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Sample records for advanced esophageal squamous

  1. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer

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    Tatsuhiro Shibata

    2011-09-01

    Full Text Available Esophageal squamous cancer (ESC is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22% in advanced ESC tumors and ESC cell lines (3/10. The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT.

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

    International Nuclear Information System (INIS)

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

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

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

    2015-09-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

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    Li Peng; Cheng Rui; Zhang Shutian

    2014-01-01

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

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

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    Yong Gao

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

  7. Chemoprevention of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

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

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

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    Hu GF

    2016-07-01

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

  9. Serological identification of tumor antigens of esophageal squamous cell carcinoma.

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    Shimada, Hideaki; Nakashima, Kazue; Ochiai, Takenori; Nabeya, Yoshihiro; Takiguchi, Masaki; Nomura, Fumio; Hiwasa, Takaki

    2005-01-01

    Autoantibodies are often detected in the patients with esophageal cancer. We applied serological analysis of recombinant cDNA expression libraries (SEREX) to a case of esophageal squamous cell carcinoma in order to identify tumor antigens. A cDNA library derived from an esophageal cancer cell line was bacterially expressed and screened for interaction with antibodies in five allogeneic sera of patients with esophageal squamous cell carcinoma. To examine the specific immunoreactivity of the antigens, sera from 16 more patients with esophageal squamous cell carcinoma, 16 patients with gastric cancer, 16 patients with colon cancer, 16 patients with breast cancer and 37 healthy volunteers were screened. We identified 11 independent cDNA clones that potentially encoded esophageal cancer tumor antigens. The identified cDNA clones were SURF1, HOOK2, CENP-F, ZIC2, hCLA-iso, Ki-1/57, enigma, HCA25a, SPK and two EST clones named LOC146223 and AGENCOURT_7565913. The sero-positive rates of antibodies against SURF1 (48%), LOC146223 (38%), HOOK2 (14%) and AGENCOURT_7565913 (14%) were significantly higher in esophageal cancer patients than in healthy controls. At least one of these antibodies was detected in 18 (86%) of 21 sera from esophageal cancer patients. A disease-specific humoral immune response against SURF1, LOC146223, HOOK2 or AGENCOURT_7565913 was observed in most patients with esophageal squamous cell carcinoma. Antibodies against these SEREX antigens may represent a pool of candidates for serum tumor markers of esophageal squamous cell carcinoma. PMID:15586227

  10. Metastatic Esophageal Squamous Cell Carcinoma in the Kidney

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    Sunita Singh

    2014-06-01

    Full Text Available Metastases from esophageal cancers represent only 4.8 per cent of secondary renal tumors. The kidney is known to be the 4th or 5th most common visceral metastasis site of esophageal carcinomas. More than 50% of renal metastases typically show bilateral involvement. Solitary, unilateral renal metastasis is extremely rare. Therefore, the diagnosis of renal metastases is very difficult. We report a case of solitary unilateral renal metastases in an esophageal squamous cell carcinoma in a 66 year old man's autopsy. [J Interdiscipl Histopathol 2014; 2(3.000: 163-166

  11. Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms

    OpenAIRE

    Baeg, Myong Ki; Choi, Myung-Gyu; Jung, Yun Duk; Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Hyung Hun; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang-Woo

    2016-01-01

    Background/Aims Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients. Methods ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 1:3 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of t...

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

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

    2014-01-01

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

  13. 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.

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

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    Kobayashi Noritoshi

    2009-05-01

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

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

    International Nuclear Information System (INIS)

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

  16. Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer: A Supplementary Analysis of JCOG0303.

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    Tsushima, Takahiro; Mizusawa, Junki; Sudo, Kazuki; Honma, Yoshitaka; Kato, Ken; Igaki, Hiroyasu; Tsubosa, Yasuhiro; Shinoda, Masayuki; Nakamura, Kenichi; Fukuda, Haruhiko; Kitagawa, Yuko

    2016-05-01

    Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated.We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models.Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45-171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13-5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation.Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma. PMID:27196482

  17. Identification of human papillomavirus in esophageal squamous papillomas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  18. Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma

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    Murakami Akihiro; Hachiya Takahisa; Kurei Shunsuke; Nishimori Takanori; Yasuraoka Mari; Nakashima-Fujita Kazue; Kuboshima Mari; Shiratori Tooru; Shimada Hideaki; Kagaya Akiko; Tamura Yutaka; Nomura Fumio; Ochiai Takenori; Matsubara Hisahiro; Takiguchi Masaki

    2011-01-01

    Abstract Background Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. Results Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of the...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  20. Esophageal squamous cell carcinoma in six harbor seals (Phoca vitulina spp.).

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    Flower, Jennifer E; Gamble, Kathryn C; Stone, Michael; Lyons, Jeremiah A; Maganti, Rajanikanth J; Tuomi, Pamela A; Olds, June E; Sims, Michele A; Gauger, Phillip; Tuttle, Allison D

    2014-09-01

    Six cases of esophageal squamous cell carcinoma were identified in six captive adult Pacific (Phoca vitulina richardsii; n = 2) and Atlantic (Phoca vitulina concolor; n = 4) harbor seals. These seals presented with intermittent dysphagia, regurgitation, inappetence, and abnormal posturing. Common clinical pathology findings in these seals included azotemia, hyperproteinemia, hyperglobulinemia, and leukocytosis. Gastrointestinal endoscopy commonly revealed an ulcerated mass near the gastroesophageal junction. Each seal was euthanized (n = 3) due to poor prognosis, subsequently died while undergoing an anesthetic procedure (n = 2), or found dead (n = 1). The diagnosis of squamous cell carcinoma was confirmed via biopsy of esophageal mucosa during endoscopy or histopathologic examination of affected tissues after necropsy. On the basis of clinical and postmortem findings, esophageal squamous cell carcinoma should be considered as a differential diagnosis in aged harbor seals exhibiting clinical signs of regurgitation, decreased appetite or anorexia, vomiting, and/or abnormal posturing. PMID:25314830

  1. Efficacy of intensity-modulated radiotherapy for resected thoracic esophageal squamous cell carcinoma

    OpenAIRE

    Zhang, Wencheng; Liu, Xiao; Xiao, Zefen; Wang, Lvhua; Zhang, Hongxing; Chen, Dongfu; Zhou, Zongmei; Feng, Qinfu; Hui, Zhouguang; Liang, Jun; Yin, Weibo; He, Jie

    2015-01-01

    Background Little is known about the clinical use of intensity-modulated radiotherapy (IMRT) in postoperative radiotherapy (PORT) of esophageal cancer; therefore, we retrospectively investigated the clinical value of postoperative IMRT among resected thoracic esophageal squamous cell carcinoma (TESCC) patients. Methods We enrolled a total of 228 patients with resected TESCC who underwent IMRT between January 2004 and June 2009 in the study. PORT was applied via IMRT with a median total dose o...

  2. Solitary renal metastasis of esophageal squamous cell carcinoma mimicking primary renal neoplasm – A case report and literature review

    OpenAIRE

    Chang, Kai-Po; Huang, Chi-Ping; Chang, Han

    2016-01-01

    Solitary renal metastasis of esophageal cancer is rare clinically, with only 14 cases being reported in the literature. The authors here report a case of a 53-year-old man with a metachronous hypopharyngeal and esophageal squamous cell carcinoma who developed a solitary renal metastasis after complete chemoradiotherapy for esophageal cancer, and subsequently received a left nephrectomy. The metastatic esophageal cancer was indistinguishable from primary renal neoplasm in the computed tomograp...

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

    OpenAIRE

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  5. 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, ...

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

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

    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 app...

  7. CT and 18FDG PET/CT findings of esophageal squamous cell papillomatosis: a case report

    International Nuclear Information System (INIS)

    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 [18F] 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 [18F] FDG PET/CT, with a review of the clinical literature

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

    Science.gov (United States)

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

    2011-11-01

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

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

    International Nuclear Information System (INIS)

    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

  10. Esophageal Squamous Cell Carcinoma Recurring as a Solitary Renal Mass

    OpenAIRE

    Lim, Do Hyoung; Im, Young-Hyuck; Ji, Sang Hoon; Park, Byeong-Bae; Oh, Mi Jung; Lee, Jeeyun; Park, Keun Woo; Lee, Se-Hoon; Park, Joon-Oh; Kim, Kihyun; Kim, Won Seog; Jung, Chul Won; Park, Young Suk; Kang, Won Ki; Lee, Mark H

    2004-01-01

    Herein, a case of solitary, unilateral renal metastasis in a patient with curatively resected thoracic esophageal carcinoma, who achieved a pathological complete remission after neoadjuvant concurrent chemoradiotherapy, is reported. The kidney is the 4th or 5th most common visceral metastasis site of a primary esophageal carcinoma. More than 50% of renal metastases typically show bilateral involvement. Solitary, unilateral renal metastasis is extremely rare. Renal metastases from a primary es...

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

    Directory of Open Access Journals (Sweden)

    Wang Junsheng

    2010-07-01

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

  12. Technological advances in radiotherapy for esophageal cancer

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

  14. Novel esophageal squamous cell carcinoma bone metastatic clone isolated by scintigraphy, X ray and micro PET/CT

    OpenAIRE

    Zhao, Bi-Zeng; Cao, Jie; Shao, Jin-chen; Sun, Yan-Bing; Fan, Li-Min; Wu, Chun-Yu; Liang, Sheng; Guo, Bao-Feng; Yang, Guang; Xie, Wen-Hui; Yang, Qing-cheng; Yang, Shun-Fang

    2014-01-01

    AIM: To establish a Chinese esophageal squamous cell carcinoma (ESCC) cell line with high bone metastasis potency using 99mTc-methylene diphosphonate (99mTc-MDP) micro-pinhole scintigraphy, X ray and micro-positron emission tomography/computed tomography (PET/CT) for exploring the mechanism of occurrence and development in esophageal cancer.

  15. Advanced esophageal cancer and esophageal stenosis endoscopic treatment

    International Nuclear Information System (INIS)

    Advanced esophageal cancer (AEC) is diagnosed during those stages in which surgery is possible, it is palliative for disphagia, with high morbimortality.In inoperable or irresectable cases, resorting to alternative treatment such as radiotherapy or endoscopy may palliate dsphagia.Endoscopically it is possible to place a transtumoral nasogastric catheter (NGC) for preoperative nutrition or branchial therapy (intratumoral iridium).It is possible to dilate the tumor and place and indwelling plastic or auto expandable prosthesis or to inject absolute intratumoral alcohol.There is and evaluation of results and morbimortality of personal case material through the retrospective study of 54 patients in whom 120 procedures such as those referred to above were carried out.The series includes 41 men and 13 women (3-1), 79.5% of which were of ages between 61 and 90.Optic fiber endoscopes or video endoscopes, coaxial dilators, hydro-pneumatic balloons, metallic guides and non industrial and autoexpandable plastic prosthesis were used; 34.1% of procedures were performed under used; 34.1% of procedures were performed under radioscopy.Eleven patient (8 for nutritional purposes and 3 for brachiotherapy)form part of Groups 1 and 2 of NGC.Group 3 consist of:dilations of radicular stenosis with or without neopasic recurrence, or neoplasic infiltration of esophagus, 6 patient; Group 4: 14 patients for the purpose of dilation of esophageal neoplasm; Group 5:prosthesis, 12 patients; Group 6: 11 patients with anastomotic stenosis.In patients in Group 1-2-3 solution was achieved.In Group 3 there was 1 perforation.In Group 4, out of 14 patient 13 were dilated.In Group 5 it proved impossible to place prosthesis in 2 patient, (3.7%).The conclusion arrived at is that various endoscopic techniques may palliate disphagia in patient with AEC, collaborate with preoperative nutrition through enteral path, with brachioterapy or by treating post surgical stenosis, with low mortality

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  17. Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma

    OpenAIRE

    Wang, Qifeng; Zhu, Hongxia; Xiao, Zefen; Zhang, Wencheng; Liu, Xiao; Zhang, Xun; He, Jie; Kelin SUN; Wang, Lvhua; Xu, Ningzhi

    2013-01-01

    Background The overall survival of patients with esophageal squamous cell carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based on histological assessment of tumor invasion and lymph node metastasis, but a biomarker with better predictive accuracy could be more useful. Because overexpression of epidermal growth factor receptor (EGFR) has been associated with poor prognosis, this study investigated whether EGFR is an independent prognostic factor for overall survival ...

  18. Prognostic CpG Methylation Biomarkers Identified by Methylation Array in Esophageal Squamous Cell Carcinoma Patients

    OpenAIRE

    Kuo, I-Ying; Chang, Jia-Ming; Jiang, Shih-Sheng; Chen, Chung-Hsin; Chang, I-Shou; Sheu, Bor-Shyang; Lu, Pei-Jung; Chang, Wei-Lun; Lai, Wu-Wei; Wang, Yi-Ching

    2014-01-01

    Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with poor prognosis. We aimed to identify a panel of CpG methylation biomarkers for prognosis prediction of ESCC patients. Methods: Illumina's GoldenGate methylation array, supervised principal components, Kaplan-Meier survival analyses and Cox regression model were conducted on dissected tumor tissues from a training cohort of 40 ESCC patients to identify potential CpG methylation biomarkers. Pyrosequencing quantit...

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  2. MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Min; Hu, Yi; Zhang, Mei-Fang; Luo, Kong-Jia; Xie, Xiu-Ying; Wen, Jing; Fu, Jian-Hua; Yang, Hong

    2016-07-10

    Matrix metalloproteinases play an essential role in the progression of esophageal squamous cell carcinoma (ESCC). Here, we show that MMP1 expression was markedly increased in a majority of ESCC compared with nontumorous tissue. High expressions of MMP1 were closely associated with lymph node metastasis, microvessel density and advanced TNM stage. Kaplan-Meier and multivariate analyses indicated MMP1 as an independent factor for overall survival in two independent cohorts of 613 patients with ESCC. In vitro studies demonstrated that MMP1 overexpression resulted in enhanced cell viability, abilities of colony formation and cell migration. The knockdown of MMP1 in ESCC cells resulted in the opposite phenomenon. Consistently, in vivo data showed that ectopic expression of MMP1 promoted tumor growth and metastasis. Further study revealed that MMP1 facilitated ESCC through the activation of the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway by LY294002 significantly attenuated MMP1-mediated cell proliferation and migration. Taken together, our data suggest that MMP1 functions as an oncogene and serves as a prognostic biomarker and a potential therapeutic target in ESCC. PMID:27130665

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

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    Sadat Noori

    2012-06-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    International Nuclear Information System (INIS)

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

  6. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ma, Kai; Cao, Baoping; Guo, Mingzhou

    2016-01-01

    Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smoking and alcohol consumption are two major risk factors for ESCC, and both tobacco and alcohol were found to induce methylation changes in ESCC. Growing evidence demonstrates that aberrant epigenetic changes play important roles in the multiple-step processes of carcinogenesis and tumor progression. DNA methylation may occur in the key components of cancer-related signaling pathways. Aberrant DNA methylation affects genes involved in cell cycle, DNA damage repair, Wnt, TGF-β, and NF-κB signaling pathways, including P16, MGMT, SFRP2, DACH1, and ZNF382. Certain genes methylated in precursor lesions of the esophagus demonstrate that DNA methylation may serve as esophageal cancer early detection marker, such as methylation of HIN1, TFPI-2, DACH1, and SOX17. CHFR methylation is a late stage event in ESCC and is a sensitive marker for taxanes in human ESCC. FHIT methylation is associated with poor prognosis in ESCC. Aberrant DNA methylation changes may serve as diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC will help to better understand its mechanisms and develop improved therapies. PMID:27110300

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

    Directory of Open Access Journals (Sweden)

    Yan Wusheng

    2012-01-01

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

  8. Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Murakami Akihiro

    2011-06-01

    Full Text Available Abstract Background Diagnosis of esophageal squamous cell carcinoma (SCC may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. Results Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a. Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA. The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. Conclusions We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.

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

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    Glutathione S-transferase pi (GST pi) is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and p = 0.004, respectively) and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively). In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore

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

    Directory of Open Access Journals (Sweden)

    Zhang B

    2016-06-01

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

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

    International Nuclear Information System (INIS)

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

  16. Multistage resection of esophageal squamous cell cancer of the cardia – successful despite complications

    Science.gov (United States)

    Ptach, Anna; Sadowski, Andrzej; Chruścicka, Iwona; Pęksa, Rafał; Rak, Piotr

    2015-01-01

    Surgery is the treatment of choice for squamous cell esophageal cancer. Complete resection of the esophagus with reconstruction of the digestive tract is performed for tumors located in the chest or cardia. The aim of the report is to present the case of a complete esophageal and gastric resection complicated by colon graft necrosis. The patient was a 45-year-old woman diagnosed with cancer of the cardia infiltrating the distal section of the esophagus and the body and fundus of the stomach. The initial surgical procedure included the opening of three body cavities followed by resection of the thoracic esophagus, stomach, and a portion of the left hepatic lobe. Right colon interposition was performed to restore digestive tract continuity. On the 8th day, a leak was observed in the esophagointestinal anastomosis. Management consisted in two surgical procedures, one of which ended in the removal of the colon patch. The fourth and final procedure was conducted after 10 months. PMID:26702285

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    OpenAIRE

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

    2013-01-01

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

  20. An integrated analysis of the effects of microRNA and mRNA on esophageal squamous cell carcinoma

    OpenAIRE

    Yang, Yong; Li, Dianbo; Yang, Yang; Jiang, Gening

    2015-01-01

    Esophageal squamous cell cancer (ESCC) is an aggressive type of cancer with poor prognosis and leading to decreased quality of life. The identification of patients at increased risk of esophageal squamous cell cancer may improve current understanding of the role of micro (mi)RNA in tumorigenesis, since the miRNA pattern of these patients may be associated with tumorigenesis. In the present study, the miRNA and mRNA expression profiles of ESCC tissue samples and adjacent normal control tissue ...

  1. Novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase overexpression

    OpenAIRE

    Kikuchi, Osamu; Ohashi, Shinya; Nakai, Yukie; Nakagawa, Shunsaku; Matsuoka, Kazuaki; Kobunai, Takashi; Takechi, Teiji; Amanuma, Yusuke; Yoshioka, Masahiro; Ida, Tomomi; Yamamoto, Yoshihiro; Okuno, Yasushi; Miyamoto, Shin’ichi; Nakagawa, Hiroshi; Matsubara, Kazuo

    2015-01-01

    5-Fluorouracil (5-FU) is a key drug for the treatment of esophageal squamous cell carcinoma (ESCC); however, resistance to it remains a critical limitation to its clinical use. To clarify the mechanisms of 5-FU resistance of ESCC, we originally established 5-FU-resistant ESCC cells, TE-5R, by step-wise treatment with continuously increasing concentrations of 5-FU. The half maximal inhibitory concentration of 5-FU showed that TE-5R cells were 15.6-fold more resistant to 5-FU in comparison with...

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

    OpenAIRE

    Peng-Cheng Chen; Ji-Feng Feng

    2016-01-01

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

  3. Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China

    OpenAIRE

    Hu, Nan; Wang, Chaoyu; Ng, David; Clifford, Robert; Yang, Howard H.; Tang, Ze-Zhong; Wang, Quan-Hong; Han, Xiao-You; Giffen, Carol; Goldstein, Alisa M; Taylor, Philip R.; Lee, Maxwell P.

    2009-01-01

    Genomic instability plays an important role in most human cancers. To characterize genomic instability in esophageal squamous cell carcinoma (ESCC), we examined loss of heterozygosity (LOH), copy number (CN) loss, CN gain, and gene expression using the Affymetrix GeneChip Human Mapping 500K (n=30 cases) and Human U133A (n=17 cases) arrays in ESCC cases from a high-risk region of China. We found that genomic instability measures varied widely among cases and separated them into two groups: a h...

  4. Noncoding RNA Expression Aberration Is Associated with Cancer Progression and Is a Potential Biomarker in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hidetaka Sugihara

    2015-11-01

    Full Text Available Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs function as key epigenetic regulators of gene expression and are implicated in various physiological processes. Unambiguous evidence indicates that dysregulation of ncRNAs is deeply implicated in carcinogenesis, cancer progression and metastases of various cancers, including ESCC. The current review summarizes recent findings on the ncRNA-mediated mechanisms underlying the characteristic behaviors of ESCC that will help support the development of biomarkers and the design of novel therapeutic strategies.

  5. Endoscopic palliation of advanced esophageal cancer

    OpenAIRE

    Mocanu, A.; Bârla, R; P. Hoara; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the num...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Joseph Chok Yan Ip

    2015-01-01

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

  10. Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms.

    Science.gov (United States)

    Zhai, Ya-Qi; Li, Hui-Kai; Linghu, En-Qiang

    2016-01-01

    Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD. PMID:26755889

  11. Prognosis of esophageal squamous cell carcinoma treated by endoscopic submucosal dissection

    International Nuclear Information System (INIS)

    One hundred and fifty eight patients who had esophageal squamous cell carcinoma (SCC) were treated by endoscopic submucosal dissection (ESD) from Jan. 2,000 to Dec. 2006. The invasion depth was divided as epithelium (EP), Lamina propria mucosa (LPM), muscularis mucosa (MM) and submuosal layer. When the depth of submucosal invasion was 200 micrometers or less, the invasion depth was defined as SM1. In this study, out of 158 patients 28 patients had MM SCC, and 12 patients had SM1 SCC. The additional therapies such as Esophagectomy or Chemo Radio Therapy (CRT) were recommended to the patients, when lymphatic permeation was found. Among the patients who had MM SCC, 5 patients had lymphatic permeation. Among the patients who had SM1 SCC, 4 patients had lymphatic permeation. 2 MM and 2 SM1 patients were treated by CRT and the other 5 patients who had lymphatic permeation refused the additional therapy because of other diseases. All 4 patients who were treated by CRT are alive, but lymph node metastasis was found in 2 of the patients who refused CRT. One died of esophageal SCC, and one died of another disease. No lymph node metastasis was found in 23 patients who had MM without lymphatic permeation, and 8 patients who had SM1 without lymphatic permeation. According to our data, the indication of esophageal ESD could be expanded for MM or SM1 SCC without lymphatic permeation. (author)

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Concurrent Chemoradiotherapy in Locally Advanced Esophageal Cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

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    Fabrice Paganin

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

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    Wei Ma

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

    AIM:To investigate the role of cytochrome P450(CYP)in the carcinogenesis of squamous-cell carcinoma(SCC)in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls.METHODS:mRNA expression of CYP2E1,CYP2C,CYP3A4,and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC(n = 21)and in controls(n = 10).Protein levels of CYP2E1,CYP2C8,CYP3A4,and CYP3A5 were measured by Western blot.RESULTS:Within the group of SCC patients,mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue(-39% and -74%,respectively,P < 0.05)than in normal tissue.Similar results were found in CYP3A4 protein levels.Between groups,CYP3A4,CYP3A5,and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients(4.8-,2.9-,and 1.9-fold elevation,P < 0.05)than in controls.In contrast,CYP2E1 protein levels were significantly higher in controls than in SCC patients (+46%,P < 0.05).CONCLUSION:Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue (e.g.CYP2C8,CYP3A4,CYP3A5,and CYP2E1)between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.

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

    Institute of Scientific and Technical Information of China (English)

    Baodong Liu; Zongjun Dong; Xiuyi Zhi; Qingsheng Xu

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    纪爱芳

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  5. Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

    Science.gov (United States)

    Yang, Xi; Zhu, Hongcheng; Qin, Qin; Yang, Yuehua; Yang, Yan; Cheng, Hongyan; Sun, Xinchen

    2015-01-01

    This study was designed to identify candidate single-nucleotide polymorphisms (SNPs) that may affect the susceptibility to esophageal squamous cell carcinoma (ESCC) and elucidate their potential mechanisms to generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset for ESCC, which included 453,852 SNPs from 1898 ESCC patients and 2100 control subjects of Chinese population, was reviewed. The identify candidate causal SNPs and pathways (ICSNPathway) analysis identified seven candidate SNPs, five genes, and seven pathways, which together revealed seven hypothetical biological mechanisms. The three strongest hypothetical biological mechanisms were as follows: rs4135113 → TDG → BASE EXCISION REPAIR; rs1800450 → MBL2 → MONOSACCHARIDE BINDING; and rs3769823 → CASP8 → d4gdiPathway. The GWAS dataset was evaluated using the ICSNPathway, which showed seven candidate SNPs, five genes, and seven pathways that may contribute to the susceptibility of patients to ESCC. PMID:25431829

  6. Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wang, Cong; Li, Qingbao; Liu, Fang; Chen, Xuan; Nesa, Effat Un; Guan, Shanghui; Liu, Bowen; Han, Lihui; Tan, Bingxu; Wang, Ding; Chen, Pengxiang; Liu, Xiaoyue; Zhang, Han; Sun, Ying; Cheng, Yufeng

    2016-09-01

    We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC. PMID:27152453

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

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    Hong-hua Peng

    2012-01-01

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

  8. Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts.

    Science.gov (United States)

    Kretschmer, Inga; Freudenberger, Till; Twarock, Sören; Yamaguchi, Yu; Grandoch, Maria; Fischer, Jens W

    2016-02-19

    The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less α-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4(+) but not CD8(+) cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response. PMID:26699196

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

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    Sheng-Ta Tsai

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

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

    2015-01-01

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

  14. Prognosis of patients with esophageal squamous cell carcinoma after esophagectomy using the log odds of positive lymph nodes

    OpenAIRE

    Wu, San-Gang; Sun, Jia-Yuan; Yang, Li-Chao; Zhou, Juan; Li, Feng-Yan; Li, Qun; Lin, Huan-xin; Lin, Qin; He, Zhen-Yu

    2015-01-01

    To compare the log odds of positive lymph nodes (LODDS) with the number of positive lymph nodes (pN), lymph node ratio (LNR), removed lymph node (RLN) count, and negative lymph node (NLN) count in determining the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. The records of patients with ESCC who received esophagectomy were retrospectively reviewed. The log-rank test was used to compare curves for overall survival (OS), and Cox regression analysis wa...

  15. Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma

    OpenAIRE

    Tang Ze-Zong; Hu Nan; McKenney Keith; Armistead David; Carrera Ana; Huppi Konrad; Abnet Christian C; Taylor Philip R; Dawsey Sanford M

    2004-01-01

    Abstract Background North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. Methods We used DNA sam...

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  18. High DEPTOR expression correlates with poor prognosis in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Liu NB

    2015-11-01

    Full Text Available Nan-bo Liu,1,* Jun-hua Zhang,2,* Yu-fan Liu,1,* Jun Li,3,* Zhen-zhong Zhang,1 Ji-wei Li,1 Wen-yue Liu,1 Chen Huang,1,4 Tao Shen,5 Cheng-wei Gu,6 Dong-yun Gao,7 Xia Wu,8 Xu Wu1 1Department of Thoracic Surgery, 2Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 3Department of Thoracic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 4Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, 5Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, 6Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 7Department of Oncology, Dongtai People’s Hospital, Dongtai, 8Department of Breast Cancer, Affiliated Hospital, Academy of Military Medical Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: The disheveled, Egl-10, and pleckstrin (DEP domain containing mammalian target of rapamycin (mTOR-interacting protein (DEPTOR is a binding protein containing mTOR complex 1 (mTORC1, mTOR complex 2 (mTORC2, and an endogenous mTOR inhibitor. DEPTOR shows abnormal expressions in numerous types of solid tumors. However, how DEPTOR is expressed in esophageal squamous cell carcinoma (ESCC remains elusive. Methods: The expression of DEPTOR in 220 cases of ESCC and non-cancerous adjacent tissues was detected by immunohistochemistry. DEPTOR levels in ESCC and paired normal tissue were quantified using reverse transcription-polymerase chain reaction and Western blot analysis to verify the immunohistochemical results. The relationship between DEPTOR expression and the clinicopathological features of ESCC was analyzed based on the results of immunohistochemistry. Finally, we analyzed the relationship between DEPTOR expression and the prognosis of patients with ESCC. Results: Immunohistochemical staining showed that the expression rate of DEPTOR in ESCC tissues was significantly increased

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

    International Nuclear Information System (INIS)

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

  20. Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma

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    Tang Ze-Zong

    2004-07-01

    Full Text Available Abstract Background North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. Methods We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion. Results Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17–55% tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1 and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples. Conclusions Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies.

  1. [The expression and significance of hnRNPD in esophageal squamous cell carcinoma cells].

    Science.gov (United States)

    Geng, Yangyang; Zhang, Lulu; Xu, Miaomiao; Sheng, Wenjiong; Dong, Aijing; Cao, Jinming; Cao, Jianping

    2015-12-01

    Objective To investigate the expression of heterogeneous nuclear ribonucleoprotein D (hnRNPD) in esophageal squamous cell carcinoma (ESCC) tissues and the relationship between hnRNPD expression and the clinicopathological features of ESCC, and to study the effect of down-regulated hnRNPD on the proliferation of ESCC cells and explore its potential mechanism. Methods The expression of hnRNPD protein in ESCC tissues and the normal paracancerous tissues were detected by immunohistochemistry. The siRNA-hnRNPD was transfected into ESCC cells and the silence effect was verified by Western blotting. MTT assay and clone formation assay were used to evaluate the proliferation of ESCC cells after down-regulation of hnRNPD genes. Cell apoptosis was examined by annexin V-phycoerythrin/7-aminoactinomycin D (annexin V-PE/7-AAD) staining and flow cytometry. Results The expression of hnRNPD protein in ESCC tissues was significantly higher than that of the normal paracancerous tissues, and the expression was closely related with neoplasm staging. Down-regulation of hnRNPD inhibited the proliferation and clonality of ESCC cells. Compared with the control group, siRNA targeting hnRNPD significantly promoted cell apoptosis. Conclusion Down-regulation of hnRNPD inhibits the proliferation of ESCC cells by promoting cell apoptosis. PMID:26648300

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

    Institute of Scientific and Technical Information of China (English)

    Tadahiro Nozoe; Yoshihiko Maehara; Keizo Sugimachi

    2005-01-01

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

  3. 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.

  4. Increased miRNA-22 expression sensitizes esophageal squamous cell carcinoma to irradiation

    International Nuclear Information System (INIS)

    miRNA-22 was previously reported to be a tumor suppressor. The aim of this study was to explore the expression and function of miRNA-22 in esophageal squamous cell carcinoma (ESCC). Expression of miRNA-22 in 100 ESCC tissues was examined by q-PCR. The correlation between miRNA-22 level and clinicopathological features was analyzed using SPSS16.0 statistical software. Moreover, the effect of miRNA-22 expression on radiosensitivity of ESCC cells was examined. miRNA-22 expression decreased in ESCC tissues, and statistical analyses showed that the expression of miRNA-22 was associated with the stage of clinical classification. No correlation was found between miRNA-22 expression and the overall survival of ESCC patients. However, significant positive correlation was found between miRNA-22 expression and the survival of patients who received radiotherapy (P < 0.05). Increased expression of miRNA-22 sensitized ESCC cells to γ-ray radiation and promoted the apoptosis of ESCC cells induced by γ-ray radiation. Increased expression level of miRNA-22 had effects on Rad51 expression after irradiation. These results demonstrate for the first time that decreased miRNA-22 expression correlates with increased radiotherapy resistance of ESCC, and that this effect is mediated, at least in part, by the Rad51 pathway

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

    Science.gov (United States)

    Meng, Xiangrui; Chen, Xiaoqi; Lu, Peng; Ma, Wang; Yue, Dongli; Song, Lijie; Fan, Qingxia

    2016-05-13

    Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies in the gastrointestinal tract. Emerging studies have indicated that microRNAs (miRNAs) are strongly implicated in the development and progression of ESCC. Here, we focused on the function and the underlying molecular mechanism of miR-202 in ESCC. The results showed that miR-202 was significantly down-regulated in ESCC tissues and cell lines. Overexpression of miR-202 in ECa-109 and KYSE-510 cells markedly suppressed cell proliferation and cell migration, and induced cell apoptosis. Furthermore, laminin α1 (LAMA1) expression was frequently positive in ESCC tissues and inversely correlated with miR-202 expression. Then we demonstrated that miR-202 targeted 3'-untranslated region (UTR) of LAMA1 and inhibited its protein expression. Additionally, LAMA1 overexpression rescued the proliferation inhibition and cell apoptosis elevation induced by miR-202. MiR-202 also inhibited the protein expression of p-FAK and p-Akt, which were all reversed by LAMA1 overexpression. Taken together, these findings suggest that miR-202 may function as a novel tumor suppressor in ESCC by repressing cell proliferation and migration, and its biological effects may attribute the inhibition of LAMA1-mediated FAK-PI3K-Akt signaling. PMID:27045085

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

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    He Zu-gen

    2006-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    汤小伟

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  12. Analysis of survival prediction value using modification 7th UICC esophageal cancer staging system for esophageal squamous cell carcinoma with preoperative radiotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate the value of the international union against cancer (UICC)stage,pathologic complete response (pCR), and the estimated treatment response as various means for prognostic stratifying patients after surgery in patients with squamous cell carcinoma of the esophagus who received preoperative radiotherapy (RT). Methods: A retrospective review was performed on 311 patients with esophageal squamous cell carcinoma who received RT before the esophagectomy. Data collected included the demographics, the RT details, the pathologic findings,and the survival. Prognostic survival was analyzed by Kaplan-Meier method and Logrank test. Results: The follow-up rate was 96.5%, 89 and 43 patients, respectively were followed up more than 5 and 10 years. In univariate analysis, residual disease and the number of positive lymph node were predictors of the overall survival (T-pCR, χ2 =11.53, P =0.001; 0, 1 -3, ≥4, χ2=42.13, P=0.000, respectively). Further study found the 7th stage system of UICC cannot (can or cannot) entirely predict the prognosis of this group of patients. If categorizing the stages of their lymph nodes into three groups: N0 (0), N1 (1-3) and N2 (≥4)), and the modified UICC system can accurately distinguish ypStage I with ypStage II (T0-3 N1 M0 + T3 N0 M0) (χ2 =11.15, P =0.001) and ypStage II with ypStage III (T4 N0-1 M0 and T0-3 N2 M0) (χ2 =23.39, P =0.000). Conclusions: The pathologic post-radiotherapy T stage and the number of positive lymph node are predictors for esophageal squamous cell carcinoma receiving preoperative radiotherapy. The modified UICC stage system can be a better survival predictor than the 7th UICC stage system. (authors)

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

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    Peng Zhang

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

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

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    Luo J

    2014-09-01

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

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

    KAUST Repository

    Essack, Magbubah

    2012-10-26

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

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

    OpenAIRE

    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 complete...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Ilyar; Sheyhidin

    2010-01-01

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

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

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    Yan Li

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

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

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    Zhang Shaoyan

    2011-05-01

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

  1. Prognostic factor analysis of preoperative radiotherapy for esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the prognostic factors affecting preoperative radiotherapy for esophageal squamous cell carcinoma (ESCC). Methods: Three hundred and eleven patients with ESCC undergone preoperative radiotherapy were retrospectively analyzed. Detailed clinical and histological materials and radiotherapy and surgery records were examined. Univariate and multivariate analyses were used to study the factors affecting prognosis. Results: The follow-up rate was 96.5%, 123 and 86 patients,respectively were followed up more than 3 and 5 years. The 5-year survival rates of patients without (106 patients) and with (205 patients) tumorremnants in primary locations after radiotherapy were 43.2% and 23. 2%, respectively (χ2 = 11.53, P =0.001). The 5-year survival rates of 129 patients with primary tumor remnants but without lymph node metastasis in the T1 +T2 phase, the T3 phase and the T4 phase were 42%, 30% and 16%, respectively (χ2 = 20.20, P = 0.000). The 5-year survival rates of patients without lymph node metastasis (211 patients) and those whose lymph node metastases numbered less than 4 (95 patients)was 38.3% and 13%, respectively; the 3-year survival rate of patients whose lymph node metastases numbered greater than 4 was 14%, and the 5-year survival rate was 0 (χ2 = 42.13, P= 0.000). In multivariate analysis, the local region with or without residual cancer, the depth of tumor infiltration, the status of the lymph node, the number of lymph node metastases, and gender were independent prognostic factors (χ2 = 32.20, 36.33, 18.24, 4.60, 6.21, P = 0.000, 0.000, 0.000, 0.032, 0.013, respectively). Conclusions: Histological T and N staging following preoperative radiotherapy for ESCC and numbers of lymph node metastases were critical factors affecting prognosis and could be used for better prediction of its prognosis. (authors)

  2. Microarray expression profile analysis of aberrant long non-coding RNAs in esophageal squamous cell carcinoma.

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    Yao, Juan; Huang, Jun-Xing; Lin, Mei; Wu, Zheng-Dong; Yu, Hong; Wang, Peng-Cheng; Ye, Jun; Chen, Ping; Wu, Jing; Zhao, Guo-Jun

    2016-06-01

    Increasing evidence indicates that long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the function and regulatory mechanism of lncRNAs are still unclear in esophageal squamous cell carcinoma (ESCC). To address this challenge, we screened lncRNAs expression profiles in 3 pairs of ESCC and matched non-cancerous tissues by microarray assay and identified the relationship between lncRNAs expression in ESCC tissue and clinicopathological characteristics and prognosis of patients with ESCC. We found 182 lncRNAs that were significantly differently expressed in ESCC tissues versus the matched non-cancerous tissues. Gene ontology and pathway analysis results suggested that the primary biological processes of these genes were involved in extracellular matrix, immune responses, cell differentiation and cell proliferation. Through cis and trans analyzing, we found 4 lncRNAs (ENST00000480669, NONHSAT104436, NONHSAT126998 and NONHSAT112918) may play important roles in tumorigenesis of ESCC. The four lncRNAs were checked in 73 patients with ESCC. The results showed that they mainly related to tumor metastasis. Kaplan-Meier survival analysis showed that high expression of NONHSAT104436, NONHSAT126998 and low expression of ENST00000480669 were related to poor 3-year overall survival (P=0.003, 0.032 and 0.040, respectively). Multivariate analysis showed that NONHSAT104436 was an independent prognostic factor (P=0.017). Thus we concluded that, lncRNAs showed differently expression patterns in ESCC versus matched non-cancerous tissues, and aberrantly expressed lncRNA may play important roles in ESCC development and progression. Interestingly, the overexpression of NONHSAT104436 was tightly correlated with distant metastasis and, poor survival rate, which might indicate that NONHSAT104436 might play a very important part in ESCC tumor progression. PMID:27035335

  3. Genomic imbalances in esophageal squamous cell carcinoma identified by molecular cytogenetic techniques

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    Marilanda Ferreira Bellini

    2010-01-01

    Full Text Available This review summarizes the chromosomal changes detected by molecular cytogenetic approaches in esophageal squamous cell carcinoma (ESCC, the ninth most common malignancy in the world. Whole genome analyses of ESCC cell lines and tumors indicated that the most frequent genomic gains occurred at 1, 2q, 3q, 5p, 6p, 7, 8q, 9q, 11q, 12p, 14q, 15q, 16, 17, 18p, 19q, 20q, 22q and X, with focal amplifications at 1q32, 2p16-22, 3q25-28, 5p13-15.3, 7p12-22, 7q21-22, 8q23-24.2, 9q34, 10q21, 11p11.2, 11q13, 13q32, 14q13-14, 14q21, 14q31-32, 15q22-26, 17p11.2, 18p11.2-11.3 and 20p11.2. Recurrent losses involved 3p, 4, 5q, 6q, 7q, 8p, 9, 10p, 12p, 13, 14p, 15p, 18, 19p, 20, 22, Xp and Y. Gains at 5p and 7q, and deletions at 4p, 9p, and 11q were significant prognostic factors for patients with ESCC. Gains at 6p and 20p, and losses at 10p and 10q were the most significant imbalances, both in primary carcinoma and in metastases, which suggested that these regions may harbor oncogenes and tumor suppressor genes. Gains at 12p and losses at 3p may be associated with poor relapse-free survival. The clinical applicability of these changes as markers for the diagnosis and prognosis of ESCC, or as molecular targets for personalized therapy should be evaluated.

  4. 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.

  5. 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.

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

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    Behnoush Abedi-Ardekani

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

  7. Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Thrombospondin1 (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis. The purpose of this study is to explore the expression and prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC). We used immunohistochemistry and western blotting to examine the expression status of THBS1, Cyr61 and CTGF in ESCC. Correlations of THBS1, Cyr61 and CTGF over-expressions with various clinicopathologic factors were also determined by using the Chi-square test or Fisher's exact probability test. Survival analysis was assessed by the Kaplan-Meier analysis and the log-rank test. Relative risk was evaluated by the multivariate Cox proportional hazards model. THBS1, Cyr61 and CTGF were all over-expressed in ESCC. THBS1 over-expression was significantly associated with TNM stage (P = 0.029) and regional lymph node involvement (P = 0.026). Kaplan-Meier survival analysis showed that over-expression of THBS1, Cyr61 or CTGF was related to poor survival of ESCC patients (P = 0.042, P = 0.020, P = 0.018, respectively). Multivariate Cox analysis demonstrated that Cyr61 and CTGF were independent factors in prognosis of ESCC. Cyr61, CTGF and THBS1 were all over-expressed in ESCC and might be new molecular markers to predict the prognosis of ESCC patients

  8. Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma.

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    Cheng, Caixia; Zhou, Yong; Li, Hongyi; Xiong, Teng; Li, Shuaicheng; Bi, Yanghui; Kong, Pengzhou; Wang, Fang; Cui, Heyang; Li, Yaoping; Fang, Xiaodong; Yan, Ting; Li, Yike; Wang, Juan; Yang, Bin; Zhang, Ling; Jia, Zhiwu; Song, Bin; Hu, Xiaoling; Yang, Jie; Qiu, Haile; Zhang, Gehong; Liu, Jing; Xu, Enwei; Shi, Ruyi; Zhang, Yanyan; Liu, Haiyan; He, Chanting; Zhao, Zhenxiang; Qian, Yu; Rong, Ruizhou; Han, Zhiwei; Zhang, Yanlin; Luo, Wen; Wang, Jiaqian; Peng, Shaoliang; Yang, Xukui; Li, Xiangchun; Li, Lin; Fang, Hu; Liu, Xingmin; Ma, Li; Chen, Yunqing; Guo, Shiping; Chen, Xing; Xi, Yanfeng; Li, Guodong; Liang, Jianfang; Yang, Xiaofeng; Guo, Jiansheng; Jia, JunMei; Li, Qingshan; Cheng, Xiaolong; Zhan, Qimin; Cui, Yongping

    2016-02-01

    Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs. PMID:26833333

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

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

    2006-01-01

    AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC)specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS: We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5+/GP6+primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16INK4A protein immunostaining of all the specimens was conducted.RESULTS: HPV was detected in 21 ESCC specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 (without statistical significance),but a significantly lower prevalence of HPV-18 than in Colombian cases (P = 0.011) even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC.HPV-16 genome was more frequently detected in p16positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION: HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

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

    International Nuclear Information System (INIS)

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

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

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

    2012-01-01

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

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

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    Fumiko Sunada; Masayuki Itabashi; Hisanao Ohkura; Toshiyuki Okumura

    2005-01-01

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

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

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    Jin Huang

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

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

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    Objective: To determine the extent of postoperative prophylactic radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma. Should the entire mediastinum (M), bilateral supraclavicular areas(S) and the left gastric area(L) be all included in the irradiation field. Methods The clinical data of 204 such patients treated from 1996 through 1999 were retrospectively reviewed. They were classified into four groups: group A, 26 patients given irradiation to the mediastinum M alone; group B, 139 patients given irradiation to the mediastinum and bilateral supraclavicular areas M + S; group C, 10 patients irradiation to the mediastinum plus left gastric area M + L; and group D, 29 patients irradiation to all these three areas ( M + S + L). The overall and disease-free survival rates were calculated using the Kaplan- Meier method and comparison of these groups was done with the Logrank test. Prognostic variables were entered into a Cox regression model controlling the age, gender, length, site, pT, pN, and treatment received. Results: The 1-, 3- and 5-year overall and disease-free survival rates of all 204 patients were 83.8%, 53.2%, 34.1% and 77.8%, 51.6%, 33.8% , respectively. The 5-year disease-free survival rates for patients in group A, group B, group C, and group D were 36.3%, 30.7%, 40.0% and 43.6% (χ2 = 3.05, P=0.385), respectively. Multivariate analysis showed that the pT and pN were independent risk factors for disease-free survival rate, whereas treatment arm gave no significant difference (χ2=2.77, P=0.096). None of the 43 patents without irradiation to the L had abdominal lymph node metastasis from lesions in the upper and upper-middle third (located middle third but invasion to the upper third) thoracic esophagus. The data of supraclavicular lymph node metastasis between patients with and without irradiation showed that S in lesion in the lower and middle-lower third (located middle third but invasion to the lower third) thoracic

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

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

    2016-04-15

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

  16. Multimodality approach for locally advanced esophageal cancer

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    Khaldoun Almhanna; Jonathan R Strosberg

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Objective: To analyze the application value of diffusion-weighted magnetic resonance imaging (DWMRI) in gross tumor volume (GTV) delineation of esophageal squamous cell carcinoma (SCC). Methods: Twenty-nine patients with esophageal SCC treated with radical surgery were analyzed. Routine CT scan, MRI T2-weighted and DWMRI were employed before surgery; diffusion-sensitive gradient b-values were taken 400, 600 and 800 s/mm2. GTVs were delineated using CT, MRI T2-weighted images and DWMRI under different b-value images. The length of GTVs measured under different images was compared with the pathological length and confirm the most accurate imaging condition. Use radiotherapy planning system to fuse DWMRI images and CT images to investigate the possibility of delineate GTVs on fused images. Results: The difference of GTV length value between CT, T2 WI images and specimen was 3.36 mm and 2.84 mm. When b =400,600 and 800 s/mm2, the difference between GTV length value on the DWMRI images and on specimen was 0.47 mm, -0.47 mm and - 1.53 mm; the correlation coefficient of the measuring esophageal lengths on DWMRI images and the pathological lengths was 0.928, 0.927 and 0.938. DWMRI images and CT images could fuse accurately on radiotherapy planning system. GTV margin could.show clearly on fused images. Conclusions: DWMRI images can display the esophageal carcinoma lengths and margin accurately. When DWMRI images fused with CT images, GTV margin could show clearly,it can be used to delineate GTV accurately. (authors)

  19. Molecular aspects of esophageal squamous cell carcinoma carcinogenesis Aspectos moleculares da carcinogênese do carcinoma epidermóide do esôfago

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    Dárcio Matenhauer Lehrbach

    2003-12-01

    Full Text Available BACKGROUND: The development of human esophageal cancer is a multistep, progressive process. An early indicator of this process is an increased proliferation of esophageal epithelial cells morphologically including basal cell hyperplasia, dysplasia, carcinoma in situ and advanced esophageal squamous cell carcinoma. The process of tumorigenesis at cellular level is related to disorders of the control of cell proliferation and differentiation and controlled cell death (apoptosis. Most of cancer cells contain genetic alterations related to the control of these processes, including transcription factors and apoptosis related proteins. AIM: In this review, the current knowledge of the genetic profile of this subtype of esophageal tumor is discussed, focusing on the potential of the development of novel tools for clinical management of esophageal squamous cell carcinoma. CONCLUSIONS: The advances in the field of molecular biology have let us to deeper our knowledge of the process of carcinogenesis of esophagus. Ideally, this knowledge should be translated in benefits for patients suffering from cancer. Thus, better understanding of molecular alterations during carcinogenesis is expected to improve tumor control and prevention and also may lead to better disease management.RACIONAL: O desenvolvimento do câncer de esôfago humano é um processo progressivo de diversas etapas. Um indicador precoce deste processo é o aumento na proliferação das células epiteliais esofágicas, incluindo alterações morfológicas, como hiperplasia das células basais, displasia, carcinoma in situ e carcinoma avançado de células escamosas do esôfago. Ao nível celular, o processo de carcinogênese está relacionado com alterações no controle de proliferação celular, diferenciação e morte celular programada (apoptose. A maioria das células tumorais contém alterações genéticas que se relacionam com o controle desses processos, incluindo fatores de transcri

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    Zhang Jichang; Zhang Lijian; Wang Yanmeng; Li Wei

    1998-01-01

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

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

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    Song Zhengbo

    2012-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-12-01

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

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

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    Lihong Yin

    2013-04-01

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

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

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    Tang Hong

    2011-02-01

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

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

    International Nuclear Information System (INIS)

    By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC. The mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells. We found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54%) and protein level (121/207, 58.5%), which was significantly associated with the lymph node metastasis and advanced TNM stage (P < 0.01). Functional studies showed that GPR39 has a strong tumorigenic ability. Introduction of GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells. The present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC

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

    Science.gov (United States)

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

    2015-01-01

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

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

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    Jing Liu

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

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

    Science.gov (United States)

    Thépot, Amélie; Hautefeuille, Agnès; Cros, Marie-Pierre; Abedi-Ardekani, Behnoush; Pétré, Aurélia; Damour, Odile; Krutovskikh, Vladimir; Hainaut, Pierre

    2010-11-01

    TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of DeltaNp63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA in ESCC cell lines resulted in a similar shift, characterized by increased expression of component of tight junctions, decreased cell-to-cell communication and downregulation of cell proliferation. These results indicate that DeltaNp63 may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion patterns compatible with cell proliferation. PMID:20127860

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

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    Wu Xianhua

    2012-08-01

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

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

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    Shi Y

    2013-05-01

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

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

    OpenAIRE

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

    2006-01-01

    Abstract Background Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and fo...

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

    OpenAIRE

    Wang, Qifeng; Shufei YU; Xiao, Zefen; Liu, Xiao; Zhang, Wencheng; Zhang, Xun; He, Jie; Kelin SUN; Xu, Ting; Feng, Qinfu; Zhou, Zongmei; Wang, Lvhua; Yin, Weibo

    2015-01-01

    Objective To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Patients and methods Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of resi...

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

    OpenAIRE

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

    2016-01-01

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

  17. Recent advancement of therapeutic endoscopy in the esophageal benign diseases.

    Science.gov (United States)

    Bechara, Robert; Inoue, Haruhiro

    2015-05-16

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

    Etiology of esophageal cancer has not yet been clearly documented, especially in high-risk regions. To evaluate the association between salted meat intake and esophageal squamous-cell carcinoma (ESCC) and to explore its joint effects with alcohol drinking and smoking, a population-based case-control study was conducted in a high ESCC risk area in China, including 942 incident ESCC cases and 942 age- and sex-matching controls. A validated food frequency questionnaire was used to collect information on dietary factors, alcohol drinking and tobacco smoking. Conditional logistic regressions were applied to estimate the association between salted meat intake and ESCC and its interactions with alcohol drinking and smoking, with adjustment for other confounders, including total energy intake. Salted meat intake was associated with an increased risk of ESCC, showing an exposure-response relationship (p for trend Consumption of 50 g salted meat per week was related to an increased risk by 18% (odds ratio = 1.18, 95% confidence interval: 1.13-1.23). Salted meat in combination with either alcohol drinking or smoking had a greater risk than salted meat alone, which was more than additive. The strongest association was seen in the combination of all the three factors, particularly at the highest level of salted meat intake (odds ratio = 29.27, 95% confidence interval: 13.21-64.89). Salted meat intake is strongly associated with ESCC and its interactions with alcohol drinking and/or smoking highlights the significance of reducing salted meat intake among smokers and drinkers with respect to ESCC prevention. PMID:25544988

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

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

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

    2013-07-15

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

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

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    Lin Wang

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

  4. Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P=0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis. (author)

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  6. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  8. Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop) from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion. Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17–55%) tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1) and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples. Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies

  9. REG Iα activates c-Jun through MAPK pathways to enhance the radiosensitivity of squamous esophageal cancer cells.

    Science.gov (United States)

    Wakita, Akiyuki; Motoyama, Satoru; Sato, Yusuke; Koyota, Souichi; Usami, Shuetsu; Yoshino, Kei; Sasaki, Tomohiko; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro

    2015-07-01

    Identification of the key molecules that mediate susceptibility to anticancer treatments would be highly desirable. Based on clinical and cell biological studies, we recently proposed that regenerating gene (REG) Iα may be such a molecule. In the present study, we hypothesized that REG Iα increases radiosensitivity through activation of mitogen-activated protein kinase (MAPK) pathways. To test that idea, we transfected TE-5 and TE-9 squamous esophageal cancer cells with REG Iα and examined its involvement in MAPK signaling and its effect on susceptibility to radiotherapy. We found that REG Iα-expressing cells showed increased expression of c-Jun messenger RNA (mRNA) and phospho-c-Jun protein mediated via the c-Jun N-terminal kinase (JNK) pathway and extracellular signal-regulated kinase (ERK) pathway, as well as increased radiosensitivity. Immunohistochemical analysis confirmed the activation of c-Jun in tumors expressing REG Iα. Collectively, these findings suggest that REG Iα activates c-Jun via the JNK and ERK pathway, thereby enhancing radiosensitivity. PMID:25656613

  10. Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications.

    Science.gov (United States)

    Li, Shu-Ping; Guan, Quan-Lin; Zhao, Da; Pei, Guang-Jun; Su, Hong-Xin; Du, Lan-Ning; He, Jin-Xiang; Liu, Zhao-Chen

    2016-01-01

    BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC. PMID:27184872

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

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    Xiaoyu Liao

    2015-07-01

    Full Text Available Lysosomal-associated membrane protein 3 (LAMP3, identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR. LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC. Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001. LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037. Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010 and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006. In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.

  12. Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma.

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    Yin, Yachao; Dou, Xiaoyan; Duan, Shimiao; Zhang, Lei; Xu, Quanjing; Li, Hongwei; Li, Duojie

    2016-09-30

    Radiation therapy is one of the most important methods of contemporary cancer treatment. Cells in the G2 and M phases are more sensitive to radiation therapy, and cell division cycle 25 homolog C (CDC25C) is essential in shifting the cell cycle between these two phases. In this study, the knockdown of CDC25C in human esophageal squamous carcinoma EC9706 cells was mediated by transfecting shRNA against human CDC25C-subcloning into pGV248. The levels of CDC25C mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Moreover, cell proliferation and radiosensitivity were measured. Stable CDC25C-knockdown EC9706 cell lines were successfully established. Furthermore, the proliferation of both control and CDC25C-shRNA-EC9706 cells was inhibited after the cells were treated with increasing X-ray doses, and the proliferation of the control cells was affected more significantly (p<0.05). Moreover, cell colony formation assays allowed us to reach the same conclusion. Taken together, our experiments demonstrated that the knockdown of CDC25C can reduce both the radiotherapy sensitivity and the proliferation activity of EC9706 cells. Thus, CDC25C might be a potential biomarker for radiotherapy treatment. PMID:27188256

  13. Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway.

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    Lu, Chi; Xie, Conghua

    2016-06-01

    Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro. Inhibition of autophagy also reduced the clonogenic survival of the Eca-109 cells. When treated with radiation alone, human esophageal carcinoma xenografts showed increased LC3B and p-LKB1 expression, which was decreased by the autophagy inhibitor chloroquine. In vivo inhibition of autophagy disrupted tumor growth and increased tumor apoptosis when combined with 6 Gy of ionizing radiation. In summary, our findings elucidate a novel mechanism of resistance to radiotherapy in which radiation-induced autophagy, via the LKB1 pathway, promotes tumor cell survival. This indicates that inhibition of autophagy can serve as an adjuvant treatment to improve the curative effect of radiotherapy. PMID:27109915

  14. 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

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

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-08-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm-1) and high-wavenumber (HW)(2800-3600 cm-1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.

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

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-01-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800–1800 cm−1) and high-wavenumber (HW)(2800–3600 cm−1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy. PMID:26243571

  17. Krüppel-like factor 9 was down-regulated in esophageal squamous cell carcinoma and negatively regulated beta-catenin/TCF signaling.

    Science.gov (United States)

    Qiao, Fan; Yao, Feng; Chen, Ling; Lu, Chengjun; Ni, Yiqian; Fang, Wentao; Jin, Hai

    2016-03-01

    Krüppel-like factor 9 (KLF9) has been found to play suppressive roles in several types of tumor. However, the expression pattern and biological functions of KLF9 in esophageal squamous cell carcinoma (ESCC) are still unknown. In this study, it was found that the expression of KLF9 was significantly down-regulated in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, the expression of KLF9 was inversely correlated with the clinical features of ESCC patients. Moreover, in the biological function study, KLF9 was further validated to inhibit the growth, migration, and metastasis of ESCC cells in vitro and in vivo. Mechanistically, KLF9 bind with TCF4 and suppressed the beta-catenin/TCF signaling as well as the expression of its target gene Cyr61. Collectively, our study clarified the function of KLF9 in both ESCC progression and the regulation of beta-catenin/TCF signaling. PMID:25641762

  18. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies

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    Abnet, Christian C.; Wang, Zhaoming; SONG, XIN; Hu, Nan; Zhou, Fu-You; Freedman, Neal D.; Li, Xue-Min; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Dawsey, Sanford M.; Liao, Linda M.; Lee, Maxwell P.; DING, Ti

    2012-01-01

    Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) o...

  19. Increased serum cell-free DNA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma

    OpenAIRE

    TOMOCHIKA, SHINOBU; Iizuka, Norio; Watanabe, Yusaku; TSUTSUI, MASAHITO; Takeda, Shigeru; Yoshino, Shigefumi; ICHIHARA, KIYOSHI; Oka, Masaaki

    2010-01-01

    Distant metastasis hinders a favorable outcome for patients with esophageal squamous cell carcinoma (ESCC) by limiting the surgical cure. The levels of cell-free DNA (cfDNA) in the blood have served as a predictor for metastasis and recurrence in distant organs in liver cancer. Thus, this study tested the clinical efficacy of serum cfDNA levels as a predictive marker for distant metastasis of ESCC. We investigated cfDNA levels in a cohort of 101 ESCC patients and 46 age- and gender-matched co...

  20. A Meta-Analysis of the Association between the hOGG1 Ser326Cys Polymorphism and the Risk of Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Zhang, Junjie; Zhou, Jingshi; Zhang, Ping; Wang, Weiping; Tao, Shiheng; Wang, Minghua

    2013-01-01

    Background Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated in the risk of Esophageal Squamous Cell Carcinoma (ESCC). However, the published findings are inconsistent. We therefore performed a meta-analysis to derive a more precise estimation of the association between the hOGG1 Ser326Cys polymorphism and ESCC risk. Methodology/Principal Findings A comprehensive search was conducted to identify eligible studies of hOGG1 Ser326Cys polym...

  1. Alterations in expression, proteolysis and intracellular localizations of clusterin in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Zhi He; Xiao-Hang Zhao; Zhen-Mei Song; Kun Wang; Liang-Hong Teng; Fang Liu; You-Sheng Mao; Ning Lu; Shang-Zhong Zhang; Min Wu

    2004-01-01

    AIM: To investigate biogenesis and intracellular localizations of clusterin to elucidate the potential molecular mechanisms implicated in tumorigenesis of esophageal mucosa.METHODS: Semi-quantitative RT-PCR for multi-region alteration analysis, Western blot for different transcriptional forms and immunohistochemical staining for intracellular localizations of clusterin were carried out in both tissues and cell lines of ESCC.RESULTS: The N-terminal deletions of the clusterin gene and the appearance of a 50-53 ku nuclear clusterin, an uncleaved, nonglycosylated, and disulfide-linked isoform,were the major alterations in cancer cells of esophagus.Naturally the 40 ku clusterin was located in the connective tissue of the lamina propria of epithelial mucosa and right under the basal membrane of epithelia, but it was disappeared in stromal mucosa of esophagus and the pre-matured clusterin was found positive in cancerous epithelia.CONCLUSION: The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

    AIM: To investigate telomerase activity and hTERT, TP-1 expression and their relationships in esophageal squamouscell carcinoma (ESCC).METHODS: Telomerase activity was measured in 60 ESCCtissues using telomeric repeat amplification protocol (TRAP)assay by silver staining. In situ hybridization was used for detecting hTERT and TP-lmRNA.RESULTS: The telomerase activity was detected in 83.3 % of ESCC tissues. The difference of telomerase activity was significant between well and poorly cancer differentiated lesions (P<0.05). The positive rate of telomerase activity was higher in patients with lymphatic metastasis than in patients without lymphatic metastasis. In cancer tissues hTERT mRNA expression was 75 % and TP-1 mRNA expression was 71.7 %. The expression of hTERT, TP-1 mRNA in well and poorly differentiated carcinoma was not significant. The expression of hTERT mRNA was correlated with telomerase activity, but TP-1 mRNA expression was not correlated with it.CONCLUSION: Telomerase activity and hTERT, TP-1 mRNA expression are up-regulated in ESCC. Telomerase activity in ESCC is correlated with lymphatic metastasis and cancer differentiation. Telomerase activity may be used as a prognostic marker in ESCC. hTERT mRNA expression is correlated with telomerase activity. Enhanced hTERT mRNA expression may initially comprehend the telomerase activity level, but it is less sensitive than TRAP assay.

  3. miR141 expression is downregulated and negatively correlated with STAT5 expression in esophageal squamous cell carcinoma

    Science.gov (United States)

    TAN, HONGWU; ZHU, YUNFENG; ZHANG, JILING; PENG, LIJUN; JI, TAO

    2016-01-01

    The aim of the present study was to investigate the association between microRNA-141 (miR141) and signal transducer and activator of transcription 5 (STAT5) expression levels in human esophageal squamous cell carcinoma (ESCC) and to investigate the effects of miR141 on ESCC cells. A total of 45 consecutive patients with ESCC were enrolled in the study. The expression of miR141 in ESCC tissue samples was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression of STAT5 in the ESCC tissues was detected using immunohistochemical staining and western blotting. In addition, Eca109 cells were transfected with miR141 mimic, and the levels of STAT5 were detected using western blotting. The effects of miR141 on the proliferation, invasion and migration of the cells were also detected using MTT, scratch and Transwell invasion assays, respectively. The miR141 expression level in the ESCC tissue samples was significantly decreased compared with that in the adjacent normal tissues (Pgender, age, tumor size, lesion location, differentiation and invasion (P>0.05). The results suggest that the miR141 mimic significantly inhibited the proliferation, migration and invasion of Eca109 cells in vitro. miR141 and STAT5 expression levels exhibited a negative association in the ESCC tissues, and were both closely associated with the progression of ESCC. Therefore, it appears that miR141 plays an important role in the development, invasion and metastasis of ESCC by regulating the expression of STAT5.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-31

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

  6. CC-Chemokine receptor CCR7: a key molecule for lymph node metastasis in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    CC-chemokine receptor 7 (CCR7), a known lymph node homing receptor for immune cells, has been reported as a key molecule in lymph node metastasis. We hypothesized a clinicopathological correlation and functional causality between CCR7 expression and lymph node metastasis in patients with esophageal squamous cell carcinoma (ESCC). We performed immunohistochemical analysis of 105 consecutive and 61 exclusive pathological T1 ESCC patients, followed by adhesion assay and in vivo experiment using a newly developed lymph node metastasis mouse model. The adhesive ability in response to CC-chemokine ligand 21/secondary lymphoid-tissue chemokine (CCL21/SLC) was assessed in the presence or absence of lymphatic endothelial cells and anti-CCR7 antibody. We established a heterotopic transplantation mouse model and analyzed lymph node metastasis by quantitative real-time RT-PCR. Positive CCR7 expression in immunohistochemistory was detected in 28 (27%) of 105 consecutive patients and 17 (28%) of 61 T1 patients, which significantly correlated with lymph node metastasis (p = 0.037 and p = 0.040, respectively) and poor five-year survival (p = 0.013 and p = 0.012, respectively). Adhesion assay revealed an enhanced adhesive ability of CCR7-expressing cells in response to CCL21/SLC, in particular, in the presence of lymphatic endothelial cells (p = 0.005). In the mouse model, lymph nodes from mice transplanted with CCR7-expressing cells showed significantly higher DNA levels at 5 weeks (p = 0.019), indicating a high metastatic potential of CCR7-expressing cells. These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients

  7. Combined modality therapy for the thoracic esophageal squamous cell carcinoma; Skojarzone leczenie plaskonablonkowego raka piersiowego odcinka przelyku

    Energy Technology Data Exchange (ETDEWEB)

    Kopacz, A.; Jaskiewicz, J.; Jastrzebski, T. and others [Klinika Chirurgii Onkologicznej, Akademia Medyczna, Gdansk (Poland)

    1995-12-31

    A total of 674 patients with thoracic esophageal squamous cell carcinoma (EC) were treated at Oncological Surgery Clinic Medical University of Gdansk between 1970 and 1994. Of these patients 164 received respective surgery and 382 palliative surgery. The rate of resection was 24.2% and the rate of operation was 80.9%. Combined modality therapy (preoperative chemotherapy) was applied in 47 cases. Radiation therapy volume include the primary tumor and the regional lymph nodes. The tumor dose was 3000 cGy, five-day-a-week 200 cGy fractions delivered by megavoltage radiation, in conventional: 15 fractions 2 parallel opposite fields or 3, 4 oblique fields. In the same time patients received chemotherapy with: 5-Fu, 1000 mg/m{sup 2}, 24-h infusion, i.v., 1-21 day, and CDDP, 20 mg/m{sup 2}, 24-h infusion, i.v., 1-5 and 17-21 day. 21 days after radio-chemotherapy subtotal esophagectomy by 3 approaches: right thoracotomy, laparotomy, left or right cervical incision was performed. Surgical procedure include one stage on block resection of the tumor and an clearance of the regional lymph node. Reconstruction of the alimentary tract was performed with the use of stomach by retrosternal tunnel. When neoadjuvant chemotherapy has been combined with radiotherapy and then followed by surgery, operability improved as a result of reducing tumor volume. The use of combined modality therapy seems worth investigating to try to improve survival. (author) 17 refs, 4 tabs, 1 fig

  8. Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Ni, Sujie; Zhu, Junya; Zhang, Jianguo; Zhang, Shu; Li, Mei; Ni, Runzhou; Liu, Jinxia; Qiu, Huiyuan; Chen, Wenjuan; Wang, Huijie; Guo, Weijian

    2015-02-01

    NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression. PMID:25286760

  9. p53功能失活在食管鳞癌中的表达及意义%Significance of Functional Inactivation of p53 in Esophageal Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    李小东; 戎铁华; 傅剑华; 龙浩

    2001-01-01

    目的:建立一种评价肿瘤生物学特性的新方法棗p53功能失活检测法,并探讨p53功能失活与食管鳞癌TNM分期(tumor,nodes,metastasisstaging)和组织学分级的关系。方法:采用p53功能测定法对45例新鲜食管鳞癌组织和正常食管组织进行p53功能检测(p53基因突变检测作为对照),将检测结果与患者的TNM分期和组织学分级进行统计学分析。结果:p53功能失活率为64%,明显高于p53基因突变率49%。p53功能失活和食管鳞癌的TNM分期有关,分期越高,p53功能失活率越高;p53功能失活和食管鳞癌的组织学分级有关,分级越高,p53功能失活率越高。结论:p53功能失活有望成为一种评价食管鳞癌生物学特性的新指标;p53功能失活与食管鳞癌的TNM分期和组织学分级有关。%Objective: The current study was designed to establish a new method to evaluate biological activity of carcinoma— functional status of p53, and investigate the relationship between functional inactivation of p53 and the TNM(tumor,nodes,metastasis) staging or histological classification of squamous cell carcinoma of esophagus. Methods: A total of 45 samples of fresh esophageal tissues of squamous cell carcinoma and normal esophageal tissues were examined for functional inactivation of p53 by detection of functional inactivation of p53 ( comparison with detection of p53 gene mutation ) . Then the analyses of detected results and the TNM stagings or the histological classifications of the carcinoma were statistically analyzed in SPSS. Results: The rate of functional inactivation of p53 (64% ) seemed to be obviously higher than that of p53 gene mutation (49% ) with a significant difference (P=0.046). There was a significant relationship between functional inactivation of p53 and the TNM staging of esophageal squamous cell carcinoma. Its rate tended to be increased with the advance of the TNM staging; there was a significant

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    1998-01-01

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

  12. 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...

  13. Epidermal growth factor receptor is a possible predictor of sensitivity to chemoradiotherapy in the primary lesion of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Chemoradiotherapy (CRT) is currently performed for patients with esophageal squamous cell carcinoma (SCC). Some reports have revealed that patients who responded well to CRT had favorable outcomes, whereas poor responders conversely showed a worse prognosis. The aim of this study was to identify molecular markers predicting sensitivity to CRT. We reviewed 62 patients with T3-4, N-any, and M-any esophageal SCC treated with definitive CRT. The regimen comprised protracted 5-fluorouracil infusion and a 2-h infusion of cisplatinum combined with radiation therapy (2 Gy/day) at a total radiation dose of 60 Gy. The expressions of epidermal growth factor receptor (EGFR), vascular endothelial growth factor, cyclin D1, and proliferating cell nuclear antigen were investigated immunohistochemically in biopsy specimens obtained before treatment from all 62 patients. The immunoreactivities were compared with responsiveness to CRT, as evaluated by endoscopy. The complete response rate of the primary tumor estimated by endoscopy was 62% (13/21) in patients in the EGFR-positive group. The difference in the CR rate between EGFR-positive and -negative groups was significant (p=0.037). The immunoreactivities of the other molecular markers did not show a significant correlation with the responsiveness of the primary lesion to CRT. Multiple logistic regression analysis revealed that positive immunostaining for EGFR was significantly correlated with primary CR for CRT in esophageal SCC. Among 62 patients with esophageal SCC, differences in the responsiveness of primary lesions to CRT were correlated with EGFR immunoreactivity assessed in the biopsy specimens. These results suggest that EGFR may help to predict the response of primary sites to definitive CRT in esophageal SCC, although the results should be confirmed in a larger, more homogeneous series. (author)

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

    Directory of Open Access Journals (Sweden)

    Fauze Maluf-Filho

    2006-06-01

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

  15. Atlas of the thoracic lymph nodal delineation and recommendations for lymph nodal CTV of esophageal squamous cell cancer in radiation therapy from China

    International Nuclear Information System (INIS)

    Purpose: To construct an anatomical atlas of thoracic lymph node regions of esophageal cancer (EC) based on definitions from The Japan Esophageal Society (JES) and generate a consensus to delineate the nodal clinical target volume (CTVn) for elective nodal radiation (ENI) of esophageal squamous cell carcinoma (ESCC). Methods and materials: An interdisciplinary group including two dedicated radiation oncologists, an experienced radiologist, a pathologist and two thoracic surgeons were gathered to generate a three-dimensional radiological description for the mediastinal lymph node regions of EC on axial CT scans. Then the radiological boundaries of lymph node regions were validated by a relatively large number of physicians in multiple institutions. Results: An atlas of detailed anatomic boundaries of lymph node station No. 105–114 was defined on axial CT, along with illustrations. From the previous work, the study provided a guide of CTVn contouring for ENI of thoracic ESCC from a single center. Conclusion: It is feasible to use such an atlas of thoracic lymph node stations for radiotherapy planning. A phase III study based on the atlas is ongoing in China to measure quantitatively the ENI received by patients with ESCC

  16. Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Wen-Qing Li

    Full Text Available The epidermal growth factor receptor (EGFR signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs, 1758 gastric cancers (GCs, and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10(-3. Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05. For ESCC, we did not observe a significant pathway-level association (P = 0.72, but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05. Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.

  17. Trimodal therapy in squamous cell carcinoma of the esophagus

    OpenAIRE

    Matuschek C; Bölke E; Zahra T; Knoefel WT; Peiper M; Budach W; Erhardt A; Scherer A; Baldus SE; Gerber PA; Buhren BA; Schauer M; Hoff N-Ph; Gattermann N; Orth K

    2011-01-01

    Abstract Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often r...

  18. Authentication of newly established human esophageal squamous cell carcinoma cell line (YM-1) using short tandem repeat (STR) profiling method.

    Science.gov (United States)

    Ayyoob, Khosravi; Masoud, Khoshnia; Vahideh, Kazeminejad; Jahanbakhsh, Asadi

    2016-03-01

    Cross-contamination during or early after establishment of a new cell line could result in the worldwide spread of a misidentified cell line. Therefore, newly established cell lines need to be authenticated by a reference standard method. This study was conducted to investigate the authenticity of a newly established epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM-1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC epithelial cells were cultured from the fresh tumor tissue of an adult female patient. Growth characteristics and epithelial originality of YM-1 cells were studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and ESCC donor tumor sample on two different days to prevent probable DNA contamination. STR profiling was performed using AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration as the passage number increases, STR profiling was performed again on harvested cells at passage 51. YM-1 cells grew as a monolayer with a population doubling time of 40.66 h. Epithelial originality of YM-1 cells was confirmed using ICC/IF staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample was the same with YM-1 cells at passage 22. However, STR profile of the donor tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re-profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at D18S51 locus. This suggests that long-term culture of cell lines may alter their DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR profiling databases confirmed unique identity of YM-1 cell line. This study provides an easy, fast, and reliable procedure for authentication of newly established cell lines, which helps in preventing the spread of misidentified cells and improving the reproducibility and validity of experiments, consequently. PMID:26432330

  19. Aspirin inhibits the proliferation of tobacco-related esophageal squamous carcinomas cell lines through cyclooxygenase 2 pathway

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiao-Zhi; LIU Hai-bo; DING Xin-chun; LI Peng; ZHANG Shu-tian; YU Zhong-lin

    2007-01-01

    Background Cigarette smoking has been verified as the risk factor of esophageal squamous cell carcinoma(ESCC).Overexpression of cyclooxygenase 2(COX-2)is shown in ESCC.The objective of this study was to investigate the effects of cigarette smoking ethanol extract(EE)on the proliferation of the human ESCC cell Iines,and to explore the correlation between the proliferation rate of human ESCC cell lines and the expression pattern of COX-2.Whether aspirin can inhibit the proliferation of the ESCC cell lines pretreated with EE.and regulate the mRNA expression levels of COX-2 are also examined.Methods Two human ESCC cell Iines were selected.EC109 was poorly differentiated and EC9706 was highly differentiated.EC109 and EC9706 were treated with EE and aspirin for different time course.The cell growth of ESCC was measured by MTT reduction assay and the expression of COX-2 was measured by RT-PCR and Western blot analysis.Results EE promoted the proliferation of EC109 and EC9706 in dose- and time-dependent manners.In the concentration range (10-100 μg/ml for EE)and in the time range(24-72 hours)after addition of EE,the cell proliferation was prominent in an up-scaled manner respectively.Aspirin could inhibit the proliferation of cell lines EC109 and EC9706.pretreated with EE for 5 hours,in a dose-dependent manner.In the concentration range (0.5-8.0 mmol/L for aspirin),the cell growth inhibition was prominent in an up-scaled manner accordingly (P<0.05).The effect of EE on cell proliferation was correlated with the up-regulation of COX-2 gene.However,the cell growth inhibition of aspirin was correlated with the down-regulation of COX-2 gene.Conclusions EE can stimulate the proliferation of human ESCC cell lines EC109 and EC9706,most likely through up-regulating the expression of COX-2.Aspirin can inhibit the proliferation of ESCC cell lines induced by EE,which suggests it may be advantageous in the chemoprevention and therapy of human tobacco-related ESCC.And its effect is

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

    OpenAIRE

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

    2015-01-01

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

  1. Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer

    International Nuclear Information System (INIS)

    Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m2 was given on days 1 and 29, and S-1 80 mg/m2 on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. Between August 2011 and June 2015, 89 patients (age range, 44–86 years; K-PS 90–100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT

  2. Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings. One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification. The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no

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

    Science.gov (United States)

    Jing, Rongrong; Chen, Wen; Wang, Huimin; Ju, Shaoqing; Cong, Hui; Sun, Baolan; Jin, Qin; Chu, Shaopeng; Xu, Lili; Cui, Ming

    2015-11-01

    The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker

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

    Science.gov (United States)

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

    2015-01-01

    To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (PNF-kB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (PNF-kB p65 in ESCC tissues (PNF-kB p65. PMID:26617724

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Daisuke [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Kato, Kazunori, E-mail: kzkatou@juntendo.ac.jp [Department of Biomedical Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585 (Japan); Department of Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki [Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2013-05-17

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

  7. Insights into anticancer activity and mechanism of action of a ruthenium(II) complex in human esophageal squamous carcinoma EC109 cells.

    Science.gov (United States)

    Guo, Liubin; Lv, Gaochao; Qiu, Ling; Yang, Hui; Zhang, Li; Yu, Huixin; Zou, Meifen; Lin, Jianguo

    2016-09-01

    A ruthenium(II) complex [Ru(p-cymene)(NHC)Cl2] (NHC=1,3-bis(4-(tert-butyl)benzylimidazol-2-ylidene), referred to as L-4, has been designed and synthesized recently in order to look for new anticancer drugs with high efficacy and low side effects. The anticancer activity and mechanism of action of L-4 in human esophageal squamous carcinoma EC109 cells were systematically investigated. The results revealed that L-4 exerted strong inhibitory effect on the proliferation of EC109 cells, and it arrested EC109 cells at G2/M phase, accompanied with the up-regulation of p53 and p21 and the down-regulation of cyclin D1. The results also showed that the reactive oxygen species (ROS)-dependent apoptosis of EC109 can be induced by L-4 via inhibiting the activity of glutathione reductase (GR), decreasing the ratio of glutathione to oxidized glutathione (GSH/GSSG), and leading to the generation of reactive oxygen species. The mitochondria-mediated apoptosis of EC109 induced by L-4 was also observed from the increase of Bax/Bcl-2 ratio, overload of Ca(2+), disruption of mitochondrial membrane potential (MMP), redistribution of cytochrome c, and activation of caspase-3/-9. However, the effects of L-4 on the cell viability, GR activity, GSH/GSSG ratio, reactive oxygen species level, mitochondria dysfunction and apoptosis induction were remarkably attenuated by adding the reactive oxygen species scavenger, NAC. Therefore, it was concluded that L-4 can inhibit the proliferation of EC109 cells via blocking cell cycle progression and inducing reactive oxygen species-dependent and mitochondria-mediated apoptosis. These findings suggested that the ruthenium(II) complex might be a potential effective chemotherapeutic agent for human esophageal squamous carcinoma (ESCC) and worthy of further investigation. PMID:27262377

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

    Science.gov (United States)

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

    2014-02-01

    Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of typical squamous cell carcinoma (SCC) associated with poor survival. A characteristic feature is nuclear accumulation of β-catenin, without a mutation of the gene. We studied the methylation status of Wnt antagonist genes, such as secreted frizzled-related protein (sFRP) gene family members, Wnt inhibitory factor-1 (WIF-1), Dickkopf-1 (Dkk-1), and human Dapper protein-1 (HDPR-1), and alterations of the APC, Axin1, and Axin2 genes in 30 cases of esophageal BSCC. β-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression was examined by immunohistochemistry. APC, Axin1, and Axin2 gene mutations were detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least 1 alteration in these genes. Methylation of the sFRP-2 promoter region was observed in all cases, and methylation was frequent in sFRP-1 and sFRP-5, but infrequent in Dkk-1, WIF-1, sFRP-4, and HDPR-1. sFRP-2 expression was almost completely absent in 25 cases (83 %), consistent with the methylation status. Nuclear accumulation of β-catenin was observed in all cases. sFRP-5 expression was associated with a low nuclear β-catenin labeling index. These results show that sFRP-2 is a target gene of hypermethylation in esophageal BSCC and suggest that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/β-catenin signaling pathway. PMID:24464051

  9. DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ng, Hoi Yan; Ko, Josephine Mun-Yee; Yu, Valen Zhuoyou; Ip, Joseph Chok Yan; Dai, Wei; Cal, Santiago; Lung, Maria Li

    2016-06-15

    Esophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr-AKT, abolished the apoptosis-sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three-dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway. PMID:26856390

  10. Advanced Pyoderma Gangrenosum Previously Treated as Squamous Cell Carcinoma

    OpenAIRE

    Tamara Čuk Radović; Krešimir Kostović; Jaka Radoš; Zrinjka Paštar; Gordana Pavliša; Branka Marinović

    2015-01-01

    Pyoderma gangrenosum is a rare, neutrophilic ulcerative skin disease of unknown etiology often associated with an underlying systemic disease. We present a case of a pyoderma gangrenosum that was initially misdiagnosed and treated as squamous cell carcinoma in another hospital. Multiple surgical treatments triggered postoperative exacerbations and further rapid progression of the lesions. History of pathergy, clinical findings, and histopathological features examined at our Department indicat...

  11. CRCT1 regulated by microRNA-520 g inhibits proliferation and induces apoptosis in esophageal squamous cell cancer.

    Science.gov (United States)

    Wu, Ning; Song, Yang; Pang, Liewen; Chen, Zhiming

    2016-06-01

    Cysteine-rich C-terminal 1 (CRCT1) is encoded by the epidermal differentiation complex (EDC), a gene cluster that was recently linked to esophageal cancer. However, the role of CRCT1 in esophageal squamous cell cancer (ESCC) and the underlying mechanism remain unclear. In the present study, we show that CRCT1 is downregulated in ESCC in association with TNM stage and lymph node metastasis. Restoring CRCT1 in ESCC cells by lentivirus-mediated gene transfer inhibited cell proliferation and xenograft tumor formation. CRCT1 overexpression promoted ESCC cell apoptosis and upregulated the expression of apoptosis-related proteins. CRCT1 expression was inversely correlated with the levels of microRNA-520 g (miR-520 g) in ESCC tissues, and CRCT1 was identified as a direct target gene of miR-520 g in ESCC cells. Consistent with the effects of CRCT1 overexpression, knockdown of miR-520 g inhibited growth and induced apoptosis in ESCC cells. Our results suggest that CRCT1 functions as a tumor suppressor gene in ESCC and is regulated by miR-520 g, providing potential therapeutic targets for the treatment of ESCC. PMID:26718216

  12. Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

    International Nuclear Information System (INIS)

    To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors

  13. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma

    International Nuclear Information System (INIS)

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient

  14. Evaluation of advanced cooling therapy's esophageal cooling device for core temperature control.

    Science.gov (United States)

    Naiman, Melissa; Shanley, Patrick; Garrett, Frank; Kulstad, Erik

    2016-05-01

    Managing core temperature is critical to patient outcomes in a wide range of clinical scenarios. Previous devices designed to perform temperature management required a trade-off between invasiveness and temperature modulation efficiency. The Esophageal Cooling Device, made by Advanced Cooling Therapy (Chicago, IL), was developed to optimize warming and cooling efficiency through an easy and low risk procedure that leverages heat transfer through convection and conduction. Clinical data from cardiac arrest, fever, and critical burn patients indicate that the Esophageal Cooling Device performs very well both in terms of temperature modulation (cooling rates of approximately 1.3°C/hour, warming of up to 0.5°C/hour) and maintaining temperature stability (variation around goal temperature ± 0.3°C). Physicians have reported that device performance is comparable to the performance of intravascular temperature management techniques and superior to the performance of surface devices, while avoiding the downsides associated with both. PMID:27043177

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  16. Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Endothelin(ET) axis plays a key role in many tumor progression and metastasis via various mechanisms such as angiogenesis, mediating extracellular matrix degradation and inhibition of apoptosis. However, there is limited information regarding the clinical significance of plasma big ET-1 levels in esophageal cancer patients. Circulating plasma big ET-1 levels were measured in patients with esophageal squamous cell carcinoma(ESCC) to evaluate the value of ET-1 as a biomarker for predicting tumor recurrence and patients survival. Preoperative plasma big ET-1 concentrations were measured by an enzyme linked immunosorbent assay(ELISA) in 108 ESCC patients before surgery, and then again at 1,2,3,10 and 30 days after curative radical resection for ESCC. The association between preoperative plasma big ET-1 levels and clinicopathological features, tumor recurrence and patient survival, and their changes following surgery were evaluated. The preoperative plasma big ET-1 levels in ESCC patients were significantly higher than those in controls. And there was a significant association between plasma big ET-1 levels and disease stage, as well as invasion depth of the tumor and lymph node status. Furthermore, plasma big ET-1 levels decreased significantly after radical resection of the primary tumor and patients with postoperative recurrence had significantly higher plasma big ET-1 levels than that of patients without recurrence. Finally, the survival rate of patients with higher plasma big ET-1 concentrations (>4.3 pg/ml) was significantly lower than that of patients with lower level (≤ 4.3 pg/ml). Multivariate regression analysis showed that plasma big ET-1 level is an independent prognostic factor for survival in patients with ESCC. Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for choice of multimodality therapy in ESCC

  17. 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)

    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

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

    Science.gov (United States)

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

    2015-04-01

    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. PMID:25641622

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

    Science.gov (United States)

    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. PMID:25641622

  20. Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin-based chemotherapy for esophageal squamous cell carcinoma: a phase II study

    International Nuclear Information System (INIS)

    In this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC). Patients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT. The median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II–III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%. ENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Yamashita Shunichi

    2011-03-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  6. Metallic stents provide better QOL than plastic stents in patients with stricture of unresectable advanced esophageal cancer

    International Nuclear Information System (INIS)

    The aim of this study was to elucidate the utility and safety of treatment with esophageal stents (plastic and metallic stents) for unresectable advanced esophageal cancer. Between 1992 and 2002, 14 cases of unresectable advanced esophageal cancer were treated with esophageal stents (the plastic stent group, 7 cases; and the metallic stent group, 7 cases). Of these, 10 cases had a history of chemotherapy and or radiotherapy. An improvement in oral intake and performance status (PS), survival time, periods at home, and adverse events were compared between the two groups. After stenting, oral intake and PS were significantly improved in the metallic stent group. Follow-up at home was possible in 71.4%. There was no significant difference in survival or duration of time at home between the two groups. All adverse events were controllable and there was no difference between the two groups. Stenting not only improved oral intake and PS but also allowed a stay at home, resulting in a marked improvement in patients' quality of life (QOL). Stenting was performed safely even in cases with a history of radiotherapy. There was no difference in survival, ratios of staying at home, and safety between the two groups, but QOL was significantly improved in the metallic stent group. These outcomes indicate that placement of metallic stents should be actively considered to treat stricture due to advanced esophageal cancer. (author)

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

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

    2013-04-01

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

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

    International Nuclear Information System (INIS)

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

  9. Human papillomavirus shows highly variable prevalence in esophageal squamous cell carcinoma and no significant correlation to p16INK4a overexpression

    DEFF Research Database (Denmark)

    Michaelsen, Sanne Høxbroe; Larsen, Christian Grønhøj; von Buchwald, Christian

    2014-01-01

    INTRODUCTION: This review investigates the role of p16(INK4a) as a marker of transcriptionally active human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) and the regional prevalence of HPV in ESCC. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched...... statistically significant difference, neither for the combined data (p = 0.7507) nor for any individual study, and detection of p16(INK4a) overexpression did not affect the odds of tumors being HPV positive (odds ratio = 1.0666 with 95% confidence interval 0.7040-1.6157). In a pooled analysis, the sensitivity...... of p16(INK4a) overexpression as a marker of HPV DNA presence was 0.35, the specificity 0.67, and the positive predictive value 0.25. CONCLUSIONS: This systematic review reports great regional variation in the prevalence of HPV in ESCC and suggests that p16(INK4a) is not a reliable marker of HPV...

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

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    Goldstein Alisa M

    2006-11-01

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

  12. Secreted recombinant human IL-24 protein inhibits the proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro and in vivo.

    Science.gov (United States)

    Ma, Qunfeng; Jin, Bangming; Zhang, Yao; Shi, Yinan; Zhang, Chi; Luo, Dan; Wang, Pengkun; Duan, Cuimi; Song, Heyu; Li, Xue; Deng, Xuefeng; Chen, Zhinan; Wang, Ziling; Jiang, Hong; Liu, Yan

    2016-05-01

    Interleukin-24 (IL-24) displays cancer-specific apoptosis-inducing properties in a broad spectrum of human tumors without harmful effects on normal cells. The human IL-24 protein is secreted as a glycosylated protein and functions as a pro-Th1 cytokine and a potent antiangiogenic molecule. However, the function of secreted recombinant human IL-24 (srhIL-24) protein in esophageal squamous cell carcinoma (ESCC) cells has not been studied. In the present study, we prepared a stable site-specific-integrated cell line, Flp-InTMCHO/IL-24 (FCHO/IL-24), which secreted rhIL-24 at a higher level than three random-integrated cell lines. In vitro, we identified that the purified srhIL-24 inhibited proliferation and induced the apoptosis of ESCC Eca-109 cells and activated STAT3, which was related with the IL-20 receptors. In vivo, the tumorigenicity of Eca-109 cells was significantly inhibited by s.c. injection of FCHO/IL-24 cells. Decreased tumor microvessel density and an increased number of TUNEL-positive tumor cells were associated with tumor growth inhibition, indicating the presence of antiangiogenic activity and induction of apoptotic activity. In summary, the present study demonstrated that srhIL-24 induced growth inhibition and apoptosis in ESCC Eca-109 cells in vitro and in vivo, which may be mediated by the receptor pathway. PMID:26935394

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  14. Induction of cytotoxic T lymphocytes primed with Tumor RNA-loaded Dendritic Cells in esophageal squamous cell carcinoma: preliminary step for DC vaccine design

    International Nuclear Information System (INIS)

    Dendritic Cells (DC) are potent antigen presenting cells with the ability to prime naïve T cells and convert them to cytotoxic T-lymphocytes (CTL). We evaluated the capability of autologous DCs transfected with total tumor and normal RNA to induce cytotoxic CTL as the preliminary step to design a DC-based vaccine in the esophageal squamous cell carcinoma (ESCC). Monocytes-derived DCs were electroporated with either total tumor RNA or normal RNA. T cells were then primed with tumor RNA transfected DCs and lytic effects of the generated CTL were measured with Cytotoxicity assay and IFN-γ Release Elispot assay. Cytotoxicity was induced against DCs loaded with tumoral RNA (%24.8 ± 5.2 SEM) while in normal RNA-loaded DCs, it was minimal (%6.1 ± 2.4 SEM) and significantly lower (p < 0.05). INF-γ secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNA-loaded DCs (p < 0.05). Electroporating DCs with tumor RNA generated tumor antigen presenting cells which in turn enhanced cytotoxic effects of the T cells against ESCC. This may be a useful autologous ex vivo screening tool for confirming the lytic effects of primed T cells on tumors and evaluate probable further adverse effects on noncancerous tissues. These data provide crucial preliminary information to establish a total tumor RNA-pulsed DC vaccine therapy of ESCC

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  16. Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study

    International Nuclear Information System (INIS)

    Background: Previous studies from South Africa have established that fractionated high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation and survival in advanced esophageal cancer. A multicenter, prospective randomized study was therefore conducted under the auspices of the International Atomic Energy Agency to evaluate two HDR regimens. Methods and Materials: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score >50, age 17-70 years, primary disease in the thoracic esophagus, no prior malignancy within the past 5 years, and any N or M status were included in the study. Exclusion criteria included cervical esophagus location, tumor extending 0.05). The overall survival was 7.9 months for the whole group (Group A, 9.1 months; Group B, 6.9 months; p>0.05). On univariate analysis, the presenting weight (p=0.0083), gender (p=0.0038), race (p=0.0105), the presenting dysphagia score (p=0.0083), the treatment center (p=0.0029), and tumor grade (p=0.0029) had an impact on the dysphagia-free survival, and gender (p=0.0011) and performance score (p=0.0060) had an impact on dysphagia-free survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p=0.0430) and multivariate (p=0.0331) analysis. The incidence of strictures (Group A, n=12; Group B, n=13; p>0.05) and fistulas (Group A, n=11; Group B, n=12; p>0.05) was similar in both groups. Conclusion: Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers, surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8 Gy x 2 give similar results for dysphagia-free survival, overall survival, strictures, and fistulas and are equally effective in palliation of advanced esophageal cancer

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common...

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Gao Weimin

    2006-12-01

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

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

    International Nuclear Information System (INIS)

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

  1. Genetic variant rs401681 at 5p15.33 modifies susceptibility to lung cancer but not esophageal squamous cell carcinoma.

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    Man Jiang

    Full Text Available BACKGROUND: The human 5p15.33 locus contains two well-known genes, the telomerase reverse transcriptase (TERT and cleft lip and palate transmembrane 1-like (CLPTM1L genes, which have been implicated in carcinogenesis. A common sequence variant, rs401681, located in an intronic region of CLPTM1L, has been reported to be associated with lung cancer risk based on genome-wide association study. However, subsequent replication studies in diverse populations have yielded inconsistent results. In addition, genetic variants at 5p15.33, including rs401681, have been shown to be involved in the susceptibility to multiple malignancies. Nevertheless, the role of these TERT-CLPTM1L variants in the etiology of esophageal squamous cell carcinoma (ESCC remains unknown. METHODS: We genotyped the rs401681 polymorphism using TaqMan methodology and analyzed its association with the risk of lung cancer and ESCC in a case-control study of 1,479 cancer patients (726 with lung cancer and 753 with ESCC and 860 healthy individuals. RESULTS: Logistic regression analyses revealed that rs401681 T genotypes were associated with a significantly decreased risk of lung cancer (CT vs. CC: adjusted OR=0.782, 95% CI=0.625-0.978, P=0.031; CT/TT vs. CC: adjusted OR=0.786; 95% CI=0.635-0.972, P=0.026. Stratification analysis by histology type indicated that rs401681 T genotypes were associated with a significantly reduced risk of both adenocarcinoma and squamous cell carcinoma. Furthermore, no significant association was observed between rs401681 and the risk of ESCC (CT vs. CC: adjusted OR=0.910, 95% CI=0.734-1.129, P=0.392; TT vs. CC: adjusted OR=0.897, 95%CI=0.624-1.290, P=0.558; CT/TT vs. CC: adjusted OR=0.908, 95% CI=0.740-1.114, P=0.355. CONCLUSIONS: Our findings provide further evidence supporting rs401681 as a genetic variant associated with the risk of lung cancer. In addition, we investigated the correlation between the rs401681 variant and the risk of ESCC in a Han Chinese

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  4. Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancer

    International Nuclear Information System (INIS)

    We conducted a pilot study of nedaplatin+5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin+5-FU combined with radiotherapy might not differ from that of cisplatin+5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials. (author)

  5. Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-Fu, and VP-16 for advanced esophageal cancer

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    Mukaida, Hidenori; Hirai, Toshihiro; Yamashita, Yoshinori; Yoshida, Kazuhiro; Hihara, Jun; Kuwahara, Masaki; Inoue, Hideki; Toge, Tetsuya [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1998-01-01

    The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer. We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m{sup 2} was administered on days 1 and 7.5-FU at 500 mg/m{sup 2} and VP-16 at 60 mg/m{sup 2} were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation. Side-effects of severe anorexia (grade 3) and leukocytopenia (<1900/{mu}l) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no significant difference. These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer. (author)

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-03-01

    Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders. PMID:25851181

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

    International Nuclear Information System (INIS)

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

  9. Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo.

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    Hui Li

    Full Text Available We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism.Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo.Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039. HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2. Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341-0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350-0.844], p = 0.024 for cohort 2. Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably.HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  11. Regulation of Mcl-1 by constitutive activation of NF-kappaB contributes to cell viability in human esophageal squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments. Mcl-1 expression was measured by reverse transcription (RT)-PCR and Western blotting. Human Mcl-1 promoter activity was evaluated by reporter gene assay. The interactions between DNA and transcription factors were confirmed by electrophoretic mobility shift assay (EMSA) in vitro and by chromatin immunoprecipitation (ChIP) assay in cells. Four human ESCC cell lines, TE-1, Eca109, KYSE150 and KYSE510, are revealed increased levels of Mcl-1 mRNA and protein compare with HaCaT, an immortal non-tumorigenic cell line. Results of reporter gene assays demonstrate that human Mcl-1 promoter activity is decreased by mutation of kappaB binding site, specific NF-kappaB inhibitor Bay11-7082 or dominant inhibitory molecule DNMIkappaBalpha in TE-1 and KYSE150 cell lines. Mcl-1 protein level is also attenuated by Bay11-7082 treatment or co-transfection of DNMIkappaBalpha in TE-1 and KYSE150 cells. EMSA results indicate that NF-kappaB subunits p50 and p65 bind to human Mcl-1-kappaB probe in vitro. ChIP assay further confirm p50 and p65 directly bind to human Mcl-1 promoter in intact cells, by which regulates Mcl-1 expression and contributes to the viability of TE-1 cells. Our data provided evidence that one of the mechanisms of Mcl-1 expression in human ESCC is regulated by the activation of NF-kappaB signaling. The newly identified mechanism might provide a scientific basis for developing effective approaches to treatment human ESCC

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

    Science.gov (United States)

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

    2016-09-01

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

  13. Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1.

    Science.gov (United States)

    Phatak, P; Byrnes, K A; Mansour, D; Liu, L; Cao, S; Li, R; Rao, J N; Turner, D J; Wang, J-Y; Donahue, J M

    2016-04-21

    Based on its marked overexpression in multiple malignancies and its roles in promoting cell survival and proliferation, survivin is an attractive candidate for targeted therapy. Toward this end, a detailed understanding of the mechanisms regulating survivin expression in different cancer cells will be critical. We have previously shown that the RNA-binding protein (RBP) CUG-BP1 is overexpressed in esophageal cancer cells and post-transcriptionally regulates survivin in these cells. The objective of this study was to investigate the role of microRNAs (miRs) in regulating survivin expression in esophageal cancer cells. Using miR expression profiling analysis, we found that miR-214-3p is one of the most markedly downregulated miRs in two esophageal squamous cancer cell lines compared with esophageal epithelial cells. Interestingly, using miR target prediction programs, both survivin and CUG-BP1 mRNA were found to contain potential binding sites for miR-214-3p. Forced expression of miR-214-3p in esophageal cancer cells leads to a decrease in the mRNA and protein levels of both survivin and CUG-BP1. This effect is due to decreased mRNA stability of both targets. By contrast, silencing miR-214-3p in esophageal epithelial cells leads to an increase in both survivin and CUG-BP1 mRNA and protein. To determine whether the observed effect of miR-214-3p on survivin expression was direct, mediated through CUG-BP1, or both, binding studies utilizing biotin pull-down assays and heterologous luciferase reporter constructs were performed. These demonstrated that the mRNA of survivin and CUG-BP1 each contain two functional miR-214-3p-binding sites as confirmed by mutational analysis. Finally, forced expression of miR-214-3p enhances the sensitivity of esophageal cancer cells to cisplatin-induced apoptosis. This effect is abrogated with rescue expression of survivin or CUG-BP1. These findings suggest that miR-214-3p acts as a tumor suppressor and that its downregulation contributes

  14. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone

    International Nuclear Information System (INIS)

    Purpose: To identify prognostic factors for local and distant relapse and perform risk stratification for patients with advanced cervical cancer treated with radiotherapy (RT) alone. Methods and Materials: A total of 1031 patients with Stage IB-IVA squamous cell carcinoma of the cervix treated with full-course RT but without any chemotherapy were included for analysis. Of these, 311 patients with nonbulky Stage IB-IIA disease were designated the reference group and the other 720 patients were the study group. The associations of stage, squamous cell carcinoma antigen (SCC-ag) level, hemoglobin level, age, cell differentiation, and pelvic lymph node status with treatment failure were evaluated. The independent prognostic factors were identified by multivariate analysis. The study group was further stratified into subgroups using combinations of these risk factors. Results: In the study group, independent risk factors for local relapse were advanced stage and age 2, and positive pelvic lymph nodes. The 5-year distant relapse-free survival rate was 83% for patients with bulky Stage IB-IIA and IIB disease, SCC-ag level 2, and positive lymph nodes. Conclusion: The risk of treatment failure in advanced-stage cervical cancer patients treated by RT alone can be more precisely predicted by risk stratification. A certain subgroup of patients had better control than the others. The benefit of treating these relatively low-risk patients with additional treatment such as concurrent chemotherapy should be further evaluated in prospective studies or meta-analyses

  15. Role of Barium Esophagography in Patients with Locally Advanced Esophageal Cancer: Evaluation of Response to Neoadjuvant Chemoradiotherapy

    International Nuclear Information System (INIS)

    This retrospective study examined the usefulness of barium esophagography, focusing on the luminal stenosis, in the response evaluation of neoadjuvant chemoradiotherapy (NACRT) in patients with esophageal cancer. Materials and Methods. Thirty-four patients with primary advanced esophageal cancer (≥T2) who were treated with NACRT before surgical resection were analyzed. All patients underwent barium esophagography before and after NACRT. The tumor length, volume, and percent esophageal stenosis (PES) before and after NACRT were measured. These values and their changes were compared between histopathologic responders (Ρ=22) and nonresponders ( Ρ=12). Results. Posttreatment tumor length and PES in responders (4.5 cm ± 1.1 and 33.0% ± 18.5) were significantly smaller than those in nonresponders (5.8 cm±1.9 and 48.0% ±12.9) ( Ρ=0.018). Regarding post therapeutic changes, the decrease in Pes in responders (31.5% ± 13.9) was significantly greater than that in nonresponders (14.4% ± 10.7) ( Ρ < 0 . 0 0 1 ). The best decrease in PES cutoff with which to differentiate between responders and nonresponders was 18.8%, which yielded a sensitivity of 91% and a specificity of 75%. Conclusions. Decrease in PES is a good parameter to differentiate responders from nonresponders for NACRT. Barium esophagography is useful in response evaluation to NACRT in patients with locally advanced esophageal cancer.

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

    OpenAIRE

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

    2013-01-01

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

  17. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

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    Minami S

    2015-01-01

    Full Text Available Seigo Minami,1 Takashi Kijima2 1Department of Respiratory Medicine, Osaka Police Hospital, 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan Abstract: Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC. Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  19. ShRNA-mediated Ku80 gene silencing inhibits cell proliferation and sensitizes to γ-radiation and mitomycin C-induced apoptosis in esophageal squamous cell carcinoma lines

    International Nuclear Information System (INIS)

    To investigate the effects of Ku80 depletion on cell growth and sensitization to γ-radiation and Mitomycin C (MMC)-induced apoptosis in esophageal squamous cell carcinoma lines. Six human carcinoma cell lines (LNcaP, K562, MDA-MB-231, MCF-7, EC9706, and K150) and normal HEK293 cell line were examined for basal levels of Ku80 protein by western blotting analysis. The suppression of Ku80 expression was performed using vector-based shRNA in EC9706 cells. Cell proliferation was determined with MTT assay and colony formation assay and tumorigenicity in a xenograft model in vitro and in vivo. Sensitivity of EC9706 cells treated with shRNA vector to γ-radiation and MMC was determined with colony formation assay and MTT assay. The cell cycle distribution was determined by Flow cytometry. Apoptosis induced by γ-radiation and MMC was analyzed using GENMED-TUNEL FACS kit. Ku80 showed higher basal levels in six carcinoma cell lines than in HEK293. The suppression of Ku80 expression decreased cellular proliferation, colony formation and inhibited tumorigenicity in a xenograft model. Furthermore, it sensitized apoptosis of the cancer cells induced by γ-radiation and MMC. Ku80 plays an important role not only in tumorigenesis but also in radiation resistance and chemotherapy resistance in esophageal cancer cells. Hence Ku80 may serve as a promising therapeutic target, particularly for recurrent esophageal tumors. (author)

  20. 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

  1. A efficacy analysis of intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for resected thoracic esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze retrospectively the clinical therapeutic effect and toxicities of three-dimensional conformal radiotherapy (3DCRT) or intensity modulated radiotherapy (IMRT) for resected stage II/III thoracic esophageal squamous cell carcinoma (TESCC). Methods: A total of 251 patients with resected TESCC underwent 3DCRT or IMRT at the Cancer Hospital (Institute), Chinese Academy of Medical Sciences between 2004. 1 to 2009. 7 enrolled. Postoperative radiotherapy applied via 3DCRT (20 patients) or IMRT (231 patients) with a median total dose of 60 Gy. The Kaplan-Meier method was used to calculate the survival rates, and the log-rank test was used for univariate analysis. The Cox proportional model was used for multivariate analysis. Results: The follow-up rate was 98.8%. 159 and 57 patients were followed to 3 and 5 years, respectively. The 1-, 3-and 5-year overall survival (OS) rates for all the patients were 90.8%, 56.1% and 45.8%, respectively. For the stage IIa, IIb, and III stage patients , the 5-year OS rates were 65.0%, 53.8% and 38.4%, respectively (χ2 = 7.30, P = 0.026). The 5-year OS rates were 64.9% and 40.4% for the patients with negative and positive lymph node metastasis (χ2 =7.04, P = 0.008). Univariate analysis showed that the significant prognostic factors include UICC 2002 stage, the degree of differentiation, lymphatic metastasis and vascular carcinomatous thrombus (χ2 =7.30, 7.04, 8.34, 9.40, P = 0.026, 0.008, 0.004, 0.002). Multivariate analysis revealed that the grade of differentiation, lymphatic metastasis and vascular carcinomatous thrombus were independent prognostic factors (χ2 = 6.86, 5.27, 4.24, P= 0.009, 0.022, 0.040). Treatment failure occurred in 58 patients because of systemic metastases, 14 cervical lymph node recurrence, 17 abdominal lymph node metastases, and 31 of intrathoracic recurrence. Five patients had grade 2 or worse late treatment-related anastomotic stenosis, and 8 patients died from late treatment

  2. A meta-analysis of the association between the hOGG1 Ser326Cys polymorphism and the risk of esophageal squamous cell carcinoma.

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    Junjie Zhang

    Full Text Available BACKGROUND: Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1 Ser326Cys (rs1052133 has been implicated in the risk of Esophageal Squamous Cell Carcinoma (ESCC. However, the published findings are inconsistent. We therefore performed a meta-analysis to derive a more precise estimation of the association between the hOGG1 Ser326Cys polymorphism and ESCC risk. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search was conducted to identify eligible studies of hOGG1 Ser326Cys polymorphism and the risk of the ESCC. Three English and two Chinese databases were used, and ten published case-control studies, including 1987 cases and 2926 controls were identified. Odds ratios (ORs and 95% confidence intervals (CIs were used to assess the strength of the association in the dominant and recessive model. Pearson correlation coefficient (PCC and standard error (SE were used to assess the number of Cys allele and ESCC risk in the additive model. Overall, significant associations between the hOGG1 Ser326Cys polymorphism and ESCC risk were found in the recessive model: OR = 1.37 (95% CI: 1.06-1.76, p = 0.02. We also observed significant associations in the Caucasian, Chinese language, population based control and tissue subgroups. In the additive model, positive correlation was found between the number of Cys allele and the risk of ESCC in overall studies (PCC = 0.109, SE = 0.046, p = 0.02, Caucasian subgroup and population subgroup. Funnel plot and Egger's test indicate there was no publication bias in this meta-analysis. CONCLUSION: Under the published data, the hOGG1 Ser326Cys polymorphism is associated with ESCC risk in the recessive and additive model. Compared with the Ser/Ser and Ser/Cys genotype, Cys/Cys genotype might contribute to increased risk of ESCC. And the risk of ESCC is positively correlated with the number of Cys allele. A better case-control matched study should be designed in order to provide a more precise

  3. Microsomal epoxide hydrolase (EPHX1), slow (exon 3, 113His) and fast (exon 4, 139Arg) alleles confer susceptibility to squamous cell esophageal cancer

    International Nuclear Information System (INIS)

    Genetic polymorphisms in xenobiotic metabolizing enzymes may alter risk of various cancers. Present case-control study evaluated the influence of EPHX1 genetic variations on squamous cell esophageal cancer (ESCC) susceptibility in 107 patients and 320 controls. EPHX1 polymorphic alleles were genotyped by direct sequencing (exon 3, Tyr113His) or PCR-RFLP (exon 4, His139Arg). Patients with exon 3 genotypes (Tyr113His, His113His) and 113His allele were at risk of ESCC (ORTyr113His 2.0, 95% CI = 1.2-3.4, p = 0.007; ORHis113His 2.3 95% CI = 1.0-5.2, p = 0.03 and ORHis 1.5, 95% CI = 1.0-2.1, p = 0.01). In contrast, individuals with exon 4, 139Arg allele were at low risk of cancer (OR 0.34, 95% CI = 0.20-0.56, p = 0.001). However, none of haplotype combinations of exon 3 (Tyr113His) and exon 4 (His139Arg) polymorphisms showed modulation of risk for ESCC. Sub-grouping of patients based on anatomical location of tumor predicted that patients with exon 3, His113His and Tyr113His genotypes were at higher risk for developing ESCC tumor at upper and middle third locations (OR 4.4, 95% CI = 1.0-18.5, p = 0.04; OR 2.5, 95% CI = 1.3-5.0, p = 0.005 respectively). The frequency of exon 4, His139Arg genotype was significantly lower in ESCC patients with lower third tumor location as compared to controls (14.8% vs. 36.3%, p = 0.02). In case-only study, gene-environment interaction of EPHX1 genotypes with tobacco, alcohol and occupational exposures did not appear to modulate the cancer susceptibility. In conclusion, exon 3, Tyr113His genotype was associated with higher risk of ESCC particularly at upper and middle-third anatomical locations of tumor. However, His139Arg genotype of exon 4, exhibited low risk for ESCC as well as its clinical characteristics

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

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    Sanambar Sadighi

    2015-06-01

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

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

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

    1991-01-01

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

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

    International Nuclear Information System (INIS)

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

  7. Quantitative real-time RT-PCR validation of differential mRNA expression of SPARC, FADD, Fascin, COL7A1, CK4, TGM3, ECM1, PPL and EVPL in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors and typically presents at an advanced and rapidly fatal stage. To better understand the role of genetics in the etiology and prevention of ESCC and to identify potential susceptibility genes as well as early detection markers, we previously compared tumor and matched normal tissues from ESCC patients from a high-risk area of China using cDNA expression microarrays and identified 41 differentially-expressed genes (13 over-expressed and 28 under-expressed). In the current study, we validated and quantitated differential mRNA expression in a sample of nine of these 41 genes, including four that were over-expressed (SPARC, FADD, Fascin, COL7A1), and five that were under-expressed (CK4, TGM3, ECM1, PPL, EVPL), in 75 new ESCC patients using quantitative Real-time RT-PCR and the 2-ΔΔCT method to examine both tumor and matched normal tissue. In addition, we examined expression patterns for these genes by selected demographic and clinical characteristics. Four previously over-expressed (tumor ≥2-fold normal) genes were all increased in the majority of new ESCC patients: SPARC was increased in 71% of patients, Fascin in 70%, FADD in 63%, and COL7A1 in 57%. Five previously under-expressed (tumor ≤0.5-fold normal) genes similarly showed decreased mRNA expression in two-thirds or more of patients: CK4 was decreased in 83% of patients, TGM3 in 77%, ECM1 in 73%, and PPL and EVPL in 67% each. In subset analyses, associations with age (for COL7A1), family history (for PPL and ECM1), and alcohol use (for SPARC and Fascin) were also noted. These data indicate that these nine genes have consistent differential mRNA expression, validating results of our previous cDNA array results, and affirming their potential role in the early detection of ESCC

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

    International Nuclear Information System (INIS)

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

  9. Prospective study of bacteremia rate after elective band ligation and sclerotherapy with cyanoacrylate for esophageal varices in patients with advanced liver disease

    OpenAIRE

    Danielle Queiroz Bonilha; Lucianna Motta Correia; Marie Monaghan; Luciano Lenz; Marcus Santos; Ermelindo Della Libera

    2011-01-01

    CONTEXT: Band ligation (BL) is the most appropriate endoscopic treatment for acute bleeding or prophylaxis of esophageal variceal bleeding. Sclerotherapy with N-butyl-2-cyanoacrylate (CY) can be an alternative for patients with advanced liver disease. Bacteremia is an infrequent complication after BL while the bacteremia rate following treatment with CY for esophageal varices remains unknown. OBJECTIVES: To evaluate and compare the incidence of transient bacteremia between cirrhotic patients ...

  10. Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Lian Wang; Zhongxing Liao; Helen Liu; Jaffer Ajani; Stephen Swisher; James D Cox; Ritsuko Komaki

    2006-01-01

    AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer.METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed.RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%).tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%)of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula.CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

  11. Advances in dosimetry and biological predictors of radiation-induced esophagitis

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    Yu Y

    2016-01-01

    Full Text Available Yang Yu,1 Hui Guan,1 Yuanli Dong,1 Ligang Xing,2 Xiaolin Li2 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan, 2Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong Province, People’s Republic of China Objective: To summarize the research progress about the dosimetry and biological predictors of radiation-induced esophagitis.Methods: We performed a systematic literature review addressing radiation esophagitis in the treatment of lung cancer published between January 2009 and May 2015 in the PubMed full-text database index systems.Results: Twenty-eight eligible documents were included in the final analysis. Many clinical factors were related to the risk of radiation esophagitis, such as elder patients, concurrent chemoradiotherapy, and the intense radiotherapy regimen (hyperfractionated radiotherapy or stereotactic body radiotherapy. The parameters including Dmax, Dmean, V20, V30, V50, and V55 may be valuable in predicting the occurrence of radiation esophagitis in patients receiving concurrent chemoradiotherapy. Genetic variants in inflammation-related genes are also associated with radiation-induced toxicity.Conclusion: Dosimetry and biological factors of radiation-induced esophagitis provide clinical information to decrease its occurrence and grade during radiotherapy. More prospective studies are warranted to confirm their prediction efficacy. Keywords: lung cancer, esophagitis, radiation injuries, predictors

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  13. 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.

  14. The Changing Face of Esophageal Cancer

    International Nuclear Information System (INIS)

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

  15. Early prediction of treatment response by serum CRP levels in patients with advanced esophageal cancer who underwent definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Serum C reactive protein (CRP) has been shown to be associated with the progression of esophageal cancer. The purpose of this study was to examine the relationship between treatment response and serum CRP levels in time course during definitive chemoradiotherapy (CRT) in terms of early prediction of CRT response by serum CRP. The subjects of this study were 36 patients with cT3/cT4 esophageal squamous cell carcinoma who underwent definitive CRT in our hospital. Serum CRP levels during definitive CRT (pretreatment, 1W, 2W and 3W after CRT initiation) were compared between CR and non-CR group. In addition, partition model was constructed to discriminate CR with non-CR and the prediction accuracy was evaluated. The patients were consisted of 28 males and 8 females. At pretreatment diagnosis, tumors were categorized as T3 (n=21) and T4 (n=15). Thirty four patients received FP-based chemotherapy and 2 patients received docetaxel-based chemotherapy. Treatment responses were categorized as CR (n=8), partial response (PR) (n=14), no change (NC) (n=2) and progressive disease (PD) (n=12). Serum CRP levels at the time of 2W after CRT initiation (CRT2W) in CR group were low compared to those in non-CR group (p=0.071). The partition model was constructed based on CRP levels at CRT2W. The prediction accuracies to discriminate CR from non-CR by CRP ≤0.1 were 50%, 82%, and 75% in sensitivity, specificity and accuracy, respectively. Serum CRP is a useful biomarker for an early prediction of CRT response. (author)

  16. Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Yu, Xian; Li, Tingting; Xia, Yifan; Lei, Jun; Wang, Yan; Zhang, Lijuan

    2016-05-01

    In the past decade, studies have revealed that the phosphatase and tensin homolog (PTEN) protein, a tumor suppressor, comprises a potential biological marker and therapeutic target for esophageal squamous cell carcinoma (ESCC). As such, the delivery of the PTEN gene represents a powerful strategy for ESCC therapy. The tegument protein VP22 of herpes simplex virus type 1 (HSV-1) has been reported to act as a transporter of heterologous proteins across the host cell membrane, thereby enhancing the biological functions of these proteins. In the present study, the intercellular delivery and antitumor activity of the fusion protein PTEN-VP22 were examined in the esophageal squamous cell carcinoma cell line Eca109 both in vitro and in vivo. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. VP22 alone did not exert antiproliferative effects or induce cell cycle arrest, induction of apoptosis, blockage of the Akt and focal adhesion kinase (FAK) pathways, tumor growth inhibition, or antiangiogenic effects in Eca109 cells. However, compared with PTEN alone, PTEN-VP22 exerted significantly higher antiproliferative effects and induced cell cycle arrest at G1 stage, apoptosis and antiangiogenic effects in Eca109 cells. Together, our findings demonstrate that VP22 alone does not exert antitumor activity directly; however, this protein mediates the intercellular delivery of PTEN and thereby increases its intracellular concentration to achieve a therapeutic steady state, leading to an overall increase in the antitumor activity of PTEN. This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment. PMID:27004535

  17. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens

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    Kono Koji

    2012-07-01

    Full Text Available Abstract Background Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK, lymphocyte antigen-6 complex locus K (LY6K, and insulin-like growth factor-II mRNA binding protein-3 (IMP3 had been shown to be promising for esophageal squamous cell carcinoma (ESCC, we further performed a multicenter, non-randomized phase II clinical trial. Patients and methods Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+ and -negative (24(− groups. Results The OS in the 24 (+ group (n = 35 tended to be better than that in the 24(− group (n = 25 (MST 4.6 vs. 2.6 month, respectively, p = 0.121, although the difference was not statistically significant. However, the PFS in the 24(+ group was significantly better than that in the 24(− group (p = 0.032. In the 24(+ group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+ group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusions The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. Trial registration ClinicalTrials.gov, number NCT00995358

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

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

    1993-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

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

  1. Multidetector CT Assessment of Lymph Node Size for Nodal Staging in Patients with Potentially Operable Squamous Esophageal Cancer and the 18F-FDG Positron Emission Tomography CT Correlation

    International Nuclear Information System (INIS)

    To investigate the size criteria of multidetector computed tomography (MDCT) for the evaluation metastatic lymph nodes (LNs) for potentially operable squamous esophageal cancer, and to compare this information with the results of positron emission tomography-CT (PET-CT). Twenty-four patients who underwent radical esophagectomy for esophageal cancer were studied. All patients had preoperative MDCT and PET-CT. The MDCT findings were compared with those of PET-CT and were correlated with the surgical records. The receiver operating characteristic (ROC) curve method was used to determine the appropriate cut-off value to distinguish benign from metastatic LNs. The size of metastatic LNs (9.35 ± 3.41 mm) was significantly larger than that of benign LNs (5.74 ± 1.64 mm) (p<0.001). The best cut-off value was 7 mm (81.8% sensitivity, 80.8% specificity). PET-CT detected all metastatic LNs except for four in the peritumoral region. The sensitivity and specificity of metastatic LN evaluation on PET-CT were 82.6% and 99.4%, respectively. Only one LN without metastasis showed increased fluoro-2-deoxy-D-glucose uptake on PET-CT. Size of metastatic LNs can typically be < 10 mm. For MDCT, the short diameter of 7 mm may be the optimal criterion. PET-CT is very accurate for the assessment of metastatic LNs except for those in the peritumoral region

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

    Science.gov (United States)

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

    2016-08-12

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

  3. A clinical trial of neoadjuvant concurrent chemoradiotherapy followed by resection for esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Kazem Anvari

    2015-01-01

    Full Text Available Background: Esophageal carcinoma is a common malignancy in the North East of Iran. Combined modality treatments have been adopted to improve survival in patients with esophageal carcinoma. In this trial, we evaluated the efficacy and toxicity of a preoperative concurrent chemoradiotherapy protocol in the patients with locally advanced esophageal carcinoma. Materials and Methods: Between 2006 and 2011, eligible patients with locally advanced esophageal carcinoma underwent concurrent radiotherapy and chemotherapy and 3-4 weeks later, esophagectomy. Pathologic response, overall survival rate, toxicity, and feasibility were evaluated. Results: One hundred ninety-seven patients with a median age of 59 (range: 27-70 entered the protocol. One hundred ninety-four cases (98.5% had esophageal squamous cell carcinoma. Grades 3-4 of toxicity in patients undergoing neoadjuvant chemoradotherapy were as follows: Neutropenia in 21% and esophagitis in 2.5% of cases. There were 11 (5.6% early death probably due to the treatment-related toxicities. One hundred twenty-seven patients underwent surgery with postsurgical mortality of 11%. In these cases, the complete pathological response was shown in 38 cases (29.9% with a 5-year overall survival rates of 48.2% and median overall survival of 44 months (95% confidence interval, 24.46-63.54. Conclusion: The pathological response rate and the overall survival rate are promising in patients who completed the protocol as receiving at least one cycle of chemotherapy. However, the treatment toxicities were relatively high.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    esophagitis though multivariable logistic regression. The optimal dose metrics were chosen using Akaike Information Criterion (AIC). All models included one dose position parameter, one dosimetric parameter, gender, and institution. Dose position was defined as the average relative position (zero at start of...

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

    Directory of Open Access Journals (Sweden)

    Ross Zeitlin

    2015-04-01

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

  6. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    Science.gov (United States)

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication. PMID:26370423

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

    Institute of Scientific and Technical Information of China (English)

    许鹏; 王丹云; 王宗明; 张志平; 沈令广; 杨长征

    2009-01-01

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

  8. Expression of MUC1 in esophageal squamous-cell carcinoma and its relationship with prognosis of patients from Linzhou city,a high incidence area of northern China

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

    AIM: To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved.METHODS: 114 specimens of ESC were collected from Linzhou city, and all patients were followed up for more than 5 years after resection. Histopathological analysis and immunohistochemical staining (ABC) were employed to detect the alteration of MUC1.RESULTS: The positive immunostaining rate for MUC1 was 79 % (90/114), and the high-expression rate was 63 %(72/114). The mean survival periods (months) of those with high- and low-expression rates of MUC1 were 41 (95 % CI:35, 47) and 52 (95 % CI: 45, 59), respectively. Patients in the low-expression group obviously survived longer than those in high-expression group, and the difference was significant (P<0.05). The expression of MUC1 protein in the esophageal carcinoma specimens with metastasis was stronger than those without metastasis, the difference was also significant (P<0.05). The stepwise multivariate analysis showed that "differentiation", "expression of MUC1" and "TNM staging" were the most important factors affecting the prognosis of esophageal carcinoma patients (P<0.05).CONCLUSION: A good correlation between the alteration of MUC1 and the regional lymph node metastasis was observed. Furthermore, high-expression of MUC1 was associated with poor prognosis for esophageal cancer patients. These results indicated that MUC1 is a promising biomarker for predicting lymph node metastasis and prognosis in esophageal cancer.

  9. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present

  10. Combination therapy for advanced oral squamous cell carcinoma with radiation and bleomycin, 1

    International Nuclear Information System (INIS)

    Twenty-five patients of advanced oral cancers (squamous cell carcinoma) were treated with combination of radiation and bleomycin in the first course of treatment, and then treated with either Ra needle or 198Au grain implantation, 2 to 3 weeks after the first course of treatment for severe mucositis. The treatments were performed during 1975 to 1977. In the combination therapy, external irradiation (daily 250 rad) of Telecobalt γ-ray or Betatron electron beam was given by 4 fractionations per week during 2.5 to 3 weeks (2,500 to 3,000 rad). Bleomycin (5 mg) was injected intramuscularly about 30 min before the irradiation, giving a total of 50 to 60 mg during therapy. In the second course of therapy, Ra needle or 198Au grain implants were employed in 14 cases and further external irradiation was given for the remaining cases except one which had two primary origins of cancer in the tongue and liver. As a result of the combination therapy, 12 primary tumors out of 25 cases markedly regressed (more than 50% regression) and by subsequent radiotherapy, 11 primary tumors out of 24 were completely controlled during more than 14 months of follow-up observation. The tongue cancer in one exceptional case was controlled by the combination of radiation (3,000 rad) and bleomycin (60 mg) alone. Fifteen of 25 patients are still alive, while 10 patients died of cancer. This therapy of combined irradiation and bleomycin seems to be effective on advanced oral cancers because the local tumor control rate increased markedly. (author)

  11. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  12. Prospective study of bacteremia rate after elective band ligation and sclerotherapy with cyanoacrylate for esophageal varices in patients with advanced liver disease

    Directory of Open Access Journals (Sweden)

    Danielle Queiroz Bonilha

    2011-12-01

    Full Text Available CONTEXT: Band ligation (BL is the most appropriate endoscopic treatment for acute bleeding or prophylaxis of esophageal variceal bleeding. Sclerotherapy with N-butyl-2-cyanoacrylate (CY can be an alternative for patients with advanced liver disease. Bacteremia is an infrequent complication after BL while the bacteremia rate following treatment with CY for esophageal varices remains unknown. OBJECTIVES: To evaluate and compare the incidence of transient bacteremia between cirrhotic patients submitted to diagnostic endoscopy, CY and BL for treatment of esophageal varices. METHODS: A prospective study comprising the period from 2004 to 2007 was conducted at Hospital of Universidade Federal de São Paulo, UNIFESP, SP, Brazil. Cirrhotic patients with advanced liver disease (Child-Pugh B or C were enrolled. The patients were divided into two groups according treatment: BL Group (patients undergoing band ligation, n = 20 and CY Group (patients receiving cyanoacrylate injection for esophageal variceal, n = 18. Cirrhotic patients with no esophageal varices or without indication for endoscopic treatment were recruited as control (diagnostic group n = 20. Bacteremia was evaluated by blood culture at baseline and 30 minutes after the procedure. RESULTS: After 137 scheduled endoscopic procedures, none of the 58 patients had fever or any sign suggestive of infection. All baseline cultures were negative. No positive cultures were observed after CY or in the control group - diagnostic endoscopy. Three (4.6 % positive cultures were found out of the 65 sessions of band ligation (P = 0.187. Two of these samples were positive for coagulase-negative staphylococcus, which could be regarded as a contaminant. The isolated microorganism in the other case was Klebsiella oxytoca. The patient in this case presented no evidence of immunodeficiency except liver disease. CONCLUSIONS: There was no significant difference in bacteremia rate between these three groups. BL or CY

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

    International Nuclear Information System (INIS)

    We report clinico-pathological studies on the effect of preoperative hyperthermia and chemotherapy combined with radiotherapy (HCR) for progress of the local curability of advanced esophageal carcinoma. The subjects of these studies were 17 patients who underwent subtotal esophagectomy after preoperative irradiation of 40 Gy from 1980 to 1989, of which 8 patients had HCR, 6 patients irradiation only (R), 3 patients both irradiation and chemotherapy (CR). The clinical response rate of the patients with R or CR was 33% (PR 3, MR 3, NC 3), and the histological effective (Ef3 or Ef2) rate was 56% (Ef3 1, Ef2 4, Ef1 4). The clinical response rate of the patients with HCR was 88% (PR 7, MR 1), and the histological effective rate was 100% (Ef3 1, Ef2 7). HCR was more effective than R or CR for the local lesion of esophageal carcinoma histopathologically (p<0.05). However, the survival rate of patients with HCR was similar to R and CR, respectively. These results suggest that further improvement of the heating methods and the methods of combining hyperthermia with irradiation and chemotherapy is needed. (author)

  14. 3'-Deoxy-3'-[18F]-fluorothymidine PET/CT in early determination of prognosis in patients with esophageal squamous cell cancer. Comparison with [18F]-FDG PET/CT

    International Nuclear Information System (INIS)

    The purpose of this work was to investigate the prognostic value of response analysis using early 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) PET/CT in esophageal squamous cancer patients and make a comparison with [18F]-fluorodeoxyglucose (18F-FDG) PET/CT. For 34 patients with esophageal squamous cell cancer, both 18F-FLT PET/CT and 18F-FDG PET/CT scans were performed at baseline (pre), 4 weeks after the start of radiotherapy or chemoradiotherapy (interim), and 2 weeks after therapy completion (final). SUVmax1, SUVmax2, and SUVmax3 represent SUVmax (SUV: standard uptake values) measured on the pre, interim, and final scans, respectively. GTVFLT-PET and GTVFDG-PET (GTV: gross tumor volume) were measured on the pre and interim scans. ΔSUV/ΔGTV represents the fractional changes of SUVmax/GTV between two different time points. PET parameters were evaluated for correlations with outcome. Regarding 18F-FLT PET/CT, according to receiver operating characteristic (ROC) curve analysis, parameters for predicting 2-year progression-free survival (PFS) and locoregional control (LRC) showed the highest area under curve (AUC) on interim 18F-FLT PET/CT scans (ΔSUV12, AUC of 0.812 for PFS, 0.775 for LRC, with a cutoff of 60 %; P = 0.008), compared with the parameters on pre and final scans. Patients with a ΔSUV12 greater than 60 %, who were defined as interim PET-negative group, were associated with better 2-year PFS and LRC than the interim PET-positive group (PFS: 70.6 % vs. 35.2 %, P = 0.025; LRC: 84.2 % vs 52.9, P = 0.046). In terms of 18F-FDG PET/CT, ΔSUV13 on the final 18F-FDG PET/CT scan demonstrated better prediction (AUC of 0.812 for PFS, 0.807 for LRC, with a cutoff of 75 %; P = 0.016) than the parameters on pre and interim scans. An SUVmax decrease ≥ 75 % on the final18F-FDG PET/CT scan was associated with better clinical outcome (PFS: 73.3 % vs. 36.8 %, P = 0.022; LRC: 86.7 % vs 52.6, P = 0.029). These correlations were most prominent in the subgroup of patients

  15. Retrospective analysis of multidisciplinary therapy for locally advanced squamous cell carcinoma of the maxillary sinus

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Hiroshi; Seo, Yuji; Nakajima, Kaori; Miyano, Takashi [Asahikawa Medical Univ., Hokkaido (Japan); Kikuchi, Yuzou [Kanazawa Univ. (Japan). School of Medicine

    2002-06-01

    The purpose of this study was to retrospectively investigate the efficacy of multidisciplinary therapy (concomitant radiotherapy and intra-arterial infusion of 5-fluorouracil (5-FU) followed by maxillectomy) in the treatment of squamous cell carcinoma of the maxillary sinus. We reviewed 71 patient records with locally advanced but respectable carcinoma of the maxillary sinus treated by means of multidisciplinary therapy between 1978 through 1997. The clinical T factor for these patients, according to the UICC definitions (1997), was 12 for T2, 46 for T3, and 13 for T4. Twelve patients were diagnosed as node-positive at initial presentation. Intra-arterial 5-FU was delivered via a superficial temporal artery in accordance with radiotherapy, and the cumulative 5-FU dose ranged from 2,900 mg to 5,250 mg (median 5,000 mg). The total radiotherapy dose ranged from 29 Gy to 48 Gy (median 48 Gy) with conventional fractionation. Patients underwent radical maxillectomy thereafter. The 5-year overall survival rate and disease-specific survival rate of all the patients were 58% and 68%, respectively. There was no significant correlation of clinical T factor or N factor with disease-specific survival on univariate and multivariate analysis. The overall treatment-related mortality rate was 3.7%. Radiation cataract later developed in all evaluable patients whose lenses were within the treatment volume. About a half of the operable T4 patients survived over 5 years by means of the above-mentioned multidisciplinary therapy. This multidisciplinary therapy should be compared to treatment with a combination of surgery and postoperative chemoradiotherapy. (author)

  16. Retrospective analysis of multidisciplinary therapy for locally advanced squamous cell carcinoma of the maxillary sinus

    International Nuclear Information System (INIS)

    The purpose of this study was to retrospectively investigate the efficacy of multidisciplinary therapy (concomitant radiotherapy and intra-arterial infusion of 5-fluorouracil (5-FU) followed by maxillectomy) in the treatment of squamous cell carcinoma of the maxillary sinus. We reviewed 71 patient records with locally advanced but respectable carcinoma of the maxillary sinus treated by means of multidisciplinary therapy between 1978 through 1997. The clinical T factor for these patients, according to the UICC definitions (1997), was 12 for T2, 46 for T3, and 13 for T4. Twelve patients were diagnosed as node-positive at initial presentation. Intra-arterial 5-FU was delivered via a superficial temporal artery in accordance with radiotherapy, and the cumulative 5-FU dose ranged from 2,900 mg to 5,250 mg (median 5,000 mg). The total radiotherapy dose ranged from 29 Gy to 48 Gy (median 48 Gy) with conventional fractionation. Patients underwent radical maxillectomy thereafter. The 5-year overall survival rate and disease-specific survival rate of all the patients were 58% and 68%, respectively. There was no significant correlation of clinical T factor or N factor with disease-specific survival on univariate and multivariate analysis. The overall treatment-related mortality rate was 3.7%. Radiation cataract later developed in all evaluable patients whose lenses were within the treatment volume. About a half of the operable T4 patients survived over 5 years by means of the above-mentioned multidisciplinary therapy. This multidisciplinary therapy should be compared to treatment with a combination of surgery and postoperative chemoradiotherapy. (author)

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

    OpenAIRE

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王皓; 钟理; 王建飞; 张小刚

    2009-01-01

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

  19. Locally-regionally advanced tonsillar squamous cell carcinoma treated with concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: To perform a retrospective review of stage III-IV squamous cell carcinoma of the tonsil managed by definitive concurrent chemoradiotherapy (CCRT) in order to analyze the patients’ outcome and to evaluate the acute and late toxic effects of this treatment modality. Material and methods: Between January 2005 and December 2010, 36 patients with locally and/or regionally advanced tonsillar cancer underwent three dimensional conformal radiotherapy (3DCRT) with concurrent platinum-based chemotherapy. The dose prescription of the planning target volume for gross tumor and low-risk subclinical disease was 70 Gy and 50 Gy, respectively. Conventional fractionation with a daily dose of 2.0 Gy, 5 times per week was used. Concurrent chemotherapy consisted of cisplatin 30 mg/m2 given on a weekly basis. Acute and late radiotherapy-related toxicities were recorded using European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) grading system. The 3-year locoregional relapse-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up of all patients was 20.5 months (range, 5 to 90 months). The median followup of living patients was 59 months (range, 30 to 90 months). Complete response rates of the primary tumor and of the nodal disease were 72.2% and 64.0%, respectively. A complete composite response was present in 25 patients (69.4%). Treatment failure occurred in 15 out of 25 patients who achieved complete composite response following CCRT. The 3-year LRRFS, DFS, and OS rate was 38.8%, 27.8%, and 27.3%, respectively. Grade 3 mucositis occurred in 58.3% of patients. Xerostomia grade 2 was revealed in 72.2% of patients. Conclusion: Taking into account the low 3-year survival rates observed in our study and the high percentage of grade 2 xerostomia, it can be concluded that in the future, instead of 3DCRT with concurrent

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-15

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

  1. Endoscopic Stent Treatment of Advanced Esophageal Cancer%内镜直视下中晚期食道癌的支架治疗

    Institute of Scientific and Technical Information of China (English)

    杜桂英; 陶中原

    2012-01-01

    Objective: To explore the approach and the therapeutic effect of endoscopic stent treatment of advanced esophageal cancer. Methods: Endoscopic stent implantation was carried out on patients diagnosed advanced esophageal cancer with endoscopy and pathological examination, who was unwilling to operate or unresectable. Results: Total 91 patients were treated with 97 stents, the success rate was 100% and efficiency was 100%. Conclusion: Endoscopic esophageal stenting is an effective method for the treatment of advanced esophageal cancer.%目的:探讨中晚期食道癌内镜下治疗的方法和疗效。方法:经过内镜检查和病理诊断的中晚期食道癌,不愿意或失去手术机会的患者进行内镜直视下支架的置入术。结果:91例患者置/L97个支架,成功率100%,有效率100%。结论:内镜直视下食道支架置入是治疗中晚期食道癌的有效方法。

  2. Ultrafast computed tomography on advanced esophageal cancer into the peripheral organs

    International Nuclear Information System (INIS)

    The evaluation of invasion of thoracic esophageal cancer into peripheral organs by ultrafast computed tomography (UFCT) was compared with operative findings. The subjects were 34 thoracic esophageal cancer patients with suspected invasion into the aorta, pericardium or tracheobronchial tree. Images obtained by the volume mode were clear and were not blurred. The cine mode showed changes in the degree of contact between the carcinoma and peripheral organs in relation to pulsation of the heart. Invasion to the aorta was examined in 32 subjects according to diagnostic criteria consisting of the condition of the aortic wall, changes in the contact angle to the aorta, presence of a low density zone, and site of the carcinoma. The changes in the contact angle to the aorta were defined as the difference between maximum and minimum contact angle. The accuracy of UFCT diagnosis determined by comparison with operative findings wes 100%. There was a statistical significance that indicated a relationship between invasion and changes in the contact angle. When the change in the contact angle was 15deg or less, invasion to the aorta could be seen; when it was 16deg or more, no invasion to the aorta could be seen. Invasion into the pericardium was examined in 25 subjects according to diagnostic criteria consisting of the presence of a low density zone, presence of marginal irregularity, and site of the carcinoma. The sensitivity of UFCT diagnosis was 50%, the specificity was 100%, and the accuracy was 92.0%. Invasion into the tracheobronchial tree was examined in 16 patients according to the diagnostic criteria of our morphological classification. The sensitivity of UFCT was 80%, the specificity was 90.9%, and the accuracy was 87.5%. UFCT is particularly useful in the evaluation of aortic and pericardial invasion of middle and lower thoracic esophageal cancer, which is often difficult to evaluate by conventional CT because of the interference caused by heart beats. (author)

  3. Prevalence of esophageal cancer during the pretreatment of hypopharyngeal cancer patients: Routinely performed esophagogastroduodenoscopy and FDG-PET/CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Nakaminato, Shuichiro; Toriihara, Akira; Makino, Tomoko; Shibuya, Hitoshi [Dept. of Radiology, Tokyo Medical and Dental Univ., Tokyo (Japan)], Email: S.Nakaminato@gmail.com; Kawano, Tatsuyuki [Dept. of Surgery, Tokyo Medical and Dental Univ., Tokyo (Japan); Kishimoto, Seiji [Dept. of Head and Neck Surgery, Tokyo Medical and Dental Univ., Tokyo (Japan)

    2012-05-15

    Background. The prevalence of esophageal cancer accompanied by hypopharyngeal cancer (HPC) is high and increasing rapidly in Asia. The purpose of this prospective study was to evaluate the prevalence of esophageal cancer during the pretreatment of HPC patients who were routinely examined using esophagogastroduodenoscopy (EGD) and 18F-fluorodeoxyglucose/computed tomography (FDG-PET/CT) and to discuss the utility of these examinations. Material and methods. Between September 2005 and September 2010, 33 patients with newly diagnosed HPC (all with squamous cell carcinoma) underwent EGD (after a conventional endoscopy, iodine staining was performed) and FDG-PET/CT examinations. We evaluated the prevalence of esophageal cancer among HPC patients according to the EGD findings and determined the sensitivity of FDG-PET/CT for the detection of esophageal primary tumors for each clinical T classification. Results. In 17 of the 33 patients (51.5%), 29 biopsy-proven esophageal squamous cell carcinomas were diagnosed using EGD. In eight of the 17 (47.1%) patients, two or more esophageal cancer lesions were diagnosed. Twenty-four of the 29 (82.8%) lesions were superficial esophageal cancers, and the remaining five (17.2%) lesions were advanced esophageal cancers. In six of the 29 (20.7%) esophageal cancer lesions that were detected using FDG-PET/CT, only one of the 29 (3.4%) lesions was evaluated as being equivocal; the remaining 22 (75.9%) lesions were not detected. The distribution of the clinical T classifications detected using FDG-PET/CT was as follows: T1a, 0/21 (0%); T1b, 1/3 (33%); and T3, 5/5 (100%). Conclusions. The prevalence of esophageal cancer during the pretreatment of HPC patients was 51.5%; this prevalence was higher than that in previous reports. We believe that the increasing proportion of superficial lesions (82.8%) detected using iodine staining and EGD may have led to the relatively high prevalence. FDG-PET/CT detected only 20.7% of the esophageal cancers

  4. The effect of tumor length, maximum diameters and volume on the response of N0 stage thoracic esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of GTV volume on response of esophageal carcinoma. Methods: From Jan. 2004 to Dec. 2008, 72 cases newly diagnosed N0 stage thoracic esophageal carcinomas were included in this retrospective study. All treatment plans were set up and designed by CT simulator and 3D TPS. They received dose 56-70 Gy/27-33 F/6-7 w with 6 MV X-ray. The GTV, the tumor length and maximum diameters were measured on the treatment planning system with the X-ray. RECIST standard was applied to evaluate the radiotherapy response of esophageal carcinoma. The effectiveness of related prognostic factors on survival was evaluated by univariate analyses. Results: The short-term response with CR were 79% with length < 5 cm, 48% with 5-7 cm and 26% with length >7 cm(P =0.003). The 1-, 2-, 3-and 5-year survival rates were 93%, 79%, 69%, 69%; 91%, 61%, 46%, 46% and 80%, 46%, 28%, 22% (P =0.037). The short-term response with CR were 56% with maximum diameters ≤3 cm and 33% with maximum diameters > 3 cm(P =0.033). The 1-, 2-, 3-and 5-year survival rates were 91%, 72%, 55%, 37% and 80%, 45%, 30%, 30% (P =0.037). The short-term response with CR were 52% with GTV volume ≤40 cm3 and 30% with GTV volume >40 cm3 (P =0.059). The 1-, 2-, 3-and 5-year survival rates were 91%, 67%, 51%, 41% and 80%, 43%, 27%, 27% (P =0.047). In the multivariate analysis, the length of GTV was likely to be the most important factor for the short-term response (P =0.005, 0.014). Conclusions: GTV volume, the tumor length and maximum diameters are factors for short-term response of N0 stage esophageal carcinoma.The GTV length is independent prognostic factor. The GTV length is the worse the prognosis will be. (authors)

  5. 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 ...

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

    Directory of Open Access Journals (Sweden)

    A. Khambati

    2016-07-01

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

  7. Understanding the sensory irregularities of esophageal disease.

    Science.gov (United States)

    Farmer, Adam D; Brock, Christina; Frøkjaer, Jens Brøndum; Gregersen, Hans; Khan, Sheeba; Lelic, Dina; Lottrup, Christian; Drewes, Asbjørn Mohr

    2016-08-01

    Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future. PMID:26890720

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

    OpenAIRE

    Ana Grilo; Carla Adriana Santos; Jorge Fonseca

    2012-01-01

    "Context - Esophageal cancer is often diagnosed at an advanced stage and has a poor prognosis. Most patients with advanced esophageal cancer have significant dysphagia that contributes to weight loss and malnutrition. Esophageal stenting is a widespread palliation approach, but unsuitable for cancers near the upper esophageal sphincter, were stents are poorly tolerated. Generally, guidelines do not support endoscopic gastrostomy in this clinical setting, but it may be the best option...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hong-Bing Shen

    2012-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-18

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

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

  14. Esophageal Cancer in Iran: A Review

    OpenAIRE

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Henríquez-Hernández Luis

    2012-08-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-04-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

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

    Science.gov (United States)

    2016-03-11

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    荣爱梅; 郭长青

    2011-01-01

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

  7. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2016-04-05

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

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

    Directory of Open Access Journals (Sweden)

    Vitor Arantes

    2012-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-15

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

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

    Science.gov (United States)

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

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

  12. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    Science.gov (United States)

    2015-12-08

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

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

    OpenAIRE

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

    2015-01-01

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

  14. p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Tumor suppressor genes p53 and p16INK4a and the proto-oncogene MDM2 are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the p16 gene and its impact on p16INK4a protein expression and correlations with p53 and MDM2 protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average. Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of p16. The expression of p16, p53 and MDM2 proteins was detected by immunohistochemical staining. Abnormal expression of p16 and p53, but not MDM2, was significantly higher in the tumoral tissue. p53 was concomitantly accumulated in ESCC tumor along with MDM2 overexpression and p16 negative expression. Aberrant methylation of the p16INK4a gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). p16INK4a aberrant methylation was significantly associated with decreased p16 protein expression (P = 0.033), as well as the overexpression of p53 (P = 0.020). p16 hypermethylation is the principal mechanism of p16 protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in p53-MDM2 and p16-Rb pathways, suggesting a possible cross-talk of the involved pathways in ESCC development

  15. A preliminary study on ras protein expression in human esophageal cancer and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Chang Wei Feng; Zhi Guo Zhao; Qi Zhou; Li Dong Wang

    2000-01-01

    @@INTRODUCTION The esophageal carcinoma is a common malignant tumor in Linzhou City (Linxian) of Henan Province in northern China. Although the etiology and natural history of esophageal carcinoma are not clear, a substantial amount of evidence has been provided to suggest that the development of human esophageal squamous cell carcinomas (SCC) is a multistage progressive process[1-4] An early indicator of abnormality in persons predisposed to esophageal SCC is an increased proliferation of esophageal epithelial cells,morphologically manifested as basal cell hyperplasia (BCH), and dysplasia (DYS), and carcinoma in situ, which could be considered precancerous lesions of esophageal SCC[1-4].

  16. Esophageal Inlet Patch

    Directory of Open Access Journals (Sweden)

    C. Behrens

    2011-01-01

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

  17. Combined-modality treatment in advanced oral squamous cell carcinoma. Primary surgery followed by adjuvant concomitant radiochemotherapy

    International Nuclear Information System (INIS)

    The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracapsular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT. (orig.)

  18. Combined-modality treatment in advanced oral squamous cell carcinoma. Primary surgery followed by adjuvant concomitant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kreppel, Matthias; Dreiseidler, Timo; Zoeller, Joachim E.; Scheer, Martin [Koeln Univ. (Germany). Dept. for Oral and Cranio-Maxillo and Facial Plastic Surgery; Center of Integrated Oncology (CIO) Koeln-Bonn, Koeln und Bonn (Germany); Drebber, Uta [Koeln Univ. (Germany). Dept. of Pathology; Center of Integrated Oncology (CIO) Koeln-Bonn, Koeln und Bonn (Germany); Eich, Hans-Theodor; Mueller, Rolf-Peter [Koeln Unvi. (Germany). Dept. of Radiation Oncology; Center of Integrated Oncology (CIO) Koeln-Bonn, Koeln und Bonn (Germany)

    2011-09-15

    The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracapsular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT. (orig.)

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  20. Comparison of treatment using teletherapy (external beam radiation) alone versus teletherapy combined with brachytherapy for advanced squamous cell carcinoma of the esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Samea, Renato; Lourenco, Laercio Gomes, E-mail: renatosamea@globo.com [Department of Surgical Oncology of Dr. Arnaldo Vieira de Carvalho Hospital, Sao Paulo, SP (Brazil)

    2011-10-15

    Background - Squamous cell carcinoma of the esophagus is still a difficult tumor to treat with very poor prognosis. Aim - To compare the response to teletherapy treatment (external beam radiotherapy) alone versus teletherapy combined with brachytherapy for patients with advanced squamous cell carcinoma of the esophagus. Methods - Were studied 49 patients with advanced squamous cell carcinoma of the esophagus on clinical stage III (TNM-1999). They were separated into two groups. The first, underwent radiation therapy alone with linear accelerator of particles, average dose of 6000 cGy and the second to external beam radiation therapy at a dose of 5040 cGy combined with brachytherapy with Iridium 192 at a dose of 1500 cGy. Brachytherapy started one to two weeks after the end of teletherapy, and it was divided into three weekly applications of 500 cGy. Age, gender, race, habits (smoking and drinking), body mass index (BMI), complications with treatment benefits (pain relief and food satisfaction) and survival were analyzed. Results - The quality of life (food satisfaction, and pain palliation of dysphagia) were better in the group treated with external beam radiation therapy combined with brachytherapy. Survival was higher in the brachytherapy combined with external beam radiation therapy alone. Conclusion - Although the cure rate of squamous cell cancer of the esophagus is almost nil when treated with irradiation alone, this therapy is a form of palliative treatment for most patients in whom surgical contraindication exists. (author)

  1. Concurrent chemoradiotherapy for locally advanced and metastatic esophageal cancer. Longterm results of a phase II study of UFT/CDDP with radiotherapy

    International Nuclear Information System (INIS)

    No effective treatment for advanced esophageal cancer extending to adjacent organs or associated with distant metastasis is known. We prospectively analyzed the efficacy of concurrent chemoradiotherapy with uracil plus tegafur (UFT) and cisplatin (CDDP) for such cases of advanced esophageal cancer. Patients with advanced cancers received 60 to 70 Gy of radiotherapy given during a period of 7 weeks, concurrently with daily oral UFT (200 mg/m2 per day), and a 24-h infusion of CDDP (70 mg/m2) on days 8 and 36. After chemoradiotherapy, UFT (250 mg/m2/per day) was administered daily for 1 year, while CDDP (80 mg/m2) was administered twice every 4 weeks. Patients with stage III disease numbered 31, while 24 had stage IV disease according to the tumor-node-metastasis (TNM) staging. Including all patients, complete response (CR) occurred in 20% and partial response (PR) in 51%. In stage III patients, CR, PR, and CR+PR rates were 29%, 48%, and 77%, respectively. In stage IV patients, CR, PR, and CR+PR rates were 8%, 54%, and 63%. Grade 4 leukocytopenia occurred in 22% of patients, and grade 3 pain, nausea/vomiting, and oral mucositis occurred in 7%, 9%, and 4% of patients respectively, but resolved after the reduction or discontinuation of chemoradiotherapy. Median survival in stage III patients was 415 days (range, 3 to 3046 days), and in stage IV patients, it was 187 days (range, 75 to 764 days). The 2-year survival rate in stage III patients was 25% and it was 4% in stage IV patients. The 5-year survival rate in stage III patients was 7%, while in stage IV patients it was 0%. This combined treatment may be a promising nonsurgical management option for locally advanced esophageal cancer, and can achieve good palliative effects in patients with distant metastasis. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In...

  6. Locally advanced hypopharyngeal squamous cell carcinoma: single-institution outcomes in a cohort of patients curatively treated either with or without larynx preservation

    Directory of Open Access Journals (Sweden)

    Isabel Reis

    2016-02-01

    Full Text Available Abstract Objective: The present study was aimed at describing a single-institution experience in the curative treatment of patients diagnosed with locally advanced hypopharyngeal squamous cell carcinoma. Materials and Methods: Data concerning all patients treated for locally advanced hypopharyngeal squamous cell carcinoma between January 2006 and June 2012 were reviewed. Results: A total of 144 patients were included in the present study. The median follow-up period was 36.6 months. Median survival was 26 months, and 2-year and 5-year overall survival rates were, 51% and 30.5%, respectively. Median recurrence-free survival was 18 months and 2-year and 5-year recurrence-free survival rates were 42.8% and 28.5%, respectively. Conclusion: The outcomes in the present series are in line with the literature.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

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

    OpenAIRE

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

  10. Esophageal manometry

    Science.gov (United States)

    ... its ability to move food toward the stomach ( achalasia ) A weak LES, which causes heartburn (GERD) Abnormal contractions of the esophagus muscles that do not effectively move food to the stomach ( esophageal spasm )

  11. Treatment of advanced esophageal cancer by means of irradiation, cisplatinum and 5-fluorouracil

    International Nuclear Information System (INIS)

    In the years 1985-1990, 30 patients with locally advanced and/or disseminated cancer of the esophagus (Stages III and IV) were treated by radiotherapy and chemotherapy containing cisplatinum and 5-fluorouracil (5-fu). The median survival of the patients was 8 months (range 2.5-39 months); 13 stage III patients survived 3-36 months respectively (median 11 months), while 17 stage IV patients survived 2.5-27 months, respectively (median 6.5 months). The survival depended statistically significantly (p<0.05) only on the presence or absence of residual tumor after therapy and not on other parameters observed. Clinical response to treatment was evaluated in 16/30 patients as follows: clinical response (CR) was obtained in 4 patients, partial response in two, and no respond in 10 patients. Median survival of 4 patients with CR was 31 months; relatively high rate of CR (4/16) could be explained by the small number of patients. However, favorable survival results in individual patients may be expected even in larger series, though the rate responders may be somewhat lower than that obtained in our study. (author)

  12. Complications and clinical outcome of salvage surgery after concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Concurrent chemoradiotherapy (CCRT) is increasingly used in organ preservation for head and neck squamous cell carcinoma (HNSCC), with surgery as second-line treatment for salvaging locoregional failure. The significance of post-CCRT salvage surgery, however, remains to be established. We report complications and clinical outcome in 34 salvage surgeries on 30 subjects with advanced HNSCC treated by docetaxel and cisplatin concurrent with conventional radiotherapy. Postoperative complications occurred in 9 (30%) subjects and 10 (29%) surgeries. There was no significant difference in complication incidence between salvage surgeries for persistent disease (7 of 19 cases, 37%) and those for recurrent disease (3 of 15 cases, 20%). Complication incidence in isolated neck dissection (6 of 21 cases, 29%) did not differ significantly from that in primary site resection (4 of 13 cases, 31%). Most frequent complications were dysphagia and skin flap necrosis, occurring in 5 subjects each. Three with dysphagia underwent percutaneous endoscopic gastrostomy, and two with skin flap necrosis led to pharyngocutaneous fistula, requiring pectoralis major myocutaneous flap repair. No carotid artery rupture or chyle fistula occurred. Overall 3-year survival after salvage surgery was 74% for persistent disease, and 87% for recurrent disease. Although post-CCRT salvage surgery harbors high risk of complication, it renders good survival and is recommendable for all whose disease is operable. (author)

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

    Institute of Scientific and Technical Information of China (English)

    张健; 王磊; 赵智宏; 王巨; 刘鑫远; 禹亮

    2012-01-01

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

  14. Surgical treatment analysis of idiopathic esophageal achalasia

    OpenAIRE

    de Aquino, José Luis Braga; SAID, Marcelo Manzano; PEREIRA, Douglas Rizzanti; do AMARAL, Paula Casals; LIMA, Juliana Carolina Alves; LEANDRO-MERHI, Vânia Aparecida

    2015-01-01

    Background Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. Aim To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Methods Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 wi...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    目的 探讨着色性干皮病基因D( xeroderma pigmentosum group D,xPD)基因多态性与食管鳞癌的关系,为揭示食管癌病因及制定食管癌干预措施提供理论依据.方法 采用病例对照研究方法,选取郑州大学附属第一医院食管鳞癌患者235例,按性别与年龄1∶1匹配选取河南省新乡县健康人群235人作为对照,采用聚合酶链反应-限制性片段长度多态性方法,检测xPD312位点和751位点基因型,采用非条件Logistic回归进行多因素和交互作用分析.结果 与野生型GG比较,xPD312位点GA、AA和(GA +AA)基因型与食管鳞癌易感性无关,分别调整后OR=0.83(95%CI=0.05~ 13.55),OR=1.12(95% CI=0.06 ~19.47)和OR=1.35(95%CI=0.73~2.51):与野生型AA比较,xPD751位点AC、CC和(AC +CC)基因型与食管鳞癌易感性无关,分别调整后OR=1.21 (95% CI =0.80 ~1.83),OR=0.99(95%CI=0.42~2.31)和OR=1.17(95% CI=0.79~1.75);以GA作为对照单体型,GC、AA和AC单体型与食管鳞癌易感性无关,未发现两位点与吸烟或饮酒之间的交互作用.结论 xPD 312和xPD 751位点多态性可能与河南汉族人群食管鳞癌的发生无关,且与吸烟或饮酒不存在交互作用.%Objective To explore the association of two single nucleotide polymorphisms (SNPs) in xeroderma pigmentosum group D gene(XPD) with esophageal squamous cell carcinoma(ESCC) risk,and to provide theoretical basis for revealing the etiology of esophageal cancer and developing intervention measures for esophageal cancer. Methods A case-control study was conducted in a Han population of Henan province. Totally 235 patients with ESCC were recruited from a hospital and 235 1:1 gender and age matched controls were selected from healthy population of a country in Henan province. Polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP) was used to detect the genotype of the two SNPs. Multiple variable analysis and gene-environment interaction analysis were

  16. Initial evidence for Sec62 as a prognostic marker in advanced head and neck squamous cell carcinoma

    Science.gov (United States)

    WEMMERT, SILKE; LINDNER, YASMIN; LINXWEILER, JOHANNES; WAGENPFEIL, STEFAN; BOHLE, RAINER; NIEWALD, MARCUS; SCHICK, BERNHARD

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a malignancy with an increasing incidence. To aid with the selection of the most appropriate therapy, biomarkers have become a specific research focus. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer. In addition, Sec62 may be a promising candidate in HNSCC. Pretreatment biopsies of 35 patients with locally advanced HNSCC, who were treated with definitive chemoradiation therapy without prior surgery, were examined for the expression of Sec62 protein, as well as the expression of epidermal growth factor receptor (EGFR), p16 and survivin proteins. Immunohistological results were correlated with patient overall survival (OS) and progression-free survival (PFS) times. In the present patient cohort, 12/35 cases (34%) demonstrated strong and 8/35 cases (23%) moderate Sec62 staining intensity. Additionally, in 11/35 cases (31%), weak staining was observed, and only 4/35 cases (11%) were Sec62-negative. Notably, a high Sec62 protein level was associated with a significantly poorer OS and PFS (P=0.020 and P=0.028, respectively). Furthermore, higher nuclear survivin expression showed a weak trend for poorer OS rate (P=0.079), whilst neither cytoplasmic survivin, EGFR nor p16 influenced OS or PFS significantly. The present study indicated that Sec62 is a promising prognostic marker for HNSCC. Increased Sec62 protein expression may indicate a poorer prognosis in advanced HNSCC. As the present study was focused on patients treated by chemoradiation therapy, further studies with larger patient cohorts and alternative treatment approaches are required in order to define the prognostic value of Sec62 in HNSCC. PMID:26998059

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Hung-Ming Wang

    2014-06-01

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

  19. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  20. Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Nan Wang; Zhi-Hua Liu; Fang Ding; Xiu-Qin Wang; Chuan-Nong Zhou; Min Wu

    2002-01-01

    AIM: Esophageal carcinoma is one of the most common malignant tumors in China. But the molecular mechanisms of esophageal carcinoma remains unclear. Gut-enriched factor which is expressed abandantly in the epithelial cells of the gastrointestinal tract and deregulation of GKLF was linked to several types of cancer. It is of interest to study the expression and role of GKLF in esophageal carcinoma.METHODS: Semi-quantitative RT-PCR was used to compare GKLF expression in esophageal squamous cell carcinoma to normal mucosa of the same patients. The serum deprivation inducibility of GKLF was observed in an esophageal squamous cancer cell line by comparison to the primary culture of human fibroblast. The effect of antisense GKLF transfection on the proliferation and adhesion of esophageal squamous cancer cell line was also observed.RESULTS: The level of GKLF transcript is lower in esophageal squamous cell carcinoma compared to paired normal-appearing mucosa in 14 of 17 of the tumors analyzed.The serum deprivation inducibility of GKLF was greatly decreased in an esophageal squamous cancer cell line compared to the primary culture of human fibroblast.Decreased expression of GKLF in the esophageal cancer cell by antisense GKLF transfection increased its proliferation rate compared with that of vector transfected cell control (P<0.05). Transfection of antisense GKLF decreased its adhesion ability (P<0.05).CONCLUSION: The findings of this study demonstrate the down-regulation of GKLF in esophageal squamous cancer,and suggest that deregulation of GKLF may play a role in initiation and/or progression as well as the metastasis of esophageal squamous cancer.

  1. Eosinophilic esophagitis

    Institute of Scientific and Technical Information of China (English)

    Anand R Gupte; Peter V Draganov

    2009-01-01

    Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is based on the presence of both typical symptoms and pathologic findings on esophageal biopsy. Patients usually present with dysphagia, food impaction and/or reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils per high-power field. In addition,it is essential to exclude the presence of known causes of tissue eosinophilia such as gastroesophageal reflux disease, infections, malignancy, collagen vascular diseases, hypersensitivity, and inflammatory bowel disease. There are no standardized protocols for the therapy of eosinophilic esophagitis. A variety of therapeutic approaches including acid suppression, dietary modi f icat ions, topical cor t icosteroids and endoscopic dilation can be used alone or in combination.

  2. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m2, every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS. (orig.)

  3. Esophageal papilloma: Flexible endoscopic ablation byradiofrequency

    Institute of Scientific and Technical Information of China (English)

    Gianmattia del Genio; Federica del Genio; Pietro Schettino; Paolo Limongelli; Salvatore Tolone; Luigi Brusciano; Manuela Avellino; Chiara Vitiello; Giovanni Docimo; Angelo Pezzullo; Ludovico Docimo

    2015-01-01

    Squamous papilloma of the esophagus is a rare benignlesion of the esophagus. Radiofrequency ablation is anestablished endoscopic technique for the eradication ofBarrett esophagus. No cases of endoscopic ablation ofesophageal papilloma by radiofrequency ablation (RFA)have been reported. We report a case of esophagealpapilloma successfully treated with a single sessionof radiofrequency ablation. Endoscopic ablation ofthe lesion was achieved by radiofrequency using anew catheter inserted through the working channelof endoscope. The esophageal ablated tissue wasremoved by a specifically designed cup. Completeablation was confirmed at 3 mo by endoscopy withbiopsies. This case supports feasibility and safety of asa new potential indication for BarrxTM RFA in patientswith esophageal papilloma.

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

    Directory of Open Access Journals (Sweden)

    Izabella Paz Danezi Felin

    2009-08-01

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

  5. A Zebrafish Model for Studies on Esophageal Epithelial Biology

    OpenAIRE

    Chen, Hao; Beasley, Andrea; Hu, Yuhui; Chen, Xiaoxin

    2015-01-01

    Mammalian esophagus exhibits a remarkable change in epithelial structure during the transition from embryo to adult. However, the molecular mechanisms of esophageal epithelial development are not well understood. Zebrafish (Danio rerio), a common model organism for vertebrate development and gene function, has not previously been characterized as a model system for esophageal epithelial development. In this study, we characterized a piece of non-keratinized stratified squamous epithelium simi...

  6. Clinical significance of expression of SASH1 in esophageal squamous cell carcinoma%SASH1基因在食管鳞癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    刘秋菊; 贺远龙; 刘红云; 卫红军; 许琳; 王青

    2013-01-01

    目的:探讨候选抑癌基因SASH1在食管鳞状细胞癌中的表达及与肿瘤相关的临床病理特征的关系,方法:应用免疫组织化学SP法检测72例食管鳞癌组织及40例癌旁组织中SASH1蛋白的表达,结果:SASH1蛋白在癌组织阳性表达率显著低于癌旁组织,统计学分析表明两者差异有显著意义(41.67% vs 80.00%,P<0.001).其表达率在食管鳞癌伴淋巴结转移组中较不伴淋巴结转移组明显降低(x2=6.583,P<0.05).其在食管鳞癌组织中的表达水平与肿瘤分化程度及TNM分期相关(P<0.05).结论:SAH1基因在食管鳞癌中表达下调,该基因可能是食管鳞癌的肿瘤抑制基因,可能作为分子标记而用于食管鳞癌的诊断和治疗.%To detect the expression of SAM-and SH3domain containing 1 (SASH1) in human esophageal squamous cell carcinoma (ESCC),and to analyze the relationship between SASH1 expression and clinical and pathological parameters of ESCC.METHODS:The expression of SASH1 was detected by immunohistochemistry in 72 ESCC specimens and 40 tumor-adjacent specimens.RESULTS:The positive rate of SASH1 protein expression in ESCC was significantly lower than that in tumor-adjacent non-carcinoma tissue (41.67% vs 80.00%,P < 0.001).The positive rate of SASH1 protein expression was significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (x2 =6.583,P < 0.05).Expression of SASH1 was associated with tumor differentiation and TNM stage in ESCC (both P < 0.05).CONCLUSION:Down-regulation of SASH1 expression occurs in ESCC.SASH1 may be a novel tumor suppressor in ESCC and can be used as a molecular maker for the diagnosis and treatment of ESCC.

  7. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  8. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    International Nuclear Information System (INIS)

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m2) and cisplatin (40 mg/m2) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m2/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R

  9. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Katsuhiko, E-mail: k.higu@kitasato-u.ac.jp [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Komori, Shouko [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Tanabe, Satoshi [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Azuma, Mizutomo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Ishiyama, Hiromichi [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Sasaki, Tohru; Ishido, Kenji [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Natsuya [Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Hayakawa, Kazushige [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Koizumi, Wasaburo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan)

    2014-07-15

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

  10. Esophageal Cancer: Role of Imaging in Primary Staging and Response Assessment Post Neoadjuvant Therapy.

    Science.gov (United States)

    Griffin, Yvette

    2016-08-01

    Advances in the early detection and treatment of esophageal cancer have meant improved survival rates for patients with esophageal cancer. Accurate pretreatment and post-neoadjuvant treatment staging of esophageal cancer is essential for assessing operability and determining the optimum treatment plan. This article reviews the multimodality imaging approach in the diagnosis, staging, and assessment of treatment response in esophageal cancer. PMID:27342898

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

    Directory of Open Access Journals (Sweden)

    Pimenta Amadeu P. A.

    1997-01-01

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

  12. Serum soluble Fas ligand (sFasL in patients with primary squamous cell carcinoma of the esophagus.

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2007-10-01

    Full Text Available Esophageal carcinomas have been shown to express Fas ligand (FasL and down-regulate Fas to escape from host immune surveillance. Circulating soluble FasL (sFasL has been suggested to provide protection from Fas-mediated apoptosis. The aim of this study was to assess serum sFasL levels in esophageal cancer. The pretreatment levels of sFasL in the serum of 100 patients with esophageal squamous cell cancer and 41 healthy volunteers were determined by ELISA. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of high and low level of sFasL was analyzed with the log-rank test. The mean serum level of sFasL in patients with esophageal cancer was significantly higher than that in healthy donors (1.567+/-1.786 vs 0.261+/-0.435, p<0.0001. The levels of serum sFasL were significantly higher in advanced stages (II vs IV p<0.034; III vs IV p<0.041; except II vs III p=0.281, patients with lymph node (N0 vs N1 p<0.0389 or distant (M0 vs. M1 p<0.0388 metastases and significantly lower in patients with well differentiated tumors (G1 vs G2 p<0.0272. The serum levels of soluble FasL were not related to gender, age, tumor size, T-stage, tobacco smoking and history of chronic alcohol intake. The survival difference between pretreatment high and low level of sFasL in surgery and chemio- and/or radiotherapy group was not statistically significant (p=0.525; p=0.840. Our results indicate that elevated serum sFasL levels might be associated with a disease progression in patients with esophageal squamous cell carcinoma.

  13. Serum soluble Fas ligand (sFasL) in patients with primary squamous cell carcinoma of the esophagus

    International Nuclear Information System (INIS)

    Esophageal carcinomas have been shown to express Fas ligand (FasL) and down-regulate Fas to escape from host immune surveillance. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The aim of this study was to assess serum sFasL levels in esophageal cancer. The pretreatment levels of sFasL in the serum of 100 patients with esophageal squamous cell cancer and 41 healthy volunteers were determined by ELISA. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of high and low level of sFasL was analyzed with the log-rank test. The mean serum level of sFasL in patients with esophageal cancer was significantly higher than that in healthy donors (1.567±1.786 vs 0.261±0.435, p<0.0001). The levels of serum sFasL were significantly higher in advanced stages (II vs IV p<0.034; III vs IV p<0.041; except II vs III p=0.281), patients with lymph node (N0 vs N1 p<0.0389) or distant (M0 vs. M1 p<0.0388) metastases and significantly lower in patients with well differentiated tumors (G1 vs G2 p<0.0272). The serum levels of soluble FasL were not related to gender, age, tumor size, Tstage, tobacco smoking and history of chronic alcohol intake. The survival difference between pretreatment high and low level of sFasL in surgery and chemo- and/or radiotherapy group was not statistically significant (p=0.525; p=0.840). Our results indicate that elevated serum sFasL levels might be associated with a disease progression in patients with esophageal squamous cell carcinoma. (authors)

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

    Science.gov (United States)

    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

  15. The candidate tumor suppressor gene ECRG4 inhibits cancer cells migration and invasion in esophageal carcinoma

    OpenAIRE

    Lu ShihHsin; Li Xiaoyan; Zhang Chunpeng; Li Linwei; Zhou Yun

    2010-01-01

    Abstract Background The esophageal cancer related gene 4 (ECRG4) was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no.AF325503). ECRG4 was a new tumor suppressor gene in esophageal squamous cell carcinoma (ESCC) associated with prognosis. In this study, we investigated the novel tumor-suppressing function of ECRG4 in cancer cell migration, invasion, adhesion and cell cycle regulation in ESCC. Methods Transwell and Boyden chamber e...

  16. The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer

    OpenAIRE

    Maciej Szmitkowski; Barbara Mroczko; Maria Siewko; Magdalena Groblewska

    2012-01-01

    Esophageal cancer (EC) is one of the most aggressive malignant tumors of the gastrointestinal tract. There are two distinct histological types of EC: esophageal squamous cell carcinoma and adenocarcinoma of the esophagus. Etiologic factors and the patterns of incidence of both subtypes are different. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in esophageal carcinogenesis. Gellatinases MMP-2 and MMP-9 are able to degrade collagen IV from basemen...

  17. 乳腺癌易感基因1在食管鳞癌中的表达及临床意义%Expression and clinical significance of BRCA1 in human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨怡轩; 薛丽燕; 董立佳; 付明; 詹启敏; 童彤

    2012-01-01

    Objective To investigate the expression of BRCA1 in esophageal squamous cell carcinoma (ESCC) tissues and evaluate its correlation with clinicopathological features as well as the prognosis of ESCC patients.Methods The expression of BRCA1 was detected by immunohistochemistry (IHC) in 201 specimens of T3 stage ESCC tissues and corresponding adjacent normal tissues using tissue microarray.The correlation between BRCA1 expression and clinicopathological features of ESCC was determined by chi-square analysis.The cumulative survival rate was analyzed by Kaplan-Meier method.Results The positive rate of BRCA1 expression in ESCC tissues was significantly higher than that in adjacent normal tissues [88.6% (178/201) vs.36.8% (74/201),P < 0.001].There was a significant correlation between the expression of BRCA1 and lymph node metastasis.In the tumors with positive lymph nodes,strong positive expression of BRCA1 was found in 45.0% (49/109),while only 19.6% (18/92) in tumors without lymph node metastasis,showing a significant difference (P < 0.001).A close relationship was also found between the expression of BRCA1 and gross typing of tumors (P < 0.05).The expression of BRCA1 was not significantly correlated with gender,age,tumor location,differentiation,and tumor thrombus (P > 0.05).The results of Kaplan-Meier analysis indicated that ESCC patients with a higher positive rate of BRCA1 expression have a poorer prognosis (P < 0.05).Conclusions The expression of BRCA1 is related to the occurrence and development of esophageal carcinoma.BRCA1 protein may serve as a new potential biomarker in estimating the biological behavior of ESCC.%目的 研究食管鳞癌组织中乳腺癌易感基因1(BRCA1)的表达与患者临床病理特征及预后之间的关系.方法 采用免疫组织化学染色法检测201例手术切除的T3期食管鳞癌患者癌与癌旁正常组织中BRCA1蛋白的表达.采用x2检验分析BRCA1蛋白的表达与患者临床病理特征间

  18. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    Science.gov (United States)

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer. PMID:27279143

  19. Radiation therapy for the treatment of feline advanced cutaneous squamous cell carcinoma; A utilizacao da radioterapia no tratamento do carcinoma de celulas escamosas cutaneo felino avancado

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, S.C.S.; Corgozinho, K.B.; Ferreira, A.M.R, E-mail: simonecsc@gmail.com [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Carvalho, L.A.V. [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COPPE/UFRJ), RJ (Brazil); Holguin, P.G.

    2014-02-15

    The efficacy of radiation therapy for feline advanced cutaneous squamous cell carcinoma was evaluated. A full course radiation therapy protocol was applied to six cats showing single or multiple facial squamous cell carcinomas, in a total of seven histologically confirmed neoplastic lesions. Of the lesions, one was staged as T{sub 1}, and six as T{sub 4} according to WHO staging system of epidermal tumors. The animals were submitted to twelve radiation fractions of 4 Gy each, on a Monday-Wednesday-Friday schedule, and the equipment used was an orthovoltage unit. Energy used was 120 kV, 15 mA and 2 mm aluminum filter. The cats were evaluated during the treatment and 30 and 60 days after the end of the radiation therapy. In this study, 87% of the lesions had complete remission and 13% partial remission to the treatment. Side effects were considered mild according to Veterinary Radiation Therapy Oncology Group Toxicity criteria, and included erythema, epilation and rhinitis. Radiation Therapy was considered safe for feline cutaneous squamous cell carcinoma, leading to mild side effects and can represent a good therapeutic option. (author)

  20. The expression of HIF-1α and VEGF as well as their correlation with angiogenesis in esophageal squamous cell carcinomas%HIF-1α与VEGF及MVD在食管鳞癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    Feng Liu; Xiaolong Yang; Boying Ding; Gang Ren; Rongfu Gong

    2009-01-01

    Objective: To investigate the correlations among the expressions of hypoxia-inducible factor-1α (HIF-1α), vas-cular endothelial cell growth factor (VEGF) and microvessel density (MVD), and their relationships to the clinicopathologic characteristics of esophageal squamous cell carcinomas (ESCC). Methods: The expressions of HIF-1α, VEGF and MVD were detected by immunohistochemical method in 45 cases of ESCC, 30 intraepithelial neoplasia and 35 normal esophageal mucosal epithelia tissues. The correlations among the expressions of HIF-1α, VEGF and MVD, and their relationships to the clinicopathologic features of ESCC were analyzed. Results: The rate of positive expression of HIF-1α and VEGF which were 80% and 84% in ESCC were significantly higher than those in intraepithelial neoplasia and normal esophageal rnucosal epi-thelium tissues (P<0.01) and so did the MVD value which was 71.10±15.02 in ESCC (P<0.01). The expression of HIF-1αand VEGF were positively correlated with the depth of tumor invasion, lymph node metastasis and TNM staging of ESCC.The expressions of HIF-1α were positively correlated with the expressions of VEGF and the value of MVD. Conclusion: Overexpression of HIF-1α is found in ESCC. HIF-la may induce the angiogenesis in ESCC by upregulating the transcription of VEGF gene. It may play an important role in the carcinogenesis and aggression in ESCC, HIF-1α, VEGF and MVD may be a useful marker for evaluating the biological behaviors of ESCC.

  1. [Eosinophilic esophagitis].

    Science.gov (United States)

    Couto, Mariana; Rodrigues, Susana; Piedade, Susana; Gaspar, Ângela; Morais-Almeida, Mário; Macedo, Guilherme

    2011-12-01

    Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by significant and isolated infiltration of the esophageal mucosa by eosinophils, associated with clinical symptoms of esophageal dysfunction, affecting children and adults. It is an increasingly frequent cause of symptoms similar to gastroesophageal reflux disease but refractory to anti-acid therapeutic. It is commonly associated with food allergies or other atopic diseases. Since there are no symptoms, signs, serological biomarkers or endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of suspicion; moreover, due to its chronic relapsing nature the potential to cause major esophageal structural changes, its early recognition and close cooperation between gastroenterologists and immunoallergologists is essential for the timely institution of appropriate therapy. The treatment is based on two main strategies: diet and / or pharmacotherapy, depending on the co-existence of sensitization to food allergens. It is our aim to review this issue, considering recent guidelines, as well as propose a diagnostic and therapeutic algorithm. PMID:22863504

  2. Investigation of the treatment results of advanced squamous cell carcinoma of the oral cavity and clinical necessity of long-term follow-up

    International Nuclear Information System (INIS)

    It has been considered that oral cancer is cured if more than five years pass without recurrence or metastasis after the initial treatment. Treatment results are usually evaluated as a 5-year survival rate, but we sometimes find recurrence more than five years after the initial treatment. We retrospectively investigated treatment results by long-term follow-up of advanced squamous cell carcinoma of the oral cavity after radical surgery, and analyzed the relation between the period of follow-up and the time to recurrence. One hundred and sixteen patients with advanced squamous cell carcinoma of the oral cavity were enrolled between November 1994 and October 2004 in this study. Seventy-six patients were Stage III and 40 were stage IV, and the mean age of this cohort was 63.0 years. All patients received radical surgery with or without preoperative chemoradiotherapy and were followed for a minimum of 5 years. Overall actuarial survival of all patients was 77.8% at 10 years. The 10-year cumulative local and regional recurrence rates were 20.1% and 12.9%, respectively. The actuarial loco-regional recurrence rate was the highest within 2 years after initial treatment at 19.0%, and was seen in 3.4% even after 5 years. These results showed that it is necessary to follow-up patients with advanced oral cancer even beyond 5 years after the initial treatment because there was delayed loco-regional recurrence in 3.4%. (author)

  3. Prognostic factors (including HPV status) for irradiation of locally advanced squamous cell carcinoma of the head and neck (SCCHN)

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk; Seibold, Nina D. [Lubeck Univ. (Germany). Dept. of Radiation Oncology; Gebhard, Maximilian P.; Noack, Frank; Thorns, Christoph [Lubeck Univ. (Germany). Inst. of Pathology; Schild, Steven E. [Mayo Clinic Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2011-10-15

    The prognosis of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) is generally poor. However, prognostic factors can help optimize the care for the individual patient. This study investigated potential prognostic factors, including HPV status, for locoregional control (LRC), metastases-free survival (MFS), and survival (OS). Twelve potential prognostic factors were investigated in 170 patients irradiated for stage III or IV SCCHN, including age ({<=} 60 vs > 60 years), gender, ECOG performance score (0-1 vs 2), preradiotherapy hemoglobin level (< 12 vs {>=} 12 g/dl), tumor site (oropharynx, oral cavity, hypopharynx, or larynx), histological grade (G1-2 vs G3), T category (T1-T2 vs T3-T4), N category (N0-N1 vs N2-N3), AJCC stage (III vs IV), surgery (no vs yes), and chemotherapy (no vs yes). On multivariate analysis, positive HPV status (RR 2.34; p = 0.014), ECOG performance score 0-1 (RR 1.94; p = 0.017), preRT hemoglobin {>=} 12 g/dl (RR 1.88; p = 0.018), T category T1-T2 (RR 2.72; p < 0.001), and surgery (RR 2.29; p = 0.007) were significantly associated with improved LRC. PreRT hemoglobin {>=} 12 g/dl (RR 1.98; p = 0.040) and T category T1-T2 (RR 3.33; p < 0.001) were significantly associated with improved MFS. Positive HPV status (RR 2.19; p = 0.019), pre-RT hemoglobin {>=} 12 g/dl (RR 2.15; p = 0.002), T category T1-T2 (RR 2.31; p = 0.002), and AJCC stage III (RR 1.91; p = 0.034) were significantly associated with improved OS. Improved treatment outcomes were significantly associated with positive HPV status, better performance status, lower tumor stage, and pretreatment hemoglobin levels {>=} 12 g/dl. These factors should be considered in future trials.

  4. Prognostic factors (including HPV status) for irradiation of locally advanced squamous cell carcinoma of the head and neck (SCCHN)

    International Nuclear Information System (INIS)

    The prognosis of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) is generally poor. However, prognostic factors can help optimize the care for the individual patient. This study investigated potential prognostic factors, including HPV status, for locoregional control (LRC), metastases-free survival (MFS), and survival (OS). Twelve potential prognostic factors were investigated in 170 patients irradiated for stage III or IV SCCHN, including age (≤ 60 vs > 60 years), gender, ECOG performance score (0-1 vs 2), preradiotherapy hemoglobin level (< 12 vs ≥ 12 g/dl), tumor site (oropharynx, oral cavity, hypopharynx, or larynx), histological grade (G1-2 vs G3), T category (T1-T2 vs T3-T4), N category (N0-N1 vs N2-N3), AJCC stage (III vs IV), surgery (no vs yes), and chemotherapy (no vs yes). On multivariate analysis, positive HPV status (RR 2.34; p = 0.014), ECOG performance score 0-1 (RR 1.94; p = 0.017), preRT hemoglobin ≥ 12 g/dl (RR 1.88; p = 0.018), T category T1-T2 (RR 2.72; p < 0.001), and surgery (RR 2.29; p = 0.007) were significantly associated with improved LRC. PreRT hemoglobin ≥ 12 g/dl (RR 1.98; p = 0.040) and T category T1-T2 (RR 3.33; p < 0.001) were significantly associated with improved MFS. Positive HPV status (RR 2.19; p = 0.019), pre-RT hemoglobin ≥ 12 g/dl (RR 2.15; p = 0.002), T category T1-T2 (RR 2.31; p = 0.002), and AJCC stage III (RR 1.91; p = 0.034) were significantly associated with improved OS. Improved treatment outcomes were significantly associated with positive HPV status, better performance status, lower tumor stage, and pretreatment hemoglobin levels ≥ 12 g/dl. These factors should be considered in future trials.

  5. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacera; Deutsch, Eric; Daly-Schveitzer, Nicolas; Tao, Yungan [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); Guigay, Joel [Gustave Roussy, Department of Medical Oncology, Villejuif (France); Janot, Francois; Temam, Stephane [Gustave Roussy, Department of Head and Neck Surgery, Villejuif (France); Bourhis, Jean [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); University Hospital Lausanne, Department of Radiation Oncology, Lausanne (Switzerland)

    2014-09-15

    The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m{sup 2}, every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS. (orig.) [German] Die Therapieeffektivitaet mit Platin

  6. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  7. Esophageal Mucormycosis

    Directory of Open Access Journals (Sweden)

    Benjamin Boatright

    2014-01-01

    Full Text Available Mucormycosis is a rare invasive fungal infection with high mortality. It usually affects patients with poorly controlled diabetes, immunosuppression, or hematological malignancies. Gastroenterologists need to be aware of this rare infection because endoscopy can facilitate early diagnosis and prompt appropriate therapy. Here we describe a case of invasive esophageal mucormycosis that developed in a 63-year-old man with diabetes, acute promyelocytic leukemia, and prolonged leukopenia after chemotherapy. Upper endoscopy showed distal circumferential esophageal wall thickening with devitalization. The mucosa did not bleed after endoscopic biopsy. Histopathology confirmed mucormycosis. He was treated with various antifungal agents including echinocandins, fluconazole, and liposomal amphotericin B. Despite aggressive antifungal therapy and supportive care, the patient died 24 days later.

  8. NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis.

    Science.gov (United States)

    Yang, Q; Pan, Q; Li, C; Xu, Y; Wen, C; Sun, F

    2016-08-01

    NRAGE, a neurotrophin receptor-interacting melanoma antigen-encoding gene homolog, is significantly increased in the nucleus of radioresistant esophageal tumor cell lines and is highly upregulated to promote cell proliferation in esophageal carcinomas (ECs). However, whether the overexpressed NRAGE promotes cell growth by participating in DNA-damage response (DDR) is still unclear. Here we show that NRAGE is required for efficient double-strand breaks (DSBs) repair via homologous recombination repair (HRR) and downregulation of NRAGE greatly sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover, NRAGE not only regulates the stability of DDR factors, RNF8 and BARD1, in a ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1 and RNF8 via their RING domains to form a novel ternary complex. Additionally, the expression of NRAGE is closely correlated with RNF8 and BARD1 in esophageal tumor tissues. In summary, our findings reveal a novel function of NRAGE that will help to guide personalized esophageal cancer treatments by targeting NRAGE to increase cell sensitivity to DNA-damaging therapeutics in the long run. PMID:27035619

  9. Squamous cell skin cancer

    Science.gov (United States)

    ... earliest form of squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type ... cancer; Squamous cell carcinoma of the skin Images Bowen's disease on the hand Keratoacanthoma Keratoacanthoma Skin cancer, squamous ...

  10. Epidemiological studies of esophageal cancer in the era of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    An-Hui; Wang; Yuan; Liu; Bo; Wang; Yi-Xuan; He; Ye-Xian; Fang; Yong-Ping; Yan

    2014-01-01

    Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.

  11. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    Science.gov (United States)

    2016-08-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  12. Esophageal Cancer Staging

    OpenAIRE

    Rice, Thomas W.

    2015-01-01

    Accurate staging of esophageal cancer is very important to achieving optimal treatment outcomes. The AJCC (American Joint Committee on Cancer) first published TNM esophageal cancer staging recommendations in the first edition of their staging manual in 1977. Thereafter, the staging of esophageal cancer was changed many times over the years. This article reviews the current status of staging of esophageal cancer.

  13. The Outline of Prognosis and New Advances in Diagnosis of Oral Squamous Cell Carcinoma (OSCC): Review of the Literature

    OpenAIRE

    Omar, Esam Ahmad

    2013-01-01

    Objective. Oral squamous cell carcinoma (OSCC) has a remarkable incidence over the world and a fairly strenuous prognosis, encouraging further research on the prognostic factors and new techniques for diagnosis that might modify disease outcome. Data Sources. A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, prognostic factors of oral cancer, diagnostic method of oral cancer, and imaging techniques for diagnosis...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-15

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

  15. Singlet oxygen prediction in gold nanoparticles-assisted PDT applied to a squamous cell carcinoma in the esophagus

    OpenAIRE

    Salas García, Irene; Fanjul Vélez, Félix; Ortega Quijano, Noé; Arce Diego, José Luis

    2014-01-01

    A predictive model for PDT singlet oxygen production in esophageal squamous cell carcinomas with gold nanoparticles is proposed. Differences enhance the ¹O₂ -mediated oxidative damage due to the optical absorption improvement by gold nanoparticles.

  16. The Outcome of Conventional External Beam Radiotherapy for Patients with Squamous Cell Carcinoma of the Esophagus

    International Nuclear Information System (INIS)

    The best treatment for advanced esophageal cancer is chemoradiotherapy followed by surgery. In spite of the advance of multimodality therapy, most patients with esophageal cancer are treated with radiation therapy alone. This study reports the outcome of the use of conventional external beam radiotherapy alone for the treatment of esophageal cancer. Between January 1998 and December 2005, 30 patients with squamous cell carcinoma of the esophagus were treated with external beam radiotherapy using a total dose exceeding 40 Gy. Radiotherapy was delivered with a total dose of 44-60 Gy (median dose, 57.2 Gy) over 36 ∼115 days (median time, 45 days). Thirteen patients (43.3%) had a history of disorders such as diabetes, hypertension, tuberculosis, lye stricture, asthma, cerebral infarct, and cancers. Four patients metachronously had double primary cancers. The most common location of a tumor was the mid-thoracic portion of the esophagus (56.7%). Tumor lengths ranged from 2 cm to 11 cm, with a median length of 6 cm. For AJCC staging, stage III was the most common (63.3%). Five patients had metastases at diagnosis. The median overall survival was 8.3 months. The survival rates at 1-year and 2-years were 33.3% and 18.7%, respectively. The complete response rate 1∼3 months after radiotherapy was 20% (6/30) and the partial response rate was 70% (21/30). Sixteen patients (53.3%) had an improved symptom of dysphagia. Significant prognostic factors were age, tumor length, stage, degree of dysphagia at the time of diagnosis and tumor response. Cox regression analysis revealed the aim of treatment, clinical tumor response and tumor length as independent prognostic factors for overall survival. Twenty-eight patients had local failure and another four patients had metastases. Three patients were detected with double primary cancers in this analysis. A complication of esophageal stricture was observed in three patients (10%), and radiation pneumonitis occurred in two patients (6

  17. Trimodal therapy in squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Matuschek C

    2011-10-01

    Full Text Available Abstract Patients with ESCC (squamous cell carcinoma of the esophagus are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.

  18. Trimodal therapy in squamous cell carcinoma of the esophagus.

    Science.gov (United States)

    Matuschek, C; Bölke, E; Zahra, T; Knoefel, W T; Peiper, M; Budach, W; Erhardt, A; Scherer, A; Baldus, S E; Gerber, P A; Buhren, B A; Schauer, M; Hoff, N-Ph; Gattermann, N; Orth, K

    2011-10-10

    Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients. PMID:22024422

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  2. Esophageal cancer in yemen

    International Nuclear Information System (INIS)

    To document the age and gender distribution, histopathologic type as well as grading characteristics of Esophageal Cancer (EC) in Yemen. Study Design: A case series. Place and Duration of Study: Department of Pathology, Sana'a University, Sana'a, Yemen, from January 2005 to December 2011. Methodology: Three hundred twenty five cases of EC were included for review. The diagnoses were made on hematoxylin and eosin stained sections and the cases were categorized into Squamous Cell Carcinoma (SCC) and adenocarcinoma (ADC). Results: Out of the 325 EC cases, 163 (50%) were SCC (females 67%, males 33%) and 158 (49%) were ADC (females 30%, males 70%). The rest of the cases were 2 adenosquamous carcinoma and 2 non-Hodgkin's lymphoma. The mean age, for SCC was 60 years while the mean age for ADC was 65 years. The peak incidence for SCC was found in the age groups of fifth and sixth decades for females and in fifth and seventh decades for males. The maximum number of patients with ADC was seen in sixth and seventh decades for both gender. Well-differentiated histological grading accounted for 247 (77%) for both genders and types. The moderately differentiated and poorly differentiated accounted, for 17% and 6% respectively. Conclusion: The EC in Yemen had a predominance of SCC in female patients and predominance of ADC in male patients which was usually of a well-differentiated grade. (author)

  3. EORTC 24051 : Unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma

    NARCIS (Netherlands)

    Lalami, Yassine; Specenier, Pol M.; Awada, Ahmad; Lacombe, Denis; Liberatoscioli, Cecilia; Fortpied, Catherine; El-Hariry, Iman; Bogaerts, Jan; Andry, Guy; Langendijk, J. A.; Vermorken, Jan B.

    2012-01-01

    Background: In this phase I/II study, the addition of lapatinib (LAP) was investigated in combination with the sequential use of both approaches TPF induction chemotherapy (ICT) followed by chemoradiation (CRT) in locally advanced larynx or hypopharynx squamous cell carcinoma. Patients and methods:

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. FINDINGS: 795 eligible...... group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none...

  5. Neoplasia avançada de esôfago: diagnóstico ainda muito tardio Advanced esophageal cancer: still a delayed diagnosis

    Directory of Open Access Journals (Sweden)

    Fernanda Prata Thuler

    2006-09-01

    tumor de esôfago em nosso meio ainda é muito tardio, limitando o benefício que poderia advir dos métodos de ponta de paliação endoscópica.BACKGROUND: Esophageal cancer is one of the 10 most common cancers in Brazil. Diagnosis is usually late and mean survival ranges from 4 to 6 months, no matter the treatment. Relief of dysphagia and increase in life quality are the main targets of palliative therapy. AIM: To evaluate patients with advanced esophageal tumor submitted to various palliative treatment options. PATIENTS AND METHOD: We prospectively evaluated 38 patients with advanced esophageal cancer, with dysphagia and no chance of curative treatment, between September 2001 and June 2005. Patients were treated according to available resources, patient or referring physician's preference: 14 patients were treated with esophageal stent (9 self-expandable metallic, 4 plastic, 1 expandable plastic, 4 with palliative surgery, 8 gastrostomy (7 surgical and 1 endoscopic and 12 nasogastric tube. RESULTS: The mean dysphagia score 30 days after the procedure was improved in all groups except in the gastrostomy. Karnofsky score, reflecting quality of life, showed no improvement. The number of hospital admissions was not different among groups. Although the length of hospitalization was longer in the surgical group (42 days, it did not reach statistical significance. There was not statistically significant difference in the mean survival time among all patients. CONCLUSION: An ideal palliative treatment does not exist. The method must be individualized for each patient. Surgical treatment is the most expensive, once it requires longer periods in hospital. Unfortunately, the diagnosis of esophageal tumors is still delayed, limiting the benefits of top endoscopic palliation therapy.

  6. Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m2) and nedaplatin (20 mg/m2) was given every week for 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m2) and nedaplatin (60 mg/m2) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.

  7. Esophageal cancer: comparative effectiveness of treatment options

    OpenAIRE

    Xu C.; Lin SH

    2016-01-01

    Cai Xu,1 Steven H Lin2 1Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Esophageal cancer is a lethal disease. Multimodal therapy has improved the survival and local control for locally advanced esophageal cancer compared to surgery alone. Neoadjuvant chemo...

  8. Concurrent three-dimensional conformal radiotherapy and chemotherapy for postoperative recurrence of mediastinal lymph node metastases in patients with esophageal squamous cell carcinoma: a phase 2 single-institution study

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the effects of radiotherapy plus concurrent weekly cisplatin chemotherapy on the postoperative recurrence of mediastinal lymph node metastases in esophageal cancer patients. Ninety-eight patients were randomly enrolled to receive either three-dimensional conformal radiotherapy alone (group A) or concurrent chemoradiotherapy (group B). A radiation dose of 62–70 Gy/31–35 fractions was delivered to the recurrent tumor. Furthermore, the patients in group B simultaneously received weekly doses of cisplatin (30 mg/m2), and the survival outcomes and toxic effects were compared. The response rate of group B (91.8%) was significantly greater than that of group A (73.5%) (χ2 = 5.765, P = 0.016). The 1- and 3-year survival rates of group B (85.7% and 46.9%, respectively) were also greater than those of group A (69.4% and 28.6%, respectively). However, there were no significant differences in the 5-year survival rates. The numbers of patients who died of distant metastases in groups A and B were 13 (26.5%) and 5 (10.2%), respectively (χ2 = 4.356, P = 0.036). Acute radiation-related esophagitis and granulocytopenia in group B was frequent. However, intergroup differences in terms of late toxicity were not significant. Three-dimensional conformal radiotherapy (3DCRT) is a practical and feasible technique to treat the recurrence of mediastinal lymph node metastases of postoperative esophageal cancer. In addition, concurrent chemotherapy can increase local tumor control, decrease the distant metastasis rate, and increase the long-term survival rate

  9. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival

  10. Advances in the research of scar stricture after esophageal burn%食管烧伤导致瘢痕狭窄的研究进展

    Institute of Scientific and Technical Information of China (English)

    赵士磊; 顾春东

    2013-01-01

    Caustic esophageal burn is a common ailment in clinical practice.In some patients,scar stricture was formed in the late stage of injury,and it seriously undermined quality of life of the patients.We adopted various clinical interventions at an early stage in order to relieve and alleviate the formation and development of corrosive esophageal stricture as a result of chemical injury as well as to avoid invasive operations to make it more acceptable for the patients.This article summarized the progress in etiology,pathological changes,identification,early prevention,and surgical management of corrosive esophageal stricture.

  11. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Tan, S [Huazhong University of Science and Technology, Wuhan (China); Kim, G [Duke University, High Point, NC (United States)

    2014-06-15

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features

  12. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    International Nuclear Information System (INIS)

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had 18F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including

  13. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  14. A pilot study of plasma metabolic biomarkers for esophageal squamous cell carcinoma by LC/TOF-MS%应用LC/TOF-MS分析食管鳞状细胞癌血浆小分子代谢物的实验研究

    Institute of Scientific and Technical Information of China (English)

    彭媛; 刘冉; 李晓波; 尹立红

    2013-01-01

    目的:利用液相色谱-飞行时间质谱(liquid chromatography-time of flight-mass spectrography,LC/TOF-MS)检测食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)血浆中小分子代谢物质的变化,探讨与ESCC相关的小分子代谢标志物。方法:收集ESCC和健康对照血浆样本各30例,应用LC/TOF-MS方法检测,采用MassHunter软件对数据进行分子特征提取,MPP软件对其进行分析,对可能的代谢物精确质量在METLIN公共数据库中进行搜索查询。结果:与健康对照组相比,ESCC组共找到差异表达的血浆小分子代谢物数目46个,其中13个上调,33个下调。经过METLIN数据库搜索后,ESCC血浆中的磷脂酸、磷脂酰丝氨酸、磷脂酰甘油碎片含量与健康对照组相比显著降低。结论:基于LC/TOF-MS的血浆小分子代谢物分析策略可有效区分食管癌和健康个体,在食管癌的早期诊断和人群筛检方面具有较好的应用前景。%OBJECTIVE: The plasma low-molecular weight metabolites of esophageal squamous cell carcinoma were analyzed by liquid chromatography-time of flight-mass spectrography( LC/TOF-MS) to explore potential biomarkers for the early detection of ESCC. METHODS:Plasma samples were obtained from 30 ESCC patients and 30 healthy volunteers,low-molecular weight metabolites were identified by LC/TOF-MS,feature detection was performed by MassHunter software MFE algorithm,statistical analysis was conducted by MPP software,and primary identification was achieved by searching METLIN database. RESULTS:Compared to healthy controls,46 differentially expressed features were detected,13 of which were up-regulated in ESCC group,while the other 33 were down-regulated. After searching with METLIN database,plasma levels of PA,PS,PG were significantly lower in ESCC group. CONCLUSION:ESCC patients are markedly different from healthy people in plasma metabolite composition,and the LC/TOF-MS plasma metabonomics

  15. Gene chip technology used in the detection of HPV infection in esophageal cancer of Kazakh Chinese in Xinjiang Province.

    Science.gov (United States)

    Chen, Wei-gang; Yang, Chun-mei; Xu, Li-hong; Zhang, Ning; Liu, Xiao-yan; Ma, Yun-gui; Huo, Xiao-ling; Han, Yu-sheng; Tian, De-an; Zheng, Yong

    2014-06-01

    This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults. PMID:24939296

  16. Expressions of PCNA, p53, p21WAF-1 and cell proliferation in fetal esophageal epithelia: Comparative study with adult esophagea lesions from subjects at high-incidence area for esophageal cancer in Henan, North China

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Yu Ning; Li-Qiang Ru; Li-Dong Wang

    2003-01-01

    AIM: To characterize the expression of p53, p21WAF-1 and proliferation-cell-nuclear-antigen (PCNA) in fetal esophageal epithelia and to determine the role of these genes in proliferation of fetal and adult esophageal epithelial cells.METHODS: Immunohistochemical avdin-biotin peroxidase complex (ABC) method was applied to 31 cases of fetal esophageal specimens and 194 cases of adult esophageal specimens to detect the expression of p53, p21WAF-1 and PCNA in fetal and adult esophageal epithelia.RESULTS: Both the PCNA positive immunostaining cell number and PCNA positive immunostaining rate in fetal esophageal epithelia (506±239) were significantly higher than those in adults,including normal epithelia (200±113) and epithelia with basal cell hyperplasia (BCH) (286±150) (P<0.05, ttest). However,the number of PCNA positive immunostaining cells in adult esophageal dysplasia (719±389) and squamous cell carcinoma (SCC) (1261±545) was apparently higher than that in fetal esophageal epithelia (506±239) (P<0.05, ttest). The positive immunostaining rate of P53 was 10 % (3/3L) in fetal esophageal epithelia, which was significantly lower than that in adult normal esophageal epithelia (50 %), adult epithelia with basal cell hyperplasia (62 %), dysplasia (73 %) and squamous cell carcinoma (86 %) (P<0.05, Fisher′s exact test). No p21WAF-1positive immunostaining cells were observed in fetal esophageal epithelia. However, p21WAF-1 positive immunostaining cells were observed in adult esophagus with 39 % (11/28) in normal, 38% (14/37) in BCH, 27 % (3/11) in DYS and 14 % (1/7) in SCC.CONCLUSION: PCNA could act as an indicator accurately reflecting the high proliferation status of fetal esophageal epithelium. p53 may play an important role in growth and differentiation of fetal esophageal epithelium. p21WAF-1 may have no physiological function in development of fetal esophageal epithelium.

  17. 人正常食管鳞状上皮不同原代培养方法的比较%Comparison of Different Methods in Primary Culture of Human Normal Esophageal Squamous Epithelium

    Institute of Scientific and Technical Information of China (English)

    何晓琳; 李月红; 张祥宏; 严霞; 王俊灵

    2011-01-01

    The purpose of this study was to compare the different methods in primary culture of human normal esophageal epithelial cells (HNEECs) and look for appropriate methods to acquire abundant and well growth esophageal epithelial cells for next experiment. The human normal esophageal epithelial cells were isolated from surgically excisional normal esophagus of patients with esophageal cancer. Tissue explant and enzyme digestion methods were used to clutrue HNEECs with DMEM/F 12 mixed medium and with serum-free medium K-SFM.Gross examination, inverted microscopy observation and immunocytochemistry had been used to observe and identify growth, morphological characteristics of the regenerate esophageal epithelial cells. In DMEM/F12 mixture medium using tissue explant method, the regenerated esophageal epithelial cells, shaping slabstone appearance, grew fast with little fibroblasts pollution, and covered 70%~80% area of culture flask after 15~17 days, but the passage cells grew with more fibroblasts pollution. In the serum-free medium K-SFM using enzyme digestion method, the cells grew as well as the former, covered 70%~80% area of culture flask after only 10~12 days. Moreover, the cells can be used for cryopreservation, recovery and passage. The cells cultured with the other methods were not as good as the cells cultured with these two methods. About 90% of the regenerated cells, cultured with above methods,were cytokeratin positive staining with immunohistochemistry, which indicated that they were all epithelial cells.For primary culture of human esophageal epithelial cells, enzyme digestion method with the serum-free medium K-SFM is the best, but expensive. Tissue explant method with DMEM/F12 mixture medium is cheap with a long culture time, but not for passage. The two methods both can be choosen for different experiments.%该研究通过比较人正常食管鳞状上皮不同的原代培养方法,以期为不同的实验目的提供不同的培养

  18. Overexpression of p53 Gene in Esophageal and Cervical Cancer and the Relationship with Radiotherapy Effects

    Institute of Scientific and Technical Information of China (English)

    张晓智; 王晓丽; 李旭

    2003-01-01

    Objective:To investigate the relationship between p53 protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for 52 cases with esophageal and cervical squamous cell cancer. The relationship between the assay results and short-term radiotherapy was investigated. Results: p53 overer-pression was 52.38% and 35. 48% respectively, in esophageal cancer and cervical cancer;p53 over-expression in high differentiated squamous cell cancer was knver than these in moderate and poor differentiated cases(P0. 05). In the cases of cervical cancer, p53 overexpression had the less short-term effect(P0. 05).Conclusion:This study suggests that p53 gene has the certain relationship with tumor radiosensitivity.

  19. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    OpenAIRE

    Shen Zhongying; Zhang Yi; Huo Leijun; Zhou Li; Zhang Qingying; Zhang Donghong; Zhu Yi

    2010-01-01

    Abstract Background Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in...

  20. Update on endoscopic diagnosis, management and surveillance strategies of esophageal diseases

    Directory of Open Access Journals (Sweden)

    Fernando Fornari

    2012-01-01

    Full Text Available In the last few decades, upper gastrointestinal endoscopy has become the most complementary test for investigation of esophageal diseases. Its accessibility and safety guarantee wide clinical utilization in patients with suspected benign and malignant diseases of the esophagus. Recent technological advances in endoscopic imaging and tissue analysis obtained from the esophagus have been useful to better understand and manage highly relevant diseases such as gastroesophageal reflux disease, eosinophilic esophagitis and esophageal cancer. Using endoscopy to elucidate esophageal disorders in children has been another field of intensive and challenging research. This editorial highlights the latest advances in the endoscopic management of esophageal diseases, and focuses on Barrett’s esophagus, esophageal cancer, eosinophilic esophagitis, as well as esophageal disorders in the pediatric population.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  2. Tissue engineering: an option for esophageal replacement?

    Science.gov (United States)

    Zani, Augusto; Pierro, Agostino; Elvassore, Nicola; De Coppi, Paolo

    2009-02-01

    Esophageal replacement is required in several pediatric surgical conditions, like long-gap esophageal atresia. Although several techniques have been described to bridge the gap, all of them could be followed by postoperative complications. Esophageal tissue engineering could represent a valid alternative thanks to the recent advances in biomaterial science and cellular biology. Numerous attempts to shape a new esophagus in vitro have been described in the last decade. Herein, we review the main studies on the experimental use of nonabsorbable and absorbable materials as well as the development of cellularized patches. Furthermore, we describe the future perspectives of esophageal tissue engineering characterized by the use of stem cells seeded on new biopolymers. This opens to the construction of a functional allograft that could allow an anatomical replacement that grows with the children and does not severely impair their anatomy. PMID:19103424

  3. A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

  4. Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer

    OpenAIRE

    Wang Yu-Fen; Bai Ren-Kui; Liu Ling-Ling; Chang Julia; Tan Duan-Jun; Yeh Kun-Tu; Wong Lee-Jun C

    2006-01-01

    Abstract Background The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. Methods The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of t...

  5. A Nomogram to Predict Prognostic Value of Red Cell Distribution Width in Patients with Esophageal Cancer

    OpenAIRE

    Gui-Ping Chen; Ying Huang; Xun Yang; Ji-Feng Feng

    2015-01-01

    Objectives. The prognostic value of inflammatory index in esophageal cancer (EC) was not established. In the present study, we initially used a nomogram to predict prognostic value of red cell distribution width (RDW) in patients with esophageal squamous cell carcinoma (ESCC). Methods. A total of 277 ESCC patients were included in this retrospective study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). A nomogram was established to predict the prognosis for CSS....

  6. Advances and Applications of Ion Torrent Personal Genome Machine in Cutaneous Squamous Cell Carcinoma Reveal Novel Gene Mutations

    Directory of Open Access Journals (Sweden)

    Yu-Ping Hsiao

    2016-06-01

    Full Text Available The Ion Torrent Personal Genome Machine (Ion PGM is a semiconductor-based sequencing technology that is high quality, scalable, and economic. Its applications include genomic sequencing, drug resistance testing, microbial characterization, and targeted sequencing in cancer studies. However, little is known about the application of Ion PGM in cutaneous squamous cell carcinoma (cSCC. We therefore investigated the utility and validity of Ion PGM in cSCC and also gained a better understanding of the underlying molecular biology of cSCC. We detected novel gene mutations (KDR, FGFR2, and EGFR in two cSCC patients. Moreover, we validated these mutations by pyrosequencing and Sanger sequencing. Our results indicated that the mutation screen using Ion PGM is consistent with traditional sequencing methods. Notably, these identified mutations were present at significantly higher rates in high-risk cSCC. Our results demonstrate a method to detect targetable genes in high-risk cSCC, and suggest that Ion PGM may enable therapeutic decision-making and future potential targets for personalized therapies in cSCC.

  7. A novel tumor suppressor gene ECRG4 interacts directly with TMPRSS11A (ECRG1) to inhibit cancer cell growth in esophageal carcinoma

    OpenAIRE

    Zhou Yun; Zhang Chun-peng; Li Xiao-yan; Li Yuan-yuan; Li Lin-wei; Lu Shih-Hsin

    2011-01-01

    Abstract Background The esophageal carcinoma related gene 4 (ECRG4) was initially identified and cloned from human normal esophageal epithelium in our laboratory (GenBank accession no.AF325503). ECRG4 has been described as a novel tumor suppressor gene associated with prognosis in esophageal squamous cell carcinoma (ESCC). Methods In this study, binding affinity assay in vitro and co-immunoprecipitation experiment in vivo were utilized to verify the physical interaction between ECRG4 and tran...

  8. Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m2 docetaxel on day 1 and 8, 60 mg/m2 cisplatin on day 1, and 70 mg/m2 S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3–4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: http://www.clinicaltrials.gov/NCT01645748

  9. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment

  10. Multidisciplinary approach for patients with esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Victoria M Villaflor; Marco E Allaix; Bruce Minsky; Fernando A Herbella; Marco G Patti

    2012-01-01

    Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced.There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease.Often,esophageal cancer is not diagnosed until patients present with dysphagia,odynophagia,anemia or weight loss.When symptoms occur,the stage is often stage Ⅲ or greater.Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection.The treatment of patients who have locally advanced esophageal cancer is more complex and controversial.Despite multiple trials,treatment recommendations are still unclear due to conflicting data.Sadly,much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically.Additionally,studies have been underpowered or stopped early due to poor accrual.In the United States,concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient.Patients who have metastatic disease are treated palliatively.The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer,and to review the literature which guides our treatment recommendations.

  11. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2012-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  12. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2011-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  13. A comparison and significance of plasma riboflavin levels in patients with esophageal squamous cell carcinoma versus Linzhou healthy migrants in Changzhi of Shanxi%山西长治地区健康林州移民及食管鳞癌患者血浆核黄素水平的比较及其意义

    Institute of Scientific and Technical Information of China (English)

    纪爱芳; 秦小琪; 贺小峰; 王立东; 魏武; 王金胜; 魏子白; 连长红; 杨建洲; 赵莉; 马良; 马莉

    2011-01-01

    目的 探讨核黄素缺乏与食管鳞癌发生的关系.方法 采用ELISA法检测山西长治地区食管鳞癌患者(445例)、长治当地健康人群(689例)及健康林州移民(347例)3组人群的血浆中核黄素水平并比较其差异.结果 长治地区食管鳞癌患者[ (731.69 ±330.67) μg/L]血浆中核黄素水平显著低于长治当地健康人群[(1090.43±445.08) μg/L]和健康林州移民[(897.58±177.78)μg/L],P值均<0.05;而长治当地健康人群血浆中核黄素水平高于健康林州移民,P<0.05.结论 在食管鳞癌患者中存在核黄素缺乏现象,长治本地健康人群血浆中核黄素水平高于健康林州移民,具体机制有待于进一步研究.%Objective To study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma.Methods We detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) and immigrants of Linzhou living in Changzhi.Plasma riboflavin levels were quantified in 445 ESCC patients,689 healthy control subjects and 347 immigrants of Linzhou living in Changzhi by using enzyme-linked immunosorbent assay.Results The plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi [ (731.69 ± 330.67 ) μg/L vs ( 1090.43 ± 445.08 ) μg/L,(731.69 ± 330.67) μg/L vs ( 897.58 ± 177.78) μg/L,respectively,all P < 0.05 ],and the plasma riboflavin levels of the healthy controls were higher than those in the immigrants of Linzhou living in Changzhi (P < 0.05).Conclusion Patients with ESCC have decreased plasma riboflavin levels as compared with the healthy controls and immigrants of Linzhou living in Changzhi,there exists a lack of riboflavin in ESCC patients,but the specific mechanism needs further study.

  14. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the sphingosine 1phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells. METHODS: S1P receptor expression profile in human esophageal squamous cell carcinoma cell line Eca109 was detected by semiquantitative reverse trans cription polymerase chain reaction. Eca109 cells were stably transfected with S1P5EGFP or controlEGFP constructs. The relation between the responses of cell prol...

  15. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned

  16. Evaluation of the prognostic role of tumor cell podoplanin expression in locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    To investigate the potential prognostic role of tumor cell podoplanin expression in patients treated with resection followed by irradiation or chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Podoplanin expression (≤10 % versus > 10 %) and 12 other factors were evaluated in 160 patients for their association with locoregional control (LRC), metastases-free (MFS) and overall survival (OS). Other factors were age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, preradiotherapy (pre-RT) hemoglobin level, tumor site, histological grading, T category, N category, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, extent of resection and concurrent chemotherapy. In multivariate analysis, ECOG performance status 0-1 (risk ratio, RR: 3.01; 95 % confidence interval, CI: 1.42-7.14; p = 0.003), pre-RT hemoglobin levels ≥ 7.45 mmol/l (12 g/dl; RR: 2.03; 95 % CI: 1.04-3.94; p = 0.038), oropharyngeal cancer (RR: 1.25; 95 % CI: 1.01-1.55; p = 0.038) and T category T1-2 (RR: 1.81; 95 % CI: 1.24-2.79; p = 0.002) were significantly associated with improved LRC. T category T1-2 (RR: 1.90; 95 % CI: 1.25-3.06; p = 0.002) and N category N0-2a (RR: 5.22; 95 % CI: 1.96-18.09; p 10 %. (orig.)

  17. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    Science.gov (United States)

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa. PMID:21733701

  18. Chemoradiotherapy using retrograde superselective intra-arterial infusion for advanced oral cancer. Therapeutic effect for T3 and T4 squamous cell carcinoma of the upper gingiva

    International Nuclear Information System (INIS)

    Concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion demonstrates good local control and overall survival rates due to the advantage of simultaneous infusion of anticancer agent with the synergistic effects of chemotherapy and radiotherapy. This study was conducted to evaluate the therapeutic results of 17 patients with locally advanced squamous cell carcinoma of the upper gingiva (T3, T4) treated with definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m2: cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total 60 Gy) for 6 weeks. Patients underwent biopsy of the primary lesion and radiological examinations 4 weeks after the completion of all treatments. Complete response (CR) of the primary site was achieved in 14 (82.4%) patients. Among them, 1 patient showed local recurrence and 1 patient showed cervical and pulmonary metastases. Four patients died, 1 of pulmonary metastases, 1 of cervical metastases, and 2 of uncontrolled local lesion during follow-up. Two-year cumulative local control and overall survival rates by the Kaplan-Meier method were 76.5% and 81.4%, respectively. (author)

  19. Esophageal Cancer in Iran: A Review

    Directory of Open Access Journals (Sweden)

    Siavosh Nasseri-Moghaddam

    2010-01-01

    Full Text Available Esophageal cancer is the second and third most common malignancy in Iranian malesand females, respectively, claiming lives of approximately 5800 Iranians each year.Squamous cell carcinoma (SCC is presently the most common type accounting forabout 90% of all esophageal cancers in Iran. Recent studies have shown that there isa gradual increase in the incidence of adenocarcinoma of the distal esophagus alongwith gastric cardia adenocarcinoma. Thirty-five years ago, the age standardizied rate (ASR of esophageal SCC in thecity of Gonbad (Golestan Province, northeast of Iran was found to be one of the highestrates for any single cancer that had been reported worldwide (ASR >100/105/year.Recent studies have shown that the incidence of SCC in Gonbad has declined to lessthan half of what it was in the past. This decline in the incidence of esophageal SCCparallels an improvement in the socioeconomic situation of people living in thisregion. According to recent cancer registry data in Iran there is still an obviousintracountry variability between the incidence of esophageal cancer in the south withan ASR of 3 for males and 2 for females in Kerman and 43 and 36 in the northeasternprovince of Golestan. The reasons for this very high rate of SCC in northeastern Iranhave been the subject of several studies during the past 35 years. According to resultsof these studies the suspected risk factors are: low intake of fruits and vegetables, drinkinghot tea, consumption of opium products and tobacco, H.pyloriinfection in the stomach,using unhealthy drinking water from cisterns and genetic susceptibility. The mainsuspected mutagens are polycyclic aromatic hydrocarbons (PAH and N-nitrosocompounds. In order to embark primary and secondary prevention of this fatal cancer,further prospective studies are presently underway in the region. The Golestanesophageal cancer cohort study which follows of 50,000 subjects is on going. We expectsimple and feasible evidence based

  20. Radioisotope esophageal transit test

    International Nuclear Information System (INIS)

    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)

  1. PET/CT planning during chemoradiotherapy for esophageal cancer

    OpenAIRE

    Seol, Ki Ho; Jeong Eun LEE

    2014-01-01

    Purpose To evaluate the usefulness of positron emission tomography/computed tomography (PET/CT) for field modification during radiotherapy in esophageal cancer. Materials and Methods We conducted a retrospective study on 33 patients that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy boost dose). Response evalu...

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

    Science.gov (United States)

    Zhong, Lai-ping; Zhang, Chen-ping; Ren, Guo-xin; Guo, Wei; William, William N; Hong, Christopher S; Sun, Jian; Zhu, Han-guang; Tu, Wen-yong; Li, Jiang; Cai, Yi-li; Yin, Qiu-ming; Wang, Li-zhen; Wang, Zhong-he; Hu, Yong-jie; Ji, Tong; Yang, Wen-jun; Ye, Wei-min; Li, Jun; He, Yue; Wang, Yan-an; Xu, Li-qun; Zhuang, Zhengping; Lee, J Jack; Myers, Jeffrey N; Zhang, Zhi-yuan

    2015-07-30

    Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC. PMID:26124084

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

    Directory of Open Access Journals (Sweden)

    Nikolaos eCharalambakis

    2013-01-01

    Full Text Available Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC. Patients and Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutation analysis for PIK3CA genes and high-risk HPV-DNA detection using PCR. Results: Median follow-up was 16 months. Six patients were TNM Stage III, 15 patients IV (IVA or IVB and 1 patient Stage II with bulky disease. During TPF-C, Grade 3 and 4 toxicities occurred in 8 patients (36.4%, dose modifications in 7 (31.8%, delays in 1 (4.5%, and unplanned admissions in 5 (22.7%. Clinical tumor response was documented in 18 of the 21 patients who completed at least 3 cycles of TPF-C (85.7% with 3 patients developing complete response and 15 partial responses. Grade 3/4 mucositis was observed in 6 (31.6% patients. At a median follow up of 19 months, 13 patients were alive and 9 (40.9% had died including 7 patients as a result of disease persistence or recurrence and two as a result of unrelated causes. PIK3CA mutations were not identified and our 2 oropharynx cases were HPV negative.Conclusions: The combination of induction TPF-C with concurrent cetuximab radioimmunotherapy in patients with locally advanced HNSCC is tolerable, with encouraging efficacy.Keywords: HNSCC, TPF-C, cetuximab radiotherapy, toxicity and outcome, mutation analysis, PIK3CA, HPV-DNA.

  4. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory

  5. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C. [Kidwai Memorial Institute of Oncology Bangalore, Karnataka (India); Pyakuryal, A [University Illinois at Chicago, Chicago, IL (United States); Narayanasamy, Ganesh [UTHSCSA, San Antonio, TX (United States)

    2014-06-01

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.

  6. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

    2009-10-15

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  7. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m2/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m2/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m2/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m2/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  8. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Tinhofer, Ingeborg, E-mail: ingeborg.tinhofer@charite.de [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); Hristozova, Tsvetana; Stromberger, Carmen [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); KeilhoIz, Ulrich [Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Universitaetsmedizin Berlin, Berlin (Germany); Budach, Volker [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany)

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  9. Esophageal capsule endoscopy

    Institute of Scientific and Technical Information of China (English)

    Ignacio Fernandez-Urien; Cristina Carretero; Raul Armendariz; Miguel Mu(n)oz-Navas

    2008-01-01

    Capsule endoscopy is now considered as the first imaging tool for small bowel examination.Recently,new capsule endoscopy applications have been developed,such as esophageal capsule endoscopy and colon capsule endoscopy.Esophageal capsule endoscopy in patients with suspected esophageal disorders is feasible and safe,and could be also an alternative procedure in those patients refusing upper endoscopy.Although large-scale studies are needed to confirm its utility in GERD and cirrhotic patients,current results are encouraging and open a new era in esophageal examination.

  10. Esophageal surgery in minimally invasive era.

    Science.gov (United States)

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-27

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  11. Tumors control and dysphagia in patients with locally advanced T3/T4 oesophageal squamous cell cancer after definitive radio-chemotherapy

    International Nuclear Information System (INIS)

    Squamous cell carcinoma of the esophagus (scc) is usually diagnosed in an advanced stage resulting in limited curative options. The aim was to evaluate immediate and long-term effects of combined chemo-radiotherapy of loco-regionally advanced scc in terms of dysphagia relief and tumors response. Between 1997 and 2003, 35 pts with scc completed full definitive non-surgical treatment. Men - 31, women -4 ; mean age: 51. Tumors stage: T4 -5, T3 - 30, node stage: N0 - 8, N1 - 27 dysphagia at presentation WHO IIIo -17%, IIo -46%, Io - 37%. Irradiation: conventional fractionation to a dose of 56-60 Gy to tumors, 54-60 Gy to large lymph nodes, 40-44 Gy electively to regional lymph nodes in combination with 2 courses of i.v. chemotherapy: 5-fluouracil: 800 mg/m2/ 24 h (day: 1-4, 22-25 ), cisplatin: 80 mg/m2 (day 1 ,22) followed by HDR brachytherapy boost using 192 Ir -6 Gy after a one week interval. During follow-up the patients were scored according to the swallowing function, weight change and pain control. Tumors regression and late radiotherapy side effects were observed. Initial improvement in dyssphagia occurred in 20/35 patients (57%) during treatment. Durable improvement at 1-year was evidenced in 19/35 (54%) pts 31% were dysphagia-free at 1 year. Average duration of dysphgia improvement was 11 months. Only patients with marked improvement in the swallowing function documented during treatment were able to maintain this function for longer time. We achieved an overall response rate to treatment of 52%.CR (local control) was noted in 26% of pts and local progression (PD) in 34% at 12 months. The medium time to tumour progression was 5.4 months. Systematic failure was not in 20% of patients. The median time to metastases was 8 months and median survival - 12.5 months with a 1-year observed survival of 54%, 2-year - 31% and 3-year - 23%. 1. Primary concurrent chemo-radiotherapy for advanced T3/T4 N0-1 scc of the oesophagus seems to be a reasonable modality to control

  12. Simultaneous radiation plus cis-platinum/5-fluorouracil infusion in locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    This paper reports twenty patients with advanced untreated head and neck cancer (curative) and five with recurrence (palliative) treated with three 2-week courses of radiation (1,500 rad/10 treatments), cis-platinum, and a 5-day 5-fluorouracil infusion. A fourth 2-week course of radiation (2,000 rad/10 treatments) brought the final tumor dose to 6,500 rad. Nineteen (95%) of the curative patients and four (80%) of the palliative patients experienced complete or partial response. There have been 12 recurrences (nine local, two distant, and one local + distant). Most patients experienced toxicity, including nausea, vomiting, weight loss, and mucositis. In this study, chemoradiotherapy was effective in achieving local/regional control in advanced head and neck cancer

  13. Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-Differences in Etiology, Epidemiology and Prevention

    Institute of Scientific and Technical Information of China (English)

    ElfriedeBollschweiler; EvaWolfgarten

    2004-01-01

    In Germany, esophageal carcinoma is one of the ten most frequent causes of death. Normally the disease is found in men over the age of 50. Although squamous cell carcinoma (SCC) of the esophagus has been more commonly diagnosed over the past 30 years, there is increasing incidence of esophageal adenocarcinoma (AC) in Western industrialized countries. For SCC the known etiological risk factors are nicotine and alcohol abuse. For AC, they are moderate nicotine and alcohol consumption as well as gastro-esophageal reflux and obesity.

  14. Initial adjuvant weekly high dose methotrexate with leucovorin rescue in advanced squamous carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Despite aggressive local therapy, advanced head and neck cancer continues to have a poor prognosis. In an attempt to improve survival in this disease, the Joint Center for Radiation Therapy and the Sidney Farber Cancer Institute instituted a pilot study employing high dose methotrexate with leucovorin rescue (3.5 to 7.5 g/m2) as an adjuvant to aggressive radiotherapy and surgery. A high response rate of 60 percent (9/15) with no compromise of definitive therapy indicates such cooperation multimodality trials may hold promise for an increase in cure rates in these patients

  15. Squamous cell cancer of the rectum

    Institute of Scientific and Technical Information of China (English)

    Tara Dyson; Peter V Draganov

    2009-01-01

    Squamous cell carcinoma of the rectum is a rare malignancy. It appears to be associated with chronic inflammatory conditions and infections. The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease. Diagnosis relies on endoscopic examination with biopsy of the lesion. Distinction from squamous cell cancer of the anus can be difficult, but can be facilitated by immunohistochemical staining for cytokeratins. Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy. At present, surgery remains the main therapeutic option; however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease. Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous cell carcinoma of the rectum has different epidemiology, etiology, pathogenesis, and prognosis but, most importantly, requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

  16. Epigenetic biomarkers in esophageal cancer.

    Science.gov (United States)

    Kaz, Andrew M; Grady, William M

    2014-01-28

    The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. PMID:22406828

  17. Baclofen-responsive hiccups after esophageal stenting for malignancy-related dysphagia.

    Science.gov (United States)

    Sharma, Vishal; De, Arka; Lamoria, Sandeep; Lamba, Brinder Mohan Singh

    2016-04-01

    Hiccups can have multiple causes, including esophageal lesions. Hiccups after insertion of self-expanding metallic stents have been reported occasionally following stenting for lesions of the gastroesophageal junction. We report a patient who developed hiccups after insertion of a stent for squamous cell carcinoma of the proximal esophagus. The hiccups responded only to the initiation of baclofen therapy. PMID:27034549

  18. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm3, and patients with a tumor volume 3 had a significantly better prognosis than those with a tumor volume >35 cm3 at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume 3 had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = 3 larger than tumors without locoregional failure (p = .028) and 27.1-cm3 larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

  19. Prognostic value of pretreatment 18F-FDG PET/CT and human papillomavirus type 16 testing in locally advanced oropharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of 18F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients. We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy 18F-FDG PET/CT scan and had completed concurrent chemoradiotherapy (n = 58) or curative radiotherapy (n = 2). All patients were followed up for ≥24 months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUVmax) of the primary tumour and neck lymph nodes from the pretherapy 18F-FDG PET/CT scan. Optimal cut-offs of the 18F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status. The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0 %). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3 g to be independently associated with overall survival (p = 0.027 and 0.011, respectively). However, only tumour TLG >135.3 g was independently associated with progression-free survival, disease-free survival and locoregional control (p = 0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG ≤135.3 g experienced better survival than those with tumour TLG >135.3 g and no HPV infection (p = 0.001). Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy. (orig.)

  20. Concurrent intra-arterial carboplatin adminis