scholarly journals Immunohistochemistry of Pancreatic Neoplasia

2012 ◽  
pp. 29-42 ◽  
Author(s):  
Sukhwinder Kaur ◽  
Tomohiro Shimizu ◽  
Michael J. Baine ◽  
Sushil Kumar ◽  
Surinder K. Batra
Keyword(s):  
Pancreatic Neoplasia

scholarly journals GnasR201C Induces Murine Pancreatic Cystic Neoplasms through Suppression of YAP1 Signaling and Transcriptional Reprogramming

2018 ◽  
Author(s):  
Noboru Ideno ◽  
Hiroshi Yamaguchi ◽  
Bidyut Ghosh ◽  
Sonal Gupta ◽  
Takashi Okumura ◽  
...  
Keyword(s):  
Protein A ◽  
Ductal Adenocarcinoma ◽  
Cystic Neoplasms ◽  
Transcriptional Reprogramming ◽  
Kaplan Meier ◽  
Stimulatory G Protein ◽  
Kinase Cascade ◽  
Well Differentiated ◽  
Underlying Mechanisms ◽  
Pancreatic Neoplasia

ABSTRACTBackground & AimsSomatic “hotspot” mutations of GNAS, which encodes for the alpha subunit of stimulatory G-protein, are present in ~60% of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. There are currently no cognate animal models that recapitulate the biology of mutant Gnas-induced IPMNs, and the underlying mechanisms that lead to the cystic pathway of neoplasia in the pancreas remain unknown.MethodsWe generated p48-Cre; LSL-KrasG12D; Rosa26R-LSL-rtTA-TetO-GnasR201C mice (Kras; Gnas mice) where pancreas-specific GnasR201C expression was induced by doxycycline administration. In this model, mutant Kras is constitutively expressed, and control mice were produced through absence of doxycycline. Separate cohorts of mice were utilized for timed necropsies and for Kaplan-Meier survival analysis. Isogenic cell lines (with doxycycline inducible mutant Gnas expression) were propagated from the resulting pancreatic ductal adenocarcinoma (PDAC).ResultsCo-expression of KrasG12D and GnasR201C resulted in the development of pancreatic cystic lesions resembling human IPMNs in 100% of mice, with higher grades of epithelial dysplasia observed over time. Approximately one-third of Kras; Gnas mice developed PDAC at a median of 38 weeks post doxycycline induction. GnasR201C did not accelerate oncogenic transformation with KrasG12D, but rather, reprogrammed Ras-induced neoplasms towards a well-differentiated phenotype. GnasR201C induction led to activation of the inhibitory Hippo kinase cascade and cytoplasmic sequestration of phosphorylated YAP1 protein, a phenomenon that was also observed in human IPMN with GNAS mutations.ConclusionsGNASR201C functions not as a traditional oncogene, but rather as an “oncomodulator” of KRAS-mediated pancreatic neoplasia, through suppression of YAP1 and transcriptional reprogramming towards a differentiated (large ductal) phenotype.

scholarly journals Endoscopic Ultrasound Findings in Patients Diagnosed with Exocrine Pancreatic Insufficiency by Low Fecal Elastase-1

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Mazen Shobassy ◽  
Nedaa Husainat ◽  
Abdalaziz Tabash ◽  
Kalpesh Patel ◽  
Hashem B. El-Serag ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Endoscopic Ultrasound ◽  
Pancreatic Insufficiency ◽  
Cross Sectional Study ◽  
Lifestyle Factors ◽  
Exocrine Pancreatic Insufficiency ◽  
Cross Sectional ◽  
Fecal Elastase ◽  
Elastase 1 ◽  
Pancreatic Neoplasia

Background and Aims. Fecal elastase-1 (FE-1) as a screening test for exocrine pancreatic insufficiency (EPI) is gaining popularity in clinical practice. The role of imaging in patients with FE-1-related suspicion of EPI remains unclear. The aim of this study was to characterize endoscopic ultrasound (EUS) findings for patients with low FE-1. Methods. A retrospective cross-sectional study was performed in 40 patients who had low FE-1 and underwent EUS to evaluate the pancreas. We obtained data on demographic and lifestyle factors, EUS findings, and histopathology results. We compared these variables between patients with FE‐1<100 mcg/g vs. 100-200 mcg/g. Results. Most patients (82.5%) established one or more new diagnoses from EUS. Diagnoses included: definitive chronic pancreatitis (n=29, 72.5%), fatty pancreas (n=9, 22.5%), and pancreatic solid mass or cyst (n=9, 22.5%). Half (n=4) of the solid or cystic lesions were neoplastic. All patients with a solid pancreatic mass also had concurrent chronic pancreatitis. There were no significant differences in EUS findings or demographic or lifestyle factors between groups with FE‐1<100 mcg/g vs. 100-200 mcg/g. Conclusion. Chronic pancreatitis is the most common EUS finding in patients with low FE-1 levels. EUS appears helpful in determining the cause of EPI in most patients with low FE-1 and may detect unsuspected pancreatic neoplasia.

scholarly journals The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Katherine A. Michaelis ◽  
Mason A. Norgard ◽  
Xinxia Zhu ◽  
Peter R. Levasseur ◽  
Shamilene Sivagnanam ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Host Responses ◽  
Ductal Adenocarcinoma ◽  
Survival Duration ◽  
Murine Models ◽  
Tumor Mass ◽  
Treg Frequency ◽  
T Cell Infiltration ◽  
Pancreatic Neoplasia

Abstract A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8+ T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia.

Somatostatin and Octreotide: Literature Review and Description of Therapeutic Activity in Pancreatic Neoplasia

1988 ◽  
Vol 22 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Stephen M. Longnecker
Keyword(s):  
The Body ◽  
Endocrine Tumors ◽  
Hormone Synthesis ◽  
System A ◽  
Inappropriate Secretion ◽  
Hormonal Imbalance ◽  
Long Acting ◽  
Therapeutic Activities ◽  
Pancreatic Neoplasia ◽  
Endogenous Substances

The somatostatins represent endogenous substances that serve a diversity of functions in the body. These activities are just beginning to be understood and could have major implications in the treatment of human disease. Their chief pharmacologic activities lie in the modification or modulation of protein hormone synthesis of the gastrointestinal system; a great many other systems may be involved as well. Since the discovery of the therapeutic potentials of naturally isolated somatostatins, attempts have been made to design newer analogs more conducive to practical use. Such an example is long-acting somatostatin analog octreotide. Literature has recently begun to appear describing the therapeutic activities of this and other similar compounds and the first steps to understanding their clinical pharmacology are being taken. Surprising activity has been found in the palliative treatment of a wide variety of formerly resistant gastrointestinal syndromes and endocrine tumors. These activities may have considerable future impact on the treatment of disease involving hormonal imbalance or inappropriate secretion.

Pathologic Classification and Biological Behavior of Pancreatic Neoplasia

2018 ◽  
pp. 51-87
Author(s):  
Olca Basturk ◽  
Michelle D. Reid ◽  
N. Volkan Adsay
Keyword(s):  
Biological Behavior ◽  
Pathologic Classification ◽  
Pancreatic Neoplasia

Abstract 2132: Mutant Kras associated protein oxidation in pancreatic neoplasia

2015 ◽  
Author(s):  
Michelle Schultz ◽  
Brian DeCant ◽  
Andrew Diaz ◽  
Sharon Solman ◽  
Rital Shah ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Pancreatic Neoplasia

Abstract 2805: Protein oxidation in pancreatic neoplasia and cancer

2016 ◽  
Author(s):  
Michelle Schultz ◽  
Andrew Diaz ◽  
Sharon Smite ◽  
Brian DeCant ◽  
David Bentrem ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Pancreatic Neoplasia
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