Project description:The increased number of pancreatic cyst lesions (PCLs) have been detected through the development of abdominal imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS). However, accurate classification of cystic lesions is difficult because of the lack of standardized diagnostic methods, and thus potentially unnecessary surgical resection has been performed on pancreatic cyst patients. Among four most common types of cystic lesions of pancreas, intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), and solid pseudopapillary neoplasms (SPNs), IPMNs, the precursor lesion of pancreatic cancer, have been detected most frequently, and are subdivided into low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive IPMN in accordance with their malignancy. To discover the potential biomarkers of the histological grades of IPMN, we investigated pancreatic cyst fluid proteins that are differentially expressed in accordance with the IPMN malignancy by LC-MS/MS analysis.
Project description:The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis, we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages.
Project description:Determination of pancreatic cyst fluids (PCF) peptidome and proteome in 5 distinct patient groups: malignant (CAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), serous cystic neoplasms (SCNs), and pseudocysts (PCs). The PCF <5kDa fraction, referred as the degradome, and proteome profiles were determined using a LTQ-Orbitrap Elite mass spectrometer coupled with a nanoAcquity LC system. Qualitative LC-MS/MS analyses were ran on pooled samples from all patients.
Project description:Intraductal papillary mucinous neoplasm (IPMN) is a benign tumor that grows within the pancreatic ducts characterized by the production of thick mucinous fluid by surrounding tumor cells. IPMN is the most important precursor lesion for pancreatic cancer that is the fourth most common cause of cancer deaths. Differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. We investigated differentially expressed proteins among pancreatic cyst fluids consisted of LGD, HGD, and invasive IPMN patients by using our novel proteomic strategy, and finally we discovered pancreatic cyst fluid protein marker candidates that can predict the malignant potential of IPMNs.
Project description:The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis, we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages. We collected normal and neoplastic epithelial cells from frozen tissue sections (normal main pancreatic duct, IPMA, IPMC, and invasive carcinoma originating in IPMN) by laser microdissection, extracted total RNA from them, and analyzed their gene expression profiles using Affymetrix microarrays.
Project description:Mutations of subunit genes of the SWI/SNF chromatin remodeling complexes were found in 12-23% of human Pancreatic Ductal Adenocarcinoma (PDAC). We previously showed that Brg1, a catalytic ATPase subunit of the SWI/SNF chromatin remodeling complexes, inhibits the formation of intraductal pancreatic mucinous neoplasms (IPMN) and IPMN-derived PDAC from ductal cells. On the other hand, ARID1A is the most frequent target of mutations in the SWI/SNF chromatin remodeling complexes in human PDAC. We found that Arid1a loss in the context of mutant Kras resulted in formation of IPMN and PDAC. We also found that the incidence of PDAC formation in Ptf1a-Cre; KrasG12D; Arid1af/f mice was markedly lower than that in Ptf1a-Cre; KrasG12D; Brg1f/f mice despite the similarities between Arid1a-deficient and Brg1-deficient IPMNs. We extracted total RNA from intraductal papillary mucinous neoplasms (IPMNs) in Ptf1a-Cre; KrasG12D; Arid1af/f and Ptf1a-Cre; KrasG12D; Brg1f/f mice and perform microarray analysis.