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Comparative Chemotherapy Studies on Primary Short-Term Cultures of Human Normal, Benign, and Malignant Tumor Tissues—a Five-Year Study^*

Jewel Plummer Cobb, Dorothy G. Walker and Jane C. Wright

( Department of Surgery, New York University, Medical School, the Fourth Surgical Division N.Y.U. of Bellevue Hospital, and the University Hospital, New York, N.Y.)

The cytological alterations in primary short-term tissue cultures of 196 malignant neoplasms, eight benign neoplasms, and fourteen normal tissues of human origin following a 96-hour exposure to several chemotherapeutic agents individually have been described and evaluated. Each replicate culture from a biopsy specimen responded in vitro as an individual entity. Cell populations were either sensitive or resistant. The test agents listed in order of their decreasing cytotoxic capacities in vitro were thioTEPA, actinomycin D, chlorambucil, methotrexate, and phenylalanine mustard. Certain trends in cell responses were apparent and included: (a) the sensitivity of lymphosarcomas, Hodgkin's lymph nodes, and lymphomas of undetermined type to chlorambucil; (b) the sensitivity of lymphomas of undetermined type to thioTEPA; (c) the sensitivity of fibrosarcomas to actinomycin D, chlorambucil, and thioTEPA; (d) the sensitivity of certain carcinomas to methotrexate and phenylalanine mustard; (e) the resistance of lymphosarcomas to methotrexate and phenylalanine mustard; (f) the resistance of breast carcinomas to chlorambucil; and (g) the resistance of all melanomas to phenylalanine mustard.

An exaggerated in vitro response to agents, observed for many malignant and benign neoplasms, was never observed in normal tissues. There was no relation between tissue culture response to drug and (a) growth rate in vitro prior to treatment, (b) primary or metastatic lesion, or (c) prior in vivo therapy. The potential role of chemotherapy studies on short-term primary human neoplastic tissue cultures was discussed.

^* This investigation was supported, in part, by research grants from the National Cancer Institute (C-2780, CY-2779) of the National Institutes of Health, and in part by the Damon Runyon Memorial Fund for Cancer Research, Inc.

Presented in part at the 51st Annual Meeting of the American Association for Cancer Research, Chicago, Illinois, April 8, 1960.

Present address: Sarah Lawrence College, Bronxville, N.Y.

Received 7/ 1/60.