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Pancreatic Neoplasms: HELP
Articles by Rennian Wang
Based on 2 articles published since 2009
(Why 2 articles?)
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Between 2009 and 2019, Rennian Wang wrote the following 2 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. 2015

Huang, Ling / Holtzinger, Audrey / Jagan, Ishaan / BeGora, Michael / Lohse, Ines / Ngai, Nicholas / Nostro, Cristina / Wang, Rennian / Muthuswamy, Lakshmi B / Crawford, Howard C / Arrowsmith, Cheryl / Kalloger, Steve E / Renouf, Daniel J / Connor, Ashton A / Cleary, Sean / Schaeffer, David F / Roehrl, Michael / Tsao, Ming-Sound / Gallinger, Steven / Keller, Gordon / Muthuswamy, Senthil K. ·Princess Margaret Cancer Center, University Health Network (UHN), University of Toronto, Toronto, Ontario, Canada. · McEwen Center for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada. · Department of Physiology, Western University, London, Ontario, Canada. · Department of Pharmacology, Western University, London, Ontario, Canada. · Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. · Structural Genomics Consortium, Toronto, Ontario, Canada. · Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada. · Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. · Pancreas Centre British Columbia, Vancouver, British Columbia, Canada. · Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. · Division of General Surgery, University of Toronto, Toronto, Ontario, Canada. · Department of Pathology, University Health Network, Toronto, Ontario, Canada. ·Nat Med · Pubmed #26501191.

ABSTRACT: There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation of human pluripotent stem cells into exocrine progenitor organoids that form ductal and acinar structures in culture and in vivo. Expression of mutant KRAS or TP53 in progenitor organoids induces mutation-specific phenotypes in culture and in vivo. Expression of TP53(R175H) induces cytosolic SOX9 localization. In patient tumors bearing TP53 mutations, SOX9 was cytoplasmic and associated with mortality. We also define culture conditions for clonal generation of tumor organoids from freshly resected PDAC. Tumor organoids maintain the differentiation status, histoarchitecture and phenotypic heterogeneity of the primary tumor and retain patient-specific physiological changes, including hypoxia, oxygen consumption, epigenetic marks and differences in sensitivity to inhibition of the histone methyltransferase EZH2. Thus, pancreatic progenitor organoids and tumor organoids can be used to model PDAC and for drug screening to identify precision therapy strategies.

2 Article Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1. 2012

Johnson, Charis L / Peat, Jodi M / Volante, Sonia N / Wang, Rennian / McLean, Carolyn A / Pin, Christopher L. ·Children's Health Research Institute, London, ON, Canada. ·J Pathol · Pubmed #22374815.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of < 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, β cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1(-/-) ). The fate of acinar cells from C57Bl6 or congenic Mist1(-/-) mice expressing an acinar specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1(CreERT/-) R26r) was determined following culture in a three-dimensional collagen matrix. Mist1(CreERT/-) R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild-type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1(-/-) cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCε accumulation and nuclear localization of PKCδ that correlated with increased duct formation. Treatment with rottlerin, a PKCδ-specific inhibitor, but not the PKCε-specific antagonist εV1-2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCδ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies.