Cytotoxic interactions of tumor necrosis factor, melphalan and 41.8 °C hyperthermia
1995; Elsevier BV; Volume: 89; Issue: 1 Linguagem: Inglês
10.1016/0304-3835(95)90158-2
ISSN1872-7980
AutoresH. Ian Robins, F d'Oleire, Mathew Kutz, Andrew Bird, Cynthia L. Schmitt-Tiggelaar, Justin D. Cohen, David R. Spriggs,
Tópico(s)Microfluidic and Bio-sensing Technologies
ResumoExperience with limb perfusion-hyperthermia, TNF, and l-PAM suggests dramatic clinical responses in sarcoma and malignant melanoma. To extrapolate these results to clinical 41.8 °C whole-body hyperthermia (WBH) and systemic therapy, we studied the cytotoxic interactions of TNF, l-PAM and hyperthermia in L929 cells. The optimal sequence was TNF preceding 41.8 °C hyperthermia by 48 h, and l-PAM given simultaneously with heat. Trimodality synergism between TNF, hyperthermia and l-PAM was demonstrated. Non-cytotoxic doses of TNF had a superadditive interaction with l-PAM/heat. Conversely, non-cytotoxic doses of l-PAM had super-additive interactions with TNF followed by hyperthermia. Relative to therapeutic index, we studied WBH, l-PAM and TNF in non-tumor bearing mice. The optimal trimodality sequence did not result in increased normal tissue toxicity compared to l-PAM alone. The concentrations and sequencing of TNF and l-PAM studied are consistent with clinical application to WBH.
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