Medicine and Health Sciences Commons^™

Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …

Assessment For Risk Factors Associated With Local Recurrence In Chordoma, John A. Abraham, Md, Wei Jiang, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Chordoma is a rare but locally aggressive malignant neoplasm showing notochordal differentiation. The clinical differential diagnoses can be extensive, and definitive diagnosis often relies on histopathologic evaluation. Histologically, chordoma shows dual epithelial and mesenchymal differentiation, with various morphologies. Despite surgical resection and use of adjuvant radiation therapy, the local recurrence rate of chordoma remains high. We aim to establish factors associated with the increased risk of recurrence and help guide treatment decisions.