Several objectives are being pursued: (1) further refinement of bivariate DNA-glucocorticoid receptor (GR) analysis of potentially glucocorticoid-sensitive hematologic neoplasms including the various forms of acute leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma. These studies will be correlated with results obtained by standard radiometric tests; (2) the bromodeoxyuridine monoclonal antibody assay will be further developed to distinguish S phase cells with varying degrees of DNA-synthetic activity, in order to examine the mechanism underlying a divergent prognostic impact of a high S phase fraction in young versus old patients with acute myeloblastic leukemia; (3) cellular pharmacologic studies with doxorubicin and m-AMSA will be pursued using native fluorescence or dye competition methodologies, respectively. The kinetics of uptake, peak level, and retention time will be evaluated by FCM and compared with standard radioisotope technology; (4) continuation of DNA-RNA and DS-RNA analysis in the malignant lymphomas is planned to investigate the independent role of ploidy, proliferative activity and ds-RNA for short- and long-term prognostic in concert with standard clinical and laboratory features; and (5) update of primary breast cancer data will be performed to determine the prognostic importance of ploidy, proliferative activity, and ER content in approximately 200 patients with regional breast cancer. Thus, this grant will continue to examine the feasibility of new probes for FCM analysis of phenotypic tumor heterogeneity and other already established probes for the diagnosis and prognosis of two particularly heterogenous malignancies, i.e., malignant lymphoma and breast cancer. (3)
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