[In vivo anti-tumour efficacy of tumour necrosis factor and interferon- alpha, -gamma on human renal cell carcinoma heterotransplanted in nude mice].
Using human renal cell carcinoma heterotransplanted in nude mice (JRC 11: anaplastic and alveolar pattern, grade IV), the in vivo anti-tumour efficacy of tumour necrosis factor (rHu-TNF-alpha: PT-050) and IFN-alpha (nHu-IFN-alpha: HLBI), IFN-gamma (nHu-IFN-gamma: OH-6000) were investigated. The dose of TNF was 1,000, 3,000, 10,000 J.R.U. (i.p., every day), that of IFN-alpha was 1 x 10(4) and 1 x 10(5) I. U. (s.c., every day) and that of IFN-gamma was 1 x 10(4) and 1 x 10(5) I.U. (s.c., every day). Mono-therapy of TNF, IFN-alpha and IFN-gamma was not effective with regard to tumour regression rates, histological degeneration rates and survival time of the host mice. Combination therapy of TNF and IFN-alpha, IFN-gamma were also not effective with regard to tumour regression rates, but when considering histological change, sporadic disappearance of endothelium of intra-tumoural vasculature, flow of tumour cells clustered in intra-vascular cavity, and extra-vascular bleeding were observed. With special reference to survival of host mice, prominent prolongation of survival time in combination treatment, especially in TNF combination therapy groups with the dosage of 10,000 J.R.U. was observed. Therefore we concluded that there is no synergistic reaction in combination therapy of TNF and IFN against JRC 11 tumour. But combined activity of TNF and IFN on the vasculature of renal cell carcinoma (JRC 11) and the suppression of cachexia related condition were detected.
Onishi
T
T
Department of Urology, The Jikei University School of Medicine.
Machida
T
T
Masuda
F
F
Iizuka
N
N
Nakauchi
K
K
Furuta
N
N
Shirakawa
H
H
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma