International Journal of Cell Cloning, Vol 7, 385-394, Copyright © 1989 by AlphaMed Press
Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma
N Zaffaroni, R Villa, MG Daidone, M Vaglini, M Santinami and R Silvestrini
Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
The effects of heat and the interaction between hyperthermia and alkylating
agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant
melanoma biopsies have been investigated by a short- term assay based upon
the inhibition of 3H-thymidine incorporation. Cell suspensions from 50
cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42
degrees C for 1 h. There were significant antiproliferative effects due to
heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees
C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43
degrees C) of tumors, and there was significant enhancement of cell growth
in 17% and 12% of tumors. The combined effects of hyperthermia and drugs
were studied on 36 tumors. Cell suspensions were exposed to different
concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C.
Synergy between heat and CDDP was observed in 7% of cases treated with the
lowest drug dose and 38% of cases treated with the highest (40.5 degrees
C), with only a slight increase in the frequency of synergy at 42 degrees
C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors
at 42 degrees C as a function of drug concentration.
