New strategy for cancerous peritonitis : cyclosporin-A combination therapy

癌性腹膜炎新策略：环孢素A联合治疗

• 批准号: 11671253
• 负责人: KATANO Mitsuo
• 金额: $ 1.98万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671253/
• 关键词: cancerous peritonitis; cyclosporin-A; interferon-gamma; carcineurin; apoptosis; JAK; STAT pathway; NF-AT; NF-κB; 胃癌細胞; インターフェロンーガンマ; FK506; カルシウム

The prognois of cancerous peritonitis originated from digestive organ cancer is very poor. This study was planned to develop new treatment for cancer patients with cancerous peritonitis. For this purpose, we used cyclosporin-A (CsA) which is a clinically important immunosuppressive drug widely used to prevent graft rejection following organ or bone marrow transplantation. Results obtained during this observation period are as follows. (1) Combination of CsA and interferon-gamma (IFN-γ) induces significant apoptosis in various types of human carcinoma cells. (2) Proposed mechamism : IFN-γ activates not only JAK/STAT pathway and caspase cascade (apotosis pathway) but also NF-AT and/or NF-κB through activastion the Ca^<2+>-/CaM-dependent carcineurin pathway (anti-apotosis pathway). Suppression of anti-apoptosis pathway by CsA induces predominance of apoptosis pathway. (3) Intraperitoneal injection of OK-432 for managenent of cancerous peritonitis induces a detectable IFN-γ production in ascitic fluids. A combination of CsA with IFN-γ-containing ascitic fluids after but not before OK-432 injection induced significant apoptosis in carcinoma cells existing in the fluids. These results indicate that a combination of CsA and the OK-432 therapy or IFN-γ may, in the near future, be a useful therapeutic strategy for gastrointestinal cancer patients with cancerous peritonitis.

起源于消化器官癌症的癌性腹膜炎的预后非常差，本研究计划为患有癌性腹膜炎的癌症患者开发新的治疗方法，为此，我们使用了临床上广泛使用的重要免疫抑制药物环孢菌素-A（CsA）。预防器官或骨髓移植后的移植物排斥反应 在此观察期间获得的结果如下： (1) CsA 和干扰素-γ (IFN-γ) 的组合诱导。 (2) 提出的机制：IFN-γ 不仅可以激活 JAK/STAT 通路和 caspase 级联（凋亡通路），还可以通过激活 Ca^< 来激活 NF-AT 和/或 NF-κB。 2+>-/CaM 依赖性癌神经磷酸酶途径（抗凋亡途径）。CsA 抑制抗凋亡途径会诱导凋亡途径占主导地位。 (3)腹膜内注射OK-432用于治疗癌性腹膜炎，在腹水中诱导可检测到的IFN-γ产生。在注射OK-432之后但不是之前，CsA与含有IFN-γ的腹水的组合诱导了显着的癌细胞凋亡。这些结果表明，CsA 和 OK-432 疗法或 IFN-γ 的组合在不久的将来可能是一种有用的方法。胃肠道癌症患者合并癌性腹膜炎的治疗策略。

项目成果

Hao Z: "Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-β1 and MMPs."Clinical & Experimental Metastasis. (In press).

郝Z：“蛋白质结合多糖PSK通过下调TGF-β1和MMP来抑制肿瘤侵袭性。”临床与实验转移（正在出版）。

Sato N: "Establishment of a new human pancreatic cancer cell line, NOR-P1, with high angiogenic activity and metastatic potential."Cancer Letters. 155. 153-161 (2000)

Sato N：“建立了一种新的人类胰腺癌细胞系 NOR-P1，具有高血管生成活性和转移潜力。”《癌症快报》。

Hao Z: "Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-b1 and MMPs."Clinical & Experimental Metastasis. (In Press). (2001)

郝Z：“蛋白质结合多糖PSK通过下调TGF-b1和MMPs抑制肿瘤侵袭性。”临床

Beppu K: "Elevation of serum hepatocyte growth factor concentration in patients with gastric cancer is mediated by production from tumor tissue."Anticancer Research. 20. 1263-1268 (2000)

Beppu K：“胃癌患者血清肝细胞生长因子浓度的升高是由肿瘤组织的产生介导的。”抗癌研究。

片野光男: "癌性胸腹水に対するOK-432/G-CSF併用療法"Therapeutic Research. 21. 1935-1938 (2000)

Mitsuo Katano：“OK-432/G-CSF 联合疗法治疗癌性胸膜腹水”治疗研究 21. 1935-1938 (2000)。