抄録
Morphologic methods offer unique opportunities to study some of the characteristics of malignant and normal cells. One of the promising areas of cancer therapy is the use of targeted toxins, such as immunotoxins, that can selectively destroy tumor cells. We have used morphologic approaches to the screening and evaluation of monoclonal antibodies for use as part of immunotoxins directed against human ovarian cancers. Screening methods that utilize immunoflorescence and immunoperoxidase methods have allowed the rapid isolation of hybridomas that react selectively with tumor cells in tissue culture and in solid tumors, while showing only limited reactivity with important normal tissues. Another area of cancer biology in which morphologic methods have proved useful is the study of multidrug resistance of human tumors. The efflux activity seen in single multidrug resistant cells can be demonstrated morphologically using fluorescent chemotherapeutic drugs, such as daunomycin. The protein responsible for this efflux pump activity, P170, has been localized morphologically to the plasma membrane in individual cultured cells, as well as located using immunohistochemistry in normal liver, kidney, GI tract, adrenal and cerebral capillaries. These locations enhance understanding of the role of this protein in the excretion of toxic hydrophobic compounds, both in chemotherapy and in normal organ physiology. These methods also allow simple and rapid screening techniques to evaluate other drugs that might be able to reverse the multidrug resistance phenotype and render human tumors more sensitive to chemotherapy.
