The Experimental Cellular Pathology Core is designed to provide investigators with centralized pathologic services, including immunohistochemical (IHC) and flow cytometric (FCM) procedures in support of all four projects. This resource combines the expertise and facilities of the UAMS Department of Pathology with those of the Myeloma Institute for Research and Therapy. Centralizing these core services will avoid the need for each investigator to establish them in their own laboratories and will have the added benefit of providing for uniformity of procedures and efficient use of materials and capitol equipment. The core will address the following specific aims:
Specific Aim 1 : Provide pathology services to investigators in each P01 project. Specifically, this will include IHC and laser capture microdissection (LCM). IHC services will be performed on patient samples provided by Project 1 and utilized in support of Projects 1, 2 and 3 as well as on in vivo animal model studies in Projects 2 and 4. A major advantage of tissue section IHC is that the topography of the tissue remains intact and morphologic and immunologic features can be integrated to allow for microanatomic analysis of the bone marrow architecture. LCM services will be instrumental in Projects 1 and 4 where studies will examine focal and interstitial disease patterns as well as the marrow microenvironment.
Specific Aim 2 : Construct tissue microarrays (TIVIAs). A central aspect of the core will be the construction of TMAs using material derived from new patients as well as patients enrolled onto treatment protocols in Project 1. Gene expression profiling and proteomics play central roles in the POI and by using materials such as the TMAs, Core E will provide an important function by assisting Project 1, in conjunction with Core C, in the validation of key genes and proteins relating to the tumor cell/bone marrow microenvironment identified through these technologies.
Specific Aim 3 : Provide flow cytometry services to validate novel markers of minimal residual disease monitoring, and for characterization and identification of myeloma subpopulations with distinct genetic and biologic properties. The relatively recent identification of aberrant immunophenotypes in malignant plasma cells and the unique ability of to identify and characterize even minor cellular subpopulations makes FCM an ideal technology to accomplish the goals delineated in Project 1. FCM will also be useful for the immunophenotypic characterization of the expanded NK cell preparations that will be developed in Project 2.

Public Health Relevance

While gains have been made, myeloma remains a difficult cancer to treat and manage. Mounting evidence indicates that the bone marrow microenvironment plays an important role in the growth and dissemination of myeloma, as well as myeloma bone disease. The mechanisms governing focal tumor growth, in the context of diffuse disease, are not understood. A major goal of this Pathology Core (Core E) is to provide comprehensive, meaningful pathology support services to project investigators addressing these issues.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055819-19
Application #
8566723
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
$177,530
Indirect Cost
$54,931
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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