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Pancreatic Neoplasms: HELP
Articles by Hae-Ryoung Kim
Based on 15 articles published since 2010
(Why 15 articles?)
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Between 2010 and 2020, Haeryoung Kim wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article It is necessary to exam bottom and top slide smears of EUS-FNA for pancreatic cancer. 2018

Lee, Jong-Chan / Kim, Haeryoung / Kim, Hyoung Woo / Lee, Jongchan / Paik, Kyu-Hyun / Kang, Jingu / Hwang, Jin-Hyeok / Kim, Jaihwan. ·Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea. · Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea. · Department of Internal Medicine, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, Korea. · Department of Internal Medicine, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon, Korea. · Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul, Korea. · Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea. Electronic address: drjaihwan@snu.ac.kr. ·Hepatobiliary Pancreat Dis Int · Pubmed #30122329.

ABSTRACT: BACKGROUND: Despite many reports on the diagnostic yield of cytology from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), inter-slide differences are unknown. This prospective study aimed to compare diagnostic yield and cellular characteristics of bottom slides (BS) and top slides (TS) from EUS-FNA cytology performed without an on-site cytopathologist. METHODS: In patients with suspected pancreatic cancer on previous imaging explorations, a single endoscopist performed EUS-FNA and obtained 2 sets of cytology slide (8 BS and 8 TS), 1 cellblock slide, and 1 biopsy slide. Both slide sets were randomly assigned. A cytopathologist with more than 10 years of expertise in pancreatic cytopathology blindly inspected and compared two slide sets. RESULTS: In total, 73 specimens [42 head (57.5%), 16 body (21.9%), and 15 tail (20.5%)] were acquired for final analysis. Seventy-one cases were finally diagnosed with pancreatic cancer. The sensitivity and specificity of BS were 80.3% and 100.0%; and of TS 78.9% and 100.0%, respectively. In analyzing inter-slide difference, 66 cases (90.4%) showed consistent results between BS and TS. However, seven (9.6%) were positive only in one slide sets (4 BS and 3 TS). The proportions of specimens more than moderate and high cellularity were 75.3% and 60.3% in both slide sets (P> 0.99), and the proportion of artifact-free sets were 50.7%, and 52.1% for the BS and TS, respectively (P= 0.869). CONCLUSIONS: Although BS and TS exhibited highly consistent diagnostic yields in cytologic smears from EUS-FNA, the proportion of inter-slide discordance is clinically considerable. Both slide sets need to be examined if there is no on-site cytopathologist.

2 Article IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth. 2017

Ayars, Michael / O'Sullivan, Eileen / Macgregor-Das, Anne / Shindo, Koji / Kim, Haeryoung / Borges, Michael / Yu, Jun / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Oncotarget · Pubmed #29137350.

ABSTRACT: Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (

3 Article The prognostic significance of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. 2017

Park, Hyunjin / Lee, Yangkyu / Lee, Hyejung / Kim, Jin-Won / Hwang, Jin-Hyeok / Kim, Jaihwan / Yoon, Yoo-Seok / Han, Ho-Seong / Kim, Haeryoung. ·1 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. · 2 Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. · 3 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. · 4 Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ·Tumour Biol · Pubmed #29025374.

ABSTRACT: Cancer-associated fibroblasts are abundant in the desmoplastic stroma of pancreatic ductal adenocarcinomas and are considered to play important roles in tumor progression. In this study, we investigated the expression status of secreted protein acidic and rich in cysteine, periostin, fibroblast-activated protein, and the newly developed proCOL11A1 antibody in the stroma of surgically resected pancreatic ductal adenocarcinomas and their prognostic implications. Tissue microarrays were constructed from 155 surgically resected pancreatic ductal adenocarcinomas and paired non-neoplastic pancreata and from another independent set of 48 normal/benign pancreata, and immunohistochemical stains were performed for proCOL11A1, fibroblast-activated protein, secreted protein acidic and rich in cysteine, and periostin. The immunohistochemical stain results were correlated with clinicopathological features and survival data. proCOL11A1, fibroblast-activated protein, secreted protein acidic and rich in cysteine, and periostin expression was significantly increased in the intratumoral stroma of pancreatic ductal adenocarcinomas compared to paired non-neoplastic pancreata (proCOL11A1: 145/155 (93.5%) vs 26/154 (16.9%); fibroblast-activated protein: 139/143 (97.2%) vs 82/132 (62.1%); secreted protein acidic and rich in cysteine: 113/150 (75.3%) vs 49/132 (37.1%); periostin: 135/151 (89.4%) vs 45/135 (33.3%); p < 0.001, all). While the four markers were expressed at lower levels in normal/benign pancreata, there were no significant differences in the expression frequencies among normal pancreas, acute pancreatitis, and chronic pancreatitis. Interestingly, on survival analysis, low intratumoral fibroblast-activated protein

4 Article Prognostic value of p21-activated kinase 4 in resected pancreatic cancer. 2017

Park, Sehhoon / Kim, Jin Won / Kim, Haeryoung / Kim, Ji-Won / Kim, Yu Jung / Lee, Keun-Wook / Kim, Jee Hyun / Kim, Jai Hwan / Hwang, Jin-Hyeok / Choi, Young Rok / Cho, Jai Young / Yoon, Yoo-Seok / Han, Ho-Seong. ·Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. · Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seongnam, Korea. · Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. · Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ·APMIS · Pubmed #28556956.

ABSTRACT: Resectable pancreatic cancer has a high recurrence rate after curative surgery. Biomarkers are needed for distinguishing patients who may benefit from curative resection. In this study, we sought to analyze the prognostic value of p21-activated kinase 1 (PAK1), p21-activated kinase 4 (PAK4), human equilibrative nucleoside transporter 1 (hENT1), and thymidylate synthase (TS) in surgically resected pancreatic ductal adenocarcinomas. A total of 160 pancreatic cancer patients who underwent surgery with curative intent were retrospectively reviewed. Tissue microarrays were constructed and immunohistochemical stains were performed for PAK1, PAK4, hENT1, and TS. The absence of PAK4 expression in pancreatic adenocarcinomas was associated with poorer histologic differentiation (p < 0.001), shorter overall survival [hazard ratio (HR) = 2.86, 95% confidence interval (CI) 1.43-5.71; p = 0.003], and disease-free survival (HR = 2.29, 95% CI: 1.11-4.74; p = 0.025) on univariate analyses. In addition, more frequent venous invasion and lymph node metastases were seen in PAK4-negative tumors although not statistically significant. PAK1, hENT1, and TS expression status did not have significant influences on patient survival. In conclusion, PAK4 of the markers tested in this study may be a potential prognostic biomarker for pancreatic adenocarcinomas.

5 Article Glucagon-Like Peptide-1 Receptor Expression in Normal and Neoplastic Human Pancreatic Tissues. 2016

Dal Molin, Marco / Kim, Haeryoung / Blackford, Amanda / Sharma, Rajni / Goggins, Michael. ·From the *Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD; †Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and the Departments of ‡Oncology and §Medicine, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD. ·Pancreas · Pubmed #26495786.

ABSTRACT: OBJECTIVES: Studies have proposed pro-oncogenic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists in the pancreas by promoting GLP-1R overactivation in pancreatic cells. However, the expression of GLP-1R in normal and neoplastic pancreatic cells remains poorly defined, and reliable methods for detecting GLP-1R in tissue specimens are needed. METHODS: We used RNA in situ hybridization to quantify glp-1r RNA in surgically resected human pancreatic specimens, including pancreatic ductal adenocarcinoma (PDAC), preinvasive intraepithelial lesions (pancreatic intraepithelial neoplasia), and non-neoplastic ductal, acinar, and endocrine cells. A mixed-effect linear regression model was used to investigate the relationship between glp-1r signals and all cells, ordered by increasing grade of dysplasia. RESULTS: All cell types had evidence of glp-1r transcripts, with the highest expression in endocrine cells and lowest in ductal cells. The slope of the fitted line was not significantly different from zero (0.07; 95% confidence interval, -0.0094 to 0.244; P = 0.39), suggesting that progression from normal cells to PDAC is not associated with a parallel increase in glp-1r RNA. A series of pairwise comparisons between all cell types with respect to their glp-1r expression showed no significant difference in glp-1r in cancer, pancreatic intraepithelial neoplasia, and acinar and ductal cells. CONCLUSIONS: Our study supports the lack of evidence for GLP-1R overexpression in PDAC.

6 Article High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor. 2015

Lee, Yoon Suk / Kim, Haeryoung / Kim, Hyoung Woo / Lee, Jong-Chan / Paik, Kyu-Hyun / Kang, Jingu / Kim, Jaihwan / Yoon, Yoo-Seok / Han, Ho-Seong / Sohn, Insuk / Cho, Jeonghee / Hwang, Jin-Hyeok. ·From the Department of Internal Medicine (YSL, HWK, JCL, KHP, JK, JK, JHH) · Department of Pathology (HK) · Department of Surgery (YSY, HSH), Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam · Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu (YSL) · Biostatistics and Clinical Epidemiology Center, Samsung Medical Center (IS) · and Samsung Genome Institute, Samsung Medical Center, Seoul · Department of Nanobiomedical Science, Dankook University, Cheonan (JC). ·Medicine (Baltimore) · Pubmed #26683934.

ABSTRACT: There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery. For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data. Eight miRNAs (miRNA-27b, -122, -142-5p, -196a, -223, -590-5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732-153.789; P = 0.015). MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.

7 Article Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients. 2015

Hwang, In Kyeom / Kim, Haeryoung / Lee, Yoon Suk / Kim, Jaihwan / Cho, Jai Young / Yoon, Yoo-Seok / Han, Ho-Seong / Hwang, Jin-Hyeok. ·Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. · Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. · Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Korea. · Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. ·Cancer Sci · Pubmed #26183380.

ABSTRACT: The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN.

8 Article Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth. 2014

Vincent, Audrey / Hong, Seung-Mo / Hu, Chaoxin / Omura, Noriyuki / Young, Angela / Kim, Haeryoung / Yu, Jun / Knight, Spencer / Ayars, Michael / Griffith, Margaret / Van Seuningen, Isabelle / Maitra, Anirban / Goggins, Michael. ·Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA. ·Oncotarget · Pubmed #24810906.

ABSTRACT: To identify potentially important genes dysregulated in pancreatic cancer, we analyzed genome-wide transcriptional analysis of pancreatic cancers and normal pancreatic duct samples and identified the transcriptional coactivator, EYA2 (Drosophila Eyes Absent Homologue-2) as silenced in the majority of pancreatic cancers. We investigated the role of epigenetic mechanisms of EYA2 gene silencing in pancreatic cancers, performed in vitro and in vivo proliferation and migration assays to assess the effect of EYA2 silencing on tumor cell growth and metastasis formation, and expression analysis to identify genes transcriptionally regulated by EYA2. We found loss of tumoral Eya2 expression in 63% of pancreatic cancers (120/189 cases). Silencing of EYA2 expression in pancreatic cancer cell lines correlated with promoter methylation and histone deacetylation and was reversible with DNA methyltransferase and HDAC inhibitors. EYA2 knockdown in pancreatic cancer cell lines increased cell proliferation. Compared to parental pancreatic cancer cells, pancreatic cancers stably-expressing EYA2 grew more slowly and had fewer metastases in orthotopic models. The transcriptional changes after stable expression of EYA2 in pancreatic cancer cells included induction of genes in the TGFbeta pathway. Epigenetic silencing of EYA2 is a common event in pancreatic cancers and stable expression EYA2 limits the growth and metastases of pancreatic adenocarcinoma.

9 Article CD24 and S100A4 expression in resectable pancreatic cancers with earlier disease recurrence and poor survival. 2014

Lee, Sang Hyub / Kim, Haeryoung / Hwang, Jin-Hyeok / Shin, Eun / Lee, Hye Seung / Hwang, Dae Wook / Cho, Jai Young / Yoon, Yoo-Seok / Han, Ho-Seong / Cha, Byung Hyo. ·From the *Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine; †Seoul National University Hospital; ‡Department of Pathology, Seoul National University College of Medicine, Seoul; §Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do; ∥Department of Surgery, Seoul National University College of Medicine, Seoul; and ¶Department of Internal Medicine, Cheju Halla General Hospital, Cheju-si, Cheju-do, Korea. ·Pancreas · Pubmed #24622067.

ABSTRACT: OBJECTIVES: The objectives of this study were to study the expression status of markers associated with epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic ductal adenocarcinomas (PDACs) and to explore the prognostic value of these markers. METHODS: Immunohistochemical stains for CD24, CD44, E-cadherin, N-cadherin, Snail, S100A4, Vimentin, urokinase-type plasminogen activator receptor, Ezrin, and matrix metalloproteinase 2 were performed on 67 resected PDACs. RESULTS: Proteins associated with EMT and metastasis were more frequently expressed in PDACs with poor differentiation, higher tumor stage, and lymphatic and perineural invasion. CD24 expression was associated with frequent expression of EMT markers (CD44 [P = 0.004], S100A4 [P < 0.001], Vimentin [P = 0.022], urokinase-type plasminogen activator receptor [P = 0.002], and Ezrin [P = 0.010]). CD24 and S100A4 expressions in PDAC were significant prognostic factors for early tumor recurrence (hazard risk [HR], 5.185 and 2.490, P = 0.048 and 0.009, respectively) and poor survival (HR, 11.977 and 3.202, P = 0.006 and 0.004, respectively). In addition, the interaction between CD24 and S100A4 expression status was a significant prognostic factor for poor survival (HR, 18.518, P = 0.003). CONCLUSIONS: The expression of markers of EMT and metastasis in PDACs was significantly associated with pathologic features of aggressiveness. CD24 and S100A4 expressions were significant predictors of poor survival; thus, immunohistochemistry for these markers in resected specimens may help to identify PDAC patients with a poor prognosis.

10 Article Having pancreatic cancer with tumoral loss of ATM and normal TP53 protein expression is associated with a poorer prognosis. 2014

Kim, Haeryoung / Saka, Burcu / Knight, Spencer / Borges, Michael / Childs, Erica / Klein, Alison / Wolfgang, Christopher / Herman, Joseph / Adsay, Volkan N / Hruban, Ralph H / Goggins, Michael. ·Authors' Affiliations: Departments of Pathology, Medicine, Oncology, Surgery and Radiation Oncology, and Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea; and Department of Pathology, Emory University Hospital, Atlanta, Georgia. ·Clin Cancer Res · Pubmed #24486587.

ABSTRACT: PURPOSE: To determine how often loss of ataxia-telangiectasia-mutated (ATM) protein expression occurs in primary pancreatic ductal adenocarcinomas and to determine its prognostic significance. EXPERIMENTAL DESIGN: The expression of ATM and TP53 was determined by immunohistochemistry in 397 surgically resected pancreatic ductal adenocarcinomas (Hopkins; Johns Hopkins Medical Institutions, Baltimore, MD), a second set of 159 cases (Emory; Emory University Hospital, Atlanta, GA), and 21 cancers after neoadjuvant chemoradiotherapy. Expression was correlated with the clinicopathologic parameters, including survival. RESULTS: Tumoral ATM loss was observed in one cancer known to have biallelic inactivation of ATM and 50 of the first 396 (12.8%) cases, significantly more often in patients with a family history of pancreatic cancer (12/49; 24.5%) than in those without (38/347; 11.0%; P = 0.019). In the Hopkins series, ATM loss was associated with a significantly decreased overall survival in patients whose cancers had normal TP53 expression (P = 0.019) and was a significant independent predictor of decreased overall survival (P = 0.014). Seventeen (10.7%) of 159 Emory cases had tumoral ATM loss and tumoral ATM loss/normal TP53 was associated with poorer overall survival (P = 0.1). Multivariate analysis of the combined Hopkins/Emory cases found that tumoral ATM loss/normal TP53 was an independent predictor of decreased overall survival [HR = 2.61; confidence interval (CI), 1.27-5.37; P = 0.009]. Of 21 cancers examined after neoadjuvant chemoradiotherapy, one had tumoral loss of ATM; it had no histologic evidence of tumor response. CONCLUSIONS: Tumoral loss of ATM protein was detected more often in patients with a family history of pancreatic cancer than in those without. Patients whose pancreatic cancers had loss of ATM but normal TP53 had worse overall survival after pancreatic resection.

11 Article MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. 2013

Li, Ang / Yu, Jun / Kim, Haeryoung / Wolfgang, Christopher L / Canto, Marcia Irene / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21231, USA. ·Clin Cancer Res · Pubmed #23697990.

ABSTRACT: PURPOSE: Our goal was to identify circulating micro RNA (miRNA) levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls. EXPERIMENTAL DESIGN: We measured 735 miRNAs in pancreatic cancer case and control sera by QRTPCR using TaqMan MicroRNA Arrays. After array analysis, we selected 18 miRNA candidates for validation in an independent set of cases and control samples. RESULTS: Of the significantly elevated circulating miRNAs in patients with pancreatic cancer compared with controls, miR-1290 had the best diagnostic performance: receiver operating characteristic (ROC) analysis on miR-1290 serum level yielded curve areas (AUC) of 0.96 [95% confidence interval (CI), 0.91-1.00], 0.81 (0.71-0.91), and 0.80 (0.67-0.93), for subjects with pancreatic cancer (n = 41) relative to healthy controls (n = 19), subjects with chronic pancreatitis (n = 35), and pancreatic neuroendocrine tumors (n = 18), respectively. Serum miR-1290 levels were also significantly higher than healthy controls among patients with intraductal papillary mucinous neoplasm (IPMN; n = 20; AUC = 0.76, 0.61-0.91). Serum miR-1290 levels distinguished patients with low-stage pancreatic cancer from controls better than CA19-9 levels, and like CA19-9, higher miR-1290 levels predicted poorer outcome among patients undergoing pancreaticoduodenectomy. Greater numbers of miR-1290 transcripts were detected by FISH in primary pancreatic cancer and IPMN than normal pancreatic duct cells. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. Several other circulating miRNAs distinguished sera of patients with pancreatic cancer from those of healthy controls with AUCs >0.7, including miR-24, miR-134, miR-146a, miR-378, miR-484, miR-628-3p, and miR-1825. CONCLUSIONS: The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer.

12 Article Postoperative prognostic predictors of pancreatic ductal adenocarcinoma: clinical analysis and immunoprofile on tissue microarrays. 2012

Park, Joo Kyung / Kim, Min A / Ryu, Ji Kon / Yoon, Yong Bum / Kim, Sun-Whe / Han, Ho-Seong / Kang, Gyeong Hoon / Kim, Haeryoung / Hwang, Jin-Hyeok / Kim, Yong-Tae. ·Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. mdsophie@gmail.com ·Ann Surg Oncol · Pubmed #22395988.

ABSTRACT: BACKGROUND: Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after curative resection. Our goal was to investigate the important factors affecting metastasis and overall survival (OS). METHODS: We studied 88 PDACs with R0 resection and evaluated immunohistochemical markers on tissue microarrays to assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met, MMP2, MMP7, MMP9, CXCR3, and CXCR4. RESULTS: The median OS in patients who had positive versus negative expression of AREG and MMP9 were 25 versus 16 months and 24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS in patients with positive versus negative expression of MMP2 was 22 versus 37 months (P = 0.04). Immunoprofiles also revealed that patients with positive expression of p-c-met or VEGF had significantly shorter distant metastasis-free survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic invasion, AREG, and MMP2 were independent prognostic factors affecting OS in multivariate analysis. CONCLUSIONS: Immunoprofiles revealed the groups with unfavorable tumor biology: negative expression of AREG and positive expression of MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with early distant organ metastasis in R0 resected PDACs; however, they still need to be further investigated. These results may give us useful insights in understanding the tumor biology and the patterns of PDAC dissemination.

13 Article Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients. 2012

Lee, Sang Hyub / Kim, Haeryoung / Hwang, Jin-Hyeok / Lee, Hye Seung / Cho, Jai Young / Yoon, Yoo-Seok / Han, Ho-Seong. ·Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea. ·Pathol Int · Pubmed #22360504.

ABSTRACT: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1-2 years postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35 (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases, respectively. The expression statuses of the MDR-related proteins were positively correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2 (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion. MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047). High BCRP expression in PDAC was a significant prognostic factor for early tumor recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR-related proteins are frequently expressed in PDAC, and high BCRP expression is a significant independent predictor for early recurrence and poor survival. Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in identifying a subgroup of patients with a poor prognosis.

14 Article Hyperbilirubinemia reduces the streptozotocin-induced pancreatic damage through attenuating the oxidative stress in the Gunn rat. 2010

Fu, Yan Yan / Kang, Kyung Ja / Ahn, Jung Myung / Kim, Hae-Ryoung / Na, Ki Young / Chae, Dong-Wan / Kim, Suhnggwon / Chin, Ho Jun. ·Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ·Tohoku J Exp Med · Pubmed #21139377.

ABSTRACT: Oxidative stress is an important pathogenic factor in diabetes. Bilirubin may serve a cytoprotective function as an anti-oxidant. The Gunn rat lacks the enzyme uridine-diphosphate glucuronosyltransferase that is responsible for conjugation of bilirubin, exhibiting elevation of plasma bilirubin. We examined the effect of hyperbilirubinemia on the pancreatic damage caused by streptozotocin (STZ) in the Gunn rat. Male Wistar rats and male Gunn rats were treated with STZ (WS and GS groups, respectively) or vehicle (WC and GC groups, respectively). All 5 rats in the WS group developed diabetes, defined as fasting blood glucose 300 mg/dL or more, at 3 days, whereas only 2 of the 5 GS rats became diabetic at 7 days after STZ injection. Without insulin supplement at 7 days after STZ injection, the WS group displayed higher levels of fasting blood glucose (510.3 ± 50.3 vs. 236.4 ± 42.5 mg/dL, p = 0.003) and HbA1c (5.0 ± 0.1 vs. 3.9 ± 0.1, p = 0.001), compared to those of GS group. In Wistar rats, STZ induced apoptosis of the pancreatic islet cells, accompanied with activation of NADPH oxidase and increased production of reactive oxygen species and nitric oxide, but not in Gunn rats. Moreover, in a rat insulinoma cell line (RIN-m5F), pre-treatment with bilirubin (0.1 mg/dL) decreased cell death and apoptosis caused by STZ, and also reduced H₂O₂ production. Considering the protective effect of hyperbilirubinemia against STZ-induced injury, we postulate that bilirubin could be a potential therapeutic modality for oxidative stress of pancreas islets.

15 Minor Serum miR-1290 as a marker of pancreatic cancer--response. 2013

Li, Ang / Yu, Jun / Kim, Haeryoung / Wolfgang, Christopher L / Canto, Marcia Irene / Hruban, Ralph H / Goggins, Michael. ·Authors' Affiliations: Departments of Pathology, Surgery, Medicine, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, Maryland. ·Clin Cancer Res · Pubmed #23881921.

ABSTRACT: -- No abstract --