The major focus of the pathology core is to facilitate the study of tumor before and after chemotherapy in order to detect residual tumor surviving therapy and describe the changes observed between tumor cells prior to and after therapy with an ultimate goal to provide support for the preclinical projects and to guide new clinical strategies within the context of high- dose therapy. The studies will involve immunohistochemistry of serial tissue specimens. Specific ELISA assays will be performed on plasma and urine samples. Unstained marrow and PB will be prepared for in situ multiple chromophore immunofluorescence studies. Within this core, we will provide uniform pathologic review, preparation and staining of histologic slides from paraffin blocks, and blinded interpretation of sections stained for selected biologically related parameters of cellular proliferation, angiogenesis, and drug resistance. Serial plasma, urine, marrow and peripheral blood mononuclear cell (PB) samples will be collected and banked prospectively. The patient population (stages II, III, and IV breast cancer, small cell lung cancer, and relapsed Hodgkins' disease) is treated for cure; thus residual tumor represents a truly enriched subpopulation of resistant cells. As a Core facility, the primary interaction is with the clinical project, and the pathological information obtained will provide preliminary data and intermediate endpoints necessary to proceed with proposed trials. The focus of the proposed tissue studies is on the tumor microenvironment (angiogenesis) and selected resistance mechanisms. As examples, the combination of chemotherapy and antiangiogenic therapy will use microvessel density and circulating levels of angiogenic peptides before and after therapy as two parameters to ascertain biologic activity. It is necessary first to examine how chemotherapy alone affects these parameters. Careful study of DF-3P expression in tissue, its plasma levels, and expression in residual tumor cells residing in marrow or peripheral blood before and after therapy will facilitate the appropriate timing for administration of a tumor vaccine. The Core extends the clinical project to provide more detailed data regarding the biologic behavior of macroscopic and microscopic tumors undergoing intensive treatment.
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