Cell killing of melanoma B16 in vivo by hyperthermia and cytotoxins

Abstract

The aim of this study was to investigate antitumour activity of cisplatin, dacarbasine, cyclophosphamide and a new compound from the nitrosourea group--acetamido-CNU ((2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea)--applied with or without local hyperthermia (43.5 degrees C/60 min). The tumour model for the investigation of antitumour activity was a mouse melanoma B16 transplanted into the footpad. Dacarbasine, cyclophosphamide and acetamido-CNU applied as a single treatment had statistically significant antitumour activity, while cisplatin applied as a single agent had no effect. Local hyperthermia alone had statistically significant antitumour activity. The best therapeutic effect (synergistic) was obtained when combined treatment (cytotoxins plus local hyperthermia) was used. Synergistic therapeutic results were achieved even when cisplatin and hyperthermia were combined, although cisplatin was ineffective when given as a single agent. Therapeutic results achieved with acetamido-CNU (newly synthesized compound) applied alone were similar to the therapeutic results achieved with dacarbasine or cyclophosphamide. In combined therapy (acetamido-CNU + HT), achieved therapeutic results were significantly better (p < 0.05) than results achieved by combining cisplatin and hyperthermia or dacarbasine and hyperthermia.

Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia

“…DTIC, an alkylating agent that inhibits purine synthesis [14] has long been applied against malignant melanoma development. Regimens such as the Dartmouth regimen and CVD regimen to combine the application of anticancer compounds are widely used in the therapy of malignancies [15,16]. The suggested combination dosage of DTIC and CDDP is one of the most recognised modality among them [17].…”

Antitumor effects of high-temperature hyperthermia on a glioma rat model

“…Studies of hyperthermia have focused on two commonly applied strategies, conventional hyperthermia at mild temperatures (42–45°C) (1,20,21) and ablation therapy at high temperatures (>70°C) (22). To the best of our knowledge, no study has examined the difference in antitumor effects between mild (42–45°C) and high temperatures (>70°C) under the same conditions as performed in the present study.…”

Antitumor effect and immune response induced by local hyperthermia in B16 murine melanoma: Effect of thermal dose

“…As a superficial tumor, melanoma can easily be administered local hyperthermia from the clinical point of view. Either as a monotherapy or as an adjuvant therapy with other treatments, such as chemotherapy or radiotherapy, the results of hyperthermia treatment from clinical trials and in vivo studies are encouraging, suggesting a promising protocol for malignant melanoma (7)(8)(9).…”

“…Results from previous studies have shown that malignant melanoma may be even more sensitive to temperature (8,9). Studies of hyperthermia have been focused on two commonly applied strategies: conventional hyperthermia at mild temperatures (42-45˚C) (6,8,9) and ablation therapy at high temperatures (>70˚C) (10).…”

“…Studies of hyperthermia have been focused on two commonly applied strategies: conventional hyperthermia at mild temperatures (42-45˚C) (6,8,9) and ablation therapy at high temperatures (>70˚C) (10). Stojkovic and Radacic reported that local hyperthermia of 43.5˚C administered alone had good antitumor activity, as in all experiments tumor growth time was prolonged by 2.3-3.5 times compared with the control (8). Results from the study of Ito et al suggested that a temperature of 43˚C was insufficiently high to destroy the malignant melanoma and a higher treatment temperature was proposed (9).…”