Analysis of the immunological role of spleen in gastric cancer patients - from the viewpoint of cytokine producing ability of splenocytes -

胃癌患者脾脏的免疫作用分析-从脾细胞产生细胞因子能力的角度-

• 批准号: 10671167
• 负责人: FUJIMOTO Toshihiro
• 金额: $ 1.98万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671167/
• 关键词: gastric carcinoma; splenocyte; Th1; Th2; IL-12; IFN-γ; OK-432; tumor bearing state; cytokine; gasteic carcinoma; 胃癌; 脾細胞; サイトカイン; 担癌状態; 脾摘

Cytokine production from splenocytes of healthy mouse induced with OK-432 differs depending their genetic background. In C57BL/6 mice with B16 melanoma, splenocytes derived from the middle stage of tumor bearing produced IL-2, IL-6, IL-10 and IFN-γ. There was little spontaneous IL-12 production from tumor bearing mice splenocytes. All cytokine production were reduced in their later stage of tumor bearing. Splenocytes derived from the middle stage of tumor bearing mice could produce IL-12 when activated with OK-432 in vitro. Furthermore, in vivo treatment with OK-432 tend to inhibit tumor growth of B16 melanoma, which was accompanied by IL-12 and IFN-γ production of splenocytes. Regarding the splenocytes of gastric cancer patients, production of IL-4, IL-6 and IFN-γ was observed but we need further investigation because there exist individual differences between the patients.In the ascitic mouse model, OK-432 could induce Th1 cytokine production such as IL-12 and IFN-γ in the ascites. In human treatment of gastric cancer, we have tried to administer MMC and OK-432 to control peritoneal carcinomatosis, and there were responder cases with increasing I L-2, IL-12, ILl5 and IFN-γ in their cancerous ascites. There was a correlation between their favorable prognosis and their Th1 cytokine production after the OK-432 treatment.

由OK-432诱导的健康小鼠脾细胞的细胞因子产生因其遗传背景而有所不同。在具有B16黑色素瘤的C57BL/6小鼠中，源自肿瘤轴承中部的脾细胞产生IL-2，IL-6，IL-10和IFN-γ。脾细胞的肿瘤轴承产生很少发作IL-12产生。在肿瘤轴承的后期，所有细胞因子的产生均降低。当用OK-432在体外激活时，源自肿瘤轴承小鼠中部的脾细胞可能会产生IL-12。此外，使用OK-432的体内治疗倾向于抑制B16黑色素瘤的肿瘤生长，这是通过IL-12和IFN-γ产生的脾细胞来抑制的。关于胃癌患者的脾细胞，观察到IL-4，IL-6和IFN-γ的产生，但我们需要进一步研究，因为患者之间存在个体差异。在Ascitic小鼠模型中，OK-432可以诱导Th1细胞因子的产生，例如IL-12和IFN-γ。在胃癌的人类治疗中，我们试图管理MMC和OK-432来控制腹膜癌，并且​​在其癌性腹水中有响应者增加I L-2，IL-12，ILL5和IFN-γ的病例。 OK-432治疗后，它们的有利预后与Th1细胞因子产生之间存在相关性。

项目成果

Fujimoto T: "Immunotherapy for liver metastasis. Liver metastasis- Its mechanism and clinical experience. (Mai M, Seiki M and Takahashi Y ed.)"Igaku-shoin, Tokyo. 212-219 (2000)

Fujimoto T：“肝转移的免疫疗法。肝转移 - 其机制和临床经验。（Mai M、Seiki M 和 Takahashi Y 编辑）”Igaku-shoin，东京。

Fujimoto, T. et al.: "The effect of OK-432 on the cytokine production of the tumor bearing mouse splenocytes"Biotherapy. (in press). (2000)

Fujimoto, T. 等人：“OK-432 对荷瘤小鼠脾细胞细胞因子产生的影响”生物疗法。

Fujimoto T, Mai M and O'Donnell MA: "Streptococcal preparation OK-432 works as a Th1 inducer."Therapeutic Research. 19(7). 2187-2193 (1998)

Fujimoto T、Mai M 和 ODonnell MA：“链球菌制剂 OK-432 可作为 Th1 诱导剂。”治疗研究。

藤本敏博、他: "癌性胸腹膜炎に対するOK-432局所投与の抗腫瘍効果と作用機序について"Biotherapy. 12巻11号. 1479-1485 (1998)

Toshihiro Fujimoto等人：“OK-432局部给药对癌性胸膜腹膜炎的抗肿瘤作用和作用机制”，生物疗法，第12卷，第11期。1479-1485 (1998)

Fujimoto T and Mai M: "Local administration of OK-432 against peritoneal carcinomatosis. New therapeutic guideline of immunochemotherapy for cancer."(Saji S and Toge T ed.) Iyaku-journal, Tokyo. 81-84 (1999)

Fujimoto T 和 Mai M：“OK-432 局部给药对抗腹膜癌病。癌症免疫化疗的新治疗指南。”（Saji S 和 Toge T 编辑）Iyaku-journal，东京。