Clinically relevant animal models are important for dissecting crucial aspects of multiple myeloma (MM) pathogenesis. During the past 10 years, the Myeloma Institute for Research and Therapy has provided excellent conditions (e.g., access to primary samples, long-term interactions between clinical and translational programs) for developing unique, clinically relevant cell lines and for establishing the SCID-hu and SCID-rab mouse models, which allow reproducible engraftment of primary myeloma and induction of typical MM manifestations, including clinically observed disease heterogeneity. Many of the models and cell lines proposed for use in Core D were developed with the help of the Core Director (Shmuel Yaccoby, PhD);Dr. Yaccoby and his team are experts in using these systems to study myeloma biology and therapy and have a history of collaborating with program investigators. Core D is fully equipped to provide In vivo modeling services particularly relevant to specific needs of program projects, including studying myeloma metastasis from one bone site to another (Projects 3 and 4), developing therapies for myeloma-induced osteolytic bone disease (Project 4), engrafting human immune cells for immunotherapy (Project 2), validating novel clinical findings (Projects 1 and 2), and developing targeted therapies (all projects). To support In vivo modeling experiments. Core D will use SCID-hu, SCID-rab, and N0D/SCID/lL2ry[null]-hu mouse models engrafted with primary myeloma cells (obtained from Core B) or myeloma cell lines (stroma-dependent or - independent) and treated according to project specific aims. Core D also will provide services for systemic, intrafibial, and subcutaneous engraftment of myeloma cell lines in SCID mice. Myeloma growth will be monitored by measuring human monoclonal immunoglobulins in mice sera, by live-animal bioluminescence imaging, and by histological examinations (through Core E). Myeloma bone disease will be assessed by X-rays, bone mineral density measurements, and histomorphometry. To provide these crucial services. Core D will conduct in vivo modeling proposed by each project of the program (Aim 1), and validate and develop molecular targets and novel interventions relevant to the investigations of each project of the program (Aim 2). Animal studies are expensive, labor and time intensive, and technically challenging;Core D will provide an efficient solution for all projects by providing centralized facilities with expert staffing, resulting in accelerated translation of research and subsequent clinical successes.

Public Health Relevance

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055819-19
Application #
8566722
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
19
Fiscal Year
2013
Total Cost
$159,924
Indirect Cost
$49,483
Name
University of Arkansas for Medical Sciences
Department
Type
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Alagpulinsa, David A; Ayyadevara, Srinivas; Yaccoby, Shmuel et al. (2016) A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition. Mol Cancer Ther 15:241-50
McDonald, James E; Kessler, Marcus M; Gardner, Michael W et al. (2016) Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma. Clin Cancer Res :
VÃ¥tsveen, Thea Kristin; Sponaas, Anne-Marit; Tian, Erming et al. (2016) Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro. J Hematol Oncol 9:75
Pawlyn, Charlotte; Kaiser, Martin F; Heuck, Christoph et al. (2016) The Spectrum and Clinical Impact of Epigenetic Modifier Mutations in Myeloma. Clin Cancer Res 22:5783-5794
Weinhold, Niels; Ashby, Cody; Rasche, Leo et al. (2016) Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood 128:1735-44
Jethava, Yogesh; Mitchell, Alan; Epstein, Joshua et al. (2016) Adverse metaphase cytogenetics can be overcome by adding bortezomib and thalidomide to fractionated melphalan transplants. Clin Cancer Res :
Weinhold, N; Heuck, C J; Rosenthal, A et al. (2016) Clinical value of molecular subtyping multiple myeloma using gene expression profiling. Leukemia 30:423-30
Pawlyn, C; Fowkes, L; Otero, S et al. (2016) Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma? Leukemia 30:1446-8
Heuck, C J; Jethava, Y; Khan, R et al. (2016) Inhibiting MEK in MAPK pathway-activated myeloma. Leukemia 30:976-80
Mitchell, Jonathan S; Li, Ni; Weinhold, Niels et al. (2016) Genome-wide association study identifies multiple susceptibility loci for multiple myeloma. Nat Commun 7:12050

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