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Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models

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World Journal of Gastroenterology 2011年第11期17卷 1434-1441页

作者： Lei Wang Hai-Lin Liu Ya Li Ping Yuan Department of Gastroenterology the Ninth People's Hospital Affiliated to the School of Medicine Shanghai Jiao Tong University Shanghai 200011 China Department of Pathology Ruijin Hospital Affiliated to the School of Medicine Shanghai Jiao Tong University Shanghai 200025 China

AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential ***:Sixty adult male Sprague Dawley rats were randomized into three *** rats had DMBA implanted into their pancreas for one(n=20)or two months(n=20)or assigned to the normal group(n =20).The rats were killed after one or two months,and were evaluated *** tissue samples from each group of rats with either normal pancreas,PanIN(PanIN-2)or PC were examined by *** different expression spot features were analyzed by matrix-assisted laser desorption/ionizationtime of flight/time of flight(MALDI-TOF/TOF)tandem mass *** expression of enolase 1,a differentially expressed protein,was identified by ***:There was significant difference in the proportions of neoplastic changes between the 1-and 2-mogroups(P=0.0488).There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group(P=0.0309).No neoplastic changes were observed in any of the animals in the normal *** 1,pancreatic ELA3B,necdin,Hbp23,CHD3,hnRNP A2/B1,Rap80,and Gnb2l1 were up-regulated in the PanIN and PC tissues,and CEL,TPT1,NME2,PCK2,an unnamed protein product,and glycine C-acetyltransferase were down-regulated in the PanIN and PC *** immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and ***:The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.

关键词： 7 12-dimethylbenzanthracene pancreatic intraepithelial neoplasia pancreatic carcinoma Proteomics

High-grade pancreatic intraepithelial lesions： prevalence and implications in pancreatic neoplasia

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Hepatobiliary & pancreatic Diseases International 2017年第2期16卷 202-208页

作者： Jean R Park Feng Li Veeral M Oza Brett C Sklaw Kevin M Cronley Michael Wellner Benjamin Swanson Somashekar G Krishna Division of Hospital Medicine The Ohio State University Wexner Medical Center Columbus Ohio USA Division of Gastroenterology Hepatology and Nutrition The Ohio State University Wexner Medical Center Columbus Ohio USA Department of Pathology The Ohio State University Wexner Medical Center Columbus Ohio USA

BACKGROUND： High-grade pancreatic intraepithelial neoplasia（Pan IN-3）, a precursor of pancreatic ductal adenocarcinoma（PDAC）, is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms（IPMNs）.METHODS： A retrospective review of a tertiary care center pathology database（1/2000-6/2014） was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were ***： A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74（16.2%） patients who either had PDAC（n=67） or main duct（MD）-IPMN（n=7）. Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival（OS） for pancreata with Pan IN-3 lesions was significantly better than those without（OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04）. Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death（HR=0.43; 95% CI： 0.23-0.82; P=0.01）.CONCLUSIONS： Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.

关键词： pancreatic intraepithelial neoplasia intraductal papillary mucinous neoplasms pancreatic neoplasia pancreatic ductal adenocarcinoma

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Nuclear receptors and pathogenesis of pancreatic cancer

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World Journal of Gastroenterology 2014年第34期20卷 12062-12081页

作者： Simone Polvani Mirko Tarocchi Sara Tempesti Andrea Galli Department of Experimental and Clinical Biomedical Sciences University of Florence50134 FlorenceItaly

pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.

关键词： Peroxisome proliferator activated receptor pancreatic intraepithelial neoplasia COUP-TFⅡ Nuclear receptors Orphan nuclear receptor Nuclear receptors 4A2 Nuclear receptors 2F2 pancreatic cancer Retinoid X receptor Testicular receptor 3

Overexpression of catechol--methyltransferase occurs early in the progression of pancreatic cancer

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胰腺病学杂志（英文） 2018年第1期 39-44页

Aims: Catechol-O-methyltransferase (COMT) plays a role in many kinds of cancer, and its high expression in pancreatic cancer has been found to be related to better prognosis. However, the expression and biological significance of COMT in multistep pancreatic cancerogenesis is not *** methods: Six LSL-KrasG12D-positive and Pdx1-Cre-positive mice (KrasG12D mice), 6 wild-type mice and 1 human tissue microarray were used in this study. COMT protein expression was measured by immunohistochemistry, and DNA chips were made for use in COMT mRNA *** findings: The expression of COMT in pancreatic intraepithelial neoplasias (PanINs) from KrasG12D mice was significantly higher than that in normal pancreatic tissue from wild-type mice, both in terms of protein level and mRNA expression. The median COMT immunohistochemistry expression scores in human PanIN-1 and PanIN-2 were 70 and 160, respectively, which were significantly lower than the score of 170 observed in pancreatic ductal adenocarcinoma (PDAC) (P= .024 and .037, respectively) and significantly higher than the score of 25 observed in pancreatitis (P=.01 and .008, respectively).Significance: In the development of pancreatic cancer from chronic pancreatitis and in the transition of PanIN to PDAC, we observed significantly increased expression of COMT. These data predict that the overexpression of COMT is an early event in the multistep process of pancreatic cancerogenesis.

关键词： Catechol-O-methyltransferase pancreatic cancer pancreatic intraepithelial neoplasia

Overexpression of catechol-O-methyltransferase occurs early in the progression of pancreatic cancer

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Journal of Pancreatology 2018年第1期1卷 39-44页

作者： Hongmei Dai Xianze Wang Xiafei Hong Huanwen Wu Wenyu Di Wenze Wang Peiran Xu Congwei Jia Jing Wang Hao Chen Jialin Jiang Rui Jiang Wenming Wu Yupei Zhao Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing Department of Pathology The First Affiliated Hospital of Xinxiang Medical UniversityWeihui Peking Union Medical College Chinese Academy of Medical SciencesChina

Aims:Catechol-O-methyltransferase(COMT)plays a role in many kinds of cancer,and its high expression in pancreatic cancer has been found to be related to better ***,the expression and biological significance of COMT in multistep pancreatic cancerogenesis is not *** methods:Six LSL-Kras^(G12D)-positive and Pdx1-Cre-positive mice(Kras^(G12D)mice),6 wild-type mice and 1 human tissue microarray were used in this *** protein expression was measured by immunohistochemistry,and DNA chips were made for use in COMT mRNA ***:The expression of COMT in pancreatic intraepithelial neoplasias(PanINs)from Kras^(G12D)mice was significantly higher than that in normal pancreatic tissue from wild-type mice,both in terms of protein level and mRNA *** median COMT immunohistochemistry expression scores in human PanIN-1 and PanIN-2 were 70 and 160,respectively,which were significantly lower than the score of 170 observed in pancreatic ductal adenocarcinoma(PDAC)(P=.024 and.037,respectively)and significantly higher than the score of 25 observed in pancreatitis(P=.01 and.008,respectively).Significance:In the development of pancreatic cancer from chronic pancreatitis and in the transition of PanIN to PDAC,we observed significantly increased expression of *** data predict that the overexpression of COMT is an early event in the multistep process of pancreatic cancerogenesis.

关键词： Catechol-O-methyltransferase pancreatic cancer pancreatic intraepithelial neoplasia

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