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.
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.
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