Elevation of plasma TGF-b in cancer patients and study on its molecular mechanism.

癌症患者血浆TGF-b升高及其分子机制研究

• 批准号: 09557052
• 负责人: KAWATA Sumio
• 金额: $ 3.2万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-09557052/
• 关键词: TGF-b; plasma TGF-b1; TGF-b receptor; anti-TGF-b therapy; TGF-βレセプター

We have reported that TGF-bl is produced by human hepatocellular carcinoma and colon cancer and that plasma TGF-bl concentration is elevated in patients with these cancers. The circulated TGF-b1 contributed to reduced anti-tumor immunity and enhanced vascularity in the timors.Our hypothesis is that the circulating TGF-bl may contribute to prognosis of the patients. We divided 70 patients with hepatocellular carcinoma into a group with high concentration of plasma TGF-IA (more than 8.7 ng/ml) and a group with low concentration (below 8.7). The survival time was short in the group with high concenteration. This result was confirmed in each tumor stage. Cox proportional-hazard regression analysis showed that plasma TGF-bl concentration is a risk factor contributing for the prognosis.We also are studying on anti-tumor effect of recombinant soluble form TGF-b receptor type II against human hepatoma transplanted in nude mice. These experiments may lead to anti-TGF-b therapy in human cancer patients.

我们已经报道了TGF-β 1由人肝细胞癌和结肠癌产生，并且在患有这些癌症的患者中血浆TGF-β 1浓度升高。循环中TGF-β_1参与了抗肿瘤免疫的降低和肿瘤血管的增加，我们的假设是循环中TGF-β_1可能有助于患者的预后。我们将70例肝细胞癌患者分为高浓度组（> 8.7 ng/ml）和低浓度组（<8.7 ng/ml）。高浓度组存活时间短。这一结果在每个肿瘤阶段都得到了证实。考克斯比例风险回归分析显示，血浆TGF-β 1浓度是影响预后的危险因素，我们还研究了重组可溶性TGF-β Ⅱ型受体对裸鼠人肝癌移植瘤的抗肿瘤作用。这些实验可能导致人类癌症患者的抗TGF-B治疗。

项目成果

K.Fukuda,S.Kawata,et al.: "Altered regulation of Src tyrosine Kinase by transforming growth Factor-β in a human hepatoma cell line." Hepatology. 28. 796-804 (1998)

K. Fukuda、S. Kawata 等人：“通过转化人肝癌细胞系中的生长因子-β 改变 Src 酪氨酸激酶的调节。”28. 796-804 (1998)。

H.Tsushima, S.Kawata, et al.: "Reduced plasma TGF-b1 levels in patients with chronic hepatitis C after interferon-alpha." J.Hepatol.30. 1-7 (1999)

H.Tsushima、S.Kawata 等人：“使用干扰素 α 后，慢性丙型肝炎患者血浆 TGF-b1 水平降低。”

T.Nagase,S.Kawata,et al.: "Effect of frnesyltrarsferase ovenexpression on cell growth and transformation." Int.J.Cancer. 80. 126-133 (1999)

T.Nagase、S.Kawata 等人：“呋喃基转移酶烤箱表达对细胞生长和转化的影响”。

N.Ito, S.Kawata et al.: "Increased ciralating TGF-β in a patient ucithgient repatic hemangioma." Hephtology. 25(1). 93-96 (1997)

N.Ito, S.Kawata 等人：“脐静脉血管瘤患者的循环 TGF-β 增加。”25(1) (1997)。

Y.Imai, S.Kawata, et al.: "Recombinant interferond 2a for trestment of chronic hepatitis C" Liver. 17. 88-92 (1997)

Y.Imai、S.Kawata 等人：“重组干扰素 2a 用于治疗慢性丙型肝炎”肝脏。