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Jung D.E.,Yonsei University | Wen J.,Yonsei University | Oh T.,Yonsei University | Song S.Y.,Yonsei University | Song S.Y.,Yonsei Institute of Gastroenterology
Pancreas | Year: 2011

Objective: The objective of this study was to analyze and identify pancreatic cancer stem cell-specific microRNAs (miRNAs) and messenger RNAs (mRNAs) to investigate their correlations to cancer stem cell biology. Methods: We used sphere cultivation methods to enrich the stem cell population and analyzed overall miRNA and mRNA expressions using microarray analysis. Results: Differentially expressed miRNAs including miR-99a, miR-100, miR-125b, miR-192, and miR-429 were detected in pancreatic cancer stem cells. Furthermore, examining both profiles, we obtained 210 miRNAs and 258 stem cell-associated mRNAs that were differentially expressed in the pancreatic cancer stem cells. These miRNAs and mRNAs were further investigated using cross-correlation analysis, which yielded 6 groups of miRNAs and 3 groups of mRNAs. The number of miRNA clusters and mRNA clusters showed high correlation based on microarray result. Conclusions: Differentially expressed miRNAs in pancreatic cancer stem cells provide insights into possible linkages between clusters of miRNAs and clusters of stem cell-associated mRNAs in cancer stem cells and have broad implications in our understanding of cancer stem cells and cancer stem cell-targeted cancer therapy. © 2011 Lippincott Williams & Wilkins. Source


Chung J.W.,Yonsei Institute of Gastroenterology | Jang H.W.,Yonsei Institute of Gastroenterology | Chung M.J.,Yonsei Institute of Gastroenterology | Park J.Y.,Yonsei Institute of Gastroenterology | And 5 more authors.
Hepato-Gastroenterology | Year: 2013

Background/Aims: This phase II study assessed the efficacy and safety of FOLFOX4 as a rescue therapy in patients with gemcitabine-refractory pancreatic cancer. Methodology: The study included patients with advanced pancreatic cancer who had failed gemcitabine-based chemotherapy. FOLFOX4 was administered biweekly as follows: oxaliplatin, 85mg/m2 as a 2-hour infusion (day 1); leucovorin, 200mg/m2/day as a 2-hour infusion (days 1 and 2); 5-fluorouracil, bolus 400mg/m2/day and 600mg/m2/day as a 22-hour infusion (days 1 and 2). Results: Forty-four patients received a total of 264 cycles of chemotherapy. There was 1 complete response (2.2%), 4 partial responses (9.1%), and 13 stable diseases (29.5%). The objective response rate was 11.4% and the tumor stabilization rate was 40.9%. The median time to progression was 9.9 weeks (95%CI: 8.2-11.5) and the median overall survival was 31.1 weeks (95%C1: 24.4-37.9). The common adverse events were hematologic toxicities: grade 3 or 4 neutropenia in 19 patients (43.2%), anemia in 9 patients (20.5%), and thrombocytopenia in 6 patients (13.5%). Grade 3 or 4 neuropathy occurred in 4 patients (9.1%). Conclusions: In gemcitabine-refractory pancreatic cancer, FOLFOX4 showed encouraging activity and was generally well-tolerated. However, careful attention needs to be paid to hematologic toxicities. © H.G.E. Update Medical Publishing S.A. Source


Chung J.W.,Yonsei Institute of Gastroenterology | Hwang H.J.,Yonsei Cardiovascular Center and Cardiovascular Research Institute | Chung M.J.,Yonsei Institute of Gastroenterology | Park J.Y.,Yonsei Institute of Gastroenterology | And 3 more authors.
Digestive Diseases and Sciences | Year: 2012

Background: The MiroCam (IntroMedic, Ltd., Seoul, Korea) is a small-bowel capsule endoscope that uses human body communication to transmit data. The potential interactions between cardiac devices and the capsule endoscope are causes for concern, but no data are available for this matter. Aim: This clinical study was designed to evaluate the potential influence of the MiroCam capsules on cardiac devices. Methods: Patients with cardiac pacemakers or implantable cardiac defibrillators referred for evaluation of small bowel disease were prospectively enrolled in this study. Before capsule endoscopy, a cardiologist checked baseline electrocardiograms and functions of the cardiac devices. Cardiac rhythms were continuously monitored by 24-h telemetry during capsule endoscopy in the hospital. After completion of procedures, functions of the cardiac devices were checked again for interference. Images from the capsule endoscopy were reviewed and analyzed for technical problems. Results: Six patients, three with pacemakers and three with implantable cardiac defibrillators, were included in the study. We identified no disturbances in the cardiac devices and no arrhythmias detected on telemetry monitoring during capsule endoscopy. No significant changes in the programmed parameters of the cardiac devices were noted after capsule endoscopy. There were no imaging disturbances from the cardiac devices on capsule endoscopy. Conclusions: Capsule endoscopy using human body communication to transmit data was safely performed in patients with cardiac pacemakers or implantable cardiac defibrillators. Images from the capsule endoscopy were not affected by cardiac devices. A further large-scale study is required to confirm the safety of capsule endoscopy with various types of cardiac devices. © Springer Science+Business Media, LLC 2012. Source


Oh T.G.,Yonsei Institute of Gastroenterology | Chung M.J.,Yonsei Institute of Gastroenterology | Park J.Y.,Yonsei Institute of Gastroenterology | Bang S.M.,Yonsei Institute of Gastroenterology | And 4 more authors.
Yonsei Medical Journal | Year: 2012

Purpose: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors. For PNETs, the predictive factors for survival and prognosis are not well known. The purpose of our study was to evaluate the predictive factors for survival and disease progression in PNETs. Materials and Methods: We retrospectively analyzed 37 patients who were diagnosed with PNET at Severance Hospital between November 2005 and March 2010. Prognostic factors for survival and disease progression were evaluated using the Kaplan-Meier method. Results: The mean age of the patients was 50.0±15.0 years. Eight cases (21.6%) were described as functioning tumors and 29 cases (78.4%) as non-functioning tumors. In univariate analysis of clinical factors, patients with liver metastasis (p=0.002), without resection of primary tumors (p=0.002), or American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage III/IV (p=0.002) were more likely to demonstrate shorter overall survival (OS). Patients with bile duct or pancreatic duct invasion (p=0.031), sized-lesions larger than 20 mm (p=0.036), liver metastasis (p=0.020), distant metastasis (p=0.005), lymph node metastasis (p=0.009) or without resection of primary tumors (p=0.020) were more likely to demonstrate shorter progression-free survival (PFS). In multivariate analysis of clinical factors, bile duct or pancreatic duct invasion [p=0.010, hazard ratio (HR)=95.046] and tumor location (non-head of pancreas) (p=0.036, HR=7.381) were confirmed as independent factors for predicting shorter PFS. Conclusion: Patients with liver metastasis or without resection of primary tumors were more likely to demonstrate shorter OS. Patients with bile duct or pancreatic duct invasion or tumors located at body or tail of pancreas were more likely to demonstrate shorter PFS. © Yonsei University College of Medicine 2012. Source


Wen J.,Yonsei Institute of Gastroenterology | Park J.Y.,Yonsei Institute of Gastroenterology | Park K.H.,Yonsei Institute of Gastroenterology | Chung H.W.,Yonsei Institute of Gastroenterology | And 4 more authors.
Pancreas | Year: 2010

Objective: To characterize the role of Oct4 and Nanog, two important homeobox transcription factors of embryonic development, in pancreatic carcinogenesis. Methods: Using a tissue microarray of human pancreatic carcinoma and adjacent noncancerous tissues as well as the N-nitrosobis(2-oxopropyl) amine-induced Syrian golden hamster pancreatic cancer model, we characterized the expression of Oct4 and Nanog. The presence of K-ras mutation with the time course of carcinogenesis in hamster model was also evaluated. Results: Oct4 expression in metaplastic ducts was significantly stronger than in normal acini and pancreatic carcinoma (P < 0.05). Of 24 cases, 19 (79.2%) showed a strong Oct4 expression in metaplastic ducts. In contrast, only 6 (19.4%) of 31 cancer tissues and 3 (16.7%) of 18 noncancer tissues showed a strong Oct4 expression. Nanog also showed similar patterns as Oct4. Restriction fragment length polymorphism-polymerase chain reaction showed the overt K-ras mutation after the expression of Oct4 in the hamster model. Conclusions: The strong expression of Oct4 and Nanog in metaplastic ducts and Oct4 expression preceding Ras mutation suggests that these homeobox transcription factors are associated with the early stage of pancreatic cancer carcinogenesis and may play an important role in that process. Copyright © 2010 by Williams & Wilkins. Source

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