The role of the Cellular Imaging and Molecular Pathology Core is to support the Program Project Grant investigators with a set of dedicated imaging, molecular biological and cytogenetic services for state-of-the- art in vivo molecular imaging and ex vivo analyses for effective assessment of disease states. The services provided in this Core are those that extend beyond the methods needed for routine preclinical studies and standard clinical care. This Core will provide molecular testing for projects that monitor treatment outcomes, detect early disease recurrence and minimal disease states. Rapid and quantitative assessment of experimental therapies is necessary for accelerated and accurate analyses of new therapeutic strategies. We have developed molecular imaging tools for such analyses in living animal models and these will be used to study and optimize the therapies proposed in this program. An established small animal imaging core at Stanford will provide the instrumentation and expertise for this investigation, and will continue to refine the methods for specific programmatic applications and move toward clinical imaging strategies. In vivo molecular imaging will be used to direct the ex vivo assays for more meaningful analyses. In vivo imaging strategies utilizing novel bioluminescent markers which allow for the quantitative, noninvasive detection of disease burden and tracking of cellular populations will be used in Projects 0009,0010,0011, and 0012. Molecular testing for chromosomal abnormalities or their transcription products will be performed for Projects 001, 0002, 0007, and 0008 as an adjunct to standard cytogenetics on leukemia, lymphoma and myeloma specimens. Quantitative assessment of minimal residual will be performed using TaqMan chemistry, for BCR-ABL (CML and ALL breakpoints) in CML and ALL patients; BCL-2-JH (major breakpoint) in lymphoma; Cyclin D1 for mantle cell lymphoma and Ig rearrangement for multiple myeloma. PCR studies will also be performed for assessment of chimerism following allogeneic bone marrow transplantation. The methodology required for conventional cytogenetics, FISH, RT-PCR and DNA PCR are routinely employed by the Core investigators, who have also contributed to the molecular characterization of genetic markers in leukemias and lymphomas throughout the course of previous studies. The centralized performance of molecular and cytogenetic procedures by this Core will avoid duplication of efforts in the program and ensure timely, efficient and consistently high quality results. This combination of in vivo and ex vivo analyses strengthens the studies by providing more data and directed evaluation of clinical and preclinical specimens in a centralized core.
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