Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium

Background: Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells. Methods: Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome. Results: Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis. Conclusion: Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker. © 2013 Malhotra et al

How Much Pharyngeal Exposure Is “Normal”? Normative Data for Laryngopharyngeal Reflux Events Using Hypopharyngeal Multichannel Intraluminal Impedance (HMII)

Laryngopharyngeal reflux (LPR) can cause atypical symptoms, asthma, and pulmonary fibrosis. The aim of this study was to establish the normative data for LPR using hypopharyngeal multichannel intraluminal impedancepH (HMII)

A Cross-sectional Analysis of the Prevalence of Barrett Esophagus in Otolaryngology Patients With Laryngeal Symptoms

Populations at risk for esophageal adenocarcinoma remain poorly defined. Laryngeal symptoms can be secondary to laryngopharyngeal reflux (LPR) and can occur without associated gastroesophageal reflux symptoms such as heartburn and regurgitation

Feasibility, safety, acceptability, and yield of office-based, screening transnasal esophagoscopy (with video)

Endoscopic screening for esophageal neoplasia can identify patients eligible for early intervention for pre-cancerous lesions. Unsedated transnasal esophagoscopy may provide an efficient and accurate endoscopic assessment with fewer risks and less cost compared to conventional upper endoscopy

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京都大学0048新制・課程博士博士(医学)甲第11380号医博第2803号新制||医||884(附属図書館)23023UT51-2005-D131京都大学大学院医学研究科外科系専攻(主査)教授 千葉 勉, 教授 中畑 龍俊, 教授 生田 宏一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA