor prognosis and tumor markers were optimized, long-term disease-free survival rate and overall survival rate are improved. It has positive clinical significance.

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

    International Nuclear Information System (INIS)

    Xiao Zefen; Zhou Zongmei; Lv Jima; Liang Jun; Ou Guangfei; Jin Jing; Song Yongwen; Zhang Shiping; Yin Weibo

    2008-01-01

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

  4. A study of survival rate of the patients with esophageal carcinoma treated by pre- and/or post-operative irradiation

    International Nuclear Information System (INIS)

    Eida, Koichiro

    1986-01-01

    So far there is still considerable disagreement as to the evaluation of the pre- and postoperative irradiation effects on the survival rate of the patients with esophageal carcinoma. From April 1973 to December 1983, 138 cases of thoracic esophageal carcinoma were surgically operated upon at our Department; 68 cases were irradiated and 70 cases were not irradiated prior to the surgical operation. Followup study was done and its result has been reported in this communication. A few cases treated by pre-operative irradiation survived longer than the expected longevity in spite of their low curative operation rates. Prognosis was better in the cases with well differentiated squamous cell carcinoma, when marked or good responses to pre-operative irradiation with the calculated total dose of 30 Gy were recorded. There were differences in responsibility in the various histological types of esophageal carcinomas; good response in the group of well differentiated squamous carcinoma, less marked response in the groups of moderately and poorly differentiated squamous carcinomas, minor response in the types of undifferentiated and unclassifed carcinomas. From our observation it seems reasonable to say that prognosis of the patients with pre- and postoperative irradiation was better than that of those who received postoperative irradiation only. (author)

  5. 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.

  6. A clinical study of esophagectomy after chemo-radiation therapy for advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Takeda, Shigeru; Tokuno, Kazuhisa; Nishimura, Taku; Yoshino, Shigefumi; Oka, Masaaki

    2007-01-01

    The aim of this study was to evaluate the efficacy of preoperative neoadjuvant therapy (NAT) including chemo-radiation or radiation in patients with T3/T4 advanced esophageal squamous cell carcinoma. We reviewed 115 patients with T3/T4 tumors from January 1994 through August 2006. Forty-seven patients received NAT, and the remaining 68 patients had surgery alone. Of these 47 patients, 14 patients underwent esophagectomy following NAT, and 33 patients underwent consecutive chemoradiation. Patients treated with esophagectomy following NAT had a better two-year survival (45.5%) and the median survival time (486 days) was compared with patients treated with chemo-radiation only (10.4%, 242 days) (p=0.026). Of these patients treated with esophagectomy following NAT, the patients undergone curative resection had a better one-year survival rate (83.3%) and the median survival time (2,055 days) was compared with the patients received with non-curative resection (20.0%, 273 days) (p=0.042). Two patients having grade 3 effect by NAT had a long disease free survival. There was no significant difference in postoperative morbidity and mortality rate between the patients received NAT and the patients treated with surgery alone. These results suggest that NAT may be useful for advanced esophageal cancer. (author)

  7. Cytological studies of esophageal carcinoma and gastric carcinoma receiving radiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, T; Nakano, N; Asakawa, H [Miyagi Prefectural Adult Disease Center, Natori (Japan)

    1982-10-01

    The cytology of the endoscopic biopsy materials from 85 cases of esophageal cancer were analyzed for effects of the combined radiotherapy with Bleomycin. Cancer cells were remarkably decreased in number after the combination therapy. Unaffected cancer cells declined to negligible levels in 64 of 79 esophageal cancer cases irradiated more than 6,000 rad. Out of 42 gastric cancer cases treated with only anticancer drugs, 37 cases exhibited cytologic changes in the smears of biopsied materials. About the remnant 5 cases, cancer cells showed partially cytoplasmic swelling, nuclear enlargement and nuclear abnormal stain. The smears of the biopsy and resected specimens from 64 gastric cancer cases with radiation and chemotherapy were cytologically discussed. The combination therapy increased the amount of both necrotic materials and neutrophils in the smears. The cytoplasms of treated cancer cells were swollen, vacuolated and stained abnormally. The nuclei of cancer cells became enlarged, multiple, piknotic and/or stained pale. Nuclear swelling was more prominent in cancer cells of differentiated adenocarcinomas. Cancer cells were decreased in number almost in inverse proportion to irradiation dose. Unaffected cancer cells were disappeared in 13 of 24 cases irradiated more than 6,000 rad, in 7 of 35 cases irradiated in the range 3,000 to 6,000 rad, in none of 5 cases irradiated less than 3,000 rad.

  8. Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

    International Nuclear Information System (INIS)

    Gockel, Ines; Galle, Peter R; Junginger, Theodor; Moehler, Markus; Schimanski, Carl C; Heinrich, Christian; Wehler, T; Frerichs, K; Drescher, Daniel; Langsdorff, Christian von; Domeyer, Mario; Biesterfeld, Stefan

    2006-01-01

    Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both

  9. Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric Junction Carcinoma: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Aiqin Gao

    2016-01-01

    Full Text Available Objective. Here we aimed to clarify the prognostic significance of perineural invasion (PNI in esophageal and esophagogastric junction (EGJ carcinoma. Methods. A comprehensive literature search for relevant reports published up to July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95% CI for overall survival (OS and disease-free survival (DFS were used to assess the prognostic value. The association of PNI with pathological characteristics was evaluated by OR and 95% CI. Results. A total of 13 cohorts were retrieved, covering 2770 patients treated by surgery. The cumulative analysis revealed a statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54–2.20, and P<0.00001, as well as poor DFS (HR = 1.96, 95% CI: 1.42–2.71, and P<0.001. Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR = 0.39, 95% CI: 0.21–0.70, and P=0.002, N+ (OR = 0.52, 95% CI: 0.40–0.69, and P<0.00001, and G3 + G4 (OR = 0.66, 95% CI: 0.48–0.90, and P=0.008 patients compared with T1 + T2, N−, and G1 + G2 ones, respectively. No significant heterogeneity was found between the studies. Conclusions. PNI is an adverse prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies advanced T, N stage and poor cell differentiation.

  10. Basaloid squamous cell carcinoma of the esophagus.

    Science.gov (United States)

    Chen, Shao-Bin; Weng, Hong-Rui; Wang, Geng; Yang, Jie-Sheng; Yang, Wei-Ping; Li, Hua; Liu, Di-Tian; Chen, Yu-Ping

    2012-07-01

    Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics. No standard treatment has been established. This retrospective study was designed to investigate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of esophageal BSCC. Clinical data were retrospectively analyzed from 26 patients with pathologically confirmed esophageal BSCC who underwent transthoracic esophagectomy with lymphadenectomy between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College. Clinicopathologic data between BSCC patients and different histologic grades of esophageal squamous cell carcinoma (ESCC) patients were statistically compared by means of the χ(2) test or Fisher's exact test. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Microscopically, BSCC was characterized by a nesting, lobular, or trabecular arrangement of small crowded cells with scant cytoplasm. None of the histologic specimens taken at preoperative esophagoscopy were diagnosed as BSCC. The median survival time (MST) of the 26 patients was 29.0 months (95% confidence interval, 9.0-49.0), and the 1-, 3-, and 5-year overall survival rates were 73.1, 42.7, and 36.6%, respectively. The MST for BSCC patients was significantly lower than that of well-differentiated SCC patients (P = 0.024), but there were no significant differences between the MST for BSCC patients and that of moderately or poorly differentiated SCC patients (P > 0.05). BSCC of the esophagus is a rare but distinctive disease and is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than well-differentiated SCC, but similar to moderately or poorly differentiated SCC.

  11. Successful treatment of esophageal metastasis from hepatocellular carcinoma using the da Vinci robotic surgical system

    Science.gov (United States)

    Boonnuch, Wiroon; Akaraviputh, Thawatchai; Nino, Carnivale; Yiengpruksawan, Anusak; Christiano, Arthur Andrew

    2011-01-01

    A 59-year-old man with metastatic an esophageal tumor from hepatocellular carcinoma (HCC) presented with progressive dysphagia. He had undergone liver transplantation for HCC three and a half years prevously. At presentation, his radiological and endoscopic examinations suggested a submucosal tumor in the lower esophagus, causing a luminal stricture. We performed complete resection of the esophageal metastases and esophagogastrostomy reconstruction using the da Vinci robotic system. Recovery was uneventful and he was been doing well 2 mo after surgery. α-fetoprotein level decreased from 510 ng/mL to 30 ng/mL postoperatively. During the follow-up period, he developed a recurrent esophageal stricture at the anastomosis site and this was successfully treated by endoscopic esophageal dilatation. PMID:21765971

  12. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  13. Stages of Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  14. Gingival squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Amit Walvekar

    2017-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is the most common epithelial malignancy affecting the oral cavity. The most common sites for the development are lateral surface of tongue and floor of mouth; the least common sites are soft palate, gingiva, and buccal mucosa. Gingival squamous cell carcinoma can mimic a multitude of oral lesions and enlargements, especially those of inflammatory origin. In addition, predisposing and presenting factors are different from those of other OSCCs. Careful examination as well as routine biopsy are crucial for accurate diagnosis.

  15. Dysphagia after Colon Interposition Graft for Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    C. Spitali

    2012-01-01

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

  16. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Intraosseous acinic cell carcinoma

    African Journals Online (AJOL)

    2011-12-17

    Dec 17, 2011 ... Salivary gland tumors are also known to develop within jaw bones, arising within the jaw as a ... Treatment of acinic cell carcinoma in most cases is surgical. High recurrence rates ... Panoramic radiograph [Figure 3] showed a ...

  18. Gallium imaging of esophageal carcinoma: Increased sensitivity with lateral views of the thorax

    International Nuclear Information System (INIS)

    Sostre, S.; Romero, I.; Rivera, J.V.; Baez, L.; Cintron, E.

    1990-01-01

    Ga-67 imaging has not been very successful in the detection of esophageal carcinoma. In most reports, sensitivity for the primary tumor ranged from 25-61%, but imaging had been done only in anterior and posterior (A-P) projections. We performed gallium scans in 30 patients with esophageal carcinoma, adding lateral views to the routine A-P projections, to study the effect of lateral views on tumor detection. The A-P views detected only 57% of the tumors while the right lateral visualized 89%, and the left lateral detected 100%. Some lesions may be hidden by the sternum and the spine in the routine A-P views. Previous disappointments with Ga-67 imaging of esophageal carcinoma were probably due to this technical factor. Being gallium-avid, esophageal tumors deserve further studies with this agent to determine the role of Ga-67 imaging in this condition. These studies should be performed with multiple views of the thorax or, better yet, with SPECT imaging of the chest, to circumvent the problem of sternum and spine interference

  19. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

    Science.gov (United States)

    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  20. Transcriptional regulation of miR-146b by C/EBPβ LAP2 in esophageal cancer cells

    International Nuclear Information System (INIS)

    Li, Junxia; Shan, Fabo; Xiong, Gang; Wang, Ju-Ming; Wang, Wen-Lin; Xu, Xueqing; Bai, Yun

    2014-01-01

    Highlights: • MiR-146b promotes esophageal cancer cell proliferation. • MiR-146b inhibits esophageal cancer cell apoptosis. • C/EBPβ directly binds to miR-146b promoter conserved region. • MiR-146b is up-regulated by C/EBPβ LAP2 transcriptional activation. - Abstract: Recent clinical study indicated that up-regulation of miR-146b was associated with poor overall survival of patients in esophageal squamous cell carcinoma. However, the underlying mechanism of miR-146b dysregulation remains to be explored. Here we report that miR-146b promotes cell proliferation and inhibits cell apoptosis in esophageal cancer cell lines. Mechanismly, two C/EBPβ binding motifs are located in the miR-146b promoter conserved region. Among the three isoforms of C/EBPβ, C/EBPβ LAP2 positively regulated miR-146b expression and increases miR-146b levels in a dose-dependent manner through transcription activation of miR-146b gene. Together, these results suggest a miR-146b regulatory mechanism involving C/EBPβ, which may contribute to the up-regulation of miR-146b in esophageal squamous cell carcinoma

  1. Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: Two Interesting Entities Identified in the Same Patient

    Directory of Open Access Journals (Sweden)

    Alfredo J. Lucendo

    2008-02-01

    Full Text Available We illustrate the case of a 41-year-old male with allergic manifestations since childhood. He sought medical attention for intermittent, progressive dysphagia from which he had been suffering for a number of years, having felt the sensation of a retrosternal lump and a self-limited obstruction to the passage of food. Endoscopy detected a submucosal tumor in the upper third of the esophagus, which was typified, via biopsy, as a granular cell tumor with benign characteristics and probably responsible for the symptoms. Two years later, the patient sought medical attention once again as these symptoms had not abated, hence digestive endoscopy was repeated. This revealed stenosis of the junction between the middle and lower thirds of the organ which had not been detected previously but was passable under gentle pressure. Eosinophilic esophagitis was detected after biopsies were taken. Esophageal manometry identified a motor disorder affecting the esophageal body. Following three months of treatment using fluticasone propionate applied topically, the symptoms went into remission, esophageal stenosis disappeared and the esophageal biopsies returned to normal. This is the first documented case of the link between granular cell tumors and Eosinophilic esophagitis, two different disorders which could cause dysphagia in young patients.

  2. Palliative radiation therapy practice for advanced esophageal carcinoma in Africa.

    Science.gov (United States)

    Sharma, V; Gaye, P M; Wahab, S A; Ndlovu, N; Ngoma, T; Vanderpuye, V; Sowuhami, A; Dawotola, D A; Kigula-Mugambe, J; Jeremic, B

    2010-04-01

    While numerous surveys of pattern of practices of palliative radiotherapy (RT) in advanced esophageal cancers have been published in developed countries, there is no such survey in African countries. During and after a regional training course by the International Atomic Energy Agency (IAEA) in palliative cancer care, a questionnaire was distributed to African RT centers to gather information about infrastructure and human resources available, and the pattern of practice of palliative RT for esophageal cancers. Twenty-four of the 35 centers (60%) completed the questionnaire. Twenty out of 23 (87%) centers treat patients with esophageal cancer presenting with dysphagia using external beam RT (16 centers external beam RT alone and 4 centers also use brachytherapy as a boost). Twelve (60%) centers prescribe RT doses of 30 Gy in 10 fractions and 2 centers 20 Gy in 5 fractions. Eighteen centers (78%) have low dose rate (LDR) brachytherapy, and 9 (39%) centers have high dose rate (HDR) brachytherapy. One center only used HDR brachytherapy alone to a dose of 16 Gy in 2 fractions over 8 days. RT remains a major component of treatment of patients with esophageal cancers in African countries. Still, there is a great variety among centers in both indications for RT and its characteristics for a treatment indication.

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

    NARCIS (Netherlands)

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

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

  4. Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tomohiro; Kaneko, Kazuhiro; Makino, Reiko; Ito, Hiroaki; Konishi, Kazuo; Kurahashi, Toshinori; Kitahara, Tadashi; Mitamura, Keiji [Showa Univ., Tokyo (Japan). School of Medicine

    2001-05-01

    A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P=0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis. (author)

  5. Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Ito, Tomohiro; Kaneko, Kazuhiro; Makino, Reiko; Ito, Hiroaki; Konishi, Kazuo; Kurahashi, Toshinori; Kitahara, Tadashi; Mitamura, Keiji

    2001-01-01

    A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P=0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis. (author)

  6. Single nucleotide polymorphism rs13042395 in the SLC52A3 gene as a biomarker for regional lymph node metastasis and relapse-free survival of esophageal squamous cell carcinoma patients

    International Nuclear Information System (INIS)

    Tan, Hua-Zhen; Wu, Zhi-Yong; Wu, Jian-Yi; Long, Lin; Jiao, Ji-Wei; Peng, Yu-Hui; Xu, Yi-Wei; Li, Shan-Shan; Wang, Wei; Zhang, Jian-Jun; Li, En-Min; Xu, Li-Yan

    2016-01-01

    SLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC). However, associations between the single nucleotide polymorphisms (SNPs) rs13042395 (C > T) and rs3746803 (G > A) in SLC52A3 and risk, tumor characteristics and survival of ESCC patients remain inconclusive and of unknown prognostic significance. Analyses of the association between SNPs in SLC52A3 and ESCC risk were performed on 479 ESCC cases, together with 479 controls, in a case-control study. Blood samples for cases and controls were collected and genotyped by real-time polymerase chain reaction (PCR) using TaqMan assays. Among the 479 ESCC cases, 343 cases with complete clinical data were used to investigate the association between SNPs and ESCC clinical characteristics; 288 cases with complete clinical data and 5-year follow-up data were used to analyze the association between SNPs and prognosis. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSAs) were used to investigate the biological function of rs13042395. No association was found between SLC52A3 rs3746803 and susceptibility, tumor characteristics or survival of ESCC patients. For rs13042395, TT genotype carriers were likely to have reduced lymph node metastasis (odds ratio (OR) = 0.55, 95 % confidence interval (CI), 0.31–0.98) and longer relapse-free survival time (P = 0.03) . Also, both rs13042395 (hazard ratio (HR) = 0.62, 95 % CI, 0.38–0.99) and regional lymph node metastasis (HR = 2.06, 95 % CI, 1.36–3.13 for N1 vs. N0; HR = 2.88, 95 % CI, 1.70–4.86 for N2 vs. N0; HR = 2.08, 95 % CI, 1.01–4.30 for N3 vs. N0) were independent factors affecting relapse-free survival for ESCC patients who underwent surgery. Dual luciferase reporter assays and EMSAs suggested that the CC genotype of rs13042395 enhanced SLC52A3 expression, probably via binding with specific transcription factors. The rs13042395 polymorphism in SLC52A3 is associated with regional lymph node

  7. Esophageal carcinoma treatment with self-expanding covered stent implanted in esophagus

    International Nuclear Information System (INIS)

    Liu Mingguo; Ji Yan; He Nengwei

    2006-01-01

    Objective: To investigate the clinical significance of the treatment to esophageal cancer by self- expanding covered stent implanted into esophagus. Methods: Under fluoroscopic guidance and with guidance wire , 20 self-expanding covered stents were implanted into stenotic part of esophagus to recanalize the esophagus, then follow up to observe the clinical symptom improved. Results: Technical success was obtained 20 cases without any complication. Clinical symptom were improved in shot time. Conclusions: self-expanding covered stent is implanted in stenotic part of esophageal carcinoma to treat esophageal stenosis and enable to improved clinical symptom in shot time, if combined with transcatheter arterial infusion and embolization, Radiotherapy, Chinese medical treatment, it enable to lengthen life time remarkably. (authors)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

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

    International Nuclear Information System (INIS)

    Wang, Zhihui; He, Wei; Yang, Guanrui; Wang, Junsheng; Wang, Zhong; Nesland, Jahn M; Holm, Ruth; Suo, Zhenhe

    2010-01-01

    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. 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. 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 < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and 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 < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. 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

  10. Cryospray ablation (CSA in the palliative treatment of squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Johnston Mark H

    2007-03-01

    Full Text Available Abstract Background Esophageal carcinoma is the ninth most prevalent cancer worldwide with squamous cell carcinoma (SCCA and adenocarcinoma accounting for the vast majority of new cases (13,900 in 2003. Cure rates in the U.S. are less than 10%, similar to lung cancer. More than 50% of patients with esophageal carcinoma present with unresectable or metastatic disease, are not surgical candidates, or display disease progression despite the addition of neoadjuvant chemoradiotherapy to surgery. Need for improved palliation exits. Case presentation This case describes a 73-year-old African American male who presented with recurrent squamous cell carcinoma (SCCA of the esophagus who has a achieved complete remission for 24 months via endoscopic cryospray ablation. Conclusion Endoscopic cryo spray ablation warrants further investigation as a palliative treatment modality for esophageal cancer. This is the first reported case in the medical literature.

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

    International Nuclear Information System (INIS)

    Lin Qiang; Gao Xianshu; Qiao Xueying; Zhou Zhiguo; Zhang Jun; Yang Xiangran; Wan Xin

    2006-01-01

    Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m 2 D1 and 5-fluorouracil 500 mg/m 2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m 2 and 5- fluorouracil 100 mg/m 2 . Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m 2 . MTD was defined as cisplatin 52.5 mg/m 2 , 5- fiuorouracil 700 mg/m 2 . The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m 2 D1-5, repeated 4 times every 28 days. (authors)

  12. Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

    2017-02-01

    Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

  13. Local control and image diagnosis of cases of esophageal carcinoma treated by external and intracavitary irradiation

    International Nuclear Information System (INIS)

    Hishikawa, Yoshio; Miura, Takashi

    1984-01-01

    Discussions are made on local control of 31 cases of esophageal carcinoma which were treated by external and intracavitary irradiation between May 1980 and March 1983. X-ray and endoscopic findings have been used for the image diagnosis. Before the begining of radiotherapy, types of esophageal carcinoma were determined from X-ray findings according to Borrmann's classification. There were 10 cases of types 1 and 2, and 21 cases of types 3 and 4. After completion of external and intracvitary irradiation, all 10 cases of types 1 and 2 were locally controlled. Of the 21 cases of types 3 and 4, 8 cases which developed stenosis or deep ulcer after external irradiation all failed in local control. The remaining 13 cases of types 3 and 4 were locally controlled except 2 by radiotherapy. (author)

  14. MDM2, p53 and pRb Expression Prior to Definitive Chemoradiotherapy in Esophageal Carcinoma

    International Nuclear Information System (INIS)

    Yoon, Mee Sun; Nam, Taek Keun; Lee, Jae Hyuk; Cho, Sang Hee; Song, Ju Young; Ahn, Sung Ja; Chung, Ik Joo; Chung, Woong Ki; Nah, Byung Sik

    2007-01-01

    Purpose: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. Materials and Methods: Fifty-one patients that were treated with definitive hemoradiotherapy for stage I∼ IVa esohageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily 1.8∼2 Gy fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5-fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. Results: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. Conclusion: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response

  15. Selenium Status and the Risk of Esophageal and Gastric Cancer Subtypes: The Netherlands Cohort Study

    NARCIS (Netherlands)

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

    2010-01-01

    Background & Aims: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies

  16. Telomerase variant A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuwei Zhang

    Full Text Available Although implicated in the pathogenesis of several chronic inflammatory disorders and hematologic malignancies, telomerase mutations have not been thoroughly characterized in human cancers. The present study was performed to examine the frequency and potential clinical relevance of telomerase mutations in esophageal carcinomas.Sequencing techniques were used to evaluate mutational status of telomerase reverse transcriptase (TERT and telomerase RNA component (TERC in neoplastic and adjacent normal mucosa from 143 esophageal cancer (EsC patients. MTS, flow cytometry, time lapse microscopy, and murine xenograft techniques were used to assess proliferation, apoptosis, chemotaxis, and tumorigenicity of EsC cells expressing either wtTERT or TERT variants. Immunoprecipitation, immunoblot, immunofluorescence, promoter-reporter and qRT-PCR techniques were used to evaluate interactions of TERT and several TERT variants with BRG-1 and β-catenin, and to assess expression of cytoskeletal proteins, and cell signaling. Fluorescence in-situ hybridization and spectral karyotyping techniques were used to examine telomere length and chromosomal stability.Sequencing analysis revealed one deletion involving TERC (TERC del 341-360, and two non-synonymous TERT variants [A279T (2 homozygous, 9 heterozygous; A1062T (4 heterozygous]. The minor allele frequency of the A279T variant was five-fold higher in EsC patients compared to healthy blood donors (p<0.01. Relative to wtTERT, A279T decreased telomere length, destabilized TERT-BRG-1-β-catenin complex, markedly depleted β-catenin, and down-regulated canonical Wnt signaling in cancer cells; these phenomena coincided with decreased proliferation, depletion of additional cytoskeletal proteins, impaired chemotaxis, increased chemosensitivity, and significantly decreased tumorigenicity of EsC cells. A279T expression significantly increased chromosomal aberrations in mouse embryonic fibroblasts (MEFs following Zeocin

  17. Preoperative CT assessment of esophageal carcinoma : comparison between the patients with and without recurrence of esophageal carcinoma after surgical resection

    International Nuclear Information System (INIS)

    Lee, Young Hen; Oh, Yu Whan; Cho, Kyu Ran; Park, Bum Jin; Lee, Nam Jun; Chung, Kyoo Byung

    2001-01-01

    To determine whether preoperative CT is helpful in predicting the development of recurrent tumor following surgical resection in patients with esophageal cancer. Thirty patients with esophageal cancer in whom preoperative CT of the chest had been performed were included in the study. All had undergone esophagectomy, esophagogastrostomy and lymph node dissection at our institution between 1995 and 1997. They were divided into two groups according to the development of tumor recurrence during the follow-up period of three years. Sixteen patients (group I) suffered tumor recurrence, while the other 14 (group II) remained tumor-free after surgery. In each group, a review of the preoperative CT scans indicated the length, thickness, location and margin of the tumor, and the presence or absence of lymphadenopathy in the mediastinum and/or upper abdomen. Differences in preoperative CT findings between the two groups were assessed by statistical testing. Lymphadenopathy of the mediastinum and/or upper abdomen was seen in 11 (69%) of 16 patients in group I and three (21%) of 14 in group II (p .05). In group I, five esophageal tumors were located in the middle esophagus and eleven in the lower esophagus. In group II, such tumor was located one in the upper esophagus, six in the middle esophagus, and seven in the lower esophagus (p>.05). Patients with preoperative CT findings of lymphadenopathy and/or and indistinct primary tumor margin are more likely to develop tumor recurrence following surgical resection than those without these findings

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

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

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

  19. Treatment results of chemoradiotherapy for clinical stage I (Taman) esophageal carcinoma

    International Nuclear Information System (INIS)

    Yamada, Kazunari; Murakami, Masao; Okamoto, Yoshiaki; Okuno, Yoshishige; Nakajima, Toshifumi; Kusumi, Fusako; Takakuwa, Hiroshi; Matsusue, Satoru

    2006-01-01

    Purpose: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (Crt) for clinical Stage I (Taman) esophageal cancer. Patients and Methods: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T 1a) in 23 and submucosal cancer (T 1b) in 40. Crt consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. Results: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T 1a and T 1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T 1a and T 1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G: 1; G: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. Conclusion: We confirmed that patients with Taman esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive Crt, and the survival rates were equivalent to those of previous reports of surgery

  20. A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Czito, Brian G.; Kelsey, Chris R.; Hurwitz, Herbert I.; Willett, Chris G.; Morse, Michael A.; Blobe, Gerard C.; Fernando, Nishan H.; D'Amico, Thomas A.; Harpole, David H.; Honeycutt, Wanda R.N.; Yu Daohai; Bendell, Johanna C.

    2007-01-01

    Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. Methods and Materials: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. Results: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m 2 twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m 2 weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m 2 twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m 2 ). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. Conclusions: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m 2 twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m 2 weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis

  1. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  2. Evaluation of the palliative effect of radiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Albertsson, M.; Ewers, S.B.; Widmark, H.; Hambraeus, G.; Lillo-Gil, R.; Ranstam, J.; Lund Univ. Hospital

    1989-01-01

    149 patients with carcinoma of the esophagus treated with radiotherapy were evaluated. Eighty-one patients had treatment with palliative intent and 68 with curative intent. The 4-year actuarial survival was 1 and 5% respectively. The tumor size, Karnofsky index (KI) and radiation dose were prognostic factors. The duration of palliation of the patients dysphagia was dose-dependant. (orig.)

  3. Squamous cell carcinoma - invasive (image)

    Science.gov (United States)

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  4. Incidence of Esophageal Carcinomas After Surgery for Achalasia: Usefulness of Long-Term and Periodic Follow-up.

    Science.gov (United States)

    Ota, Masaho; Narumiya, Kosuke; Kudo, Kenji; Yagawa, Yohsuke; Maeda, Shinsuke; Osugi, Harushi; Yamamoto, Masakazu

    2016-11-14

    BACKGROUND Patients with esophageal achalasia are considered to be a high-risk group for esophageal carcinoma, and it has been reported that this cancer often arises at a long interval after surgery for achalasia. However, it is unclear whether esophageal carcinoma is frequent when achalasia has been treated successfully and the patient is without dysphagia. In this study, we reviewed patients with esophageal carcinoma who were detected by regular follow-up after surgical treatment of achalasia.   CASE REPORT Esophageal cancer was detected by periodic upper GI endoscopy in 6 patients. Most of them had early cancers that were treated by endoscopic resection. All 6 patients had undergone surgery for achalasia and the outcome had been rated as excellent or good. Annual follow-up endoscopy was done and the average duration of follow-up until cancer was seen after surgery was 14.3 years (range: 5 to 40 years). Five patients had early cancer. Four cases had multiple lesions.   CONCLUSIONS In conclusion, surgery for achalasia usually improves passage symptoms, but esophageal cancer still arises in some cases and the number of tumors occurring many years later is not negligible. Accordingly, long-term endoscopic follow-up is needed for detection of malignancy at an early stage.

  5. Cutaneous Squamous Cell Carcinoma.

    Science.gov (United States)

    Parekh, Vishwas; Seykora, John T

    2017-09-01

    Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

    International Nuclear Information System (INIS)

    Dreilich, Martin; Bergqvist, Michael; Moberg, Martin; Brattström, Daniel; Gustavsson, Inger; Bergström, Stefan; Wanders, Alkwin; Hesselius, Patrik; Wagenius, Gunnar; Gyllensten, Ulf

    2006-01-01

    Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma

  7. Laser-induced fluorescence in the detection of esophageal carcinoma

    Science.gov (United States)

    Wang, Kenneth K.; Gutta, Kumar; Laukka, Mark A.; Densmore, John

    1995-01-01

    Laser induced fluorescence (LIF) is a technique which can perform an 'optical biopsy' of gastrointestinal mucosa. LIF was performed in resected specimens using a pulsed N2-laser coupled fiberoptically to a probe. Fluorescence was measured using a 0.2 meter spectroscope with an intensified photodiode array. Measurements were made on fresh (esophagus, and adenocarcinoma. Each tissue section was examined using an optical probe consisting of a central fiber for delivering the excitation energy and a 6 fiber bundle surrounding the central fiber for detection of the fluorescence. An excitation wavelength of 337 nm was used which generated 3-ns pulses while fluorescence intensities were acquired from 300-800 nm. Spectra were obtained from each section in a standardized fashion and background spectra subtracted. Fluorescence readings were taken from 54 normal esophageal sections and 32 sections of adenocarcinoma. A fluorescence index obtained from the tumor sections was 0.68+/- 0.01 compared with 0.51+/- 0.01 for the normal sections (pesophagus with good accuracy.

  8. The impact of postoperative supraclavicular radiotherapy on tracheoesophageal groove lymph node metastasis in esophageal carcinoma

    International Nuclear Information System (INIS)

    Qian Pudong; Lu Jinchen; Mei Zeru; Zhu Jun

    2005-01-01

    Objective: To evaluate the prognostic factors of tracheoesophageal groove lymph node (TEGLN) metastasis in postoperative esophageal carcinoma. Methods: From January 1996 to December 1997, 101 postoperative cervical and thoracic esophageal carcinoma patients proved absence from tracheoesophageal groove lymph node (TEGIAN) metastasis before and after operation by physical examination and computer tomography examination were entered into this study. The patients were divided into three groups according to the treatment of supraclavicular region: no prophylactic radiotherapy (group A-, 30 patients); prophylactic radiotherapy with local dose < 45 Gy (Group B-, 71 patients); and prophylactic radiotherapy with local dose ≥45 Gy (Group C-, 19 patients). Radiotherapy was delivered by cobalt- 60 or 6 MV X-ray with the prescribed dose normalized to the point of tracheoesophageal groove, i. e, 5 cm in depth. The tracheoesophageal groove lymph node metastasis after treatment was observed. Results: The incidence of tracheoesophageal groove lymph node metastasis was 20% (6/30), 9.6% (5/71) and 0% (0/19) in groups A, B and C. Univariate analysis showed that there was significant difference of TEGLN metastasis between groups A and C only (P=0.039), but higher dose to supraclavicular region tended to lower the incidence of TEGLN metastasis. Multivariate analysis showed that only prophylactic radiotherapy to the supraclavicular region was independent prognostic factor for TEGLN metastasis (P=0.037). Gender, primary tumor site and pathological stage had no significant impact on TEGLN metastasis. Conclusions: Postoperative prophylactic supraclavicular region irradiation can lower the incidence of tracheoesophageal groove lymph node metastasis in esophageal carcinoma. Radiotherapy dose should not be less than 45 Gy and should be routinely normalized to a point 5 cm deep in the tracheoesophageal groove. (authors)

  9. Setup error in three-dimensional conformal radiotherapy for thoracic esophageal carcinoma

    International Nuclear Information System (INIS)

    Hong Jinsheng; Zhang Weijian; Chen Jinmei; Cai Chuanshu; Ke Chunlin; Chen Xiuying; Wu Bing; Guo Feibao

    2009-01-01

    Objective: To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods: Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs (DRR). Then the setup margins from CTV to PTV were calculated. By using self paired design, 22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes; Group B: the margins were aquired in this study. The difference were compared by Paired t-test or Wilcoxon signed-rank test. Results: The margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy ± 1449.6 cGy vs. 4310.2 cGy ± 1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82% ± 5.99% vs. 3.64% ± 4.70%; Z=-2.70, P=0.007). Conclusions: For patients with thoracic esophageal carcinoma who receive 3DCRT in author's department, the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis. (authors)

  10. Large mid-esophageal granular cell tumor: benign versus malignant

    Directory of Open Access Journals (Sweden)

    Prarthana Roselil Christopher

    2015-06-01

    Full Text Available Granular cell tumors are rare soft tissue neoplasms, among which only 2% are malignant, arising from nervous tissue. Here we present a case of a large esophageal granular cell tumor with benign histopathological features which metastasized to the liver, but showing on positron emission tomography-computerized tomography standardized uptake value suggestive of a benign lesion.

  11. Esophageal Metastasis From Occult Lung Cancer

    Directory of Open Access Journals (Sweden)

    Po-Kuei Hsu

    2010-06-01

    Full Text Available A 66-year-old man with dysphagia was found to have a poorly differentiated esophageal carcinoma by incision biopsy. Following esophagectomy, reconstruction with a gastric tube was performed. Pathological examination and immunohisto-chemistry showed infiltration of adenocarcinoma cells with positive thyroid transcription factor 1-staining in the submucosal layer, which indicated metastatic esophageal carcinoma. Although no pulmonary lesion could be visualized by imaging or bronchoscopy, pulmonary origin was highly suspected as a result of positive thyroid transcription factor 1-staining. To the best of our knowledge, this is the first reported case of metastatic esophageal carcinoma from occult lung cancer (AJCC TNM stage TX.

  12. The Changing Face of Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Rachel E. Melhado

    2010-06-01

    Full Text Available 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.

  13. The Changing Face of Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. The Changing Face of Esophageal Cancer

    International Nuclear Information System (INIS)

    Melhado, Rachel E.; Alderson, Derek; Tucker, Olga

    2010-01-01

    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

  15. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  16. Argon plasma coagulation for a patient with locoregional failure after definitive chemoradiotherapy for esophageal carcinoma. A case report

    International Nuclear Information System (INIS)

    Nomura, Tsutomu; Miyashita, Masao; Makino, Hiroshi; Okawa, Keiichi; Katsuta, Miwako; Tajiri, Takashi

    2008-01-01

    Patients who undergo definitive chemoradiotherapy (CRT) face a risk of residual resistant disease or disease recurrence at the primary site; therefore, salvage treatment may be required. An optimum strategy to minimize these risks clearly needs to be established. Argon plasma coagulation (APC) is a safe and convenient procedure now applied widely for therapeutic endoscopy. In this report we describe the successful use of APC over 6 years for the treatment of recurrent esophageal cancer after CRT. A 61-year-old Japanese man underwent CRT for a thoracic esophageal cancer. Pathological examination before CRT revealed a well-differentiated squamous cell carcinoma. Locoregional failure was observed 2 years after CRT, and an initial APC treatment was performed. The patient has now undergone APC ablation 7 times with no postoperative complications. No metastasis to lymph nodes or to other organs has been detected during the last 6 years. The usefulness of APC as a salvage treatment for locoregional failure after definitive CRT has not been established. In our experience, salvage APC is the best treatment option for some patients. (author)

  17. Expression of Cat Podoplanin in Feline Squamous Cell Carcinomas.

    Science.gov (United States)

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2017-12-01

    Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis. Until now, we have established several mAbs against podoplanin in humans, mice, rats, rabbits, dogs, cattle, and cats. We have reported podoplanin expression in canine melanoma and squamous cell carcinomas using an anti-dog podoplanin mAb PMab-38. In this study, we investigated podoplanin expression in 40 feline squamous cell carcinomas (14 cases of mouth floor, 13 of skin, 9 of ear, and 4 of tongue) by immunohistochemical analysis using an anti-cat podoplanin mAb PMab-52, which we recently developed by cell-based immunization and screening (CBIS) method. Of the total 40 cases, 38 (95%) showed positive staining for PMab-52. In particular, 12 cases (30%) showed a strong membrane-staining pattern of squamous cell carcinoma cells. PMab-52 can be useful for antibody therapy against feline podoplanin-expressing squamous cell carcinomas.

  18. Diagnosis of the depth of invasion of esophageal carcinoma using digital radiography

    International Nuclear Information System (INIS)

    Ito, Bunichi; Niwa, Yasumasa; Ando, Nobuhiro; Ohmiya, Naoki; Miyahara, Ryoji; Ohashi, Akira; Itoh, Akihiro; Hirooka, Yoshiki; Goto, Hidemi

    2005-01-01

    Objective: The purpose of our investigation was to determine the usefulness of digital radiography (DR) for diagnosing the depth of invasion of esophageal carcinoma. Methods: We evaluated 59 patients with esophageal carcinomas who underwent DR. During continuous DR in tangential views, the most distended image of the esophagus was chosen. Percent esophageal stenosis (PES) was based on the diameter across the lesion of maximal narrowing and the average of the normal oral and anal side diameters. The maximal thickness of the tumor was measured on sequentially prepared specimens. We evaluated whether the percent of esophageal stenosis correlated with the maximal thickness of the tumor on histologic findings. Receiver-operating characteristic (ROC) curves were constructed to establish the cut-off level for PES in diagnosing the depth of tumor invasion. Accuracies for the depth of the invasion were calculated based on PES using DR. For the accuracy rate, DR was compared with endoscopy and endoscopic ultrasonography (EUS). Results: There was a close correlation between PES and pathological thickness of the tumor. PES values (mean ± S.D.) were 2.45 ± 0.75% in Tis and T1a tumors, 13.3 ± 10.9% in T1b tumors, 35.2 ± 11.1% in T2 tumors, 55.2 ± 18.1% in T3 tumors, and 86.1 ± 7.5% in T4 tumors. Using the ROC analysis, 12.5, 37.5, and 44.4% were the highest cut-off values of PES for differentiating ≤T1a, ≤T1b, and ≤T2 tumors. Regarding T staging, 45 (76%) of 59 lesions were staged correctly with EUS, whereas 47 (80%) were staged correctly with DR. Conclusion: DR is useful for diagnosing the depth of the invasion because esophageal stenosis calculated using DR is an objective index of tumor infiltration. The accuracy rate of the depth of invasion with DR was as good as that of EUS

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

    International Nuclear Information System (INIS)

    Zhang, Peng; Xi, Mian; Zhao, Lei; Li, Qiao-Qiao; He, Li-Ru; Liu, Shi-Liang; Shen, Jing-Xian; Liu, Meng-Zhong

    2014-01-01

    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

  20. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    International Nuclear Information System (INIS)

    Lee, Jae Seo

    2006-01-01

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present

  1. Analyzing esophageal squamous cell papillomas for the presence of human papilloma virüs.

    Science.gov (United States)

    Tiftikçi, Arzu; Kutsal, Eser; Altıok, Ender; İnce, Ümit; Çicek, Bahattin; Saruç, Murat; Türkel, Nurten; Ersoy, Özdal; Yenmiş, Güven; Tözün, Nurdan

    2017-05-01

    Human Papilloma Virus (HPV) infection can be a predisposing condition for the development of squamous cell papilloma (SCP) of the esophagus, which can progress to dysplasia and to carcinoma as a result of chronic infection. The aim of the present study was to search for the presence of HPV in the esophageal SCP, and to genotype the detected HPV. Data from patients with definite diagnosis of SCP of the esophagus were identified from pathology records for two years period at different Hospitals. Slides from each patient were reviewed and samples with satisfactory papilloma tissues were submitted to molecular analysis. DNA has been isolated. DNA sequencing has been performed for genotyping HPV for all types. Our study group consisted of 21 women and 17 men (a total of 38 patients), mean age was 41 years (range 17-67 years). Most of the papillomas were located at mid-esophagus (68%). Eight out of 38 patients (21%) had associated erosive esophagitis, and fourteen patients (36.8%) had Helicobacter Pylori (H. pylori). Of the 38 SCP analyzed, seven (19%) were positive for HPV DNA. Three of them were of genotype 6, whereas four were of genotype 16, 18, 31, 81 that are known as highly oncogenic. There were no correlations between the presence of HPV and the patient's age, the presence of reflux esophagitis or H. pylori, smoking habit and the location of the papillomas. The presence of high-risk type HPV in esophageal SCP may implicate a role of the virus in the pathogenesis of the esophageal tumor.

  2. [Esophageal sarcomatoid carcinoma: report of a case with morphological, immunohistochemical and molecular study].

    Science.gov (United States)

    Regragui, Asmaa; Lakhdar, Hind; Abderrahman Alaoui Belabbas, Moulay; Amrani, Meryem; Gamra, Lamia; Alaoui Belabbas, Mohamed

    2004-05-01

    Sarcomatoïd carcinoma is a rare tumor of the esophagus, characterized macroscopically by a polypoid aspect and histologically by the association of spindle cell carcinoma with sarcomatous pleomorphic component. We report here a case of esophagus sarcomatoïd carcinoma. Diagnosis was based on immunohistochemical analysis of tIssue samples. Human papillomavirus (HVP) detection by PCR amplification of DNA extracted from tumoral tIssue was negative, ruling out the role of HPV infection in this tumor.

  3. Small-cell carcinoma of the esophagus with regression after combination chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Hirsch, J.A.; Levine, M.S.; Silberg, D.G.; Phillipe, L.

    1995-01-01

    The authors present an unusual case of small-cell carcinoma of the esophagus, which manifested on double-contrast esophagography as an ulcerated submucosal mass. The lesion underwent dramatic regression after combination chemotherapy and radiation therapy, which has occasionally been used as an alternative to surgery in patients with this rare but aggressive esophageal neoplasm. (author). 8 refs., 4 figs

  4. Large-Cell Neuroendocrine Carcinoma of the Esophagus: A Case from Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Hadi Kuriry

    2015-10-01

    Full Text Available Neuroendocrine carcinomas of the esophagus are very rare, and the majority are high grade (poorly differentiated. They occur most frequently in males in their sixth and seventh decades of life. There have been no concrete data published on clinical features or on prognosis. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 66-year-old Saudi female with progressive dysphagia and weight loss. Upper endoscopy revealed an esophageal ulcerated mass.

  5. Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances the efficacy of near-infrared targeted photodynamic therapy in esophageal adenocarcinoma cell lines

    NARCIS (Netherlands)

    Hartmans, Elmire; Linssen, Matthijs D.; Sikkens, Claire; Levens, Afra; Witjes, Max J. H.; van Dam, Gooitzen M.; Nagengast, Wouter B.

    2017-01-01

    Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we

  6. The integration of 18-fluoro-deoxy-glucose positron emission tomography and endoscopic ultrasound in the treatment-planning process for esophageal carcinoma

    International Nuclear Information System (INIS)

    Konski, Andre; Doss, Mohan; Milestone, Barton; Haluszka, Oleh; Hanlon, Alexandra; Freedman, Gary; Adler, Lee

    2005-01-01

    Purpose: Accurate delineation of the gross tumor volume (GTV) is important in radiation therapy treatment planning. We evaluated the impact of PET and endoscopic ultrasound (EUS) compared with CT simulation in the planning of radiation fields for patients with esophageal carcinoma. Material and methods: Twenty-five patients presenting with esophageal carcinoma for radiation therapy underwent PET scans in the treatment position after conventional CT simulation. Patients underwent PET/CT scanning after being injected with 10 to 20 mCi of [F-18]-2-deoxy-2-fluro-D-glucose. The length of the abnormality seen on the CT portion of the PET/CT scan vs. the PET scan alone was determined independently by 2 separate investigators. The length of the GTV and detection of regional adenopathy by PET was also correlated with EUS in 18 patients. Of the 18 patients who had EUS, 2 had T2 tumors and 16 had T3 tumors. Eighteen patients had adenocarcinoma and 7 had squamous cell carcinoma. Nine tumors were located at the gastroesophageal junction, 8 at the lower esophagus, 7 in the middle esophagus, and 1 in the cervical esophagus. The PET scans were reviewed to determine the length of the abnormality by use of a standard uptake value (SUV) of 2.5 to delineate the tumor extent. Results: The mean length of the cancer was 5.4 cm (95% CI 4.4-6.4 cm) as determined by PET scan, 6.77 cm (95% CI, 5.6-7.9 cm) as determined by CT scan, and 5.1 cm (95% CI, 4.0-6.1 cm) for the 22 patients who had endoscopy. The length of the tumors was significantly longer as measured by CT scans compared with PET scans (p = 0.0063). EUS detected significantly more patients with periesophageal and celiac lymphadenopathy compared to PET and CT. The SUV of the esophageal tumors was higher in patients with peri-esophageal lymphadenopathy identified on PET scans. Conclusion: Endoscopic ultrasound and PET scans can add additional information to aid the radiation oncologist's ability to precisely identify the GTV in

  7. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  8. General Information about Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  9. Small cell carcinoma arising in Barrett's esophagus: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Markogiannakis Haridimos

    2008-01-01

    Full Text Available Abstract Introduction Gastrointestinal tract small cell carcinoma is an infrequent and aggressive neoplasm that represents 0.1–1% of gastrointestinal malignancies. Very few cases of small cell esophageal carcinoma arising in Barrett's esophagus have been reported in the literature. An extremely rare case of primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus is herein presented. Case presentation A 62-year-old man with gastroesophageal reflux history presented with epigastric pain, epigastric fullness, dysphagia, anorexia, and weight loss. Esophagogastroscopy revealed an ulceroproliferative, intraluminar mass in the distal esophagus obstructing the esophageal lumen. Biopsy showed small cell esophageal carcinoma. Contrast-enhanced chest and abdominal computed tomography demonstrated a large tumor of the distal third of the esophagus without any lymphadenopathy or distant metastasis. Preoperative chemotherapy with cisplatine and etoposide for 3 months resulted in a significant reduction of the tumor. After en block esophagectomy with two field lymph node dissection, proximal gastrectomy, and cervical esophagogastric anastomosis, the patient was discharged on the 14th postoperative day. Histopathology revealed a primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus. The patient received another 3 month course of postoperative chemotherapy with the same agents and remained free of disease at 12 month review. Conclusion Although small cell esophageal carcinoma is rare and its association with dysplastic Barrett's esophagus is extremely infrequent, the high carcinogenic risk of Barrett's epithelium should be kept in mind. Prognosis is quite unfavorable; a better prognosis might be possible with early diagnosis and treatment strategies incorporating chemotherapy along with oncological radical surgery and/or radiotherapy as part of a

  10. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  11. Diagnostic value of multiple tumor markers for patients with esophageal carcinoma.

    Science.gov (United States)

    Zhang, Jun; Zhu, Zhenli; Liu, Yan; Jin, Xueyuan; Xu, Zhiwei; Yu, Qiuyan; Li, Ke

    2015-01-01

    Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer. We systematically searched PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM), through February 28, 2013, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. Of 4391 studies initially identified, 44 eligible studies including five tumor markers met the inclusion criteria for the meta-analysis, while meta-analysis could not be conducted for 12 other tumor markers. Approximately 79.55% (35/44) of the included studies were of relatively high quality (QUADAS score≥7). The summary estimates of the positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for diagnosing EC were as follows: CEA, 5.94/0.76/9.26; Cyfra21-1, 12.110.59/22.27; p53 antibody, 6.71/0.75/9.60; SCC-Ag, 7.66/0.68/12.41; and VEGF-C, 0.74/0.37/8.12. The estimated summary receiver operating characteristic curves showed that the performance of all five tumor markers was reasonable. The current evidence suggests that CEA, Cyfra21-1, p53, SCC-Ag and VEGF-C have a potential diagnostic value for esophageal carcinoma.

  12. Improving the quality of pretreatment staging in patients with esophageal carcinoma - a fast track study

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    Didden, Paul; Spaander, Manon C. W.; Kuipers, Ernst J.; Bruno, Marco J. (Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam (Netherlands)), E-mail: v.spaander@erasmusmc.nl; Wijnhoven, Bas P. L. (Department of Surgery, Erasmus University Medical Center, Rotterdam (Netherlands))

    2012-03-15

    Background: Current guidelines for esophageal cancer recommend series of diagnostic investigations to determine pretreatment TNM stage. When investigations are done sequentially, diagnostic work-up time may be prolonged considerably. Aim of the study was to determine the feasibility and efficacy of a fast track staging strategy within five days after the first consultation. Material and methods: Between 2007 and 2010 all patients presenting with esophageal cancer at the Department of Gastroenterology in a tertiary referral center were prospectively analyzed. At Day 1 all patients underwent computed tomography (CT), endoscopic ultrasound (EUS) and ultrasonography of the neck (United States). Results and treatment implications were discussed within a multidisciplinary meeting. This fast track strategy was considered completed successfully if pre-treatment TNM classification was achieved and therapy was proposed to the patient at the outpatient clinic at Day five. In those cases where staging period time was prolonged, the number and type of additional tests were documented including the ensuing time delay. Results: In 111 patients CT, EUS and US were performed in 100%, 88.3% and 97.3% respectively. A final TNM stage and treatment proposal was reached at Day 5 in 60% of the patients. Additional tests were diverse and mainly used to prove local irresectability or presence of distant metastasis. Multivariate analysis identified presence of lymphadenopathy (HR 0.25 p 0.03) and metastasis (HR 0.27 p = 0.03) as significant predictors of not completing the staging period within five days. In 18% of patients overuse of at least one test occurred, most commonly because CT already revealed distant metastasis. Conclusion: Employment of a fast track five day staging strategy in patients with esophageal carcinoma is feasible. Definite TNM stage and treatment proposal can be achieved in 60% of cases, but comes at the expense of test overuse in about one fifth of patients

  13. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

    International Nuclear Information System (INIS)

    Haj Mohammad, Nadia; Hulshof, Maarten CCM; Bergman, Jacques JGHM; Geijsen, Debby; Wilmink, Johanna W; Berge Henegouwen, Mark I van; Laarhoven, Hanneke WM van

    2014-01-01

    Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group

  14. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

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    Haj Mohammad, Nadia [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hulshof, Maarten CCM [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Bergman, Jacques JGHM [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Geijsen, Debby [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Wilmink, Johanna W [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Berge Henegouwen, Mark I van [Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Laarhoven, Hanneke WM van [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-01-31

    Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

  15. Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

    International Nuclear Information System (INIS)

    Masao, Murakami; Yasumasa, Kuroda; Yosiaki, Okamoto; Koichi, Kono; Eisaku, Yoden; Fusako, Kusumi; Kiyoshi, Hajiro; Satoru, Matsusue; Hiroshi, Takeda

    1997-01-01

    Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for the esophageal carcinoma. Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (stage 0 to III: UICC 1987), aged 45 to 78 (mean:64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44Gy in 40 fractions for 4 weeks (2.2Gy/2Fr./day) through 10MVX rays, with one or two courses of cisplatin (80-150mg/body, mean:90mg/m 2 , day 1, bolus injection) and 5-fluorouracil (500-1500mg/body/day, mean:600mg/m 2 , day 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, clinical complete response (CR) was observed in 16 patients, partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR:16, PR:14) entered in CRT group, and 10 non-responding patients (PR:8, NC:2) followed by surgery (CRT-S group). A cumulative median dose of 66Gy for Tis,T1 and 71Gy for T2-T4 tumor with/without high-dose-rate intraluminal brachytherapy, and one to three courses of chemotherapy were delivered in CRT group. Intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added in CRT-S group. Results: Clinical CR rate at the completion of treatment showed 90% in CRT group, and pathological CR rate 10% in CRT-S group. The overall median survival was 45 months, survival at 1, 2, 3 years being 100%, 72%, 56%, respectively. Loco-regional failure was observed in 7 patients (all in CRT group), distant failure in 6 (3 in CRT group, 3 in CRT-S group) and loco-regional with distant failure in 1 (CRT group). Four patients of loco-regional recurrence in CRT group were salvaged by surgery. Overall survival at 2-, 3-years for CRT vs. CRT-S group was 72%, 64% vs. (1(1)); 100

  16. Overexpression of DNA damage-induced 45 α gene contributes to esophageal squamous cell cancer by promoter hypomethylation

    Directory of Open Access Journals (Sweden)

    Wang Bao xiang

    2012-02-01

    Full Text Available Abstract Background Environmental factors-induced dysfunction of esophageal squamous epithelium, including genomic DNA impairment and apoptosis, play an important role in the pathogenesis of esophageal squamous cell cancer. DNA damage-induced 45α (GADD45α has been found promoting DNA repair and removing methylation marker, Therefore, in this study we will investigate whether GADD45α expression is induced and its mechanism in esophageal squamous cell cancer. Methods Two human esophageal squamous cell lines (ESCC, ECA109 and KYSE510 were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS. Lipofectamine 2000 was used to transfect cells. mRNA level of GADD45α was measured by reverse transcription-quantitive PCR (RT-qPCR, protein level of GADD45α was detected by western blot and Immunohistochemistry. Global DNA methylation of tissue sample was measured using the Methylamp Global DNA Methylation Quantification Ultra kit (Epigentek Group and promoter methylation was measured by bisulfite sequencing. Results GADD45a mRNA and protein levels were increased significantly in tumor tissue than that in adjacent normal tissue. Hypomethylation of global genomic DNA and GADD45α promoter were found in ESCC. The cell sensitivity to Cisplatin DDP was decreased significantly in Eca109 and Kyse510 cells, in which GADD45α expression was down-regulated by RNA interference (RNAi. In addition, silence of GADD45a expression in ESCC cells inhibited proliferation and promoted apoptosis. Conclusion Overexpression of GADD45α gene is due to DNA hypomethylation in ESCC. GADD45α may be a protective factor in DDP chemotherapy for esophageal squamous cell carcinoma.

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

    International Nuclear Information System (INIS)

    Isono, Kaichi; Koide, Yoshio

    1996-01-01

    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.)

  18. Electrocardiographic changes is patients with esophageal carcinoma exposed to radiotherapy by a continuous and split course

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    Sarkisyan, Yu Kh; Goncharova, I M; Kallistova, L P; Syromyatnikova, E N; Slaviner, S I; Abramchenko, Yu A [Nauchno-Issledovatel' skij Inst. Rentgenologii i Radiologii, Moscow (USSR)

    1980-10-01

    An analysis of clinical, electrocardiographic, roentgenological and biochemical changes was made in 170 patients with esophageal carcinoma before, during and after radiation therapy conducted by a continuous (34 patients) and split course (136 patients). A rise in sinus tachycardia, appearance of extrasystolia and His' bundle right branch block, lowering of the ST-segment, flattening or appearance of negative T wave, an increase in the activity of creatine phosphokinase and aspartate aminotransferase in the blood serum were noted in a number of patients during radiation therapy. The changes were observed more often and were more marked in patients who had received continuous telegammatherapy. Irrespective of the method of radiotherapy in the restoration of the processes of excitation and conduction, improvement of metabolism in the cardiac muscle, a decrease in dysproteinemia, an increase in the content of electrolytes in the blood were noted.