The overall goal of this study is to evaluate inappropriate tumor model systems the biological and therapeutic activity of potential antitumor agents and biological response modifiers, derived from within this program or if relevant to its goals, obtained from outside sources. Based on information on the activity and mode of action of new compounds, combinations of agents or treatments will also be assessed. Initial cytotoxicity screening of all agents is performed using a panel of human and murine tumor cell lines including human MCF7 mammary ca., A121 ovarian ca., WiDr colon ca., DMS114 small cell lung ca., H125 non small cell lung ca. and murine L1210 leukemia. IC50 and IC90 (growth inhibitory concentrations) are established for each drug in vitro using a semiautomated colorimetric assay. Promising new agents, having a unique structure or biological activity, are further evaluated for therapeutic activity in mice, syngeneic and nude athymic, transplanted with murine or human tumor, respectively. Studies are also proposed to evaluate in vitro drug sensitivity using freshly isolated human tumor cells grown on bovine corneal endothelial cell extracellular matrix (ECM). Endpoint analysis will include the measurement of cellular fluorescence generated by specific fluorescent tumor marker (FITC-conjugated monoclonal antibodies) using a Pandex FCA to quantitate tumor cell number and response to drug treatment. These studies are aimed at the development of a fresh human tumor model system for the evaluation of new antitumor agents and treatments. Finally, compounds that demonstrate antiproliferative or therapeutic activity are routinely evaluated for their ability to inhibit the incorporation of various labeled precursors into tumor cell nucleic acids, protein and glycoconjugates, and for their effects on intracellular pool sizes and tumor cell ultrastructure. These studies contribute to the rational development of new treatments of cancer.
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