Jeong Youp Park

Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis.

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.

Active locomotion of a paddling-based capsule endoscope in an in vitro and in vivo experiment (with videos)

BACKGROUND Capsule endoscopy that could actively move and approach a specific site might be more valuable for the diagnosis or treatment of GI diseases. OBJECTIVE We tested the performance of active locomotion of a novel wired capsule endoscope with a paddling-based locomotion mechanism, using 3 models: a silicone tube, an extracted porcine colon, and a living pig. DESIGN In vitro, ex vivo, and in vivo experiments in a pig model. SETTING Study in an animal laboratory. INTERVENTIONS For the in vitro test, the locomotive capsule was controlled to actively move from one side of a silicone tube to the other by a controller-operated automatic traveling program. The velocity was calculated by following a video recording. We performed ex vivo tests by using an extracted porcine colon in the same manner we performed the in vitro test. In in vivo experiments, the capsule was inserted into the rectum of a living pig under anesthesia, and was controlled to move automatically forward. After 8 consecutive trials, the velocity was calculated. MAIN OUTCOME MEASUREMENTS Elapsed time, velocity, and mucosal damage. RESULTS The locomotive capsule showed stable and active movement inside the lumen both in vitro and ex vivo. The velocity was 60 cm/min in the silicone tube, and 36.8 and 37.5 cm/min in the extracted porcine colon. In the in vivo experiments, the capsule stably moved forward inside the colon of a living pig without any serious complications. The mean velocity was 17 cm/min over 40 cm length. We noted pinpoint erythematous mucosal injuries in the colon. LIMITATION Porcine model experiments, wired capsule endoscope. CONCLUSIONS The novel paddling-based locomotive capsule endoscope performed fast and stable movement in a living pig colon with consistent velocity. Further investigation is necessary for practical use in humans.

CXCL5 overexpression is associated with late stage gastric cancer

PurposeChemokines play multiple roles in the development and progression of many different tumors. Our cDNA array data suggested that chemokine CXCL5 was upregulated in gastric cancer. Here, we analyzed CXCL5 protein expression in gastric cancer and investigated the clinical implications of CXCL5 upregulation.MethodsImmunostaining for CXCL5 was performed on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The intensity of immunostaining in tumor tissue was considered strong when tumor tissue staining was more intense than in normal tissue; the intensity was null when staining was weaker in the tumor than in normal tissue; and the intensity was weak when staining was similar in both tissues. Serum CXCL5 levels and microvascular density in tumor tissue were measured by ELISA and monoclonal antibody to Factor VIII.ResultsStrong CXCL5 expression correlated with tumor stage. CXCL5 expression did not correlate with T stage. However, N stage positively correlated with CXCL5 expression. Serum CXCL5 levels in late stage (IIIB, IV) gastric cancer patients were higher than in patients with benign conditions. Microvascular density was higher in tumors with strong CXCL5 expression, but the correlation with CXCL5 was not linear. Multiple logistic regression analyses showed that, compared to no or weak expression, strong expression of CXCL5 was a significant risk factor for high N stage (N2, N3).ConclusionsCXCL5 overexpression was associated with late stage gastric cancer and high N stage. These results suggest a role for CXCL5 in the progression of gastric cancer, specifically in lymph node metastasis.

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

Background:  The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer.

Development, validation, and responsiveness of a novel disease activity index for intestinal Behçet's disease

Background: There is no disease activity index (DAI) currently available that can objectively assess the disease status of intestinal Behcets disease (BD). The aim of this study was to develop a novel specific DAI for intestinal BD through a prospective study. Methods: Items included in the index were produced and graded by experts in intestinal BD. Two separate cohorts of patients (weighting and validation cohorts) with intestinal BD were prospectively enrolled, and their clinical and laboratory data were collected. Through weighting items by multiple regression modeling, the DAI for intestinal BD (DAIBD) was derived using the weighting cohort and validated using the validation cohort. The indexs responsiveness was evaluated using a longitudinal cohort derived from the weighting cohort at a follow‐up visit 2‐3 months later. Results: A total of 110 patients with intestinal BD were enrolled in the weighting cohort. Eight of the 17 items selected by the experts accounted for 86.8% of the physicians global assessment (PGA) variance. The DAIBD calculated with gradations of weighted items correlated more strongly with PGA (r = 0.850) than did the Crohns disease activity index (CDAI) (r = 0.649) in 50 patients of the validation cohort. Furthermore, quiescent, mild, moderate, and severe could be discriminated using the best cutoff scores. The DAIBD showed much higher responsiveness than did the CDAI (r = 0.812 vs. 0.645, respectively) in 109 patients in the longitudinal cohort. Conclusions: This novel DAIBD is an easy, valid, and responsive index to assess disease activity and can be useful to physicians who treat intestinal BD. Inflamm Bowel Dis 2011

The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma

Objectives:Vascular endothelial growth factor-C (VEGF-C) is known to be an important lymphangiogenetic factor. Lymphatic spread is a key prognostic factor in intrahepatic cholangiocarcinoma (ICC). We studied the expression of VEGF-C in ICC tissues to clarify its clinicopathologic significance. Methods:The expression of VEGF-C in surgical specimens obtained from 36 patients with ICC who underwent hepatic resection was examined by immunohistochemistry and Western blotting. Strong staining was defined as the presence of VEGF-C immunoreactivity in at least 50% of the tumor cells. Immunoreactivity in ∼10% to ∼50% of the tumor cells was considered as weak staining, and less than 10% as no staining. Results:Of the 36 patients with ICC, 15 patients (41.7%) showed a strong positive result for VEGF-C. Eleven cases (30.6%) were negative and 10 cases (27.8%) showed weak immunoreactivity. VEGF-C expression was significantly correlated with lymph node metastasis (P = 0.032) and positive surgical margin (P = 0.03). Patients who had strong positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative or weak staining (P < 0.01). Other significant prognostic factors by univariate analysis were vascular invasion, lymph node involvement, and positive surgical margin. Multivariate analysis demonstrated that strong VEGF-C expression (P = 0.028) and vascular invasion (P = 0.021) were independent factors indicating poor prognosis. Conclusions:Our data suggest that VEGF-C expression serves as an independent and important prognostic factor in ICC patients, and it may play an important role in the lymph node metastasis of ICC.

Long‐term follow up of gallbladder polyps

Background and Aim:  The management of gallbladder polyps (GBP) is directly linked to the early diagnosis of gallbladder cancer (GBC). This study aimed to evaluate the malignant risk of GBP.

Endoscopic Papillary Balloon Dilation with Large Balloon after Limited Sphincterotomy for Retrieval of Choledocholithiasis

Endoscopic papillary balloon dilation (EBD) for choledocholithiasis is known to be comparable to endoscopic sphincterotomy (EST) especially in cases of small stones. With larger stones, EBD with conventional balloon, which have a diameter of 6-8 mm, was reported as less effective for extraction of stones. We evaluated the efficacy and complications of EBD with large balloons (10-15 mm) after limited EST for retrieval of choledocholithiasis. From February 2005, we have performed EBD with limited EST for retrieval of common bile duct (CBD) stones. The patients who admitted with hyperamylasemia and gallstone pancreatitis were excluded. In cases without CBD dilation, EPBD with 12 mm for 40 seconds was performed. And in cases with CBD dilation, we dilated the sphincters with 15 mm sized balloon for 40 seconds. Total 22 patients (11 of male) were performed EBD with limited EST for retrieval of CBD stones. The median diameter of the stones was 10 mm (5-25 mm). Ten cases had multiple stones and 6 cases periampullary diverticuli. Successful stone removal in the initial session of ERCP with EBD was accomplished in 16 patients (72.7%). And complete retrieval of bile duct stones was achieved in all patients with repeated ERCP. In the aspect of complications, any episodes of perforation, bleeding was not developed. Only one case of mild grade of post-procedural pancreatitis was noted. However, post-procedural hyperamylasemia was developed in 16 cases (68.2%). EBD with larger balloon seems to be a feasible and safe alternative technique for conventional EST in CBD stone extraction.

A Pilot Study of Sequential Capsule Endoscopy Using MiroCam and PillCam SB Devices with Different Transmission Technologies.

BACKGROUND/AIMS Studies have investigated the use of different types of radiofrequency capsules for comparison or sequential capsule endoscopy, but none have compared the MiroCam device - which utilizes a novel data transmission technology - with other capsules. This study compared the feasibility of sequential capsule endoscopy using the MiroCam and PillCam SB devices, which employ different transmission technologies. METHODS Patients with diseases requiring capsule endoscopy were enrolled. After a 12-hour fast, one randomly selected capsule was swallowed. The second capsule was swallowed once fluoroscopy had indicated that the first capsule had migrated below the gastric outlet. RESULTS The total operating time in 24 patients was 702+/-60 min (mean+/-SD) for the MiroCam and 446+/-28 min for the PillCam SB (p<0.0001). The rate of a complete examination to the cecum was 83.3% for the MiroCam and 58.3% for the PillCam SB (p=0.031). Diagnostic yields for the MiroCam, PillCam SB, and sequential capsule endoscopy were 45.8%, 41.7%, and 50.0%, respectively. The agreement rate between the two capsules was 87.5%, with a kappa value of 0.74. Electrical interference in data transmission between the two capsules was not observed, but temporary visual interferences were observed in seven patients (29.2%). CONCLUSIONS Sequential capsule endoscopy with the MiroCam and PillCam SB produced slight but nonsignificant increases in the diagnostic yield, and the two capsules did not exhibit electrical interference. A larger trial is necessary for elucidating the usefulness of sequential capsule endoscopy.

Pancreatic adenocarcinoma up‐regulated factor (PAUF), a novel up‐regulated secretory protein in pancreatic ductal adenocarcinoma

The identification of novel tumor‐specific proteins or antigens is of great importance for diagnostic and therapeutic applications in pancreatic cancer. Using oligonucleotide microarrays, we identified a broad spectrum of differentially expressed pancreatic cancer‐related genes. Of these, we selected an overexpressed expressed sequence taq and cloned a 721‐bp full‐length cDNA with an open reading frame of 196 amino acids. This novel gene was localized on the Homo sapiens 16p13.3 chromosomal locus, and its nucleotide sequence matched the Homo sapiens similar to common salivary protein 1 (LOC124220). We named the gene pancreatic adenocarcinoma up‐regulated factor. The pancreatic adenocarcinoma up‐regulated factor was secreted into the culture medium of pancreatic adenocarcinoma up‐regulated factor‐overexpressing Chinese hamster ovary cells, had an apparent molecular mass of ~25 kDa, and was N‐glycosylated. The induction of pancreatic adenocarcinoma up‐regulated factor in Chinese hamster ovary cells increased cell proliferation, migration, and invasion ability in vitro. Subcutaneous injection of mice with Chinese hamster ovary/pancreatic adenocarcinoma up‐regulated factor cells resulted in 3.8‐fold greater tumor sizes compared to Chinese hamster ovary/mock cells. Reverse transcription–polymerase chain reaction and western blotting with antirecombinant human pancreatic adenocarcinoma up‐regulated factor antibodies confirmed that pancreatic adenocarcinoma up‐regulated factor was highly expressed in six of eight pancreatic cancer cell lines. Immunohistochemical staining of human pancreatic cancer tissues also showed pancreatic adenocarcinoma up‐regulated factor overexpression in the cytoplasm of cancer cells. Transfection with pancreatic adenocarcinoma up‐regulated factor‐specific small‐interfering RNA reduced cancer cell migration and invasion in vitro. Treatment with antirecombinant human pancreatic adenocarcinoma up‐regulated factor in vitro and in vivo reduced proliferation, migration, invasion, and tumorigenic ability. Collectively, our results suggest that pancreatic adenocarcinoma up‐regulated factor is a novel secretory protein involved in pancreatic cancer progression and might be a potential target for the treatment of pancreatic cancer. (Cancer Sci 2009; 100: 828–836)