• 한국임상수의학회지
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• 제34권4호
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• pp.229-233
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• 2017

The object of the present study was to compare abnormal serum canine pancreas-specific lipase results and pancreatic ultrasonographic findings in dogs with pancreatitis. Pancreatitis is a common disease in dogs that is difficult to diagnose. The noninvasive diagnostic procedures, including a serum canine pancreatic-specific lipase (cPL) test and ultrasonographic changes in the pancreas, can be considered for the diagnosis of canine pancreatitis in clinical practice. A retrospective study was performed to assess pancreatitis in dogs. Forty client-owned dogs were suspected to have pancreatitis, which was confirmed by abnormal serum SNAP cPL results. Abdominal ultrasound examinations were also performed. The present study investigated the distribution of clinical signs associated with pancreatitis, and the dogs were divided into two groups: group 1 (clinical signs compatible with pancreatitis; n = 30) and group 2 (no clinical signs; n = 10). Based on this study, an abnormal result on the SNAP cPL assay can still present as a normal pancreas through an ultrasonographic examination, and a normal health status can identify the status of pancreatic ultrasonographic abnormal lesions. Therefore, for dogs with suspected pancreatitis, it is important to repeat an ultrasonographic evaluation. There is no significant difference between clinical symptoms and ultrasonographic changes in the pancreas.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1917-1921
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• 2012

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.261-266
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• 2003

Type 1 diabetes is an organ-specific autoimmune disease caused by the cytotoxic T cells-mediated destruction of the insulin-producing beta cells in the Langerhans pancreatic islets. Hepatocyte growth factor (HGF) is a potent mitogen and a promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF via viral vector in the development of streptozotocin (STZ)-induced diabetes in mice, we have developed an adenoviral vector genetically engineered to carry the gene for human HGF (hHGF) and evaluate the change of blood glucose, insulin level, and insulin-secreting beta cells of pancreatic islets. We demonstrate that the treatment with hHGF gene prevented the development of STZ-induced diabetes and increased serum insulin level to above normal range. Furthermore, it preserved pancreatic beta cells from destruction. These in vivo results may support previous findings that HGF is insulinotropic agent for beta cells and HGF treatment renders the cells to be resistant to the development of diabetes from STZ administration. We suggest that an adenoviral mediated hHGF gene therapy is a good candidate for the prevention and treatment of type 1 diabetes.

• Molecules and Cells
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• 제40권7호
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• pp.457-465
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• 2017

Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic ${\beta}$-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic ${\beta}$-cell apoptosis via an ER stress-dependent signaling pathway. STZ-induced diabetic WT and CHOP deficient mice were i.p. injected every 2 days for 6 days under BIX02189 (a specific ERK5 inhibitor) treatment in order to evaluate the role of ERK5. Hyperglycemia was exacerbated by co-treating C57BL/6J mice with STZ and BIX02189 as compared with mice administered with STZ alone. In addition, immunoblotting data revealed that ERK5 inhibition activated the unfolded protein response pathway accompanying apoptotic events, such as, PARP-1 and caspase-3 cleavage. Interestingly, ERK5 inhibition-induced exacerbation of pancreatic ${\beta}$-cell apoptosis was inhibited in CHOP deficient mice. Moreover, transduction of adenovirus encoding an active mutant form of $MEK5{\alpha}$, an upstream kinase of ERK5, inhibited STZ-induced unfolded protein responses and ${\beta}$-cell apoptosis. These results suggest that ERK5 protects against STZ-induced pancreatic ${\beta}$-cell apoptosis and hyperglycemia by interrupting the ER stress-mediated apoptotic pathway.

• Journal of Gastric Cancer
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• 제21권1호
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• pp.16-29
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• 2021

Purpose: Incidence, risk factors, and clinical consequences of pancreatic fistula (POPF) after D1+/D2 radical gastrectomy have not been well investigated in Western patients, particularly those from Eastern Europe. Materials and Methods: A total of 358 D1+/D2 radical gastrectomies were performed by surgeons with high caseloads in a single surgical center from 2002 to 2017. A retrospective analysis of data that were prospectively gathered in an electronic database was performed. POPF was defined and graded according to the International Study Group for Pancreatic Surgery (ISGPS) criteria. Uni- and multivariate analyses were performed to identify potential predictors of POPF. Additionally, the impact of POPF on early complications and long-term outcomes were investigated. Results: POPF was observed in 20 patients (5.6%), according to the updated ISGPS grading system. Cardiovascular comorbidities emerged as the single independent predictor of POPF formation (risk ratio, 3.051; 95% confidence interval, 1.161-8.019; P=0.024). POPF occurrence was associated with statistically significant increased rates of postoperative hemorrhage requiring re-laparotomy (P=0.029), anastomotic leak (P=0.002), 90-day mortality (P=0.036), and prolonged hospital stay (P<0.001). The long-term survival of patients with gastric adenocarcinoma was not affected by POPF (P=0.661). Conclusions: In this large series of Eastern European patients, the clinically relevant rate of POPF after D1+/D2 radical gastrectomy was low. The presence of co-existing cardiovascular disease favored the occurrence of POPF and was associated with an increased risk of postoperative bleeding, anastomotic leak, 90-day mortality, and prolonged hospital stay. POPF was not found to affect the long-term survival of patients with gastric adenocarcinoma.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권4호
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• pp.332-339
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• 2022

Purpose: Although endoscopic retrograde cholangiopancreatography (ERCP) has been used for more than five decades, its applicability in Bangladeshi children has recently become more common. Therefore, this manuscript aims to describe our experience in performing ERCPs in Bangladeshi children with hepatopancreaticobiliary diseases, focusing on presenting diseases, as well as the diagnostic and therapeutic efficacy. Methods: Between 2018 and 2021, 20 children underwent 30 ERCP procedures at the Bangladesh Specialized Hospital, Dhaka. A single trained adult gastroenterologist performed all procedures using a therapeutic video duodenoscope. The indications for ERCP, diagnostic findings, therapeutic procedures, and complications were documented. Results: The median age of the study patients was 10 years (range, 1.7-15 years). Successful cannulation of the papilla was achieved in 28 procedures and failed in 2 cases. Repeated ERCP was required in seven patients. Nine patients had biliary indications and 11 had pancreatic indications. Choledocholithiasis was the most common indication for ERCP in patients with biliary disease, while chronic pancreatitis was common among patients with pancreatic indications. Pancreatic divisum was observed in only one patient. Pancreatic and biliary sphincterotomy was performed in 14 and 9 cases, respectively. A single pigtail or straight therapeutic stent was inserted in seven cases and removed in five cases. Stone extraction was performed in six procedures, and balloon dilatation was performed in five procedures. The post-procedural period for these patients was uneventful. Conclusion: We found that ERCP is a practical and successful therapeutic intervention for treating hepatopancreaticobiliary disorders in children when performed by experienced endoscopists.

• Journal of Digestive Cancer Research
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• 제6권2호
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• pp.73-77
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• 2018

췌장암으로 진단된 70세 여자 환자가 유문보존 췌십이지장 절제술 및 5-fluorouracil 동시항암화학요법으로 치료받았다. 수술 후 병리학적으로 pT3N0 (stage IIA)의 췌장선암이 확진되었다. 14개월 뒤 복부 전산화단층촬영에서 10 mm 크기의 단일 간 재발 병소가 간 3번 분엽에서 발견되었다. Gemcitabine 12주기 및 capecitabine plus oxaliplatin 9주기 항암치료를 시행했으나 전이병소는 27mm로 크기가 증가하였다. 이에 간 3번 분엽의 종양절제술을 시행하였다. 종양절제술 시행 25개월 뒤 흉부 전산화단층촬영에서 23 mm 크기의 단일 공동성 폐결절이 발견되었고, 조직검사에서 전이성 선암으로 확인되었다. 환자는 두 차례의 정위적 체부 방사선 치료 후 질병의 진행 없이 진단 후 6년 이상 장기 생존 중이다. 본 증례를 통해 수술 후 단일 간 전이 혹은 폐 전이가 발견된 일부 환자들에서 수술적 절제를 비롯한 국소 치료가 장기생존에 도움이 될 것으로 사료된다.

• BMB Reports
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• 제46권7호
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• pp.338-345
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• 2013

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from defects in several gene sets; therefore, disease progression could be prevented using miRNAs targeting multiple genes. Moreover, recent studies suggest that miRNAs reflect the stage of the specific disease, such as carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic liver disease, pancreatic cystic disease, and ovarian cystic disease, have common processes of cyst formation in the specific organ. Specifically, epithelial cells initiate abnormal cell proliferation and apoptosis as a result of alterations to key genes. Cysts are caused by fluid accumulation in the lumen. However, the molecular mechanisms underlying cyst formation and progression remain unclear. This review aims to introduce the key miRNAs related to cyst formation, and we suggest that miRNAs could be useful biomarkers and potential therapeutic targets in several cystic diseases.

• Journal of Veterinary Science
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• 제21권2호
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• pp.26.1-26.14
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• 2020

Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selected Kras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) and Streptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4349-4352
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• 2014

Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed late. Since little is known about this cancer in Iran, with the aim of improving this knowledge deficiency, we evaluated clinical, laboratory biomarkers, imaging findings and treatment modalities in Iranian patients with pancreatic adenocarcinoma. Materials and Methods: 131 cases of pancreatic adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and surgery examination were included. We excluded those with incomplete medical records. Results: The study included 131 subjects between 24 and 97 years of age and a mean age of $63{\pm}13.4$ years. Eighty (61.1%) were male and 51 (38.9%) female. Previous history included diabetes mellitus in 36 (27.5%), alcohol drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%). The common presenting history included weight loss in 79 (60.3%), abdominal pain in 77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%), pruritus in 52 (39.7) and anemia in 33 (25.2%). CA19-9 levels with cut offs of 50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients, respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients, respectively. Conclusions: This disease affected older people and there was a male preponderance. The commonest risk factors were diabetes mellitus, smoking and cholelithiasis. The majority of patients presented with loss of appetite, loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at late stages of the disease so that curative surgery was impossible. Also chemotherapy was only performed in a few patients as a neoadjuant treatment.