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

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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

ABT-263 induces G1/G0-phase arrest, apoptosis and autophagy in human esophageal cancer cells in vitro.

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Lin, Qing-Huan; Que, Fu-Chang; Gu, Chun-Ping; Zhong, De-Sheng; Zhou, Dan; Kong, Yi; Yu, Le; Liu, Shu-Wen

2017-12-01

Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC 50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 μmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 μmol/L) dose-dependently induced G 1 /G 0 -phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21 Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G 1 /G 0 -phase arrest. Knockdown of p21 Waf1/Cip1 attenuated ABT-263-induced G 1 /G 0 -phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.

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

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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

Identification of differentially expressed proteins between human esophageal immortalized and carcinomatous cell lines by two-dimensional electrophoresis and MALDI-TOF-mass spectrometry

Institute of Scientific and Technical Information of China (English)

Xing-Dong Xiong; Li-Yan Xu; Zhong-Ying Shen; Wei-Jia Cai; Jian-Min Luo; Ya-Li Han; En-Min Li

2002-01-01

AIM: To identify the differentially expressed proteins between the human immortalized esophageal epithelial cell line (SHEE) and the malignant transformed esophageal carcinoma cell line (SHEEC), and to explore new ways for studying esophageal carcinoma associated genes. METHODS: SHEE and SHEEC cell lines were used to separate differentially expressed proteins by two-dimensional electrophoresis/The silver-stained 2-D gels was scanned with EDAS290 digital camera system and analyzed with the PDQuest 6.2 Software. Six spots in which the differentially expressed protein was more obvious were selected and analyzed with matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS).RESULTS: There were 107±4.58 and 115±9.91 protein spots observed in SHEE and SHEEC respectively, and the majority of these spots between the two cell lines matched each other (r＝-0.772), only a few were expressed differentially. After analyzed by MALDI-TOF-MS and database search for the six differentially expressed proteins, One new protein as well as other five sequence-known proteins including RNPEP-like protein, human rRNA gene upstream sequence binding transcription factor, uracil DNA glycosylase,Annexin A2 and p300/CBP-associated factor were preliminarily identified.CONCLUSION: These differentially expressed proteins might play an importance role during malignant transformation of SHEEC from SHEE. The identification of these proteins may serve as a new way for studying esophageal carcinoma associated genes.

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

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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.

[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.

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.

Cox2 and β-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

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Jianping Kong

2011-09-01

Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles.

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Chiappini, Ciro; Campagnolo, Paola; Almeida, Carina S; Abbassi-Ghadi, Nima; Chow, Lesley W; Hanna, George B; Stevens, Molly M

2015-09-16

Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor over a large array of nano-needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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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

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

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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

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

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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.

Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: Two Interesting Entities Identified in the Same Patient

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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.

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.

[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.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

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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

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

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

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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.

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.

Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells

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Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Li, Lin; Chan, Kar-Man; Wong, Eric Chun-Wai; Chan, Judy Yuet-Wah; Fung, Kwok-Pui; Lui, Vivian Wai Yan; Chiu, Philip Wai-Yan; Lau, Clara Bik-San

2015-01-01

Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers’ great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP-treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications. PMID

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

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Cong Wang

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

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

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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

Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

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Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

2006-01-01

Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

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

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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

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.

Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

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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.

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis.

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Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas; Mishra, Anil

2014-09-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. Copyright © 2014 the American Physiological Society.

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

The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

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Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic; Mariette, Christophe; Van Seuningen, Isabelle

2011-01-01

Highlights: → Loss of MUC4 reduces proliferation of esophageal cancer cells. → MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. → Loss of MUC4 significantly reduces in vivo tumor growth. → Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

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Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Mariette, Christophe [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France); Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, 1 place de Verdun, 59045 Lille Cedex (France); Van Seuningen, Isabelle, E-mail: isabelle.vanseuningen@inserm.fr [Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 ' Mucins, Epithelial Differentiation and Carcinogenesis' , rue Polonovski, 59045 Lille Cedex (France); Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex (France)

2011-09-23

Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

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

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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

Overexpression of DNA damage-induced 45 α gene contributes to esophageal squamous cell cancer by promoter hypomethylation

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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.

STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cells

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Akhtar, Javed; Wang, Zhou; Yu, Che; Li, Chen-Sheng; Shi, Yu-Long; Liu, Hong-Jun

2014-01-01

Distal esophageal adenocarcinoma is a highly aggressive neoplasm. Despite advances in diagnosis and therapy, the prognosis is still poor. Stathmin (STMN-1) is a ubiquitously expressed microtubule destabilizing phosphoprotein. It promotes the disassembly of microtubules and prevents assembly. STMN-1 can cause uncontrolled cell proliferation when mutated and not functioning properly. Recently, found to be overexpressed in many types of human cancers. However, its clinical significance remains elusive in distal esophageal adenocarcinoma. Here, we reported for the first time that STMN-1 is highly overexpressed in adenocarcinomas of the distal esophagus and strongly associated with lymph node metastasis. STMN-1 expression in 63 cases of distal esophageal adenocarcinoma was analyzed by immunoblotting, while expression in esophageal adenocarcinoma cells was determined by immunocytochemistry, immunofluorescence, qRT-PCR and western blotting. Lentivirus-mediated RNAi was employed to knock-down STMN-1 expression in Human esophageal adenocarcinoma cells. The relationship between STMN-1 expression and lymph node metastasis in distal esophageal adenocarcinoma was determined by univariate and multivariate analyses. STMN-1 was detected in 31 (49.21%) of the 63 cases. STMN-1 was highly overexpressed in specimens with lymph node metastasis pN (+), but its expression was almost undetected in pN (−) status. Multivarian regression analysis demonstrated that STMN-1 overexpression is an independent factor for lymph node metastasis in distal esophageal adenocarcinoma. STMN-1 shRNA effectively reduced STMN-1 expression in esophageal adenocarcinoma cells (P < 0.05), which significantly suppressed proliferation (P < 0.05), increased migration (P < 0.05) and invasion ability (P < 0.05) and G1 phase arrest (P < 0.05) which lead to induction of apoptosis in esophageal adenocarcinoma cells in vitro. To verify the in vitro data, we conducted in vivo tumor xenograft studies. Esophageal

Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

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Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2016-10-01

Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

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�

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

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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.

Polycyclic Aromatic Hydrocarbons and Esophageal Squamous Cell Carcinoma-A Review

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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

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model

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Diletta Arcidiacono

2018-04-01

Full Text Available Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC and its pre-cancerous lesion, Barrett’s Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain MKR (muscle (M-IGF1R-lysine (K-arginine (R mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT and MKR mice underwent jejunum-esophageal anastomosis side—to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1 signal transduction analyses. Most of the WT mice (63.1% developed dysplasia, whereas most of the MKR mice (74.3% developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2. Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR and IGF1 receptor (IGF1R were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model.

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Arcidiacono, Diletta; Dedja, Arben; Giacometti, Cinzia; Fassan, Matteo; Nucci, Daniele; Francia, Simona; Fabris, Federico; Zaramella, Alice; Gallagher, Emily J; Cassaro, Mauro; Rugge, Massimo; LeRoith, Derek; Alberti, Alfredo; Realdon, Stefano

2018-04-14

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

Esophago-pleural fistula with multiple esophageal ulcers in human immunodeficiency virus infected patients: A case report

International Nuclear Information System (INIS)

Kwon, Soo Hee; Lee, Young Kyung; Choi, Jae Phil; Son, Jin Sung

2014-01-01

Esophagitis is a common complication in patients with human immunodeficiency virus (HIV) infection. Esophagitis in HIV infected patient is caused by candidiasis, cytomegalovirus, herpes simplex virus, or idiopathic esophagitis with no detectable etiology. Esophagitis in HIV infected patient is occasionally combined with esophageal ulcers. We report chest CT findings and clinical manifestation of esophago-pleural fistula with pneumothorax in a HIV infected patient, who was treated for aspiration pneumonia and esophageal ulcers.

Esophago-pleural fistula with multiple esophageal ulcers in human immunodeficiency virus infected patients: A case report

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Kwon, Soo Hee; Lee, Young Kyung; Choi, Jae Phil; Son, Jin Sung [Seoul Medical Center, Seoul(Korea, Republic of)

2014-03-15

Esophagitis is a common complication in patients with human immunodeficiency virus (HIV) infection. Esophagitis in HIV infected patient is caused by candidiasis, cytomegalovirus, herpes simplex virus, or idiopathic esophagitis with no detectable etiology. Esophagitis in HIV infected patient is occasionally combined with esophageal ulcers. We report chest CT findings and clinical manifestation of esophago-pleural fistula with pneumothorax in a HIV infected patient, who was treated for aspiration pneumonia and esophageal ulcers.

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.

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

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 

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

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

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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

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

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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

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...

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

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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.

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.

Esophageal tissue engineering: a new approach for esophageal replacement.

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Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

2012-12-21

A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds

Esophageal tissue engineering: A new approach for esophageal replacement

Institute of Scientific and Technical Information of China (English)

Giorgia Totonelli; Panagiotis Maghsoudlou; Jonathan M Fishman; Giuseppe Orlando; Tahera Ansari; Paul Sibbons; Martin A Birchall

2012-01-01

A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a

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.

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

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

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

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

Dihydroartemisinin Accentuates the Anti-Tumor Effects of Photodynamic Therapy via Inactivation of NF-κB in Eca109 and Ec9706 Esophageal Cancer Cells

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Yan Jing Li

2014-05-01

Full Text Available Background: Photodynamic therapy (PDT is a new treatment for esophageal cancer which has been shown to be effective in the elimination of tumor. However, PDT could induce the activation of nuclear factor-kappa B (NF-κB in many photosensitizers based PDT, which plays a negative role in PDT. In addition, our previous results have shown that dihydroartemisinin (DHA, which was the most potent one of artemisinin derivatives, has anticancer activity in esophageal cancer cells. Methods: Cell viability was determined by MTT analysis, and apoptosis was evaluated by flow cytometry. Nuclear extract was obtained for determining NF-κB DNA-binding activity, while total protein extract obtained for downstream gene expression by western blot. Results: We demonstrated DHA enhanced PDT-induced growth inhibition and apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vitro. The mechanism was at least partially due to DHA deactivated PDT-induced NF-κB activation, so as to decrease tremendously the expression of its target gene Bcl-2. Conclusion: Our results demonstrate that DHA augments PDT-induced growth inhibition and apoptosis in esophageal cancer cells, and that inactivation of NF-κB activity is a potential mechanism by which DHA sensitizes esophageal cancer cells to PDT-induced growth inhibition and apoptosis.

Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells.

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Xi Zhang

Full Text Available Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD nevertheless can respond to proton pump inhibitors (PPIs, which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE. The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.

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

Effect of x-irradiation on cell kinetics of esophageal membrane cells in mice

International Nuclear Information System (INIS)

Ando, Koichi; Tsunemoto, Hiroshi; Urano, Muneyasu; Koike, Sachiko

1977-01-01

Effect of x-irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x-rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started. (auth.)

Effect of x irradiation on cell kinetics of esophageal membrane cells in mice

Energy Technology Data Exchange (ETDEWEB)

Ando, K; Tsunemoto, H; Urano, M; Koike, S [National Inst. of Radiological Sciences, Chiba (Japan)

1977-05-01

Effect of x irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started.

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

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Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

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.

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.

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

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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.

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

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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)

Large mid-esophageal granular cell tumor: benign versus malignant

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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.

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

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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

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....

Esophageal Cancer—Patient Version

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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.

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

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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.

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

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

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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

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

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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.

The Changing Face of Esophageal Cancer

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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.

The Changing Face of Esophageal Cancer

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

2010-06-28

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

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

Study of radiosensitization of chloroquine on esophageal cancer cell line

International Nuclear Information System (INIS)

Yuan Xiaoli; Li Tao; Huang Jianming; Zha Xiao; Deng Bifang; Lang Jinyi

2014-01-01

Objective: To investigate the possibility of chloroquine radiosensitization of esophageal cancer cell line TE-1 and its further mechanism. Methods: Effect of chloroquine on cell viability of TE-1 cells was determined by MTT method. Expression of LC3, Beclin-1 and formation of acidic vesicular organelles (AVOs) were determined by Western blot, and fluorescence staining with Lyso-Tracker Red DND-99, respectively. Clonogenic survival of TE-1 cells was examined by clonogenic forming assay. Results: Chloroquine showed dose-dependent inhibition of TE-1 cell growth, and its values of IC_5_0 and IC_1_0 were (72.33±5.28) and (15.42±3.33) μmol/L, respectively. The expression of Beclin-1 and LC3-II/I markedly increased in irradiated TE-1 cells. The addition of chloroquine with IC_1_0 concentration significantly reduced the fluorescence and intensity of AVOs accumulation in the cytoplasm of TE-1 cells. Clonogenic survival fraction decreased obviously in TE-1 cells with addition of chloroquine after radiation and the value of SERD0 was 1.439. Conclusions: Chloroquine could radiosensitize esophageal cancer cells by blocking autophagy-lysosomal pathway and be used as a potential radiosensitizing strategy. (authors)

Esophageal Cancer: Insights from Mouse Models

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Marie-Pier Tétreault

2015-01-01

Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

Automated detection of esophageal dysplasia in in vivo optical coherence tomography images of the human esophagus

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Kassinopoulos, Michalis; Dong, Jing; Tearney, Guillermo J.; Pitris, Costas

2018-02-01

Catheter-based Optical Coherence Tomography (OCT) devices allow real-time and comprehensive imaging of the human esophagus. Hence, they provide the potential to overcome some of the limitations of endoscopy and biopsy, allowing earlier diagnosis and better prognosis for esophageal adenocarcinoma patients. However, the large number of images produced during every scan makes manual evaluation of the data exceedingly difficult. In this study, we propose a fully automated tissue characterization algorithm, capable of discriminating normal tissue from Barrett's Esophagus (BE) and dysplasia through entire three-dimensional (3D) data sets, acquired in vivo. The method is based on both the estimation of the scatterer size of the esophageal epithelial cells, using the bandwidth of the correlation of the derivative (COD) method, as well as intensity-based characteristics. The COD method can effectively estimate the scatterer size of the esophageal epithelium cells in good agreement with the literature. As expected, both the mean scatterer size and its standard deviation increase with increasing severity of disease (i.e. from normal to BE to dysplasia). The differences in the distribution of scatterer size for each tissue type are statistically significant, with a p value of < 0.0001. However, the scatterer size by itself cannot be used to accurately classify the various tissues. With the addition of intensity-based statistics the correct classification rates for all three tissue types range from 83 to 100% depending on the lesion size.

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

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

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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.

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.

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

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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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.

[Determination of hyperregeneratory esophagopathy in dogs with clinical signs attributable to esophageal disease].

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Münster, M; Kook, P; Araujo, R; Hörauf, A; Vieth, M

2015-01-01

It was hypothesized that typical characteristics of hyperregeneratory esophagopathy (HRE) in humans such as basal cell hyperplasia and elongation of stromal papillae are also histologically detectable in canine esophageal epithelium, and that these changes are associated with clinical signs and endoscopic findings suggesting gastroesophageal reflux (GER). Sixty-five adult dogs with clinical signs attributable to esophageal disease underwent esophagoscopy and biopsy. Clinical signs suggesting GER (regurgitation, ptyalism, painful discomfort) were prospectively evaluated through a questionnaire. Endoscopic mucosal alterations suggesting GER such as minimal endoscopic changes and obvious mucosal defects were assessed via video endoscopy. Biopsy specimens obtained from the esophageal squamous epithelium were evaluated histologically. The squamous epithelium's substructures of esophageal biopsies were quantitatively assessed through microscopic morphometry. Esophageal squamous epithelium was considered normal in 48 dogs, and HRE was detected histologically in 17 dogs; both pathognomonic changes (basal cell hyperplasia, elongation of stromal papillae) were consistently present. Morphometrically assessed stromal papillary length and basal cell layer thickness was significantly (each, p HRE than in the 48 dogs without HRE, respectively. Overall, clinical signs suggesting GER were significantly (p = 0.02) more frequently encountered and regurgitation was significantly (p = 0.009) more common in the 17 dogs with HRE than in the 48 dogs without HRE. Similarly, endoscopic changes were significantly (p = 0.002) more frequently observed and minimal endoscopic changes suggesting GER were significantly (p = 0.004) more common in 17 dogs with HRE than in the 48 dogs without HRE. Typical characteristics of hyperregeneratory esophagopathy in humans are also histologically detectable in canine esophageal epithelium. Histological changes are associated with clinical signs and

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

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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.

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

Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

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Jian Liu

Full Text Available Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

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

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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, ...

T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

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Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-05-01

Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced

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.

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

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Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

2017-06-01

Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa.

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van Roon, Aafke H C; Mayne, George C; Wijnhoven, Bas P L; Watson, David I; Leong, Mary P; Neijman, Gabriëlle E; Michael, Michael Z; McKay, Andrew R; Astill, David; Hussey, Damian J

2008-08-01

Changes in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in patients with and without reflux. MUC-1, MUC-3, MUC-4, and MUC-5AC gene expressions were investigated in the HET-1A cell line following exposure to acid (pH 4) and/or bile (120 muM of a bile salt milieu), and in esophageal mucosal biopsies from controls, subjects with non-erosive gastro-esophageal reflux, and subjects with reflux associated with ulcerative esophagitis (erosive). The mucosal biopsies were also evaluated for IL-6 mRNA expression (inflammatory marker) and CK-14 mRNA expression (mucosal basal cell layer marker). Gene expression was determined using real-time reverse transcriptase-polymerase chain reaction analysis. In the cell line studies, there were differences in mRNA levels for all of the evaluated mucins following treatment with either acid or the acid and bile combination. In the studies which evaluated tissue specimens, IL-6 and CK-14 mRNA levels increased according to degree of reflux pathology. The expression of MUC-1 and MUC-4 in mucosa from patients with erosive reflux was lower than in subjects without reflux and in patients with non-erosive reflux, whereas the expression of MUC-3 and MUC-5AC was increased (although these differences did not reach significance at p reflux groups. The correlation between IL-6 and MUC-3 was significant within the control and erosive reflux groups, and the correlation between MUC-1 and MUC-5AC was significant within the erosive reflux group. The results of this study suggest that the profile of mucin expression in the esophageal mucosa is influenced by the pH and composition of the gastro-esophageal reflux. Further work should explore the

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

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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

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.

Interferon γ-Induced Nuclear Interleukin-33 Potentiates the Release of Esophageal Epithelial Derived Cytokines.

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Jing Shan

Full Text Available Esophageal epithelial cells are an initiating cell type in esophageal inflammation, playing an essential role in the pathogenesis of gastroesophageal reflux disease (GERD. A new tissue-derived cytokine, interleukin-33 (IL-33, has been shown to be upregulated in esophageal epithelial cell nuclei in GERD, taking part in mucosal inflammation. Here, inflammatory cytokines secreted by esophageal epithelial cells, and their regulation by IL-33, were investigated.In an in vitro stratified squamous epithelial model, IL-33 expression was examined using quantitative RT-PCR, western blot, ELISA, and immunofluorescence. Epithelial cell secreted inflammatory cytokines were examined using multiplex flow immunoassay. IL-33 was knocked down with small interfering RNA (siRNA in normal human esophageal epithelial cells (HEECs. Pharmacological inhibitors and signal transducers and activators of transcription 1 (STAT1 siRNA were used to explore the signaling pathways.Interferon (IFNγ treatment upregulated nuclear IL-33 in HEECs. Furthermore, HEECs can produce various inflammatory cytokines, such as IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1, regulated on activation normal T-cell expressed and presumably secreted (RANTES, and granulocyte-macrophage colony-stimulating factor (GM-CSF in response to IFNγ. Nuclear, but not exogenous IL-33, amplified IFN induction of these cytokines. P38 mitogen-activated protein kinase (MAPK and janus protein tyrosine kinases (JAK/STAT1 were the common signaling pathways of IFNγ-mediated induction of IL-33 and other cytokines.Esophageal epithelial cells can actively participate in GERD pathogenesis through the production of various cytokines, and epithelial-derived IL-33 might play a central role in the production of these cytokines.

Transient lower esophageal sphincter relaxation and esophageal motor response.

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Schneider, Joachim H; Küper, Markus A; Königsrainer, Alfred; Brücher, Björn L D M

2010-04-01

Gastroesophageal reflux is caused by transient lower esophageal sphincter relaxations (TLESRs) in healthy individuals and in most patients with gastroesophageal reflux disease (GERD). Refluxate is normally propelled by pharyngeally induced swallowing events, but TLESRs may also be accompanied by retrograde esophageal motor responses (EMRs). These contractions have not previously been investigated and their effect on esophageal clearance is not known. The aim of this study was to assess the frequency of EMRs after TLESR in healthy individuals and GERD patients and to develop an animal model for further investigation of EMRs. The frequency of TLESRs and esophageal body contractions after TLESRs was assessed using ambulatory manometry in five healthy individuals and five GERD patients. An animal model was developed for reproducible provocation of TLESRs and subsequent EMRs. Patients with GERD have significantly more TLESRs than healthy individuals. However, post-TLESR EMRs were not more frequent in the GERD group. All post-TLESR EMRs presented as simultaneous contractions of the esophagus. The feline model allowed reproducible initiation of the esophageal motor response after TLESR, showing that EMRs can be induced by external mechanoreceptor stimulation simultaneously with LES relaxation. This experimental design imitates the conditions after fundoplication in humans. The study demonstrated that GERD patients have significantly more TLESRs in comparison with healthy individuals, but these were only incidental to EMRs. Further research is needed to improve our understanding of esophageal motility disorders. The animal model presented offers a feasible tool for investigating TLESR-induced esophageal motility.

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

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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.

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

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Patel, Zarana S.; Kalabis, Jiri; Rustgi, Anil K.; Cucinotta, Francis A.; Huff, Janice L.

2010-01-01

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

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

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

Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

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Chen Xiaoxin

2009-07-01

Full Text Available Abstract Background Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed. Methods We performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet, iron (50 mg/kg/m, i.p., or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis. Results At week 20, we observed metaplasia in wild-type mice (5%, 1/20 and p53A135V mice (5.3%, 1/19. At week 40, metaplasia was found in wild-type mice (16.2%, 6/37, p53A135V mice (4.8%, 2/42, and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15. Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14, and wild-type mice receiving gastrectomy and iron (21.4%, 3/14. Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3% developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma. Conclusion Surgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma.

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

International Nuclear Information System (INIS)

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.

Esophageal motility in eosinophilic esophagitis.

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Weiss, A H; Iorio, N; Schey, R

2015-01-01

Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on

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.

Dosimetry analysis on radiation-induced acute esophagitis after three-dimensional conformal radiotherapy for non-small cell lung cancer

International Nuclear Information System (INIS)

ZZhu Shuchai; Cui Yanli; Li Juan; Liu Zhikun; Shen Wenbin; Su Jingwei; Wang Yuxiang

2010-01-01

Objective: To analyze the related factors with radiation-induced esophagitis after threedimensional conformal radiotherapy for non-small cell lung cancer (NSCLC), in order to explore the predictors for optimizing the treatment planning of NSCLC. Methods: From Aug 2000 to Dec 2004, 104 NSCLC patients received radiotherapy and were eligible for this study, 45 cases squamous cell carcinoma, 20 cases adenocarcinoma, 33 cases carrying with cancer cells by test and 6 case with no definitive pathologic feature.46 patients were treated with three dimensional conformal radiotherapy (3DCRT), the other 58 patients conventional radiotherapy (CRT) before later-course 3DCRT. All the patients received the prescribed dose between 60-78 Gy and the median dose 66 Gy. The correlation of the variables were evaluated by Spearman relationship analysis. The morbidity of radiation-induced esophagitis was analyzed by X 2 test. The multivariate effect on radiation-induced esophagitis was statistically processed by Logistic regression model. Results: In 104 patients, the morbidity of radiation- induced esophagitis was 46.2%, including 32 cases at grade 1, 15 cases at grade 2, 1 case at grade 3. Univariate analysis showed the maximal and mean dose of esophagus, the volume of esophagus irradiated, the values of V 40 , V 45 , V 50 , V 55 , V 60 , LETT 45 , LETT 50 , LETT 55 , LETT 60 for the esophagus were correlated with radiation-induced esophagitis. Logistic regression model showed that the maximum dose received by the esophagus was the independent factor of ≥ 2 grade radiation-induced esophagitis. Conclusions: The maxmal dose of esophagus received might be the important factor of radiation-induced esophagitis. (authors)

[Esophageal papilloma: case report, molecular identification of human papillomavirus and literature review].

Science.gov (United States)

Barbaglia, Yanina; Jiménez, Félix; Tedeschi, Fabián; Zalazar, Fabián

2013-09-01

sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor of the squamous epithelium consisting of a raised, sessile, small and round (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with a male/female ratio of 3:1. The etiology and pathogenesis appear to be a mechanical or chemical irritation of the mucosa in addition to the presence of human papillomavirus (HPV), important agent in the evolution to a squamous carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of esophageal papilloma whose diagnosis involved endoscopic images, pathological studies and detection of viral DNA by polymerase chain reaction. By using molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been obtained. The patient underwent polypectomy and currently, after 3 years of diagnosis, he remains asymptomatic. This work is one of the first national reports of a patient with esophageal papilloma in which one of the most frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been detected.

Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

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Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Ping, Yu; Liu, Shasha [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); School of Life Sciences, Zhengzhou University, Zhengzhou 450000 (China); Shi, Xiaojuan; Li, Lifeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wang, Liping [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Huang, Lan [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Zhang, Bin [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Sun, Yan [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (China); and others

2015-08-01

Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells.

Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

International Nuclear Information System (INIS)

Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng; Ping, Yu; Liu, Shasha; Shi, Xiaojuan; Li, Lifeng; Wang, Liping; Huang, Lan; Zhang, Bin; Sun, Yan

2015-01-01

Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells

Involvement of the iNKT Cell Pathway Is Associated With Early-Onset Eosinophilic Esophagitis and Response to Allergen Avoidance Therapy

Science.gov (United States)

Lexmond, Willem S.; Neves, Joana F.; Nurko, Samuel; Olszak, Torsten; Exley, Mark A.; Blumberg, Richard S.; Fiebiger, Edda

2014-01-01

OBJECTIVES Recent experimental evidence suggests that environmental microbial factors early in life determine susceptibility to allergic diseases through inappropriate chemotaxis and local activation of CD1d-restricted, invariant chain natural killer T (iNKT) cells. In this study, we analyzed the involvement of these pathways in pediatric patients with eosinophilic esophagitis (EoE) before and after dietary allergen elimination. METHODS mRNA expression levels of components of the C-X-C motif chemokine ligand 16 (CXCL16)–iNKT–CD1d axis were compared in esophageal biopsies from EoE patients vs. normal or inflammatory controls and before and after treatment. RESULTS CXCL16, iNKT cell–associated cell marker Vα24, and CD1d were significantly upregulated in esophageal biopsies from EoE patients and correlated with the expression of inflammatory mediators associated with allergy. Upregulation of each of these factors was significantly more pronounced in patients aged < 6 years at diagnosis, and this early-onset EoE subpopulation was characterized by a more prominent food allergic disease phenotype in a cohort-wide analysis. Successful, but not unsuccessful, treatment of early-onset EoE patients with dietary elimination of instigating allergens led to reduction in infiltrating iNKT cells and complete normalization of mRNA expression levels of CXCL16 and CD1d. CONCLUSIONS Our observations place iNKT cells at the center of allergic inflammation associated with EoE, which could have profound implications for our understanding, treatment and prevention of this and other human allergic diseases. PMID:24513807

Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.

Science.gov (United States)

Björkman, Eleonora; Edebo, Anders; Fändriks, Lars; Casselbrant, Anna

2015-09-01

The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD). Esophageal biopsies were collected from healthy volunteers (n: 19) and individuals with erosive reflux disease (n: 14). Gene transcripts and protein expression of aminopeptidase A, -B and -M, and the AT4R were investigated by reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and immunohistochemistry (IHC). The functional impact of AngIV was examined in an Ussing chamber. Aminopeptidase A, -B and -M and the AT4R were expressed in the esophageal epithelium. The AT4R was less prominent in certain areas in the mucosa of reflux patients. AngIV influenced the esophageal epithelial ion transport. The impact was lower in patients with GERD. The AT4R and formation enzymes of AngIII and AngIV are present in the human esophageal epithelium. Moreover, the present results suggest that AngIV exert regulatory impact on the epithelium and that RAS is involved in mucosal aberrations associated with GERD. © The Author(s) 2014.

Postoperative radiation in esophageal squamous cell carcinoma and target volume delineation

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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 �

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

Cytoplasmic Overexpression of CD95L in Esophageal Adenocarcinoma Cells Overcomes Resistance to CD95-Mediated Apoptosis

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Gregory A. Watson

2011-03-01

Full Text Available Introduction: The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. Methods: CD95L expression was characterized in immortalized squamous esophagus (HET-1A and Barrett esophagus (BAR-T cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control; and KFL cells (+ control. Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. Results: Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. Conclusions: CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis.

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...

The Pathophysiology of Eosinophilic Esophagitis

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Daniel Avi Lemberg

2014-05-01

Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

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

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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.

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

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Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B. [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Revetta, Frank [Department of Pathology, Vanderbilt University, Nashville, TN (United States); Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Department of Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States)

2015-01-01

The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. - Highlights: • Chemical inhibition of TGFβ signaling advances collective invasion

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.

Reevaluation of Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

OpenAIRE

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...

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

Directory of Open Access Journals (Sweden)

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.

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

GPR84 and TREM-1 signaling contribute to the pathogenesis of reflux esophagitis.

Science.gov (United States)

Abdel-Aziz, Heba; Schneider, Mathias; Neuhuber, Winfried; Kassem, Abdel Meguid; Khailah, Saleem; Müller, Jürgen; Gamaleldeen, Hadeel; Khairy, Ahmed; Khayyal, Mohamed T; Shcherbakova, Anastasiia; Efferth, Thomas; Ulrich-Merzenich, Gudrun

2015-11-24

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a non-uniform etiology. Thus the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients.To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced sub-chronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cellline HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein coupled receptor (GPR) 84 in human tissue.Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known pro-inflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was up-regulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly up-regulated in patients with grade B reflux esophagitis.The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

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

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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

Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell.

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Aikou, Susumu; Aida, Junko; Takubo, Kaiyo; Yamagata, Yukinori; Seto, Yasuyuki; Kaminishi, Michio; Nomura, Sachiyo

2013-09-01

The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro-esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side-to-side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow-derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP-marked bone marrow after the operation. Seventy-three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow-derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago-jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow-derived cells do not contribute directly to columnar metaplasia in this mouse model. © 2013 Japanese Cancer Association.

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

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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.

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

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Gyawali, C P; Roman, S; Bredenoord, A J; Fox, M; Keller, J; Pandolfino, J E; Sifrim, D; Tatum, R; Yadlapati, R; Savarino, E

2017-12-01

High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM. © 2017 John Wiley & Sons Ltd.

Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized MedicineSummary

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Kelly A. Whelan

Full Text Available The stratified squamous epithelium of the esophagus shows a proliferative basal layer of keratinocytes that undergo terminal differentiation in overlying suprabasal layers. Esophageal pathologies, including eosinophilic esophagitis, gastroesophageal reflux disease, Barrett's esophagus, squamous cell carcinoma, and adenocarcinoma, cause perturbations in the esophageal epithelial proliferation-differentiation gradient. Three-dimensional (3D culture platforms mimicking in vivo esophageal epithelial tissue architecture ex vivo have emerged as powerful experimental tools for the investigation of esophageal biology in the context of homeostasis and pathology. Herein, we describe types of 3D culture that are used to model the esophagus, including organotypic, organoid, and spheroid culture systems. We discuss the development and optimization of various esophageal 3D culture models; highlight the applications, strengths, and limitations of each method; and summarize how these models have been used to evaluate the esophagus under homeostatic conditions as well as under the duress of inflammation and precancerous/cancerous conditions. Finally, we present future perspectives regarding the use of esophageal 3D models in basic science research as well as translational studies with the potential for personalized medicine. Keywords: Organotypic Culture, Organoid, Spheroid Culture, Esophageal Disease

Esophagitis dissecans associated with eosinophilic esophagitis in an adolescent

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Marjorie-Anne R. Guerra

2015-03-01

Full Text Available Esophagitis dissecans superficialis and eosinophilic esophagitis are distinct esophageal pathologies with characteristic clinical and histologic findings. Esophagitis dissecans superficialis is a rare finding on endoscopy consisting of the peeling of large fragments of esophageal mucosa. Histology shows sloughing of the epithelium and parakeratosis. Eosinophilic esophagitis is an allergic disease of the esophagus characterized by eosinophilic inflammation of the epithelium and symptoms of esophageal dysfunction. Both of these esophageal processes have been associated with other diseases, but there is no known association between them. We describe a case of esophagitis dissecans superficialis and eosinophilic esophagitis in an adolescent patient. To our knowledge, this is the first case describing an association between esophageal dissecans superficialis and eosinophilic esophagitis.

Novel strategy for prevention of esophageal stricture after endoscopic surgery.

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Mizutani, Taro; Tadauchi, Akimitsu; Arinobe, Manabu; Narita, Yuji; Kato, Ryuji; Niwa, Yasumasa; Ohmiya, Naoki; Itoh, Akihiro; Hirooka, Yoshiki; Honda, Hiroyuki; Ueda, Minoru; Goto, Hidemi

2010-01-01

Recently, novel endoscopic surgery, including endoscopic submucosal dissection (ESD), was developed to resect a large superficial gastrointestinal cancer. However, circumferential endoscopic surgery in the esophagus can lead to esophageal stricture that affects the patient's quality of life. This major complication is caused by scar formation, and develops during the two weeks after endoscopic surgery. We hypothesized that local administration of a controlled release anti-scarring agent can prevent esophageal stricture after endoscopic surgery. The aims of this study were to develop an endoscopically injectable anti-scarring drug delivery system, and to verify the efficacy of our strategy to prevent esophageal stricture. We focused on 5-Fluorouracil (5-FU) as an anti-scarring agent, which has already been shown to be effective not only for treatment of cancers, but also for treatment of hypertrophic skin scars. 5-FU was encapsulated by liposome, and then mixed with injectable 2% atelocollagen (5FLC: 5FU-liposome-collagen) to achieve sustained release. An in vitro 5-FU releasing test from 5FLC was performed using high-performance liquid chromatography (HPLC). Inhibition of cell proliferation was investigated using normal human dermal fibroblast cells (NHDF) with 5FLC. In addition, a canine esophageal mucosal resection was carried out, and 5FLC was endoscopically injected into the ulcer immediately after the operation, and compared with a similar specimen injected with saline as a control. 5-FU was gradually released from 5FLC for more than 2 weeks in vitro. The solution of 5-FU released from 5FLC inhibited NHDF proliferation more effectively than 5-FU alone. In the canine model, no findings of stricture were observed in the 5FLC-treated dog at 4 weeks after the operation and no vomiting occurred. In contrast, marked esophageal strictures were observed with repeated vomiting in the control group. Submucosal fibrosis was markedly reduced histologically in the 5FLC

Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients.

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Lv, Bei; Cheng, Xin; Gao, Jackson; Zhao, Hong; Chen, Liping; Wang, Liwei; Huang, Shaoping; Fan, Zhenyu; Zhang, Renfang; Shen, Yinzhong; Li, Lei; Liu, Baochi; Qi, Tangkai; Wang, Jing; Cheng, Jilin

2016-01-01

This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients.

Immunohistochemical assessment of NY-ESO-1 expression in esophageal adenocarcinoma resection specimens.

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Hayes, Stephen J; Hng, Keng Ngee; Clark, Peter; Thistlethwaite, Fiona; Hawkins, Robert E; Ang, Yeng

2014-04-14

To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas. A retrospective search of our tissue archive for esophageal resection specimens containing esophageal adenocarcinoma was performed, for cases which had previously been reported for diagnostic purposes, using the systematised nomenclature of human and veterinary medicine coding system. Original haematoxylin and eosin stained sections were reviewed, using light microscopy, to confirm classification and tumour differentiation. A total of 27 adenocarcinoma resection specimens were then assessed using immunohistochemistry for NY-ESO-1 expression: 4 well differentiated, 14 moderately differentiated, 4 moderate-poorly differentiated, and 5 poorly differentiated. Four out of a total of 27 cases of esophageal adenocarcinoma examined (15%) displayed diffuse cytoplasmic and nuclear expression for NY-ESO-1. They displayed a heterogeneous and mosaic-type pattern of diffuse staining. Diffuse cytoplasmic staining was not identified in any of these structures: stroma, normal squamous epithelium, normal submucosal gland and duct, Barrett's esophagus (goblet cell), Barrett's esophagus (non-goblet cell) and high grade glandular dysplasia. All adenocarcinomas showed an unexpected dot-type pattern of staining at nuclear, paranuclear and cytoplasmic locations. Similar dot-type staining, with varying frequency and size of dots, was observed on examination of Barrett's metaplasia, esophageal submucosal gland acini and the large bowel negative control, predominantly at the crypt base. Furthermore, a prominent pattern of apical (luminal) cytoplasmic dot-type staining was observed in some cases of Barrett's metaplasia and also adenocarcinoma. A further morphological finding of interest was noted on examination of haematoxylin and eosin stained sections, as aggregates of lymphocytes were consistently noted to surround submucosal glands. We have demonstrated for the first time NY-ESO-1 expression by esophageal

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

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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.

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.

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

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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

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

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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

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

Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer

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HONJO, SOICHIRO; AJANI, JAFFER A.; SCOTT, AILING W.; CHEN, QIONGRONG; SKINNER, HEATH D.; STROEHLEIN, JOHN; JOHNSON, RANDY L.; SONG, SHUMEI

2014-01-01

Our clinical study indicates esophageal adenocarcinoma patients on metformin had a better treatment response than those without metformin. However, the effects of metformin and the mechanisms of its action in esophageal cancer (EC) are unclear. EC cell lines were used to assess the effects of metformin alone or in combination with 5-fluorouracil on survival and apoptosis. RPPA proteomic array and immunoblots were used to identify signaling affected by metformin. Standard descriptive statistic...

Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro: Possible involvement of inhibition of survival signal transduction pathways

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Akimoto, Tetsuo; Nonaka, Tetsuo; Ishikawa, Hitoshi; Sakurai, Hideyuki; Saitoh, Jun-ichi; Takahashi, Takeo; Mitsuhashi, Norio

2001-01-01

Purpose: The effect of genistein, a tyrosine kinase inhibitor, on radiosensitivity was examined, especially focusing on 'survival signal transduction pathways'. Methods and Materials: Two human esophageal squamous cell cancer cell lines, TE-1 (p53, mutant) and TE-2 (p53, wild), were used. Radiosensitivity was determined by clonogenic assay, and activation of survival signals was examined by Western blot. Results: Genistein (30 μM) greatly enhanced radiosensitivity in these cell lines by suppressing radiation-induced activation of survival signals, p42/p44 extracellular signal-regulated kinase and AKT/PKB. Significant increase in the percentage of apoptotic cells and increased poly[ADP-ribose] polymerase cleavage were observed in TE-2, but not in TE-1 even after combination of genistein with irradiation. In terms of changes in expression of p53-related proteins, increase in expression of Bax and decrease in that of Bcl-2 were observed in TE-2 but not in TE-1, suggesting that the main mode of cell death induced by genistein in a cell line with wild type p53 differed from that with mutant p53. Conclusions: This study suggested that survival signals, including p42/p44 ERK and AKT/PKB, may be involved in determining radiosensitivity, and genistein would be a potent therapeutic agent that has an enhancing effect on radiation

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

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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)

Two cases of esophageal eosinophilia: eosinophilic esophagitis or gastro-esophageal reflux disease?

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Ozlem Yilmaz

2014-06-01

Full Text Available Eosinophilic esophagitis (EoE and gastro-esophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE. Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders. In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts.

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

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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

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

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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.

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

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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

Preoperative chemoradiotherapy for stage 2 or 3 esophageal squamous cell carcinoma

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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)

Delayed esophageal perforation from stereotactic body radiation therapy for locally recurrent central nonsmall cell lung cancer

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Sandeep Sainathan

2014-01-01

Full Text Available Stereotactic body radiation therapy (SBRT is a novel form of external beam radiation therapy. It is used to treat early and locally recurrent nonsmall cell lung cancer (NSLC in medically inoperable patients. It uses high dose, hypofractionated radiotherapy, with targeting of the tumor by precise spatial localization, thus minimizing injury to surrounding tissues. It can be safely used to ablate NSLC in both central and peripheral locations. We present two cases of delayed esophageal perforation after SBRT for locally recurrent central NSLC. The perforations occurred several months after the therapy. They were treated with covered esophageal stents, with mortality, due to the perforation in one of the patients. SBRT should be judiciously used to ablate centrally located NSLC and patients who develop episodes of esophagitis during or after SBRT, need to be closely followed with endoscopy to look for esophageal ulcerations. These ulcers should be closely followed for healing as these may degenerate into full thickness perforations several months after SBRT.

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...

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

Institute of Scientific and Technical Information of China (English)

Asbj(φ)rn Mohr Drewes; Lars Arendt-Nielsen; Peter Funch-Jensen; Hans Gregersen

2006-01-01

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

Microaspiration of esophageal gland cells and cDNA library construction for identifying parasitism genes of plant-parasitic nematodes.

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Hussey, Richard S; Huang, Guozhong; Allen, Rex

2011-01-01

Identifying parasitism genes encoding proteins secreted from a plant-parasitic nematode's esophageal gland cells and injected through its stylet into plant tissue is the key to understanding the molecular basis of nematode parasitism of plants. Parasitism genes have been cloned by directly microaspirating the cytoplasm from the esophageal gland cells of different parasitic stages of cyst or root-knot nematodes to provide mRNA to create a gland cell-specific cDNA library by long-distance reverse-transcriptase polymerase chain reaction. cDNA clones are sequenced and deduced protein sequences with a signal peptide for secretion are identified for high-throughput in situ hybridization to confirm gland-specific expression.

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

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Liu, T T; Yi, C H; Lei, W Y; Hung, X S; Yu, H C; Chen, C L

2014-10-01

The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p sauce enhanced heartburn perception (p sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus. © 2014 John Wiley & Sons Ltd.

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

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Yan Wusheng

2012-01-01

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

Deglutitive inhibition, latency between swallow and esophageal contractions and primary esophageal motor disorders.

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Sifrim, Daniel; Jafari, Jafar

2012-01-01

Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm.

Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM–Chk1/2–Cdc25C pathway

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Ma, Yong-Cheng [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Su, Nan [Department of Quality Detection and Management, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan (China); Shi, Xiao-Jing; Zhao, Wen; Ke, Yu [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China); Zi, Xiaolin [Department of Urology, University of California, Irvine, Orange, CA (United States); Department of Pharmacology, University of California, Irvine, Orange, CA (United States); Department of Pharmaceutical Sciences, University of California, Irvine, Orange, CA (United States); Zhao, Ning-Min; Qin, Yu-Hua; Zhao, Hong-Wei [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Liu, Hong-Min, E-mail: liuhm@zzu.edu.cn [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China)

2015-01-15

Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway. - Highlights: • Jaridonin induced G2/M phase arrest through induction of redox imbalance. • Jaridonin increased the level of ROS through depleting glutathione in cell. • ATM–Chk1/2–Cdc25C were involved in Jaridonin-induced cell cycle arrest. • Jaridonin selectively inhibited cancer cell viability and cell cycle progression.

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

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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

Esophageal heterotopic gastric mucosa in esophageal atresia

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Lachlan J.R. Harrison

2018-05-01

Full Text Available Heterotopic gastric mucosa (HGM is occasionally found at endoscopy in the proximal esophagus of adults and children, when it manifests as an asymptomatic small island of reddish pink mucosa just below the upper esophageal sphincter. There are few reports of esophageal HGM detected by endoscopy after repair of esophageal atresia (EA with tracheo-esophageal fistula (TEF. We report a child with multiple patches of HGM in the proximal and distal esophagus seen at endoscopy after EA/TEF repair. No obvious symptoms were related to the HGM and she remains under endoscopic surveillance. The incidence of esophageal HGM may be increased in patients with EA and its distribution can be more extensive than a simple “inlet patch”. There is evidence to suggest that esophageal HGM increases the risk of developing Barrett's esophagus and has a malignant potential. Heterotopic gastric mucosa extends the spectrum of potential pathologies affecting the esophagus in patients with EA/TEF and supports current international guidelines for endoscopic surveillance of these patients. Keywords: Tracheo-esophageal fistula, Ectopic mucosa, Esophageal malignancy

Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells.

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J Dinesh Kumar

Full Text Available Stromal cells such as myofibroblasts influence tumor progression. The mechanisms are unclear but may involve effects on both tumor cells and recruitment of bone marrow-derived mesenchymal stromal cells (MSCs which then colonize tumors. Using iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as overexpressed in esophageal squamous cancer associated myofibroblasts (CAMs compared with adjacent tissue myofibroblasts (ATMs. The chemerin receptor, ChemR23, is expressed by MSCs. Conditioned media (CM from CAMs significantly increased MSC cell migration compared to ATM-CM; the action of CAM-CM was significantly reduced by chemerin-neutralising antibody, pretreatment of CAMs with chemerin siRNA, pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 receptor antagonist, CCX832. Stimulation of MSCs by chemerin increased phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases and PKC reversed chemerin-stimulated MSC migration. Chemerin stimulation of MSCs also induced expression and secretion of macrophage inhibitory factor (MIF that tended to restrict migratory responses to low concentrations of chemerin but not higher concentrations. In a xenograft model consisting of OE21 esophageal cancer cells and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus, chemerin secreted from esophageal cancer myofibroblasts is a potential chemoattractant for MSCs and its inhibition may delay tumor progression.

CT and {sup 18F}DG PET/CT findings of esophageal squamous cell papillomatosis: a case report

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Park, Soon Chang; Park, Won Kyu; Lee, Jae Kyo; Kim, Kum Rae; Hwang, Mi Soo [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

2008-02-15

Esophageal squamous cell papillomatosis is a rare disorder that is usually found incidentally on an upper gastrointestinal endoscopy examination or autopsy. A 70-year-old woman presented with a two-month history of dysphagia and abdominal discomfort. A chest CT scan showed diffuse marked thickening of the esophageal wall along the entire length and multiple small enhancing polypoid projections in the distal esophagus. Diffuse circumferential FDG uptake in the entire esophagus was seen on [{sup 18}F] FDG PET/CT. Squamous papillomatosis was diagnosed by an endoscopic biopsy. We report a case of extensive esophageal papillomatosis with imaging features on CT and [{sup 18}F] FDG PET/CT, with a review of the clinical literature.

Esophageal circumferential en bloc endoscopic submucosal dissection: assessment of a new technique.

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Barret, Maximilien; Pratico, Carlos Alberto; Beuvon, Frédéric; Mangialavori, Luigi; Chryssostalis, Ariane; Camus, Marine; Chaussade, Stanislas; Prat, Frédéric

2013-10-01

Endoscopic esophageal piecemeal mucosectomy for high-grade dysplasia on Barrett's esophagus leads to suboptimal histologic evaluation, as well as recurrence on remaining mucosa. Circumferential en bloc mucosal resection would significantly improve the management of dysplastic Barrett's esophagus. Our aim was to describe a new method of esophageal circumferential endoscopic en bloc submucosal dissection (CESD) in a swine model. After submucosal injection, circumferential incision was performed at each end of the esophageal segment to be removed. Mechanical submucosal dissection was performed from the proximal to the distal incision, using a mucosectomy cap over the endoscope. The removed mucosal ring was retrieved. Clinical, endoscopic, and histologic data were prospectively collected. Esophageal CESD was conducted on 5 pigs. A median mucosal length of 6.5 cm (range, 4 to 8 cm) was removed in the lower third of the esophagus. The mean duration of the procedure was 36 minutes (range, 17 to 80 min). No procedure-related complication, including perforation, was observed. All animals exhibited a mild esophageal stricture at day 7, and a severe symptomatic stricture at day 14. Necropsy confirmed endoscopic findings with cicatricial fibrotic strictures. On histologic examination, an inflammatory cell infiltrate, diffuse fibrosis reaching the muscular layer, and incomplete reepithelialization were observed. CESD enables expeditious resection and thorough examination of large segments of esophageal mucosa in safe procedural conditions, but esophageal strictures occur in the majority of the cases. Efficient methods for stricture prevention are needed for this technique to be developed in humans.

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.

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)

TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

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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.

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

Science.gov (United States)

Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Funch-Jensen, Peter; Gregersen, Hans

2006-01-01

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy. PMID:16718803

Cytotoxic effects of replication-competent adenoviruses on human esophageal carcinoma are enhanced by forced p53 expression

International Nuclear Information System (INIS)

Yang, Shan; Kawamura, Kiyoko; Okamoto, Shinya; Yamauchi, Suguru; Shingyoji, Masato; Sekine, Ikuo; Kobayashi, Hiroshi; Tada, Yuji; Tatsumi, Koichiro; Hiroshima, Kenzo; Shimada, Hideaki; Tagawa, Masatoshi

2015-01-01

Improvement of transduction and augmentation of cytotoxicity are crucial for adenoviruses (Ad)-mediated gene therapy for cancer. Down-regulated expression of type 5 Ad (Ad5) receptors on human tumors hampered Ad-mediated transduction. Furthermore, a role of the p53 pathways in cytotoxicity mediated by replication-competent Ad remained uncharacterized. We constructed replication-competent Ad5 of which the E1 region genes were activated by a transcriptional regulatory region of the midkine or the survivin gene, which is expressed preferentially in human tumors. We also prepared replication-competent Ad5 which were regulated by the same region but had a fiber-knob region derived from serotype 35 (AdF35). We examined the cytotoxicity of these Ad and a possible combinatory use of the replication-competent AdF35 and Ad5 expressing the wild-type p53 gene (Ad5/p53) in esophageal carcinoma cells. Expression levels of molecules involved in cell death, anti-tumor effects in vivo and production of viral progenies were also investigated. Replication-competent AdF35 in general achieved greater cytotoxic effects to esophageal carcinoma cells than the corresponding replication-competent Ad5. Infection with the AdF35 induced cleavages of caspases and increased sub-G1 fractions, but did not activate the autophagy pathway. Transduction with Ad5/p53 in combination with the replication-competent AdF35 further enhanced the cytotoxicity in a synergistic manner. We also demonstrated the combinatory effects in an animal model. Transduction with Ad5/p53 however suppressed production of replication-competent AdF35 progenies, but the combination augmented Ad5/p53-mediated p53 expression levels and the downstream pathways. Combination of replication-competent AdF35 and Ad5/p53 achieved synergistic cytotoxicity due to enhanced p53-mediated apoptotic pathways. The online version of this article (doi:10.1186/s12885-015-1482-8) contains supplementary material, which is available to authorized

Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm.

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Matsumoto, Hideo; Kubota, Hisako; Higashida, Masaharu; Manabe, Noriaki; Haruma, Ken; Hirai, Toshihiro

2015-01-01

Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. In this case, the patient's symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm

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Matsumoto, Hideo; Kubota, Hisako; Higashida, Masaharu; Manabe, Noriaki; Haruma, Ken; Hirai, Toshihiro

2015-01-01

Introduction: Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. Presentation of case: We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diver...

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.

Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

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Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

2014-02-01

The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

Esophageal tissue engineering: Current status and perspectives.

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Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

2016-02-01

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

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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

Diagnosis and Treatment of Esophageal Granular Cell Tumor: A Case Report and Review of the Literature

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Ramin Niknam

2017-01-01

Full Text Available Gastrointestinal granular cell tumors are uncommon. The most common site of gastrointestinal granular cell tumor (GCT is esophagus. We report a case of esophageal GCT incidentally diagnosed by endoscopy. The lesion was evaluated by endoscopic ultrasonography and resected using the endoscopic technique without complication.

Molecular Genetics and Gene Therapy in Esophageal Cancer: a Review Article

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Mohammad Reza Noori Daloii Ph.D.

2011-06-01

Full Text Available Background: With approximately 386,000 deaths per year, esophageal cancer is the 6th most common cause of death due to cancer in the world. This cancer, like any other cancer, is the outcome of genetic alterations or environmental factors such as tobacco smoke and gastro-esophageal reflux. Tobacco smoking is a major etiologic factor for esophageal squamous cell carcinoma in western countries, and it increases the risk by approximately 3 to 5 folds. Chronic gastro-esophageal reflux usually leads to the replacement of squamous mucosa by intestinal-type Barrett’s metaplastic mucosa which is considered the most important factor causing esophageal adenocarcinoma. In contrast to esophageal adenocarcinoma, different risk factors and mechanisms, such as mutations in oncogenes and tumor suppressor genes, play an important role in causing esophageal squamous cell carcinoma. Molecular studies on esophageal cancers have revealed frequent genetic abnormalities in esophageal squamous cell carcinoma and adenocarcinoma, including altered expression of p53, p16, cyclin D1, EGFR, E-cadherin, COX-2, iNOS, RARs, Rb, hTERT, p21, APC, c-MYC, VEGF, TGT-α and NF-κB. Many studies have focused on the role of different polymorphisms such as aldehyde dehydrogenase 2 and alcohol dehydrogenase 2 in causing esophageal cancer. Different agents including bestatin, curcumin, black raspberries, 5-lipoxygenase (LOX and COX-2 inhibitors have been found to play a role in inhibiting esophageal carcinogenesis. Different gene therapy approaches including p53 and p21WAF1 replacement gene therapies and therapy by suicide genes have also been experimented. Moreover, efforts have been made to use nanotechnology and aptamer technology in this regard.

Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

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Liu, Ting; Wu, Hai-Jun; Liang, Yu; Liang, Xu-Jun; Huang, Hui-Chao; Zhao, Yan-Zhong; Liao, Qing-Chuan; Chen, Ya-Qi; Leng, Ai-Min; Yuan, Wei-Jian; Zhang, Gui-Ying; Peng, Jie; Chen, Yong-Heng

2016-06-21

To develop a potent and safe gene therapy for esophageal cancer. An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

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.

Esophageal motor disorders in adults with eosinophilic esophagitis.

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Moawad, Fouad J; Maydonovitch, Corinne L; Veerappan, Ganesh R; Bassett, John T; Lake, Jason M; Wong, Roy K H

2011-05-01

An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

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Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L; Han, Jessica H; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H; Bussey, Kimberly J; Meldrum, Deirdre R

2016-08-09

The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

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

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Pan, Yi; Brink, Carsten; Knap, Marianne

2016-01-01

PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40Gy (L40, OR=4.03/5cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity...... than men. CONCLUSION: V40 and L40 were most effective dosimetric predictors of grade ⩾2 esophagitis. The upper part of esophagus was more sensitive....

SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells

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Shinozuka, Eriko; Miyashita, Masao; Mizuguchi, Yoshiaki; Akagi, Ichiro; Kikuchi, Kunio; Makino, Hiroshi; Matsutani, Takeshi; Hagiwara, Nobutoshi; Nomura, Tsutomu; Uchida, Eiji; Takizawa, Toshihiro

2013-01-01

Highlights: ► SnoN modulated miR-720, miR-1274A, and miR-1274B expression levels in TE-1 cells. ► miR-720 and miR-1274A suppressed the expression of target proteins p63 and ADAM9. ► Silencing of SnoN significantly upregulated cell proliferation in TE-1 cells. ► Esophageal cancer tissues have lower SnoN expression levels than normal tissues. ► Esophageal cancer tissues have higher miR-720 expression levels than normal tissues. -- Abstract: It is now evident that changes in microRNA are involved in cancer progression, but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski-related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential key regulator within a complex network of p53 transcriptional repressors. SnoN has pro- and anti-oncogenic functions in the regulation of cell proliferation, senescence, apoptosis, and differentiation. We characterized the roles of SnoN in miRNA transcriptional regulation and its effects on cell proliferation using esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set of miRNA expression profiles in TE-1cells, and the expression levels of miR-720, miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs resulted in changes to the target protein p63 and a disintegrin and metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly upregulated cell proliferation in TE-1 cells, indicating a potential anti-oncogenic function. These results support our observation that cancer tissues have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent normal tissues from ESCC patients. These data demonstrate a novel mechanism of miRNA regulation, leading to changes in cell proliferation.

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

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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.

Viruses, Other Pathogenic Microorganisms and Esophageal Cancer.

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Xu, Wenji; Liu, Zhongshu; Bao, Quncha; Qian, Zhikan

2015-05-01

Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC.

Impaired esophageal motor function in eosinophilic esophagitis.

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Santander, Cecilio; Chavarría-Herbozo, Carlos M; Becerro-González, Irene; Burgos-Santamaría, Diego

2015-10-01

Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

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

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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

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

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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)

Esophageal microbiome in eosinophilic esophagitis.

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J Kirk Harris

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

The adjuvant value of Andrographis paniculata in metastatic esophageal cancer treatment - from preclinical perspectives.

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Li, Lin; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Wong, Eric Chun-Wai; Fung, Kwok-Pui; Yu, Jun; Lau, Clara Bik-San; Chiu, Philip Wai-Yan

2017-04-12

Esophageal cancer (EC) is the fourth and sixth leading cause of cancer-related deaths in China and United States, respectively. The dismal prognosis of EC is mainly attributed to distant metastases, which may not be overcome by chemotherapy alone. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of patients. Our previous study demonstrated the in vivo anti-tumor and in vitro anti-invasion activities of Andrographis paniculata (AP) in esophageal cancer. In the present study, the chemical constituents of absorbed AP components through human intestinal Caco-2 cell monolayer were verified for the first time. The anti-migratory activities and suppressive effects on metastasis-related factors such as HER2, MMP2, MMP9, TM4SF3, CXCR4 of the absorbed AP components were revealed in esophageal cancer cells EC-109. The anti-tumor and anti-metastatic effects of AP water extract (1600 mg/kg) were further confirmed in metastatic esophageal xenograft-bearing mice. Besides, AP water extract acted synergistically with cisplatin plus 5-fluorouracil on inhibiting tumor nodule growth (with combination index present findings provide evidence on safety and advantages of the combined use of AP with chemotherapeutics in pre-clinical setting.

Esophageal scintigraphy: Applications and limitations in the study of esophageal disorders

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O'Connor, M.K.; Byrne, P.J.; Keeling, P.; Hennessy, T.P.

1988-01-01

This study examines the scintigraphic transit pattern in a variety of esophageal disorders. Scintigraphy was performed with a semi solid bolus and the patient in an upright position. Condensed esophageal images were obtained from which we derived the esophageal transit time. The pattern of bolus transit was graded by the duration of transit and by the presence of hold up or retrograde motion. Scintigrams were performed in 11 volunteers and 88 patients whose esophageal function had been confirmed by conventional gastroesophageal techniques. Esophageal disorders examined included achalasia, scleroderma, esophageal carcinoma, Barrett esophagus, and reflux esophagitis. We also examined the effects of gastroesophageal surgery on esophageal function. Transit times distinguished grossly abnormal esophageal function from normal but did not distinguish between different esophageal disorders. Graded transit patterns were a more sensitive indicator of esophageal function and permitted some differentiation between esophageal disorders and allowed evaluation of the effects of gastroesophageal surgery. (orig.)

Esophageal scintigraphy: Applications and limitations in the study of esophageal disorders

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O' Connor, M.K.; Byrne, P.J.; Keeling, P.; Hennessy, T.P.

1988-06-01

This study examines the scintigraphic transit pattern in a variety of esophageal disorders. Scintigraphy was performed with a semi solid bolus and the patient in an upright position. Condensed esophageal images were obtained from which we derived the esophageal transit time. The pattern of bolus transit was graded by the duration of transit and by the presence of hold up or retrograde motion. Scintigrams were performed in 11 volunteers and 88 patients whose esophageal function had been confirmed by conventional gastroesophageal techniques. Esophageal disorders examined included achalasia, scleroderma, esophageal carcinoma, Barrett esophagus, and reflux esophagitis. We also examined the effects of gastroesophageal surgery on esophageal function. Transit times distinguished grossly abnormal esophageal function from normal but did not distinguish between different esophageal disorders. Graded transit patterns were a more sensitive indicator of esophageal function and permitted some differentiation between esophageal disorders and allowed evaluation of the effects of gastroesophageal surgery.

Impaired esophageal motor function in eosinophilic esophagitis

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Cecilio Santander

2015-10-01

Full Text Available Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.

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)

An evaluation of the 'criteria for tumor response after radiotherapy in esophageal cancer' of the Japanese Society for Esophageal Disease

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Morita, Kozo; Yamada, Tetsuya; Takagi, Iwao

1991-01-01

The criteria covering tumor response after radiotherapy for an esophageal cancer proposed by the Japanese Society for Esophageal Diseases in March, 1989, has been evaluated in a study of 300 patients who were irradiated preoperatively or radically for an esophageal cancer. Results have revealed that the appearance that of EF-3, meaning no or few residual tumor cells in the esophageal specimen after resection, in the CR, PR, and NC Groups were 88.9%, 58.5%, and 30.3%, respectively, these differences among the groups considered highly significant (p<0.001). Thus, it has been concluded that this criteria can be clinically applied to evaluate the tumor response after radiotherapy. (author)

Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

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Matthew D Fountain

2016-11-01

Full Text Available Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by H&E, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45 respectively. Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as one week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.Conclusions: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients

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Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

2015-01-01

Abstract Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups. We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors. Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients

Esophageal bypass after failed chemoradiotherapy for unresectable esophageal cancer

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Matono, Satoru; Tanaka, Toshiaki; Mori, Naoki; Nagano, Takeshi; Fujita, Hiromasa; Shirouzu, Kazuo

2013-01-01

Esophageal stenosis and/or fistula often occur after chemoradiotherapy (CRT) for unresectable esophageal cancer. In such patients, an esophageal stent can help achieve oral intake. However an esophageal stent cannot be inserted where there is complete stenosis or where the tumor is located. In such cases, esophageal bypass surgery may be necessary. Here, we investigated the clinical characteristics and outcomes in patients who underwent esophageal bypass surgery in our institution. We reviewed 10 cases of esophageal bypass surgery (gastric tube in 8 cases, colon in 2 cases) after CRT for unresectable esophageal cancer, between 2001 and 2009. There were 5 of stenosis-only cases, 4 fistula-only cases, and 1 case of stenosis and fistula. There were postoperative complications in 5 cases (50%), and all these were treated conservatively and healed. The median survival from surgery to peroral intake was 20 days (range 9-90 days), and the median survival after starting peroral intake was 130 days (range 48-293 days). Esophageal bypass surgery can achieve good performance status and improve peroral intake. (author)

Endoscopic submucosal dissection for esophageal squamous cell neoplasms.

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Fujishiro, Mitsuhiro; Kodashima, Shinya; Goto, Osamu; Ono, Satoshi; Niimi, Keiko; Yamamichi, Nobutake; Oka, Masashi; Ichinose, Masao; Omata, Masao

2009-04-01

Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard treatments for early esophageal cancer, as well as for early gastric cancer in Japan, but standardization of the knowledge is still incomplete. The final goal to perform ESD is not to resect the lesion in an en bloc fashion, but to save the patient from esophageal cancer-related death. Thus, the indications should be considered based on the entire patient, not just the target lesion itself, and pre-, peri- and postoperative management of the patient is also very important, as well as technical aspects of ESD. In terms of the techniques of ESD, owing to refinement of the procedural strategy, invention of the devices, and the learning curve, acceptable safety and favorable middle-term efficacy have been obtained. We believe that ESD will become a standard treatment for early esophageal cancer not only in Japan but also worldwide in the near future.

Radionuclide Esophageal Transit Study in the Esophageal Motility Disorders

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Choi, Jae Gol; Lee, Min Jae; Song, Chi Wook [Korea University College of Medicine, Seoul (Korea, Republic of)

1993-07-15

Esophageal motility was evaluated from the analysis of 10 consecutive swallows using liquid bolus containing 0.5 mCi of {sup 99m}Tc tin colloid. We have reviewed our experience of esophageal transit study in the 20 normal volunteers and 55 patients with dysphagia that was not related to mechanical obstruction. The purpose of this study is to measure the esophageal transit in normal subjects and in patients with various esophageal motility disorders. The overall sensitivity and specificity of radionuclide esophageal transit study in detecting esophageal motor abnormality were compared with manometric results as a gold standard, which were 80% and 100% respectively. Radionuclide transit study is a safe, rapid, noninvasive test and suitable as a screening test for esophageal motor disorders.

Radionuclide Esophageal Transit Study in the Esophageal Motility Disorders

International Nuclear Information System (INIS)

Choi, Jae Gol; Lee, Min Jae; Song, Chi Wook

1993-01-01

Esophageal motility was evaluated from the analysis of 10 consecutive swallows using liquid bolus containing 0.5 mCi of 99m Tc tin colloid. We have reviewed our experience of esophageal transit study in the 20 normal volunteers and 55 patients with dysphagia that was not related to mechanical obstruction. The purpose of this study is to measure the esophageal transit in normal subjects and in patients with various esophageal motility disorders. The overall sensitivity and specificity of radionuclide esophageal transit study in detecting esophageal motor abnormality were compared with manometric results as a gold standard, which were 80% and 100% respectively. Radionuclide transit study is a safe, rapid, noninvasive test and suitable as a screening test for esophageal motor disorders.

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

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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.

Esophageal Metastasis From Occult Lung Cancer

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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.

Esophageal Intramural Pseudodiverticulosis: A Rare Endoscopic Finding

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Luciana Lopes de Oliveira

2013-01-01

Full Text Available A 76-year-old woman, presenting with a 4-year history of progressive dysphagia, was submitted to endoscopic examination. The upper endoscopy revealed a proximal esophageal stricture and inflammatory mucosa associated with multiples small orifices in the esophageal wall, some of them fulfilled with white spots suggestive of fungal infection. This was a typical endoscopic finding of esophageal intramural pseudodiverticulosis, a benign and rare condition, related to chronic esophagitis and others comorbid states, such as gastroesophageal reflux disease or infectious esophagitis, diabetes mellitus, alcohol consumption, and achalasia. Dysphagia is the predominant symptom and can be accompanied by esophageal stricture in 80% to 90% of patients. The pathogenesis is unknown, and as the pseudodiverticulosis is an intramural finding, endoscopy biopsies are inconclusive. The main histological finding is dilation of the submucosal glands excretory ducts, probably obstructed by inflammatory cells. The treatment consists in management of the underlying diseases and symptoms relief. In this particular case, the patient was submitted to antifungal drugs followed by endoscopic dilation with thermoplastic bougies, with satisfactory improvement of dysphagia.

Radiation-induced esophageal structure in patients with non-small cell lung cancer treated with chemoradiotherapy

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Kataoka, Masaaki; Itoh, Hisao; Kawamura, Masashi

1989-01-01

Five out 165 cases (3.0%) which were treated for non-small cell lung cancer with radiotherapy (98 cases were treated with chemoradiotherapy, and the other 67 case, radiotherapy alone) developed esophageal stricture. Their clinical courses, the relationship among radiation dosage, combination with chemotherapy, the length of the irradiated esophagus, and the occurrence of esophageal stricture were reviewed. One of the 5 cases was a case with lung cancer in Bloom's syndrome, which developed an esophageal stricture after receiving only 30.6 Gy (the TDF value was 46.2) to the esophagus. This case suggests the possibility that a patient with Bloom's syndrome is more radiosensitive than normal controls. The other 4 cases were treated with combined chemoradiotherapy. One of the 4 cases was treated with concomitant use of bleomycin (BLM), while the TDF value was not more than 100 (75.4). The concomitant use of BLM was almost certainly the cause of the esophageal stricture. The other 3 cases were treated with chemoradiotherapy, the TDF values of which were more than 100 (108.7, 112.5, and 129.3). The chemotherapy combined with radiotherapy and the overdosage were considered to be the cause of the esophageal stricture in these 3 cases. These data suggest that in Bloom's syndrome, radiotherapy should be performed carefully and that BLM should not be used simultaneously with irradiation to the esophagus. It is also believed that a radiation dose over 100 in TDF value to the esophagus should be discouraged when chemotherapy is codmbined. (author)

Esophageal Rupture as a Primary Manifestation in Eosinophilic Esophagitis

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Natalia Vernon

2014-01-01

Full Text Available Eosinophilic esophagitis (EoE is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave’s syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE.

Dynamic esophageal scintigraphy

International Nuclear Information System (INIS)

Reilley, J.J.; Malmud, L.S.; Fisher, R.S.; Applegate, G.; DeVegvar, M.L.

1982-01-01

Esophageal scintigraphy was developed in order to quantitatively evaluate esophageal transit in patients with a variety of esophageal disorders. The study is performed with orally administered technetium-99m sulfur colloid in water, using a gamma camera on-line to a digital computer. Esophageal transit is expressed as the percent emptying for each of the first 15-sec intervals for 10 min after an initial swallow and at 15-sec intervals after serial swallows. Esophageal transit is significantly decreased in patients with motor disorders of the esophagus, compared to normal controls. In patients with reflux esophagitis, esophageal transit was abnormal when the reflux disease was accompanied by abnormal motor function. The technique we describe is the first quantitative test of esophageal function; it is a useful, sensitive, scintigraphic technique for evaluation of esophageal transit

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

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Wang YY

2015-02-01

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

[Primary esophageal motility disorders; especially about esophageal achalasia].

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Miyazaki, Tatsuya; Sohda, Makoto; Sakai, Makoto; Tanaka, Naritaka; Suzuki, Shigemasa; Yokobori, Takehiko; Inose, Takanori; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kusano, Motoyasu; Kuwano, Hiroyuki

2011-07-01

Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

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

21 CFR 868.1920 - Esophageal stethoscope with electrical conductors.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal stethoscope with electrical conductors. 868.1920 Section 868.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... stethoscope with electrical conductors. (a) Identification. An esophageal stethoscope with electrical...

Late stage and grave prognosis of esophageal cancer in Thailand.

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Nun-Anan, Pongjarat; Vilaichone, Ratha-Korn

2015-01-01

Esophageal cancer is one of the major health concerns in Southeast Asian countries, including Thailand. However, only a limited number of studies have been reported from this region. This study was designed to evaluate the prevalence, clinical characteristics and survival rate of esophageal cancer in Thailand. Clinical information, histological features and endoscopic findings were collected from a tertiary care center in central region of Thailand between September 2011- November 2014 and reviewed. A total of 64 esophageal cancer patients including 58 men and 6 women with mean age of 62.6 years were enrolled. Common presenting symptoms were dysphagia (74%), dyspepsia (10%) and hematemesis (8%). Mean duration of symptoms prior to diagnosis was 72 days. Esophageal stenosis with contact bleeding was the most common endoscopic finding (55.6%). The location of cancer was found in proximal (16%), middle (50%) and distal (34%) esophagus. Squamous cell carcinoma was far more common histology than adenocarcinoma (84.2% vs 10.5%). However, esophageal adenocarcinoma was significantly more common than squamous cell carcinoma in distal area of esophagus (100% vs 22.9%; p=0.0001, OR=1.6, 95%CI=1.1-2.2). Esophageal cancer stages 3 and 4 accounted for 35.2% and 59.3% respectively. Overall 2-year survival rate was 20% and only 16% in metastatic patients. Most esophageal cancer patients in Thailand have squamous cell carcinoma and nearly all present at advanced stage with a grave prognosis. Screening of high risk individuals and early detection might be important keys to improve the survival rate and treatment outcome in Thailand.

Neoadjuvant chemoradiotherapy for advanced esophageal cancer

International Nuclear Information System (INIS)

Natsugoe, Shoji; Matsumoto, Masataka; Okumura, Hiroshi

2011-01-01

The limitations of surgical treatment for advanced esophageal cancer have been clarified, although esophagectomy with extended lymph node dissection has been widespread in Japan. Preoperative adjuvant therapy has been investigated in Western countries, and recently preoperative chemoradiotherapy (CRT) has been introduced for the treatment of resectable esophageal cancer. There are several reports of randomized controlled trials (RCTs) comparing CRT followed by surgery and surgery alone. According to the results of a meta-analysis, preoperative CRT is considered to be the standard therapy in Western countries. However, problems in the clinical heterogeneity of meta-analyses include: small number of patients in each RCT; differences in stage grouping; presence of both squamous cell carcinoma and adenocarcinoma; various surgical techniques used; and differences in the amount of radiation administered. Preoperative CRT appears to be a promising method for the treatment of potentially resectable advanced esophageal cancer patients with nodal metastasis. Currently, phase I and II trials of new anticancer agents or molecular targeting agents are ongoing. However, since the surgical procedure in the Western method is still being debated, well-designed RCTs are necessary, especially in esophageal squamous cell carcinoma. The effectiveness of CRT followed by surgery should be clarified based on excellent Japanese surgical techniques. (author)

Morphofunctional analysis of experimental model of esophageal achalasia in rats.

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Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

2010-10-01

We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

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

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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.

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.

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

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

A Dilemma in Staging of Esophageal Cancer: How Should We Stage ypT0 N2 M0 Esophageal Cancer after Neoadjuvant Therapy?

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Sebahattin Celik

2015-01-01

Full Text Available Background. Since neoadjuvant treatment in esophageal cancer began to become popular, a complete pathological response at the primary tumour site has been commonly reported. An issue of conflict is whether complete response in the esophageal lumen means that the esophagus is completely tumour-free. Another important issue is whether lymph nodes that are retrieved from pathologically complete response cases are also tumour-free or not. There is a gap in the esophageal cancer staging system for ypT0 N2 M0 tumours that have received neoadjuvant therapy. Here, we will discuss the problem about staging of esophageal cancer associated with neoadjuvant therapy. Case. A female aged 40 years complaining of dysphagia was diagnosed as having locally advanced thoracic esophageal cancer. Neoadjuvant therapy decision was taken by oncology committee. Six weeks after neoadjuvant therapy, with a curative intention, minimal invasive surgery was performed. The pathology report was as follows. “There were no neoplastic cells in the suspected area of the esophageal mucosa upon examination with all staining. There was no cancer at resection margins. Four metastatic lymph nodes were infiltrated with squamous cell cancer.” Conclusion. Despite the growing use of neoadjuvant treatment in locally advanced esophageal cancer in world, we do not have a protocol for the evaluation of these patients’ pathology reports. We believe that new studies and new ideas are needed to resolve this dilemma associated with neoadjuvant therapy.

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

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Ana Grilo

2012-09-01

Full Text Available CONTEXT: Esophageal cancer is often diagnosed at an advanced stage and has a poor prognosis. Most patients with advanced esophageal cancer have significant dysphagia that contributes to weight loss and malnutrition. Esophageal stenting is a widespread palliation approach, but unsuitable for cancers near the upper esophageal sphincter, were stents are poorly tolerated. Generally, guidelines do not support endoscopic gastrostomy in this clinical setting, but it may be the best option for nutritional support. OBJECTIVE: Retrospective evaluation of patients with dysphagia caused advanced esophageal cancer, no expectation of resuming oral intake and with percutaneous endoscopic gastrostomy for comfort palliative nutrition. METHOD: We selected adult patients with unresecable esophageal cancer histological confirmed, in whom stenting was impossible due to proximal location, and chemotherapy or radiotherapy were palliative, using gastrostomy for enteral nutrition. Clinical and nutritional data were evaluated, including success of gastrostomy, procedure complications and survival after percutaneous endoscopic gastrostomy, and evolution of body mass index, albumin, transferrin and cholesterol. RESULTS: Seventeen males with stage III or IV squamous cell carcinoma fulfilled the inclusion criteria. Mean age was 60.9 years. Most of the patients had toxic habits. All underwent palliative chemotherapy or radiotherapy. Gastrostomy was successfully performed in all, but nine required prior dilatation. Most had the gastrostomy within 2 months after diagnosis. There was a buried bumper syndrome treated with tube replacement and four minor complications. There were no cases of implantation metastases or procedure related mortality. Two patients were lost and 12 died. Mean survival of deceased patients was 5.9 months. Three patients are alive 6, 14 and 17 months after the gastrostomy procedure, still increasing the mean survival. Mean body mass index and laboratory

Esophageal carcinoma originating in a duplication cyst: case report

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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.

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

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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.

Novel device to sample the esophageal microbiome--the esophageal string test.

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Sophie A Fillon

Full Text Available A growing number of studies implicate the microbiome in the pathogenesis of intestinal inflammation. Previous work has shown that adults with esophagitis related to gastroesophageal reflux disease have altered esophageal microbiota compared to those who do not have esophagitis. In these studies, sampling of the esophageal microbiome was accomplished by isolating DNA from esophageal biopsies obtained at the time of upper endoscopy. The aim of the current study was to identify the esophageal microbiome in pediatric individuals with normal esophageal mucosa using a minimally invasive, capsule-based string technology, the Enterotest™. We used the proximal segment of the Enterotest string to sample the esophagus, and term this the "Esophageal String Test" (EST. We hypothesized that the less invasive EST would capture mucosal adherent bacteria present in the esophagus in a similar fashion as mucosal biopsy. EST samples and mucosal biopsies were collected from children with no esophageal inflammation (n = 15 and their microbiome composition determined by 16S rRNA gene sequencing. Microbiota from esophageal biopsies and ESTs produced nearly identical profiles of bacterial genera and were different from the bacterial contents of samples collected from the nasal and oral cavity. We conclude that the minimally invasive EST can serve as a useful device for study of the esophageal microbiome.

MicroRNA alterations in Barrett′s esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: Insights for chemoprevention

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Laura A Kresty

2011-01-01

Full Text Available Background: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs is documented to occur in multiple cancer types including esophageal adencarcinoma (EAC and its only known precursor, Barrett′s esophagus (BE. Recent studies have linked dysregulation of specific miRNAs to histological grade, neoplastic progression and metastatic potential. Materials and Methods: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract′s (C-PAC ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19. Results: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC-induced modulation of five miRNAs in three EAC cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis. Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG, Protein Analysis Through Evolutionary Relationships (PANTHER, and MetaCore analysis tools. Conclusions: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC′s ability to modify miRNA profiles within EAC cells. A number of C-PAC-modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in high-risk cohorts.

Tracheal Penetration and Tracheoesophageal Fistula Caused by an Esophageal Self-Expanding Metallic Stent

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Karan Madan

2014-01-01

Full Text Available Tracheal penetration of esophageal self-expanding metallic stents (SEMS with/without tracheoesophageal fistula (TEF formation is a rare occurrence. We report the case of a 66-year-old female patient with advanced esophageal squamous cell carcinoma who had undergone palliative esophageal stenting on three occasions for recurrent esophageal stent obstruction. On evaluation of symptoms of breathing difficulty and aspiration following third esophageal stent placement, tracheal erosion and TEF formation due to the tracheal penetration by esophageal stent were diagnosed. The patient was successfully managed by covered tracheal SEMS placement under flexible bronchoscopy.

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)

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

Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography–Based Metrics

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Niedzielski, Joshua S., E-mail: jsniedzielski@mdanderson.org [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Yang, Jinzhong [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Stingo, Francesco [Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Martel, Mary K.; Mohan, Radhe [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Briere, Tina M. [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Court, Laurence E. [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States)

2016-02-01

Purpose: To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. Methods and Materials: Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. Results: Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. Conclusions: Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced

Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography–Based Metrics

International Nuclear Information System (INIS)

Niedzielski, Joshua S.; Yang, Jinzhong; Stingo, Francesco; Martel, Mary K.; Mohan, Radhe; Gomez, Daniel R.; Briere, Tina M.; Liao, Zhongxing; Court, Laurence E.

2016-01-01

Purpose: To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. Methods and Materials: Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. Results: Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. Conclusions: Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced

A clinical assessment of esophageal scintigraphy in patients with esophageal cancer

International Nuclear Information System (INIS)

Tsutsui, Shigeharu; Shibatsuji, Hiroshi; Takahashi, Hitoshi

1987-01-01

In patients with esophageal cancer who were treated with radiation therapy, esophageal motility was quantitatively analyzed by comparing the findings from esophageal scintigraphy with subjective symptoms and fluoroscopic findings. The subjects of this study were 5 healthy adults and 10 patients with esophageal cancer. Patients with esophageal cancer underwent radiation therapy (exposure to 50 or 60 Gy irradiation). Each subject swallowed 2 mCi of 99m Tc-DTPA, diluted in 20 ml of water, in a sitting position. The upper esophagus, the lower esophagus, the whole esophagus and the cardia were designated as regions of interest (ROI). A time activity curve was obtained for each ROI, followed by calculation of peak transit time (PTT), esophageal emptying time (EET) and gastric peak time (GPT). In healthy adults, PTT, EET and GPT averaged 0.6, 0.6 and 2.9 seconds, respectively. In patients with esophageal cancer, PTT, EET and GPT averaged 1.9, 1.8 and 6.5 seconds, respectively. Thus, mean PTT, EET and GPT were higher in the cancer patients than in the volunteers. In patients who were treated with radiation therapy, the value of the parameters determined by esophageal scintigraphy agreed well with the changes in symptoms. In patients, the smoothness of passage through the esophagus correlated better with the minimum bore of the esophagus than with the length of the narrowed area of the esophageal cancer. The results of this study indicate that esophageal scintigraphy is a useful means of esophageal examination, which allows changes in esophageal motility to be quantitatively assessed easily and physiologically. (author)

Esophageal intramural pseudodiverticulosis characterized by barium esophagography: a case report

LENUS (Irish Health Repository)

O'Connor, Owen J

2010-05-21

Abstract Introduction Esophageal intramural pseudodiverticulosis is a rare condition characterized by the dilatation of the submucosal glands. Case presentation We present a case of esophageal intramural pseudodiverticulosis in a 72-year-old Caucasian man who presented with dysphagia and with a background history of alcohol abuse. An upper gastrointestinal endoscopy of our patient showed an esophageal stricture with abnormal mucosal appearances, but no malignant cells were seen at biopsy. Appearances on a barium esophagram were pathognomonic for esophageal intramural pseudodiverticulosis. Conclusion We demonstrate the enduring usefulness of barium esophagography in the characterization of abnormal mucosal appearances at endoscopy.

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

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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.

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy

International Nuclear Information System (INIS)

Singh, Anurag K.; Lockett, Mary Ann; Bradley, Jeffrey D.

2003-01-01

Purpose: To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Results: Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients

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.

Genes Associated with Food Allergy and Eosinophilic Esophagitis

Science.gov (United States)

2013-11-01

esophageal fibrosis in a mouse model of eosinophilic esophagitis. J Allergy Clinical Immunology (2013), 507. Original Manuscripts Jae Youn Cho...Broide MB ChB1 1Allergy and Immunology , Department of Medicine, University of California San Diego. 2Allergy and Immunology , Department of...acetylglucosamine re- peats [1,2]. Chitin is highly expressed in insects and crustacean exoskeletons, fungal cell walls, and microfilarial nematode

Herpetic esophagitis

International Nuclear Information System (INIS)

Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.

1981-01-01

Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium

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.

Gastro-esophageal reflux time parameters and esophagitis in children

International Nuclear Information System (INIS)

Baulieu, F.; Baulieu, J.; Maurage, C.; Casset, D.; Itti, R.

1985-01-01

The aim of this work was to study the correlation between the reflux timing and the presence of esophagitis, an inconstant but serious complication of gastro-esophageal reflux (GER). The hypothesis was that reflux occurring late after meal can be incriminated more than early reflux in esophagitis genesis. 32 children with GER (mean age = 10.5 months, 2 to 30 months) had esophagoscopy and scintigraphy in the same week. The children were classified in two groups according to esophagoscopy: group 1 (n = 18) no esophagitis, group 2 (n = 14) esophaqgitis. The scintigraphy involved the ingestion of 0.5 mCi Tc-99m sulfur colloid milk mixture, followed by esophageal and gastric activity recording (one image per minute for 1 hour). The reflux was assessed from contrast enhanced images and esophageal time activity curves. Reflux intensity was quantitated by reflux index (Re). Mean reflux time was calculated as the mean esophageal activity peaks time (t-bar). Finally a composite parameter was calculated as the mean reflux time weighted by the relative intensity of each reflux peak (t-barw). Re was not found to be different between the two groups. t-bar was significantly higher in group 2: t-bar = 29.6 +- 3.0 mn (mean +- SD) than in group 1: t-bar = 24.5 +- 6.8 mn; rho <0.02. The difference between the two groups was enhanced by intensity weighting: group 1: t-barw = 16.6 +- 6.3 mn, group 2: t-barw = 33.5 +- 7.1 mn rho <0.001. t-barw value was not correlated to esophagitis grade. These results suggest that late reflux is more likely responsible of esophagitis

Endoscopic Assessment of Children with Esophageal Atresia: Lack of Relationship of Esophagitis and Esophageal Metaplasia to Symptomatology

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Julie Castilloux

2010-01-01

Full Text Available BACKGROUND: Late complications of esophageal atresia (EA, particularly esophagitis and Barrett’s esophagus, are increasingly being recognized. With the exception of patients with dysphagia associated with esophageal stricture, it is unknown whether patient symptomatology can predict endoscopic findings.

Increased risk of stomach and esophageal malignancies in people with AIDS.

Science.gov (United States)

Persson, E Christina; Shiels, Meredith S; Dawsey, Sanford M; Bhatia, Kishor; Anderson, Lesley A; Engels, Eric A

2012-10-01

People infected with human immunodeficiency virus (HIV) have an increased risk of some malignancies, but little is known about the effects of infection on risk of cancers of the upper gastrointestinal tract. We evaluated the risks of different histologic and anatomic subtypes of carcinomas and non-Hodgkin lymphomas (NHLs) of the stomach and esophagus in people with acquired immunodeficiency syndrome (AIDS). We analyzed data from the HIV/AIDS Cancer Match Study, which links data collected from 1980 to 2007 for 16 US population-based HIV and AIDS and cancer registries. We compared risks of stomach and esophageal malignancies in people with AIDS (N = 596,955) with those of the general population using standardized incidence ratios (SIRs). We assessed calendar trends using Poisson regression. People with AIDS had increased risks of carcinomas of the esophagus (SIR, 1.69; 95% confidence interval [CI], 1.37-2.07; n = 95) and stomach (SIR, 1.44; 95% CI, 1.17-1.76; n = 96). Risk was increased for esophageal adenocarcinoma (SIR, 1.91; 95% CI, 1.31-2.70) and squamous cell carcinoma (SIR, 1.47; 95% CI, 1.10-1.92). People with AIDS had greater risks of carcinomas of the gastric cardia (SIR, 1.36; 95% CI, 0.83-2.11) and noncardia (SIR, 1.53; 95% CI, 1.12-2.05) than the general population. Although most stomach and esophageal NHLs that developed in people with AIDS were diffuse large B-cell lymphomas, these individuals also had an increased risk of stomach mucosa-associated lymphoid tissue lymphoma (SIR, 5.99; 95% CI, 3.19-10.2; n = 13). The incidence of carcinomas remained fairly constant over time, but rates of NHL decreased from 1980 to 2007 (P(trend) AIDS are at increased risk for developing esophageal and stomach carcinomas and NHLs. Although the incidence of NHL decreased from 1980 to 2007 as treatments for HIV infection improved, HIV-infected individuals face continued risks of esophageal and stomach carcinomas. Copyright © 2012 AGA Institute. Published by Elsevier Inc

Cyclosporine in the Management of Esophageal Lichen Planus

Directory of Open Access Journals (Sweden)

M Chaklader

2009-01-01

Full Text Available Lichen planus (LP is an uncommon disorder of unknown etiology, mostly affecting patients in their fifth and sixth decade of life. It is believed to be an autoimmune process involving T cells directed against basal keratinocytes. It affects the skin, nails, oral pharynx and genitals. Esophageal involvement is quite rare and can cause strictures, ulcerations and squamous cell cancer. The present article describes the case of a 54-year-old woman who was referred for assessment of dysphagia that initially occurred with solids, which then progressed to soft foods but spared liquids. The patient reported a weight loss of 9.1 kg. An esophagogastroduodenoscopy was performed and she was subsequently diagnosed with pill esophagitis. At the same time, she was also diagnosed with oral LP, with no involvement of the esophagus. She was treated with a proton pump inhibitor that resolved her gastrointestinal symptoms. The symptoms returned one year later and a repeat esophagogastroduodenoscopy revealed white plaques due to LP. She was treated with intermittent glucocorticoids. Diagnosis of esophageal LP is crucial for the proper treatment. Some patients may require systemic immunosuppression and mechanical dilation to prevent weight loss. Surveillance endoscopies should be performed to monitor for squamous cell cancer. Cyclosporine has been used for genital and oral LP, but the present case is the first in which it has been used successfully to treat esophageal LP.

Impaired Upper Esophageal Sphincter Reflexes in Patients with Supra-Esophageal Reflux Disease

Science.gov (United States)

Babaei, Arash; Venu, Mukund; Naini, Sohrab Rahimi; Gonzaga, Jason; Lang, Ivan; Massey, Benson; Jadcherla, Sudarshan; Shaker, Reza

2015-01-01

Background & Aims Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, but abnormal responses have not been characterized. We investigated whether patients with supra-esophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. Methods We performed a prospective study of 25 patients with SERD (19–82 y old, 13 female) and complaints of regurgitation and supra-esophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; 32–60 y old, 7 female) without troublesome regurgitation and supra-esophageal symptoms and 24 healthy asymptomatic individuals (controls; 19–49 y old, 13 female). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. Results A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Conclusions Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux. PMID:26188682

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

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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

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.

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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.

Glycomic Expression in Esophageal Disease

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Sanjay Mohanty

2012-11-01

Full Text Available Glycosylation is among the most common post translation modifications of proteins in humans. Decades of research have demonstrated that aberrant glycosylation can lead to malignant degeneration. Glycoproteomic studies in the past several years have identified techniques that can successfully characterize a glycan or glycan profile associated with a high-grade dysplastic or malignant state. This review summarizes the current glycomic and glycoproteomic literature with specific reference to esophageal cancer. Esophageal adenocarcinoma represents a highly morbid and mortal cancer with a defined progression from metaplasia (Barrett's esophagus to dysplasia to neoplasia. This disease is highlighted because (1 differences in glycan profiles between the stages of disease progression have been described in the glycoproteomic literature; (2 a glycan biomarker that identifies a given stage may be used as a predictor of disease progression and thus may have significant influence over clinical management; and (3 the differences in glycan profiles between disease and disease-free states in esophageal cancer are more dramatic than in other cancers.

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

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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.

Trastuzumab Mediated T-Cell Response against HER-2/Neu Overexpressing Esophageal Adenocarcinoma Depends on Intact Antigen Processing Machinery

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Milano, F.; Guarriera, M.; Rygiel, A.M.; Krishnadath, K.K.

2010-01-01

BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor prognosis, which frequently exhibits HER-2 gene amplification. Trastuzumab, the humanized antibody against HER-2, has potent growth inhibitory effects on HER-2 overexpressing cancers. One effect of trastuzumab is

Hydrogen sulfide synthesis enzymes reduced in lower esophageal sphincter of patients with achalasia.

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Zhang, L; Zhao, W; Zheng, Z; Wang, T; Zhao, C; Zhou, G; Jin, H; Wang, B

2016-10-01

The etiology of achalasia remains largely unknown. Considerable evidence reveals that the lower esophageal sphincter dysfunction is due to the lack of inhibitory neurotransmitter, secondary to esophageal neuronal inflammation or loss. Recent studies suggest hydrogen sulfide may act as an inhibitory transmitter in gastrointestinal tract, but study about hydrogen sulfide in human esophagus still lack. The aim of the study was to investigate if hydrogen sulfide synthesis enzymes could be detected in human esophagus and if the synthesis of the endogenous hydrogen sulfide could be affected in achalasia patients. Tissue samples in cardia, lower esophageal sphincter, 2 cm and 4 cm above lower esophageal sphincter were obtained from achalasia patients undergoing peroral endoscopic myotomy. Control tissues in lower esophageal sphincter were obtained from esophageal carcinoma patients. Expression of cystathionine-β-synthase and cystathionine-γ-lyase in lower esophageal sphincter of achalasia patients and control were detected by immunohistochemical staining. In addition, expression of cystathionine-β-synthase and cystathionine-γ-lyase were compared among different parts of esophagus in achalasia patients. Compared with control, the expression of cystathionine-β-synthase and cystathionine-γ-lyase in lower esophageal sphincter of achalasia patients was significantly reduced (χ 2 = 11.429, P = 0.010). The expression of cystathionine-β-synthase and cystathionine-γ-lyase were lower in lower esophageal sphincter than that in 2 cm and 4 cm above lower esophageal sphincter, respectively (all P achalasia, which implicates the involvement of the two hydrogen sulfide synthesis enzymes in the pathophysiology of achalasia. © 2015 International Society for Diseases of the Esophagus.

Circulating Tumor Cells and Cardiac Metastasis from Esophageal Cancer: A Case Report

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Francesca Consoli

2011-05-01

Full Text Available We report the case of a 67-year-old man affected by metastatic esophageal cancer. The patient developed a symptomatic heart metastasis presenting as mimicking ST-segment elevation myocardial infarction. Cardiac magnetic resonance imaging (MRI documented the presence of a mass in the apex and septum of the left ventriculum. The dissemination of cancer was confirmed by the detection of circulating tumor cells (CTCs in the peripheral blood, measured by the CellSearch System (Veridex, LLC, Raritan, N.J., USA. The blood sample drawn at cardiac disease progression revealed the presence of 2 CTCs per 7.5 ml of blood. This report highlights the potential role of CTCs as markers of metastatic spread.

Food and aeroallergens in eosinophilic esophagitis: role of the allergist in patient management.

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Aceves, Seema S

2014-07-01

Eosinophilic esophagitis is a clinicopathologic disease of increasing worldwide prevalence that is triggered by food antigens. The concurrent management of all of the atopic diseases affecting a single individual is likely to be important for successful long-term eosinophilic esophagitis management. This review covers the role of the allergist in eosinophilic esophagitis with a focus on the literature from the past 2  years. Studies in the past 2  years document that testing for immediate and delayed allergic hypersensitivity to foods can be of utility in building elimination diets in children, but that this may not be the case in adults. In addition, it has been shown that a number of cells and interleukins involved in Th2 inflammation such as invariant natural killer T cells, basophils, and interleukin-9 are important in eosinophilic esophagitis pathogenesis. Finally, the role of foods in generating esophageal remodeling has been shown using murine models. Recent studies support the role of the allergist in eosinophilic esophagitis management, especially for food allergen testing, interpretation, and the management of food allergies concurrent atopic diatheses. In addition, allergists have made significant research contributions in our understanding of eosinophilic esophagitis.

Esophageal motility in eosinophilic esophagitis

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A.H. Weiss

2015-07-01

Conclusions: Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on patients with EoE.

Telomerase variant A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal carcinomas.

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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�

Diagnosis and management of esophageal achalasia.

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Stavropoulos, Stavros N; Friedel, David; Modayil, Rani; Parkman, Henry P

2016-09-13

Achalasia is a rare esophageal motility disorder that is usually idiopathic in origin. It is characterized by dysphagia, and patients often have chest pain, regurgitation, weight loss, and an abnormal barium radiograph showing esophageal dilation with narrowing at the gastroesophageal junction. Abnormal or absent esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) are typically seen on esophageal manometry. The advent of high resolution manometry (HRM) has allowed more precise diagnosis of achalasia, subtype designation, and differentiation from other esophageal motor disorders with an initial seminal publication in 2008 followed by further refinements of what has been termed the Chicago classification. Potential treatments include drugs, endoscopic botulinum toxin injection, balloon dilation, traditional surgery (usually laparoscopic Heller myotomy; LHM), and a novel, less invasive, natural orifice transluminal endoscopic surgery (NOTES) approach to Heller myotomy termed peroral endoscopic myotomy (POEM). The first human POEM was performed in 2008, with the first publication appearing in 2010 and evidence now rapidly accumulating showing POEM to be comparable to traditional surgery in terms of clinical success and radiologic and manometric post-therapy outcomes. This review discusses the diagnosis and management of achalasia with particular emphasis on the recent developments of HRM and POEM, which arguably represent the most important advances in the field since the advent of laparoscopic Heller myotomy in the 1990s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

International Nuclear Information System (INIS)

Fuhrmann, A; Staunton, J R; Banyai, N; Davies, P C W; Ros, R; Nandakumar, V

2011-01-01

The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial–mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force–indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their

[Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment].

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Flores, Priscila Pollo; Lemme, Eponina Maria de Oliveira; Coelho, Henrique Sérgio Moraes

2005-01-01

The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

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Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

[Management of the esophageal candidiasis by the primary care physician].

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Behrens, Garance; Bocherens, Astrid; Senn, Nicolas

2014-05-14

Esophageal candidiasis is one of the most common opportunistic infections in patients infected by human immunodeficiency virus (HIV). This pathology is also found in patients without overt immunodeficiency. Other risk factors are known to be associated with this disease like inhaled or systemic corticosteroid treatment or proton-pump inhibitors and H2 receptor antagonists. In the absence of identified risk factors, a primary immune deficiency should be sought. Prevention of esophageal candidiasis is based primarily on the identification of risk factors, and a better control of them. This article presents a review of the physiopathology, clinical presentation and management of esophageal candidiasis by primary care physicians. We will also discuss ways of preventing esophageal candidiasis when necessary.

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

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Luo J

2014-09-01

difference in YY1 expression in patients with or without lymphatic invasion. The Transwell assay revealed that the overexpression of YY1 promoted the invasion ability of TE-1 cells and the inhibition of YY1 could reverse this promotion. Conclusion: YY1 expression was associated with TNM stage and lymph node metastasis, suggesting that YY1 can influence human esophageal cancer progression and metastasis. Keywords: immunohistochemistry, transwell assay, clinicopathological features, invasion

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

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

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Nakajima, N; Sato, H; Takahashi, K; Hasegawa, G; Mizuno, K; Hashimoto, S; Sato, Y; Terai, S

2017-03-01

Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium. © 2016 John Wiley & Sons Ltd.

esophageal cancer: preliminary results

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Afsaneh Maddah Safaei

2017-01-01

Full Text Available Purpose: Dysphagia is a common initial presentation in locally advanced esophageal cancer and negatively impacts patient quality of life and treatment compliance. To induce fast relief of dysphagia in patients with potentially operable esophageal cancer high-dose-rate (HDR brachytherapy was applied prior to definitive radiochemotherapy. Material and methods : In this single arm phase II clinical trial between 2013 to 2014 twenty patients with locally advanced esophageal cancer (17 squamous cell and 3 adenocarcinoma were treated with upfront 10 Gy HDR brachytherapy, followed by 50.4 Gy external beam radiotherapy (EBRT and concurrent chemotherapy with cisplatin/5-fluorouracil. Results : Tumor response, as measured by endoscopy and/or computed tomography scan, revealed complete remission in 16 and partial response in 4 patients (overall response rate 100%. Improvement of dysphagia was induced by brachytherapy within a few days and maintained up to the end of treatment in 80% of patients. No differences in either response rate or dysphagia resolution were found between squamous cell and adenocarcinoma histology. The grade 2 and 3 acute pancytopenia or bicytopenia reported in 4 patients, while sub-acute adverse effects with painful ulceration was seen in five patients, occurring after a median of 2 months. A perforation developed in one patient during the procedure of brachytherapy that resolved successfully with immediate surgery. Conclusions : Brachytherapy before EBRT was a safe and effective procedure to induce rapid and durable relief from dysphagia, especially when combined with EBRT.

High-resolution esophageal pressure topography for esophageal motility disorders

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Hashem Fakhre Yaseri

2016-04-01

Full Text Available Background: High-resolution manometer (HRM of the esophagus has become the main diagnostic test in the evaluation of esophageal motility disorders. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The first step of the Chicago classification described abnormal esophagogastric junction deglutitive relaxation. The latest classification system, proposed by Pandolfino et al, includes contraction patterns and peristalsis integrity based on integrated relaxation pressure 4 (IRP4. It can be discriminating the achalasia from non-achalasia esophageal motility disorders. The aim of this study was to assessment of clinical findings in non-achalasia esophageal motility disorders based on the most recent Chicago classification. Methods: We conducted a prospective cross-sectional study of 963 patients that had been referred to manometry department of Gastrointestinal and Liver Research Center, Firozgar Hospital, Tehran, Iran, from April, 2012 to April, 2015. They had upper GI disorder (Dysphasia, non-cardiac chest pain, regurgitation, heartburn, vomiting and asthma and weight loss. Data were collected from clinical examinations as well as patient questionnaires. Manometry, water-perfused, was done for all patients. Manometry criteria of the patients who had integrated relaxation pressure 4 (IRP4 ≤ 15 mmHg were studied. Results: Our finding showed that the non-achalasia esophageal motility disorders (58% was more common than the achalasia (18.2%. Heartburn (68.5%, regurgitation (65.4% and non-cardiac chest pain (60.6% were the most common clinical symptoms. Although, vomiting (91.7% and weight loss (63% were the most common symptoms in referring patients but did not discriminate this disorders from each other’s. Borderline motor function (67.2% was the most common, absent peristalsis (97% and the hyper

Rapidly Growing Esophageal Carcinosarcoma Reduced by Neoadjuvant Radiotherapy Alone

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Naotaka Ogasawara

2014-06-01

Full Text Available Esophageal carcinosarcoma is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components. It is generally treated by surgery, radiotherapy and chemotherapy according to the protocols used for other esophageal cancers. However, the treatment of esophageal carcinosarcoma by radiotherapy alone before surgery has not been previously described. We report a patient with a rapidly growing esophageal carcinosarcoma that was efficiently reduced by neoadjuvant radiotherapy alone. A previously healthy 69-year-old man was admitted with dysphagia. Initial esophagogastroduodenoscopy (EGD revealed a small nodular polypoid lesion of about 10 mm in the middle esophagus. A second EGD 1 month later showed that the tumor had expanded into a huge mass. A biopsy specimen revealed that the tumor comprised squamous cell carcinoma with spindle cell components, and the tumor was diagnosed as carcinosarcoma which was diagnosed as stage I (T1bN0M0. Due to renal dysfunction, the patient was treated with neoadjuvant radiotherapy (40 Gy without chemotherapy. A third EGD 1 month later revealed remarkable tumor reduction. He then underwent total esophagectomy with regional lymph node dissection (pStage 0, pT1aN0M0. After surgical operation, the patient was followed up without adjuvant therapy. Whole body computed tomography revealed lung metastasis 14 months after surgery, and the patient died 2 months later. The neoadjuvant radiotherapy for esophageal carcinosarcoma was considered to have contributed to the subsequent surgery and his prolonged survival time. Thus, radiotherapy alone might be a suitable neoadjuvant therapy for esophageal carcinosarcomas.

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

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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.

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

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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

Investigating Esophageal Stent-Placement Outcomes in Patients with Inoperable Non-Cervical Esophageal Cancer

OpenAIRE

Forootan, Mojgan; Tabatabaeefar, Morteza; Mosaffa, Nariman; Ashkalak, Hormat Rahimzadeh; Darvishi, Mohammad

2018-01-01

Background: Esophageal stent insertion in patients with inoperable esophageal cancer is usually accompanied with relatively high adverse symptoms and even mortality. The current study aims at investigating the outcomes of esophageal stenting in patients with inoperable non-cervical esophageal cancer. Materials and Methods: The current descriptive-analytical research evaluates 25 patients with esophageal cancer. The stent was placed in esophagus based upon endoscopy analysis with or without fl...

Esophageal Stenosis Associated With Tumor Regression in Radiotherapy for Esophageal Cancer: Frequency and Prediction

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Atsumi, Kazushige [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Arimura, Hidetaka [Department of Health Sciences, Kyushu University, Fukuoka (Japan); Terashima, Kotaro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Matsuki, Takaomi [Department of Health Sciences, Kyushu University, Fukuoka (Japan); Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Nakamura, Katsumasa [Department of Radiology, Kyushu University Hospital at Beppu, Oita (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

2012-04-01

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

Directory of Open Access Journals (Sweden)

Yu-Lin Zhao

2017-07-01

Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

Esophageal motility disorders

International Nuclear Information System (INIS)

Hannig, C.; Rummeny, E.; Wuttge-Hannig, A.

2007-01-01

For the better understanding of esophageal motility, the muscle texture and the distribution of skeletal and smooth muscle fibers in the esophagus are of crucial importance. Esophageal physiology will be shortly mentioned as far as necessary for a comprehensive understanding of peristaltic disturbances. Besides the pure depiction of morphologic criteria, a complete esophageal study has to include an analysis of the motility. New diagnostic tools with reduced radiation for dynamic imaging (digital fluoroscopy, videofluoroscopy) at 4-30 frames/s are available. Radiomanometry is a combination of a functional pressure measurement and a simultaneous dynamic morphologic analysis. Esophageal motility disorders are subdivided by radiologic and manometric criteria into primary, secondary, and nonclassifiable forms. Primary motility disorders of the esophagus are achalasia, diffuse esophageal spasm, nutcracker esophagus, and the hypertonic lower esophageal sphincter. The secondary motility disorders include pseudoachalasia, reflux-associated motility disorders, functionally caused impactions, Boerhaave's syndrome, Chagas' disease, scleroderma, and presbyesophagus. The nonclassificable motility disorders (NEMD) are a very heterogeneous collective. (orig.) [de

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

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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

Radiation-induced esophagitis in local advanced non-small cell lung cancer after three-dimensional conformal radiotherapy

International Nuclear Information System (INIS)

Tian Dandan; Wang Yuxiang; Qiu Rong; Zhu Shuchai; Tian Xiuming; Qiao Xueying

2014-01-01

Objective: To explore radiation-induced esophagitis and its related factors in the patients with local advanced non-small cell lung cancer (NSCLC) which were treated with three-dimensional conformal radiation therapy (3D-CRT). Methods: From January 2001 to December 2008, 203 patients who suffered from stage Ⅲ NSCLC were achieved, including 163 males and 40 females, with a median age of 63 years old, while 79 cases were in stage Ⅲ_a and 124 in stage Ⅲ_b. The equivalent median dose of tumor was 62 Gy(range of 50-78 Gy). Among them, 74 cases were administered with radiotherapy alone, 45 with sequential radiotherapy and chemotherapy, 87 cases with concurrent radiochemotherapy. Radiation esophagitis was evaluated with RTOG standard. The dosimetric parameters was estimated from dose volume histogrma (DVH). The clinical and dosimetric parameters of radiation esophagitis were evaluated by spearman correlatived univariate and Logistic multivariable analysis.Results After radiotherapy, out of 203 patients, 87 had acute radiation esophagitis(RE), 47 in grade 1, 37 in grade 2, and 3 in grade 3 RE. According to spearman correlatived analysis, the correlatived factors included ages, chemotherapy, GTV, PTV, the mean doses of PTV and lung, the max and mean dose of esophagus, V_4_0, V_4_5, V_5_0, V_5_5, V_6_0, length of esophagus (total circumference) treated with 45 Gy (LETT_4_5), and LETT_5_0 (r = -0.162-0.235, P 0.05). There were 21 factors, such as gender, age, smoking, clinical stage, site of tumor, chemotherapy, GTV, PTV, mean dose of PTV and lung, max and mean dose of esophagus, V_4_0-V_6_0 of esophagus, LETT_4_5_-_6_0, incorporated into multivariable analysis, only chemotherapy and V_4_5 of esophagus were independent predicted factors(Wald = 4.626, 9.882, P < 0.05). Conclusions: In local advanced NSCLC after 3D-CRT, chemotherapy(especially concurrent radiochemotherapy) could increase radiation-induced esophagitis. The parameter of DVH could also be used to predict

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

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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.

[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.

Silane surface modification for improved bioadhesion of esophageal stents

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Karakoy, Mert; Gultepe, Evin; Pandey, Shivendra; Khashab, Mouen A.; Gracias, David H.

2014-08-01

Stent migration occurs in 10-40% of patients who undergo placement of esophageal stents, with higher migration rates seen in those treated for benign esophageal disorders. This remains a major drawback of esophageal stent therapy. In this paper, we propose a new surface modification method to increase the adhesion between self-expandable metallic stents (SEMS) and tissue while preserving their removability. Taking advantage of the well-known affinity between epoxide and amine terminated silane coupling agents with amine and carboxyl groups that are abundant in proteins and related molecules in the human body; we modified the surfaces of silicone coated esophageal SEMS with these adhesive self-assembled monolayers (SAMs). We utilized vapor phase silanization to modify the surfaces of different substrates including PDMS strips and SEMS, and measured the force required to slide these substrates on a tissue piece. Our results suggest that surface modification of esophageal SEMS via covalent attachment of protein-binding coupling agents improves adhesion to tissue and could offer a solution to reduce SEMS migration while preserving their removability.

Synchronous advanced gastric adenocarcinoma and advanced esophageal squamous cell carcinoma

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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.

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

Esophageal stent implantation for the treatment of esophageal strictures: its current situation and research progress

International Nuclear Information System (INIS)

Zhu Haidong; Guo Jinhe; Teng Gaojun

2011-01-01

Esophageal stent implantation has been the most common therapy for the treatment of malignant and benign esophageal stenosis. At present, this technique is widely used in treating advanced esophageal cancerous stricture, refractory esophageal benign stricture and all kinds of esophageal fistulae or perforation. This paper aims to make a comprehensive review of the current situation and research progress of the esophageal stent implantation in clinical practice. (authors)

Management of esophageal disorders

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Hill, L.D.; Mercer, C.D.; McCallum, R.W.; Kozarek, R.

1987-01-01

This book integrates gastroenterology and thoracic surgery to detail the comprehensive management of esophageal disease. It describes radiologic and functional evaluation of the esophagus, endoscopy, medical and surgical treatments, and results and also covers gastroesophageal reflux disease, tumors motility, esophageal replacement, intubation, esophageal diverticula, caustic esophageal injury. It presents Dr. Hill's surgical procedures in detail.

Esophageal Cancer

Science.gov (United States)

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

Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders.

Science.gov (United States)

van Hoeij, Froukje B; Bredenoord, Albert J

2016-01-31

Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new classification scheme: the Chicago classification. HRM measurements are more detailed and more easily performed compared to conventional manometry. The visual presentation of acquired data improved the analysis and interpretation of esophageal motor function. This led to a more sensitive, accurate, and objective analysis of esophageal motility. In this review we discuss how HRM changed the way we define and categorize esophageal motility disorders. Moreover, we discuss the clinical applications of HRM for each esophageal motility disorder separately.

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

The potential of photodynamic therapy to treat esophageal candidiasis coexisting with esophageal cancer.

Science.gov (United States)

Qiu, Haixia; Mao, Yongping; Gu, Ying; Zhu, Jianguo; Wang, Ying; Zeng, Jing; Huang, Naiyan; Liu, Qingsen; Yang, Yunsheng

2014-01-05

Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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

Directory of Open Access Journals (Sweden)

Peng Zhang

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

Denture Mis-swallowing in the Sliding Esophageal Hiatal Hernia Mimics Esophageal Perforation

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Chao-Yang Chen

2008-08-01

Full Text Available Mis-swallowing of a foreign body in the esophagus coexisting with sliding hernia might be misdiagnosed as esophageal perforation with mediastinal abscess. We report an 89-year-old woman, bedridden for a long period in a nursing home after a previous cerebrovascular accident, who was sent to our emergency department in a state of sepsis because she had swallowed a radio-opaque partial denture. The retention of the denture as an esophageal foreign body was complicated with mediastinitis and bilateral pleural effusion. The inability of the patient to give a reliable clinical history delayed the diagnosis. This report highlights the difficulty in precisely locating a partial denture because of conflicting radiologic findings and the coexistence of esophageal sliding hernia, all of which led to a misdiagnosis of possible esophageal perforation. A right posterolateral thoracotomy with gastrostomy was performed to remove the lower esophageal foreign body after esophagoscopy failed. The surgical finding of a coincidental sliding esophageal hiatal hernia correlated well with the clinical presentation. Managing such a complicated esophageal foreign body in this elderly patient was challenging.

DDEC: Dragon database of genes implicated in esophageal cancer

International Nuclear Information System (INIS)

Essack, Magbubah; Radovanovic, Aleksandar; Schaefer, Ulf; Schmeier, Sebastian; Seshadri, Sundararajan V; Christoffels, Alan; Kaur, Mandeep; Bajic, Vladimir B

2009-01-01

Esophageal cancer ranks eighth in order of cancer occurrence. Its lethality primarily stems from inability to detect the disease during the early organ-confined stage and the lack of effective therapies for advanced-stage disease. Moreover, the understanding of molecular processes involved in esophageal cancer is not complete, hampering the development of efficient diagnostics and therapy. Efforts made by the scientific community to improve the survival rate of esophageal cancer have resulted in a wealth of scattered information that is difficult to find and not easily amendable to data-mining. To reduce this gap and to complement available cancer related bioinformatic resources, we have developed a comprehensive database (Dragon Database of Genes Implicated in Esophageal Cancer) with esophageal cancer related information, as an integrated knowledge database aimed at representing a gateway to esophageal cancer related data. Manually curated 529 genes differentially expressed in EC are contained in the database. We extracted and analyzed the promoter regions of these genes and complemented gene-related information with transcription factors that potentially control them. We further, precompiled text-mined and data-mined reports about each of these genes to allow for easy exploration of information about associations of EC-implicated genes with other human genes and proteins, metabolites and enzymes, toxins, chemicals with pharmacological effects, disease concepts and human anatomy. The resulting database, DDEC, has a useful feature to display potential associations that are rarely reported and thus difficult to identify. Moreover, DDEC enables inspection of potentially new 'association hypotheses' generated based on the precompiled reports. We hope that this resource will serve as a useful complement to the existing public resources and as a good starting point for researchers and physicians interested in EC genetics. DDEC is freely accessible to academic

Advances in esophageal motor disorders.

Science.gov (United States)

Smout, André Jpm

2008-07-01

Esophageal motor disorders, often leading to dysphagia and chest pain, continue to pose diagnostic and therapeutic problems. In the past 12 months important new information regarding esophageal motor disorders was published. This information will be reviewed in this paper. A number of studies have addressed the issue of heterogeneity in achalasia, the best defined esophageal motility disorder. The spastic esophageal motility disorders nutcracker esophagus and diffuse esophageal spasm may coexist with gastroesophageal reflux disease, which has consequences for the management of patients with these disorders. The entity labelled ineffective esophageal motility is associated with reflux esophagitis, but also with morbid obesity. For the detection of disordered transit caused by ineffective esophageal motility, application of intraluminal impedance monitoring in conjunction with manometry leads to improved diagnosis. New data on the effect of Nissen fundoplication on esophageal motility were published during the last year. Recent knowledge on the heterogeneity of achalasia and the association of spastic esophageal motor disorders and ineffective motility with reflux disease will help the clinician in the management of patients with these disorders.

Radioisotope esophageal transit test

International Nuclear Information System (INIS)

Miyazono, Kazuhiro; Fukuda, Kazuo; Toyonaga, Atsushi

1982-01-01

A new technique employed sup(99m)Tc-MAA for the study of esophageal dysfunction and its clinical implication were evaluated in the patients with achalasia, progressive systemic sclerosis, reflux esophagitis and 10 normal controls. To investigate esophageal emptying and gastroesophageal reflux, a homogeneous bolus of sup(99m)Tc-MAA in 15ml of water was swallowed in the upright and supine positions under the collimeter of a gamma camera linked to nuclear medicine data analyser (Shimazu Scinti Pack 1200). This radionuclide transit studies made a quantitative evaluation of the esophageal dysfunction possible in all cases. Comparing the conventional esophageal function test procedures, this test is a safe, noninvasive and more physiological and sensitive in detecting abnormal esophageal emptying and gastroesophageal reflux. (author)

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

Science.gov (United States)

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.

Esophageal lichen planus.

Science.gov (United States)

Oliveira, Janine Pichler de; Uribe, Natalia Caballero; Abulafia, Luna Azulay; Quintella, Leonardo Pereira

2015-01-01

Lichen planus is a chronic inflammatory disease that affects the skin, mucous membranes, nails and scalp. Esophageal lichen planus is a rarely reported manifestation of lichen planus, presenting itself commonly in middle-aged women, with symptoms such as dysphagia. We report a case of esophageal lichen planus in a 54-year-old woman associated with oral, cutaneous and ungual lichen planus. Although lichen planus is a disorder well known by dermatologists, reports of esophageal lichen planus are rare in dermatologic literature. The esophageal lichen planus is little known and underdiagnosed, with a significant delay between the onset of symptoms and diagnosis.

LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?

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Otto Christoph

2011-02-01

Full Text Available Abstract Background Investigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC with and without Barrett's Esophagus (BE, with respect to a cancer stem cell (CSC hypothesis. Materials and methods Expression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with BE, 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC and in the adenocarcinoma cell line OE-33. Ki-67 and Cdx-2 were co-labelled with LgR5 in double staining experiments. Immunhistochemical expression results were confirmed by RT-PCR and correlated with tumor stage and five-year survival rates. Results LgR5was found expressed in 35 of 41 (85% EAC with BE and in 16 of 19 (81% EAC without BE. By contrast, LgR5 was not found to be expressed in ESCC. Quantification of immunolabeling showed 15% LgR5+ cells in EAC with BE, 32% LgR5+ cells in adjacent BE and 13% in EAC without BE. Immunofluorescence double staining experiments with LgR5 and Ki-67 revealed a subpopulation (~5% of proliferating LgR+/Ki-67+ cells. On mRNA-level, expression of LgR5 was higher in BE in comparison to EAC (p = 0.0159. High levels of LgR5 expression in BE associated EAC were associated with poorer survival in univariate analysis. Conclusion The stem cell marker LgR5 is expressed in EAC, irrespective of association with BE, and appears to have negative impact on survival. The subset of proliferating LgR5+ cells (

Radioisotope esophageal transit test. A new technique for esophageal emptying and gastroesophageal reflux

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Miyazono, K.; Fukuda, K.; Toyonaga, A. (Kurume Univ., Fukuoka (Japan). School of Medicine)

1982-06-01

A new technique employed sup(99m)Tc-MAA for the study of esophageal dysfunction and its clinical implication were evaluated in the patients with achalasia, progressive systemic sclerosis, reflux esophagitis and 10 normal controls. To investigate esophageal emptying and gastroesophageal reflux, a homogeneous bolus of sup(99m)Tc-MAA in 15ml of water was swallowed in the upright and supine positions under the collimeter of a gamma camera linked to nuclear medicine data analyser (Shimazu Scinti Pack 1200). This radionuclide transit study made a quantitative evaluation of the esophageal dysfunction possible in all cases. Comparing the conventional esophageal function test procedures, this test is a safe, noninvasive and more physiological and sensitive in detecting abnormal esophageal emptying and gastroesophageal reflux.

Herpes Simplex Virus-2 Esophagitis in a Young Immunocompetent Adult

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Deepak K. Kadayakkara

2016-01-01

Full Text Available Herpes simplex esophagitis (HSE is commonly identified in immunosuppressed patients. It is rare among immunocompetent patients and almost all of the reported cases are due to HSV-1 infection. HSV-2 esophagitis is extremely rare. We report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. Endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. However, classic histopathological findings of multinucleated giant cells with eosinophilic intranuclear inclusions and positive HSV-2 IgM confirmed the diagnosis of HSV-2 esophagitis. The patient rapidly responded to acyclovir treatment. Although HSV-2 is predominantly associated with genital herpes, it can cause infections in other parts of the body previously attributed to only HSV-1 infection.

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

Esophageal transit scintigraphy and structured questionnaire in patients with systemic sclerosis with endoscopically proven reflux esophagitis

International Nuclear Information System (INIS)

Nakajima, Kenichi; Inaki, Anri; Hiramatsu, Takashi; Hasegawa, Minoru; Fujimoto, Manabu; Takehara, Kazuhiko; Kinuya, Seigo

2009-01-01

Esophageal complications are common in patients with systemic sclerosis (SSc). The relationship between gastroesophageal reflux (GER) symptoms and dysmotility was examined in endoscopically confirmed patients suspected of having reflux esophagitis. A total of 32 patients with limited and diffuse type SSc (lSSc, dSSc) were examined based on a structured questionnaire score (QS) of GER symptoms, retention fraction of esophageal scintigraphy at 90 s (R 90 ) and gastric emptying time. The QS was significantly higher in the reflux esophagitis group than in the non-esophagitis group (5.4±3.5, 1.4±2.9, P=0.003). When the non-esophagitis group was further divided into lSSc and dSSc groups, R 90 was higher in the reflux esophagitis group (31±18%) and the non-esophagitis group with dSSc (34±32%) than in the non-esophagitis group with lSSc (8±3%, P=0.02). Both high R 90 ≥15% and QS≥4 indicated reflux esophagitis. Conversely, both normal R 90 and QS indicated no reflux esophagitis. A combination of esophageal scintigraphy and structured questionnaire demonstrated different aspects of esophageal dysfunction, namely dysmotility and GER. Patients with high QS and dysmotility may be indicated for further evaluation including endoscopic examination and medical treatment.(author)

Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus

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Jin, Hong; Wang, Bin; Zhang, Li-li

2018-01-01

Background The aim of this study was to undertake a histological evaluation of the presence of eosinophils in esophageal muscle in patients with achalasia before treatment with peroral endoscopic myotomy (POEM), with clinical follow-up at one year. Material/Methods Before treatment, esophageal biopsies including mucosa and esophageal muscle were obtained from 28 patients with achalasia. Nine patients who had undergone esophagectomy for esophageal carcinoma were included in the control group. The Eckardt Score was used to evaluate the clinical symptoms of achalasia. Histology of routinely processed tissue sections was used to perform eosinophil cell counts (0 to +++), and immunohistochemistry was used to detect expression of eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and S100 protein in cases of achalasia (n=28) and controls (n=9). The findings in patients with achalasia were compared before and one year following POEM. Results Esophageal tissue from patients with achalasia showed eosinophils infiltrating into the muscularis externa in 85.7% (24/28), into the muscularis propria in 28.6% (8/28), and in 89% (25/28) there were few remaining myenteric ganglion cells, before POEM. The extent of inflammation was similar in all regions of the esophagus and between subtypes of achalasia. At one year following POEM, the Eckardt Scores between the former eosinophil (0) group and the eosinophil (+++) group were significantly different (Z=3.50, P=0.030). Conclusions Achalasia of the esophagus was associated with infiltration of the esophageal muscle by activated eosinophils and a decrease in the density of ganglion cells in the myenteric esophageal plexus. PMID:29672471

Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel

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Ting Wen

2017-07-01

Full Text Available Eosinophilic esophagitis (EoE is a recently recognized upper gastrointestinal allergic disorder characterized by esophageal dysfunction (e.g., dysphagia and esophageal eosinophilia of ≥15 eosinophils/high-power field in patients who have persistent esophagitis even on proton pump inhibitor (PPI therapy. The histologic method is the gold standard of EoE diagnosis. However, EoE clinical symptoms do not always correlate with histology, and the histologic method has sensitivity and specificity issues due to the patchiness of EoE and the subjective nature of the method. The “EoE transcriptome” was initially discovered in 2006, which led to the invention of the EoE diagnostic panel (EDP. In addition to providing a definitive EoE diagnosis with high accuracy, the EDP has been useful in elucidating several key elements about the disease including the efficacy of specific drugs such as swallowed glucocorticoids and anti-IL-13 humanized antibody therapy, the relationship between EoE and PPI-responsive esophageal eosinophilia, and predicting the disease course and responsiveness to therapy. The EDP’s long-term potential arises from its plasticity to incorporate new genes and uncover novel disease pathogenesis. We expect that the EDP will be increasingly helpful for personalized medicine approaches and improved diagnostics and disease monitoring.

Esophageal pH monitoring

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pH monitoring - esophageal; Esophageal acidity test ... Esophageal pH monitoring is used to check how much stomach acid is entering the esophagus. It also checks how well the acid is cleared downward into the ...

Minimally invasive surgery for esophageal achalasia.

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Chen, Huan-Wen; Du, Ming

2016-07-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia.

Physiology of Normal Esophageal Motility

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Goyal, Raj K; Chaudhury, Arun

2009-01-01

The esophagus consists of two different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consist of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure due to its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. PMID:18364578

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

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

Balloon catheter dilatation of esophageal strictures

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Kim, Jeung Sook; Yoon, Yup; Sung, Dong Yook; Choi, Woo Suk; Nam, Kyung Jin; Lim, Jae Hoon [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

1990-07-15

The authors performed 27 fluoroscopically guided balloon dilatation in 12 patients of esophageal stricture during recent 3 years. The causes of esophageal stricture were corrosive esophagitis (N=2) and congenital narrowing (N=1), including postoperative narrowing in achalasia (N=3), esophageal varix (N=3), lye stricture (N=2) and esophageal cancer (N=1). Successful dilatation of the stricture was achieved during the procedure in 10 patients(83%). Major complication such as esophageal rupture was not found. The authors conclude that fluoroscopically guided esophageal balloon dilatation is a safe and effective method for treatment of symptomatic esophageal strictures.

Balloon catheter dilatation of esophageal strictures

International Nuclear Information System (INIS)

Kim, Jeung Sook; Yoon, Yup; Sung, Dong Yook; Choi, Woo Suk; Nam, Kyung Jin; Lim, Jae Hoon

1990-01-01

The authors performed 27 fluoroscopically guided balloon dilatation in 12 patients of esophageal stricture during recent 3 years. The causes of esophageal stricture were corrosive esophagitis (N=2) and congenital narrowing (N=1), including postoperative narrowing in achalasia (N=3), esophageal varix (N=3), lye stricture (N=2) and esophageal cancer (N=1). Successful dilatation of the stricture was achieved during the procedure in 10 patients(83%). Major complication such as esophageal rupture was not found. The authors conclude that fluoroscopically guided esophageal balloon dilatation is a safe and effective method for treatment of symptomatic esophageal strictures

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

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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.

Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

International Nuclear Information System (INIS)

Looby, Eileen; Abdel-Latif, Mohamed MM; Athié-Morales, Veronica; Duggan, Shane; Long, Aideen; Kelleher, Dermot

2009-01-01

The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate

Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells.

LENUS (Irish Health Repository)

Looby, Eileen

2009-01-01

BACKGROUND: The progression from Barrett\\'s metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. METHODS: Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. RESULTS: DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1\\/2- and p38 MAPK while Erk1\\/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK\\/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. CONCLUSION: DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.

Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

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Long Aideen

2009-06-01

Full Text Available Abstract Background The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. Methods Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. Results DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. Conclusion DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.

The Role of Esophageal PH-metri Test on Gastro-Esophageal Reflux Disease Diagnosis

OpenAIRE

Setyawati, Katharina; Abdullah, Murdani; Syam, Ari Fahrial; Fauzi, Achmad; Makmun, Dadang; Simadibrata, Marcellus; Manan, Chudahman; Rani, Abdul Aziz

2008-01-01

Gastro-esophageal reflux disease is a pathological condition of esophagus which is caused by gastric content reflux into esophagus. There is an increased prevalence of gastro-esophageal reflux disease. The roles of esophageal pH-metry in clinical application include looking for abnormal acid exposure on esophagus with no abnormality found in endoscopy; evaluating patients following the anti-reflux surgery who are being suspected for abnormal esophageal reflux; evaluating patients with normal ...

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...

Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

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Jie Hong

Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

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.

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

Science.gov (United States)

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.

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

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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

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.

Comparison of different ligature materials used for T-tube esophageal exclusion.

Science.gov (United States)

Lee, Y C; Luh, S P; Tsai, C C; Hsu, H C; Chu, S H

1992-03-01

Four different ligature materials--plain catgut, chromic catgut, dexon and silk--were used for ligature of the distal arm during T-tube exclusion of the cervical esophagus in 12 dogs. Ligature by plain catgut was maintained for only a short period, but the duration of esophageal occlusion with the other three ligature materials was around 10 days. Ligated esophageal segments were examined grossly and histologically two months after the procedure. The diameter of the esophageal lumen in the ligated segments had become smaller compared with the neighboring normal esophageal lumen. The most prominent histologic changes were atrophy and fibrosis of the muscle coat, vessel congestion and inflammatory cell infiltration in the ligated segments. These tissue reactions were more severe in the chromic catgut and silk ligatures. Among the 11 evaluable dogs, four had symptoms of dysphagia after removal of the T-tube. All four dogs had a sinus discharge and granuloma formation at the T-tube esophagostoma. The diameter of the esophageal lumen was more constricted in dogs with dysphagia. Among the four ligature materials, dexon had the advantages of a long duration of occlusion, less tissue fibrosis and little sequel of esophageal stenosis, making it the most suitable for ligature during esophageal exclusion.

Esophageal hypermotility: cause or effect?

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Crespin, O M; Tatum, R P; Yates, R B; Sahin, M; Coskun, K; Martin, A V; Wright, A; Oelschlager, B K; Pellegrini, C A

2016-07-01

Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients' symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring

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

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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.

Proteomics of a new esophageal cancer cell line established from Persian patient.

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Moghanibashi, Mehdi; Jazii, Ferdous Rastgar; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

2012-05-25

Although the highest incidence of esophageal squamous cell carcinoma (ESCC) has repeatedly been reported from Persia (Iran), nevertheless the so far proteomic published reports were limited to one study on tissue specimens. Here we report the proteome of a newly established cell line from Persian ESCC patients and compare it with the normal primary cell proteome. Among polypeptides, whose expression was different in cell line sixteen polypeptides were identified by MALDI/TOF/TOF spectrometry. S100-A8 protein, annexin A1, annexin A2, regulatory subunit of calpain, subunit alpha type-3 of proteasome and glutamate dehydrogenase 1 were proteins down-regulated in cell line while peroxiredoxin-5, non-muscle myosin light polypeptide 6, keratin 1, annexin A4, keratin 8, tropomyosin 3, stress-induced-phosphoprotein 1 and albumin were found to be subject of up-regulation in cell line compared to the primary normal cells. The proteomic results were further verified by western blotting and RT-PCR on annexin A1 and keratin 8. In addition, among the aforementioned proteins, glutamate dehydrogenase 1, regulatory subunit of calpain, subunit alpha of type-3 proteasome and annexin A4 are proteins whose deregulation in ESCC is reported for the first time by this study. Copyright © 2012 Elsevier B.V. All rights reserved.

Assessment of the incidence of squamous cell papilloma of the esophagus and the presence of high-risk human papilloma virus.

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Pantham, Ganesh; Ganesan, Santhi; Einstadter, Douglas; Jin, Ge; Weinberg, Aaron; Fass, Ronnie

2017-01-01

There has been a recent increase in the incidence of oropharyngeal cancer (OPC) associated with high-risk human papilloma virus (HPV) infection. We investigated the incidence of esophageal papilloma and the presence of high-risk HPV infection. This is a cross-sectional study conducted at a County teaching hospital. Patients with esophageal papilloma between January 2000 and December 2013 were identified. Patients with sufficient specimens were tested for the HPV virus. Sixty patients with esophageal papilloma lesions were identified from 2000 to 2013. (31 males, age 51 ± 13 years). The incidence was 0.13% in 2000 and increased to 0.57% in 2013 (P papilloma that was more than 5 mm in size, and 20% had multiple lesions. The papilloma was located in the distal esophagus in 35 (58.3%) patients, mid esophagus in 17 (28.3%) patients, and proximal in 8 (13.3%) patients. Three (5%) patients had associated OPC, and 9 (47.4%) of the 19 patients tested were positive for high-risk HPV serotype 16. The incidence of esophageal papilloma has increased by fourfolds over the past 14 years. About half of the tested patients demonstrated high risk HPV. This may suggest a potential growing risk for esophageal squamous cell cancer in the future. © 2016 International Society for Diseases of the Esophagus.

Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy

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Kim, Kyung Su [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jeon, Seong-Uk; Lee, Chan-Ju; Kim, Young-Eun; Bok, Seoyeon; Hong, Beom-Ju; Park, Dong-Young [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Ahn, G-One, E-mail: goneahn@postech.ac.kr [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-07-01

Purpose: To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro. Methods and Materials: Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways. Results: We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways. Conclusions: We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression

Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients.

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Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

2015-11-01

Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups.We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors.Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients (α, 0.85).This

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

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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.

[Effects of peroral endoscopic myotomy on esophageal dynamics in patients with esophageal achalasia].

Science.gov (United States)

Zhong, Yun-shi; Li, Liang; Zhou, Ping-hong; Xu, Mei-dong; Ren, Zhong; Zhu, Bo-qun; Yao, Li-qing

2012-07-01

To investigate the effects of peroral endoscopic myotomy(POEM) on esophageal dynamics in patients with esophageal achalasia. From September 2011 to November 2011, 20 cases with esophageal achalasia received POEM at the Endoscopic Center in the Zhongshan Hospital of Fudan University. Pre-operation esophageal dynamics of all the patients were evaluated by high resolution manometry(HRM) system and 3 days after operation the test was repeated. Lower esophagus sphincter resting pressure(LESP), 4-second integrated relaxation pressure(4sIRP), lower esophagus sphincter relax rate(LESRR), lower esophagus sphincter length(LESL), and esophageal manometry were analyzed. After POEM, LESP decreased from(29.1±17.0) mm Hg to(14.6±4.9) mm Hg, and decrease rate was 49.8%(P0.05). Esophageal peristaltic contraction was absent in all the 20 patients preoperatively. After POEM, changes in the esophageal contraction were seen in 7 patients, and peristalsis was noticed but was below normal level. There were no significant changes in peristalsis in the remaining 13 patients. POEM can significantly reduce LESP and 4sIRP in patients with achalasia, but can not affect the contraction of the esophagus.

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.

DDEC: Dragon database of genes implicated in esophageal cancer

KAUST Repository

Essack, Magbubah

2009-07-06

Background: Esophageal cancer ranks eighth in order of cancer occurrence. Its lethality primarily stems from inability to detect the disease during the early organ-confined stage and the lack of effective therapies for advanced-stage disease. Moreover, the understanding of molecular processes involved in esophageal cancer is not complete, hampering the development of efficient diagnostics and therapy. Efforts made by the scientific community to improve the survival rate of esophageal cancer have resulted in a wealth of scattered information that is difficult to find and not easily amendable to data-mining. To reduce this gap and to complement available cancer related bioinformatic resources, we have developed a comprehensive database (Dragon Database of Genes Implicated in Esophageal Cancer) with esophageal cancer related information, as an integrated knowledge database aimed at representing a gateway to esophageal cancer related data. Description: Manually curated 529 genes differentially expressed in EC are contained in the database. We extracted and analyzed the promoter regions of these genes and complemented gene-related information with transcription factors that potentially control them. We further, precompiled text-mined and data-mined reports about each of these genes to allow for easy exploration of information about associations of EC-implicated genes with other human genes and proteins, metabolites and enzymes, toxins, chemicals with pharmacological effects, disease concepts and human anatomy. The resulting database, DDEC, has a useful feature to display potential associations that are rarely reported and thus difficult to identify. Moreover, DDEC enables inspection of potentially new \\'association hypotheses\\' generated based on the precompiled reports. Conclusion: We hope that this resource will serve as a useful complement to the existing public resources and as a good starting point for researchers and physicians interested in EC genetics. DDEC is

Esophageal lichen planus

OpenAIRE

Oliveira, Janine Pichler de; Uribe, Natalia Caballero; Abulafia, Luna Azulay; Quintella, Leonardo Pereira

2015-01-01

Abstract Lichen planus is a chronic inflammatory disease that affects the skin, mucous membranes, nails and scalp. Esophageal lichen planus is a rarely reported manifestation of lichen planus, presenting itself commonly in middle-aged women, with symptoms such as dysphagia. We report a case of esophageal lichen planus in a 54-year-old woman associated with oral, cutaneous and ungual lichen planus. Although lichen planus is a disorder well known by dermatologists, reports of esophageal lichen ...

The bidirectional association between oral cancer and esophageal cancer: A population-based study in Taiwan over a 28-year period.

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Lee, Kuan-Der; Wang, Ting-Yao; Lu, Chang-Hsien; Huang, Cih-En; Chen, Min-Chi

2017-07-04

Previous studies have revealed that patients with oral or esophageal cancer are at higher risk for subsequently developing a second primary malignancy. However, it remains to be determined what association exists between oral cancer and esophageal cancer particularly in Asian countries where squamous cell carcinoma is the predominant type of esophageal cancer. A population-based study was carried out in Taiwan, where the incidence rates of both oral and esophageal squamous cell carcinomas are high, to test the hypothesis that oral cancer or esophageal cancer predisposes an individual to developing the other form of cancer. Our results showed that patients with primary oral cancer (n=45,859) had ten times the risk of second esophageal cancer compared to the general population. Within the same cohort, the reciprocal risk of oral cancer as a second primary in primary esophageal cancer patients (n=16,658) was also increased seven-fold. The bidirectional relationship suggests common risk factors between these two cancers. The present study is not only the first population-based study in Asia to validate the reciprocal relationship between oral and esophageal squamous cell carcinomas, but also will aid in the appropriate selection of high-risk patients for a future follow-up surveillance program.

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.

Prevalence of lung abnormalities in 55 patients with esophageal cancer

International Nuclear Information System (INIS)

Zan, Tiago Alves de Brito; Cordeiro, Jose Antonio; Franca, Fabricio Correa de; Muniz, Marcos Pontes; Borim, Aldenis Albenese; Cury, Patricia Maluf

2001-01-01

The objective was to identify lung abnormalities in patients with esophageal cancer, to compare the obtained data and to demonstrate its relationship with smoking. This was a series of cases type of cross-sectional study. We studied 55 patients with esophageal carcinoma diagnosed between 1998 and 2001 at Hospital de Base de Sao Jose do Rio Preto, SP, Brazil. Chest plain films and computed tomography scans were analyzed. The frequency of the tumors and other lung abnormalities in two groups of patients were compared: smokers and non-smokers. The results showed that forty-six (83%) patients had spinous cell carcinoma, seven (13%) adenocarcinomas, one (2%) carcinoma of small cells and one (2%) non-Hodgkin lymphoma. Forty-eight (87%) patients were smokers and seven (13%) were non-smokers. In the smokers group, 89% had spinous cell carcinoma, 9% adenocarcinoma and 2% small cells carcinoma. In the non-smokers group, 57% had adenocarcinoma, 28% spinous cell carcinoma and 15% non-Hodgkin lymphoma. Metastases were identified in four smokers and in two non-smokers. The prevalence of the lung abnormalities (interstitial infiltration, emphysema and pneumonia) was higher in the smokers group (73%) than in the non-smokers group (27%) (p = 0.03). We concluded that this fact reinforces the importance of evaluation of the lungs in patients with esophageal neoplasms. (author)

Nitrous oxide cryotherapy for treatment of esophageal squamous cell neoplasia: initial multicenter international experience with a novel portable cryoballoon ablation system

NARCIS (Netherlands)

Canto, Marcia Irene; Abrams, Julian A.; Kunzli, Hannah T.; Weusten, Bas; Komatsu, Yoshihiro; Jobe, Blair A.; Lightdale, Charles J.

2018-01-01

Background and Aims: Early esophageal squamous cell neoplasia (ESCN) can be successfully treated by EMR, endoscopic submucosal dissection (ESD), or radiofrequency ablation. A new portable, battery-powered cryotherapy system using nitrous oxide (cryoballoon focal ablation system [CbFAS]) has been

Esophageal scintigraphy to quantitate esophageal transit of the achalasia patients after heller's myotomy

International Nuclear Information System (INIS)

Liu Junfeng; Wang Qizhang; Li Wenqi

1995-01-01

To quantitate esophageal transit of the achalasia patients after Heller's myotomy using scintigraphic technique. After a bolus ingestion of 10 ml orange juice containing 185 MBq 99m Tc-DTPA, radioactivity was measured on the esophagus for 5 minutes by SPECT, and esophageal clearance rate was calculated. Forty-two patients and 10 normal controls were included. Esophageal transit was increased significantly after Heller's operation, but it was still lower than normal value. Heller's myotomy can significantly improve esophageal transit in the patients with achalasia, although it does not reach normal level

Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

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Power, D G; Ilson, D H

2009-11-01

Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders

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van Hoeij, Froukje B.; Bredenoord, Albert J.

2016-01-01

Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new

Esophageal trachealization: A feature of eosinophilic esophagitis

International Nuclear Information System (INIS)

AlHussaini, Abdulrahman A; Semaan, Toufic; ElHag, Imad A

2009-01-01

Eosinophilic esophagitis (EE) is an inflammatory condition characterized by intense eosinophilic infiltration of the esophagus. EE is frequently misdiagnosed as gastroesophageal reflux disease. Here, we present a child with EE and a characteristic endoscopic finding, r inged esophagus . An 11-year-old Saudi boy presented with dysphagia for 1 year. He had experienced an intermittent sensation of solid food sticking in his chest, which was relieved by drinking liquids. A barium swallow excluded anatomical causes of dysphagia, but revealed multiple-ringed esophagus. Endoscopy showed a furrowing and trachealizing appearance of the entire esophagus. Hisologically, extensive eosinophilic infiltration was a feature in biopsies obtained from the esophagus. The child responded well to a 2-month course of inhaled fluticasone. Symptoms recurred 3 months after discontinuation of therapy, which necessitated resumption of inhaled fluticasone. The endoscopic appearance of multiple esophageal rings should raise suspicion of EE and be confirmed by esophageal biopsies. (author)

Congenital esophageal atresia with tracheo-esophageal fistula

International Nuclear Information System (INIS)

Rhee, Chung Sik

1970-01-01

Three cases of esophageal atresia with tracheo-esophageal fistula. 1). Case 1: A female infant birth Wt. 1.95 kg , Apgar Score 10, Skeletal anomalies, was delivered after a pregnancy compeicated by hydroamnious on Aug. 17, 1970. The family history was not contributory. 2) Case 2: A male infant birth Wt. 2.8 kg , Apgar Score 8, was forcep delivered after a pregnancy on Feb. 8, 1970. This infant is twin. The family history was not contributory. 3) Case 3: A female infant birth Wt. 2.22 kg , Apgar Score 10, was C-section after a pregnancy on May, 16. 1970. The family history was not contributory. All cases: After 24 hours 5% glucose solution was given and immediately vomited and some of it regurgitating through the nose and mouth with associated cyanosis and dyspnea. A catheter was inserted through the nose into the esophagus under diagnosis of the esophageal atresia

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

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

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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.

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.

Esophageal manometric characteristics and outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication for epiphrenic diverticula.

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Melman, Lora; Quinlan, Jessica; Robertson, Brian; Brunt, L M; Halpin, Valerie J; Eagon, J C; Frisella, Margaret M; Matthews, Brent D

2009-06-01

The purpose of this study is to characterize the esophageal motor and lower esophageal sphincter (LES) abnormalities associated with epiphrenic esophageal diverticula and analyze outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication. The endoscopic, radiographic, manometric, and perioperative records for patients undergoing laparoscopic esophageal diverticulectomy, anterior esophageal myotomy, and partial fundoplication from 8/99 until 9/06 were reviewed from an Institutional Review Board (IRB)-approved outcomes database. Data are given as mean +/- standard deviation (SD). An esophageal body motor disorder and/or LES abnormalities were present in 11 patients with epiphrenic diverticula; three patients were characterized as achalasia, one had vigorous achalasia, two had diffuse esophageal spasm, and five had a nonspecific motor disorder. Presenting symptoms included dysphagia (13/13), regurgitation (7/13), and chest pain (4/13). Three patients had previous Botox injections and three patients had esophageal dilatations. Laparoscopic epiphrenic diverticulectomy with an anterior esophageal myotomy was completed in 13 patients (M:F; 3:10) with a mean age of 67.6 +/- 4.2 years, body mass index (BMI) of 28.1 +/- 1.9 kg/m2 and American Society of Anesthesiologists (ASA) 2.2 +/- 0.1. Partial fundoplication was performed in 12/13 patients (Dor, n = 2; Toupet, n = 10). Four patients had a type I and one patient had a type III hiatal hernia requiring repair. Mean operative time was 210 +/- 15.1 min and mean length of stay (LOS) was 2.8 +/- 0.4 days. Two grade II or higher complications occurred, including one patient who was readmitted on postoperative day 4 with a leak requiring a thoracotomy. After a mean follow-up of 13.6 +/- 3.0 months (range 3-36 months), two patients complained of mild solid food dysphagia and one patient required proton pump inhibitor (PPI) for gastroesophageal reflux disease (GERD) symptoms. The majority of patients

Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett's esophagus.

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Douglas B Stairs

Full Text Available Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD. Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined.To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett's esophagus, we performed a microarray analysis of normal esophageal, Barrett's esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett's esophagus.These data demonstrate the ability of Cdx1 and c-myc to initiate the earliest stages of transdifferentiation of esophageal keratinocytes toward a cell fate characteristic of Barrett's esophagus.

Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

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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.

Primary Esophageal Motility Disorders: Beyond Achalasia.

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Schlottmann, Francisco; Patti, Marco G

2017-06-30

The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders. The Chicago classification introduced new manometric parameters and better defined esophageal motility disorders. Motility disorders beyond achalasia with the current classification are: esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility) and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). The aim of this study was to review the current diagnosis and management of esophageal motility disorders other than achalasia.

Gastroesophageal scintigraphy and endoscopy in the diagnosis of esophageal reflux and esophagitis

International Nuclear Information System (INIS)

Fung, W.P.; Van der Schaaf, A.; Grieve, J.C.

1985-01-01

The value of gastroesophageal (G/E) scintigraphy in the diagnosis of gastroesophageal reflux was assessed in 51 subjects, who presented with heartburn and had endoscopic evidence of reflux esophagitis. G/E scintigraphy was done using /sup 99m/Tc sulfur-colloid in acidified orange juice. The G/E reflux index was calculated according to previous reports. The mean (+/- SD) G/E reflux index in 18 patients with severe esophagitis and 30 patients with moderate esophagitis were 1.6% (+/- 1.5) and 3.2% (+/- 5.0), respectively. The mean G/E reflux index in 14 control subjects was 2.4% (+/- 1.1). There was no significant difference between the esophagitis and control groups. Furthermore, if 4% was taken as upper limit of normal, this will include almost all the esophagitis patients and controls. It is concluded that the G/E reflux index based on G/E scintigraphy is of little value in the diagnosis of G/E reflux

Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

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Korsten, M.A.; Rosman, A.S.; Fishbein, S.; Shlein, R.D.; Goldberg, H.E.; Biener, A. (Gastrointestinal Section, Veterans Affairs Medical Center, Bronx, New York (USA))

1991-06-01

OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

Gastroesophageal scintigraphy and endoscopy in the diagnosis of esophageal reflux and esophagitis

Energy Technology Data Exchange (ETDEWEB)

Fung, W.P.; Van der Schaaf, A.; Grieve, J.C.

1985-04-01

The value of gastroesophageal (G/E) scintigraphy in the diagnosis of gastroesophageal reflux was assessed in 51 subjects, who presented with heartburn and had endoscopic evidence of reflux esophagitis. G/E scintigraphy was done using /sup 99m/Tc sulfur-colloid in acidified orange juice. The G/E reflux index was calculated according to previous reports. The mean (+/- SD) G/E reflux index in 18 patients with severe esophagitis and 30 patients with moderate esophagitis were 1.6% (+/- 1.5) and 3.2% (+/- 5.0), respectively. The mean G/E reflux index in 14 control subjects was 2.4% (+/- 1.1). There was no significant difference between the esophagitis and control groups. Furthermore, if 4% was taken as upper limit of normal, this will include almost all the esophagitis patients and controls. It is concluded that the G/E reflux index based on G/E scintigraphy is of little value in the diagnosis of G/E reflux.

Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

International Nuclear Information System (INIS)

Korsten, M.A.; Rosman, A.S.; Fishbein, S.; Shlein, R.D.; Goldberg, H.E.; Biener, A.

1991-01-01

OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency

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

Molecular Diagnostics in Esophageal and Gastric Neoplasms: 2018 Update.

Science.gov (United States)

Zulfiqar, Muhammad; Bluth, Martin H; Bhalla, Amarpreet

2018-06-01

Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Coffee consumption and risk of esophageal cancer incidence: A meta-analysis of epidemiologic studies.

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Zhang, Juan; Zhou, Bin; Hao, Chuanzheng

2018-04-01

In epidemiologic studies, association between coffee consumption and esophageal cancer risk is inconsistent. The aim of tjis study was to evaluate the effect of coffee on esophageal cancer by combining several similar studies. We conducted a meta-analysis for association of coffee intake and esophageal cancer incidence. Eleven studies, including 457,010 participants and 2628 incident cases, were identified. A relative risk (RR, for cohort study) or odds ratio (OR, for case-control study) of heavy coffee drinkers was calculated, compared with light coffee drinkers or non-drinkers. The analysis was also stratified by cancer types (esophageal squamous cell carcinoma and esophageal adenocarcinoma), sex, and geographic region. The summarized OR of having esophageal cancer in heavy coffee drinkers was 0.93 (95% confidence interval [CI]: 0.73-1.12), compared with light coffee drinkers. When stratified by sex, pathologic type of esophageal cancer, and type of epidemiologic study, we did not find any association of coffee consumption and esophageal cancer incidence. However, an inverse association between coffee consumption and incidence of esophageal cancer was found in East Asia participants with OR of 0.64 (95% CI: 0.44-0.83), but not in Euro-America participants (OR = 1.05; 95% CI: 0.81-1.29). There is a protective role of coffee consumption against esophageal cancer in East Asians, but not in Euro-Americans.

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.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

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Woodland, Philip; Lee, Chung; Duraisamy, Yasotha; Duraysami, Yasotha; Farré, Ricard; Dettmar, Peter; Sifrim, Daniel

2013-04-01

Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), Pheartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Science.gov (United States)

Kohli, D R; Schubert, M L; Zfass, A M; Shah, T U

2017-11-01

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking. © 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.

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

Evaluation of esophageal peristalsis in patients with esophageal tumors. Initial experience with cine MR imaging

International Nuclear Information System (INIS)

Koyama, Takashi; Kobayashi, Ari; Hiraga, Akira; Umeoka, Shigeaki; Saga, Tsuneo; Watanabe, Go; Tamai, Ken; Shimada, Yutaka; Togashi, Kaori

2005-01-01

We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR using steady-state free precession (SSFP) sequence and correlated the alteration of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen patients with pathologically proven esophageal tumors, including 12 esophageal cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging with steady precession (trueFISP) sequence, which is one SSFP sequence, after contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images were obtained within 60 s through the plane along the long axis of the esophagus while patients chewed gum. The serial trueFISP images were evaluated for the presence, frequency, speed of progression, and passage of peristalsis through the tumor. The data from cine MRI were compared with clinical symptoms and tumor stages. Peristalsis was clearly identified in all patients. Seven patients with complete interruption of peristalsis had dysphagia; one with partially impaired peristalsis could intake solid foods with discomfort; and two with partially impaired peristalsis and three with preserved peristalsis remained asymptomatic. Patients with complete or partial interruption of peristalsis had Stage T3 or T4 esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct visualization of esophageal peristalsis in relation to esophageal tumors. Complete interruption of peristalsis causes dysphagia, whereas partial interruption of and preserved peristalsis usually do not cause digestive problems. Interruption of peristalsis may indicate impaired muscle function caused by invasion of advanced esophageal cancers. (author)

Distal Esophageal Duplication Cyst with Gastro-Esophageal Reflux Disease: A Rare Association and a Management Challenge.

Science.gov (United States)

Jan, Iftikhar Ahmad; Al Nuaimi, Asma; Al Hamoudi, Basma; Al Naqbi, Khalid; Bilal, Mohammad

2016-02-01

Esophageal duplication cysts are rare congenital abnormalities of the foregut and may be associated with other conditions. Association of esophageal duplication with Gastro-Esophageal Reflux Disease (GERD) has not been reported in children. We are reporting a case of a 16 months baby who had antenatal diagnosis of diaphragmatic hernia. Postnatal CTchest, however, suggested a distal esophageal duplication cyst and a contrast esophagogram showed grade-IV GER. A thoracoscopy in another hospital excluded esophageal duplication at that time. Later, he presented with hematemesis in our department and was re-evaluated. Repeat CTconfirmed a persistent 2.5 x 1.3 cm cyst in distal esophagus. Upper GI endoscopy suggested grade-II esophagitis with a wide patent gastro-esophageal junction. The child was treated with left thoracotomy, excision of the duplication cyst and thoracic fundoplication. He had an uneventful post-operative recovery and is doing well at 6 months follow-up.

Cytogenetic radiosensitivity of G0-lymphocytes of breast and esophageal cancer patients as determined by micronucleus assay

International Nuclear Information System (INIS)

Mozdarani, H.; Mansouri, Z.; Haeri, S.A.

2005-01-01

Enhanced chromosomal radiosensitivity is a feature of many cancer predisposition conditions, indicative of the important role of chromosomal alterations in carcinogenesis. In this study the cytokinesis-blocked micronucleous assay was used to compare the radiosensitivity of blood lymphocytes obtained from Iranian breast or esophageal cancer patients (n=50, n=16; respectively) with that of control individuals (n=40). For each sample, one thousand binucleate lymphocytes were analyzed before and after in vitro exposure to 3 Gy of γ rays. The radiation-induced frequency of micronucleus was significantly higher in the breast cancer group (261/1,000 binucleated cells) than in esophageal cancer group (241/1,000 binucleated cells, P<0.01) or in the control group (240/1,000 binucleated cells, P<0.01). The results indicate that breast cancer patients are more radiosensitive compared to normal healthy individuals or esophageal cancer patients. Increased radiosensitivity could be due to defects in DNA repair genes involved in breast cancer formation. Since patients with esophageal cancer did not show elevated radiosensitivity, it is assumed that the contribution of radiosensitivity-related genes to the development of esophageal cancer may be smaller than the contribution of those genes to breast cancer. (author)