Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) The UPCI Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) is nationally recognized for its excellence in developing and delivering PK analyses of investigational agents. Furthermore, during the past grant period the shared resource has built the infrastructure to develop and validate novel pharmacodynamics (PD) methodology to confirm target engagement and determine the extent, duration, and relationship with clinically relevant outcomes of toxicity and/or activity. CPPF activities are based on state-of-the-art quantitative (assays according to FDA guidance for method validation) and qualitative mass spectrometric technologies for small molecules (PK) and quantitative and semi-quantitative analysis for characterization of drug targets (PD) such as enzyme-linked immunosorbent assays (ELISA), immunoblotting, immunohistochemistry (IHC), and quantitative nucleic acid amplification (qPCR).
The specific aims of CPPF are to: 1) provide accessible, economical, comprehensive, and state-of-the-art analytical chemical and pharmacokinetic (PK) services in support of basic and clinical UPCI research programs; and 2) provide integrated pharmacodynamic (PD) services in support of translational and clinical UPCI research programs . Working with scientists and clinicians, CPPF (1) provides administrative support for preclinical/clinical protocol submissions, (2) coordinates acquisition and banking of high quality pre-and post-treatment biological samples, (3) identifies and quantitates drugs, metabolites, and other chemical moieties in biological samples, (4) measures serum/plasma cytokines and growth factors, (5) estimates intracellular protein expression (in PBMC, tumor, skin) by various techniques for biomarker development, (6) assists in development of novel detection methodologies for PK and PD, and (7) analyzes the PK-PD relationship within the protocol. The Facility maintains, and continues to expand, a diverse array of analytical chemistry instrumentation operated under accepted practice standards and FDA guidelines for assay implementation and validation. The Co-Directors and key personnel have a combined experience of over 50 years in PK/PD analysis. The provided services are designed to complement existing shared resources in pathology, immunology, and analytical pharmacology with the ultimate goal of advancing clinical/translational research. During the current project period investigators from all 10 UPCI Research Programs used the CPPF.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA047904-27
Application #
8928838
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
27
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Steinman, Justin; Epperly, Michael; Hou, Wen et al. (2018) Improved Total-Body Irradiation Survival by Delivery of Two Radiation Mitigators that Target Distinct Cell Death Pathways. Radiat Res 189:68-83
Yockey, Laura J; Jurado, Kellie A; Arora, Nitin et al. (2018) Type I interferons instigate fetal demise after Zika virus infection. Sci Immunol 3:
Chen, Jingci; Nagle, Alison M; Wang, Yu-Fen et al. (2018) Controlled dimerization of insulin-like growth factor-1 and insulin receptors reveals shared and distinct activities of holo and hybrid receptors. J Biol Chem 293:3700-3709
Qin, Ye; Vasilatos, Shauna N; Chen, Lin et al. (2018) Inhibition of histone lysine-specific demethylase 1 elicits breast tumor immunity and enhances antitumor efficacy of immune checkpoint blockade. Oncogene :
Diaz-Perez, Julio A; Killeen, Meaghan E; Yang, Yin et al. (2018) Extracellular ATP and IL-23 Form a Local Inflammatory Circuit Leading to the Development of a Neutrophil-Dependent Psoriasiform Dermatitis. J Invest Dermatol 138:2595-2605
Evdokimova, Viktoria N; Gandhi, Manoj; Nikitski, Alyaksandr V et al. (2018) Nuclear myosin/actin-motored contact between homologous chromosomes is initiated by ATM kinase and homology-directed repair proteins at double-strand DNA breaks to suppress chromosome rearrangements. Oncotarget 9:13612-13622
Bissel, Stephanie J; Gurnsey, Kate; Jedema, Hank P et al. (2018) Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment. Retrovirology 15:17
Knickelbein, Kyle; Tong, Jingshan; Chen, Dongshi et al. (2018) Restoring PUMA induction overcomes KRAS-mediated resistance to anti-EGFR antibodies in colorectal cancer. Oncogene 37:4599-4610
Redner, Robert L; Beumer, Jan H; Kropf, Patricia et al. (2018) A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia. Leuk Lymphoma 59:2595-2601
Ancevski Hunter, Katerina; Socinski, Mark A; Villaruz, Liza C (2018) PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer. Mol Diagn Ther 22:1-10

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