Cytotoxic interactions of tumor necrosis factor, melphalan and 41.8 degrees C hyperthermia.
Cancer Lett
; 89(1): 55-62, 1995 Feb 10.
Article
em En
| MEDLINE
| ID: mdl-7882302
ABSTRACT
Experience 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 degrees 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 degrees 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 super-additive 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Hipertermia Induzida
Limite:
Animals
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article