Recombinant human tumor necrosis factor — II. Antitumor effect on murine and human tumors transplanted in mice

Sohmura, Yasunobu; Nakata, Katsuhisa; Yoshida, Hiroaki; Kashimoto, Shigeki; Y, Matsui; Furuichi, Hatsuo

doi:10.1016/0192-0561(86)90118-9

Cited by 57 publications

(11 citation statements)

References 17 publications

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“…However, systemic administration of rHu-TNF showed less antitumor effect. Our results are in accor dance with previous studies reporting that intratumoral injection of TNF showed superior antitumor activity with less toxicity than intravenous administration [7], Several researchers have reported that when TNF is administered in vivo, it disappears completely from the circulation within 3 h by any route [14][15][16], And in vitro studies show that exposure to TNF for 3 h/day is not suffi cient to kill sensitive cell lines [14][15][16], Therefore, phar macokinetic factors have been speculated to be one of the reasons that systemic administration of TNF had less antitumor effects than intratumoral administration.…”

Section: Histological Examinationsupporting

confidence: 81%

Antitumor Effect of Recombinant Human Tumor Necrosis Factor on Human Testicular Tumors Heterotransplanted in Nude Mice

Miki

Ishiguro²,

Sawada³

et al. 1994

Eur Urol

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Section: Histological Examinationsupporting

confidence: 81%

Antitumor Effect of Recombinant Human Tumor Necrosis Factor on Human Testicular Tumors Heterotransplanted in Nude Mice

Miki

Ishiguro²,

Sawada³

et al. 1994

Eur Urol

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“…Recombinant human interleukin-1 alpha (IL-la ; LAF activity, 2.26 X lo' U/mg protein) (Nakamura et al 1986) and recombinant human tumor necrosis factor alpha (TNFa, 3 x 106 U/mg protein) (Sohmura et al 1986) were provided by Dainippon Pharmaceutical Co., Ltd., Osaka, and OK-432 (Mizushima et al 1988) by Chugai Pharmaceutical Co., Ltd., Tokyo, recombinant human interleukin-1 beta (IL-lb ; LAF activity, 2 X 10? U/mg protein) (Kikumoto et al 1987) by Otsuka Pharmaceutical Co., Ltd., Tokushima, human recombinant interleukin-2 (IL-2 ; 5 x 10' U/mg protein) and lentinan (LNT) (Chihara et al 1969) by Ajinomoto Co., Ltd., Tokyo, murine recombinant interferongamma (IFN-y ; 5 x 106 U/mg protein) by Shionogi Pharmaceutical Co., Ltd., Osaka, recombinant interferon alpha A/D (IFN-a ; 2 X 108 IU/mg protein) by Nippon Roche Inc., Kanagawa and sizophyllan (SPG) (Norisue et al 1980) by Kaken Pharmaceutical Co., Ltd, Tokyo.…”

Section: Methodsmentioning

confidence: 99%

Prevention of bacterial infection and LPS-induced lethality by interleukin-1.ALPHA. in mice.

Morikage

Mizushima

Yano

1991

Tohoku J. Exp. Med.

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In order to make clear the characteristic biological properties of IL-la, its protective capabilities on bacteria-induced and LPSinduced lethality were compared with other BRMs in BALB/c mice. Pretreatment with IL-la (i.p., s.c.) or OK-432 (i.p.), could protect mice from the lethality of a K. pneumoniae infection (i.p. ), and pretreatment with IL-la or TNF a could protect mice from LPS (i.p.) lethality. IL-la could protect mice from both bacteria-and LPS-induced lethality. There was no difference in serum corticosterone levels after the LPS injection between the IL-la pretreated and untreated groups. However, a more rapid clearance of LPS from the serum and a stronger LPS-neutralizing activity in serum were observed with the LAL assay in IL-la pretreated mice than in untreated mice. The enhanced LPS-clearance was suggested to be partly responsible for the increased protection against LPS-lethality. IL-la was indicated to be a unique BRM and to become a useful tool for the prevention of life-threatening bacterial infections and subsequent endotoxin shock.IL-la ; infection ; LPS ; BRM A variety of biological activities of interleukin-1(IL-1) has been reported by many investigators (Dinarello 1984;Oppenheim et al. 1986), these being induction of fever and somnolence, lymphocyte activation, induction of acute-phase reactants, augmentation of bone marrow cell proliferation, stimulation of the pituitary-adrenal axis, enhancement of resistance against infections, radioprotection, etc. Among the biological activities of IL-1, the enhancing effect of IL-1 on resistance against infections is of practical interest for medical oncologists, because

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“…Es konnte schon bald gezeigt werden, daß dieser Serumfaktor, der nun Tumor-Nekrose-Faktor genannt wurde [9], ein Sekretionspro dukt aktivierter Makrophagen ist [23]. Jedoch waren erst nach biochemischer Reinigung dieses Zytokins [1], nach molekula rer Klonierung des entsprechenden Gens [26,37] [12,38,40] besitzt TNF-alpha eine Reihe immunregulatorischer Eigenschaften. Neben der Aktivierung monozytärer Zellen [29], neutrophiler und eosinophiler Gra nulozyten [14,30,36,39] beeinflußt TNF-alpha außerdem die Funktion von T-und B-Lymphozyten [13,32].…”

Section: Introductionunclassified

Systemische versus lokale Therapie mit rekombinantem Tumor-Nekrose-Faktor-alpha (r-TNF-alpha) bei Patienten mit fortgeschrittenen Tumoren

et al. 1989

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Im Rahmen von zwei Phase-I-Prüfungen wurde rekombinanter Tumor-Nekrose-Faktor-alpha (rTNF-alpha) zur Behandlung von 44 Patienten mit fortgeschrittenen Tumoren unterschiedlichster Histologien eingesetzt. Bei 30 Patienten wurde rTNF-alpha 3 ×/Woche intramuskulär in Dosen zwischen 25–300 meg verabreicht, 14 Patienten erhielten rTNF-alpha intra/peritumoral 1–3 ×/Woche ebenfalls in diesem Dosisbereich. Die maximal tolerierte Dosis (MTD) lag für beide Applikationsformen bei 150 meg/m2 rTNF-alpha. Die Behandlungs-dauer bei systemischer Gabe betrug 1–26 Wochen, bei lokaler Applikation 2–20 Wochen. 25 Patienten, die rTNF-alpha i.m. erhielten, konnten bzgl. ihres Tumorresponse ausgewertet werden. Bei 2 Patienten wurde ein Minor Response (MR), bei 9/25 Patienten ein Wachstumsstillstand beobachtet. 5/14 Patienten, die rTNF-alpha intra/peritumoral erhielten, zeigten eine vorübergehende Tumorrückbildung (3 PR, 2 MR). An wesentlichen subjektiven Nebenwirkungen traten dosisabhängig Fieber, Schüttelfrost, Appetitlosigkeit und Übelkeit auf. In den Dosisgruppen > 50 meg/m² wurden Blutdruckerniedrigungen bis WHO-Grad III gemessen. An hämatologischen Veränderungen wurden vorübergehende Erniedrigungen von Leuko- und Thrombozyten gemessen, ohne daß sich Hinweise für eine kumulative hämatologische Toxizität ergaben. Andere Organtoxizitäten wurden nicht nachgewiesen. Die Ergebnisse aus beiden Studien belegen eine potentielle antitumorale Aktivität von rTNF-alpha, wobei eine lokoregionale Applikation auf eine höhere Effektivität hindeutet. Die bisher dokumentierten subjektiven Toxizitäten scheinen zunächst eine umfangreichere An-wendung in klinischen Studien zu limitieren.

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Recombinant human tumor necrosis factor — II. Antitumor effect on murine and human tumors transplanted in mice

Cited by 57 publications

References 17 publications

Antitumor Effect of Recombinant Human Tumor Necrosis Factor on Human Testicular Tumors Heterotransplanted in Nude Mice

Antitumor Effect of Recombinant Human Tumor Necrosis Factor on Human Testicular Tumors Heterotransplanted in Nude Mice

Prevention of bacterial infection and LPS-induced lethality by interleukin-1.ALPHA. in mice.

Systemische versus lokale Therapie mit rekombinantem Tumor-Nekrose-Faktor-alpha (r-TNF-alpha) bei Patienten mit fortgeschrittenen Tumoren

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