Radiation survival of murine and human melanoma cells utilizing two assay systems: monolayer and soft agar.

The radiation response of murine and human melanoma cells assayed in bilayer soft agar and monolayer was examined. Cells from the murine melanoma Cloudman S91 CCL 53.1 cell line and three human melanoma cell strains (C8146C, C8161, and R83-4) developed in our laboratory were irradiated by single dose X-rays and plated either in agar or on plastic. D0 values were the same within 95% confidence intervals for cells from the human melanoma cell strains C8146C, C8161, and R83-4 but were dissimilar for the murine cell line CCL 53.1 Dq values were different for all cells studied. The shape of the survival curve for all four melanomas was not identical for cells assayed in soft agar versus cells grown on plastic. This would indicate that apparent radiosensitivity was influenced by the method of assay although there were no apparent consistent differences between the curves generated by monolayer or bilayer soft agar assays

Quantitation of drug sensitivity by human metastatic melanoma colony-forming units.

We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma. Melanoma CFU demonstrated marked heterogeneity in chemosensitivity to these 9 drugs. Reduction in survival of CFU below 38% at one-tenth the pharmacologically achievable 1h concentration (our operational definition of chemosensitivity) was obtained in only 19% of 200 in vitro trials, and was usually the same whether or not patients had been exposed to prior chemotherapy, suggesting that melanoma CFU are inherently resistant to presently available chemotherapeutic drugs. The soft-agar assay was 86% accurate (25/29 cases) in identifying drugs to which the tumour was resistant in vivo, and 63% accurate (12/19 trials) in identifying drugs to which the tumour was clinically sensitive, counting mixed responses as responses. In contrast, if mixed responses were classified as progressive disease, the accuracy of identification of sensitivity fell to 42% (8/19 trials). These investigations furnish a quantitative description of the chemosensitivity of human metastatic melanoma CFU. Additionally, these studies serve as a useful step towards the development of an in vitro chemosensitivity test for human melanoma, and provide an operational quantitative basis for further exploration of in vitro-directed therapy in metastatic neoplasms

Chemoprevention of Human Cancer:A Reasonable Strategy?

The field of chemoprevention of cancer in humans is at a teenage level of maturity. There is anticipation and energy, and some promising results have come in, but it's unclear whether the entire enterprise is worth the effort. Reflecting on the status of the organism and where we are in its developmental history is therefore an important exercise at this time. Empirical and philosophical perspectives are offered for several key questions: Why prevent Cancer? What is the preclinical evidence that chemoprevention of cancer in humans should work? What is the clinical evidence that chemoprevention agents work? What is the clinical evidence that chemoprevention agent don't work? What is the status of ongoing randomized phase III/IV chemoprevention trials? The answers to each of these questions provide a part of the scaffold for a logical platform for the launching of the chemoprevention imperative as an integral part of our approach to the overall management of human cancer