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Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line
Authors:Hitoshi Maeda  Tohru Uozumi  Kaoru Kurisu  Takashi Matsuoka  Keiichi Kawamoto  Katsuzo Kiya  Hidenori Ogasawara  Kazuhiko Sugiyama  Takashi Mikami  Syuji Monden  Kunyu Harada  Yasuhiro Matsuda
Affiliation:(1) Department of Neurosurgery, Hiroshima University School of Medicine, Hiroshima, Japan;(2) Department of Neurosurgery, Matsuyama Red Cross Hospital I. Bunkyo-cho, 790 Matsuyama, Japan
Abstract:Summary The antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method): 1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (G2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G + T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G + T mice than in the T mice. Granulocytes were observed only in the tumors of the G + T mice.
Keywords:TNF  G-CSF  human medulloblastoma xenograft line  macrophage
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