Study on the inhibition of chemical carcinogenesis of buccal mucosa with a macrophage activating factor

巨噬细胞激活因子抑制颊黏膜化学癌变的研究

• 批准号: 09672086
• 负责人: URADE Masahiro
• 金额: $ 1.92万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672086/
• 关键词: hamster buccal pouch carcinogenesis; dimethylbenzanthracene; macrophage activating factor (GcMAF); inhibition of carcinogenesis; ハムスター頬襄発癌

This study was designed to investigate the inhibitory effects of a new macrophage activating factor (GcMAF) on hamster buccal pouch carcinogenesis with 9,1O-dimethyl-1,2-benzanthracene (DMBA) and on the growth of DMBA-induced tumor. GcMAF newly discovered by N.Yamamoto is a glycoprotein derived from serum Gc protein (vitamin D_3-binding protein) as precursor. The results obtained were as follows.1)Twenty-nine Syrian hamsters (5 week-old) were divided into 15 with GcMAF administration (100 pg i.m. injection twice a week) and 14 without administration, and were painted a buccal pouch 3 times a week with 1% DMBA-acetone solution. Consequently, all hamsters of the group without GcMAF administration developed squamous cell carcinoma at the 9th to 10th week after DMBA application, and died of tumor within 20 weeks. On the other hand, two of 14 hamsters with GcMAF administration did not produce tumors, and the remaining 12 hamsters showed a delay of tumor development and growth and were alive … More until the 20th week of the experimental period. Also, their weight loss by tumor burden was slight.2)Five tumor-bearing hamsters in the group without GcMAF administration showed the inhibition of tumor growth and weight loss by starting GcMAF from the 13th week. Four tumor-bearing hamsters in the group with GcMAF administration showed acceleration of tumor growth by stopping GcMAF from the 13th week.3)Treatment of hamster peritoneal macrophages with GcMAF in vitro or in vivo demonstrated increased superoxide generation indicating the macrophage activation. The GcMAF-activated peritoneal macrophages revealed a significant cytocidal effect against hamster kidney BHK21 cells and human oral floor carcinoma KB cells as compared to non-activated macrophages.From these findings, it was indicated that GcMAF inhibited or delayed the DMBA-induced hamster buccal pouch carcinogenesis and tumor growth via macrophage activation, This investigation suggested the possibility of immunotherapy for oral cancer with GcMAF. Less

本研究旨在探讨一种新的巨噬细胞激活因子(GcMAF)对9，1O-二甲基-1，2-苯并茂(DMBA)诱发的仓鼠颊囊癌的抑制作用及对DMBA诱发的肿瘤生长的抑制作用。GcMAF是由N.Yamamoto新近发现的一种以血清GC蛋白(维生素D3结合蛋白)为前体的糖蛋白。结果如下：1)29只5周龄叙利亚仓鼠随机分为15组，每组15只。每周2次注射)和14例不给药，并用1%DMBA-丙酮溶液每周涂3次口腔袋。结果，未给予GcMAF组的所有仓鼠在应用DMBA后第9~10周发生鳞状细胞癌，并在20周内死于肿瘤。另一方面，在14只给予GcMAF的仓鼠中，有两只没有产生肿瘤，其余12只仓鼠表现出肿瘤的生长和发育延缓，并且是活的…更多，直到实验期的第20周。未给予GcMAF组的5只荷瘤仓鼠从第13周开始给予GcMAF，显示出对肿瘤生长的抑制和体重减轻。GcMAF组有4只荷瘤仓鼠从第13周开始停止GcMAF，肿瘤生长加速。3)GcMAF处理金黄地鼠腹膜巨噬细胞后，体内或体外超氧化物生成增加，表明巨噬细胞被激活。与未激活的巨噬细胞相比，GcMAF激活的巨噬细胞对地鼠肾BHK21细胞和人口腔底癌KB细胞具有明显的杀伤作用，提示GcMAF通过激活巨噬细胞抑制或延缓DMBA诱导的仓鼠颊囊癌的发生和肿瘤生长，提示GcMAF用于口腔癌免疫治疗的可能性。较少

项目成果

橋谷進、岸本裕充、桜井一成、柳澤高道、浦出雅裕: "ハムスター頬粘膜発癌に対するマクロファージ活性化因子(GcMAF)の抑制効果" 口腔組織培養研究会誌. 7・1. 39-40 (1998)

Susumu Hasitani，Hiromitsu Kishimoto，Kazunari Sakurai，Takamichi Yanagisawa，Masahiro Urade：“巨噬细胞激活因子（GcMAF）对仓鼠颊粘膜癌发生的抑制作用”口腔组织培养研究会杂志7・1。

Yamamoto N,Naraparaju VR,Urade M: "Prognostic utility of serum alpha-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients." Cancer Res. 57. 295-299 (1997)

Yamamoto N、Naraparaju VR、Urade M：“口腔癌患者血清 α-N-乙酰氨基半乳糖苷酶的预后效用和血清 Gc 蛋白去糖基化导致的免疫抑制。”

橋谷進, 岸本裕充, 桜井一成, 柳澤高道, 浦出雅裕: "ハムスター頬粘膜発癌に対するマクロファージ活性化因子(GcMAF)の抑制効果" 口腔組織培養研究会誌. 7. 39-40 (1998)

Susumu Hasitani、Hiromitsu Kishimoto、Kazunari Sakurai、Takamichi Yanagisawa、Masahiro Urade：“巨噬细胞激活因子（GcMAF）对仓鼠颊粘膜癌变的抑制作用”口腔组织培养研究会杂志（1998）。

Yamamoto N, Naraparaju VR, Urade M.: "Prognostic utility of serun α-N-acetylgalactosaninidase and immunosuppression resulted from deglycosylation of serumGc protein in oral cancer patients" Cancer Research. 57. 295-299 (1997)

Yamamoto N、Naraparaju VR、Urade M.：“口腔癌患者血清 Gc 蛋白去糖基化导致血清 α-N-乙酰半乳糖苷酶的预后效用”癌症研究 57. 295-299 (1997)。

Hashitani S,Kishimoto H,Sakurai K,Yanagisawa T,Urade M: "Inhibitory effect of a macrophage activating factor (GcMAF) on carcinogenesis of hamster buccal mucosa." Jpn J Tissue Cult Dent Res (in Japanese). 7(1). 39-40 (1998)

Hashitani S、Kishimoto H、Sakurai K、Yanagisawa T、Urade M：“巨噬细胞激活因子 (GcMAF) 对仓鼠颊粘膜癌变的抑制作用。”