? Core A (Pathology Core) Pancreatic ductal adenocarcinoma (PDAC) is a uniquely challenging neoplasm because of the formidable complexities of its histopathology, and limited tissue availability and quality. The pathologic analysis of murine PDAC, and its cognate human counterpart, is an integral component for all projects of this P01. Broadly speaking, these activities include evaluation of genetically engineered mice (GEM), including mice with temporally regulated, compartment-specific disruption in epithelial and / or stromal components; analyses of tumor promoting signaling pathways with cell-type specific localization to either neoplastic cells per se, or within the host response in the tumor microenvironment (TME); identification and multi-dimensional assessments of cellular components within the TME; and the cross-species validation of observations between GEM models and human tumor samples. The Pathology Core (Core A) will collect, maintain, archive and record all human and mouse PDAC-associated biological resources. These materials include serially passaged patient-derived xenografts (PDXs) created from primary and metastatic human PDAC, and a repository of annotated low-passage PDAC cell lines. Core A will work in close collaboration with the Project Investigators to achieve three specific aims: i) to provide histology services and consultative expertise, including centralized review in the pathologic evaluation of mouse and human pancreatic neoplasms; ii) to provide infrastructure and technical expertise for a variety of immunohistochemical, immunofluorescent and in situ hybridization assays with quantitative image analysis; and iii) to generate, characterize and maintain PDX models, as well as early passage tumor and stromal cells cultures for use by the Projects and Core B (Experimental Therapeutics). A testament to this Core?s progress stems from the creation of >165 PDXs and >30 low passage PDAC cell lines during the previous cycle. Core A?s leader is Dr. Anirban Maitra at MDACC, assisted by Co-Investigator Dr. Huamin Wang - both with long-standing expertise and a strong publication record in the histopathological and molecular assessment of human and murine PDAC tissues. In addition, Core A brings together expertise from our partner institution, Harvard (Dr. Bardeesy, site PI at MGH), who is a prolific investigator in PDAC biology and an expert in GEM models thereof. Of note, despite the geographic distance, there exists outstanding published evidence for collaboration between this tightly knit team. To facilitate a seamless administration of Core A activities, we have instituted a system of regular communication through teleconferences, Skype and use of telepathology resources that enables the three significant personnel involved in the Core (Maitra, Wang and Bardeesy) to coordinate and serve the needs of this P01. Core A will build upon the solid foundation of prior and ongoing interactions between investigators at MDACC and Harvard, in order to facilitate a highly successful P01 outcome.

Public Health Relevance

? Core A (Pathology Core) The Pathology Core (Core A) will provide expertise with regards to evaluation of genetically engineered mouse models and patient-derived xenografts, provide access to all P01 investigators with annotated human and murine tissues and cell lines, and utilize state-of-the-art technology for multiplexed, dynamic assessment of immunocyte profiles in the setting of Kras extinction and other therapy-induced perturbations. Developing a bank of highly characterized patient-derived xenograft (PDX) and low-passage PDAC cell lines will be one of the key outcomes of this Core.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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University of Texas MD Anderson Cancer Center
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