Development of therapy for pancreatic cancers which targets adaptation response to hypoxia.

开发针对缺氧的适应反应的胰腺癌疗法。

• 批准号: 14370170
• 负责人: KOBAYASHI Masanobu
• 金额: $ 8.7万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370170/
• 关键词: hypoxia; hypoglycemia; Glucose transporter; pancreatic cancer; angiogenesis; adrenomedullin; adrenomedullin antagonist; glycolysis; 転移; 血管新生; 解糖系酵素; Hypoxin; AMF; adrenomedullin

1)We found that the expression of adrenomedullin, which has been reported to be a vasodilater, is enhanced by hypoxia.2)We found that the administration of adrenomedullin antagonist peptides into tumor tissues induced the disappearance of tumors through the suppression of angiogenesis.3)We found that dominant negative HIF-1α decreased the resistance to apoptosis induced by hypoglycemia.4) We also found that dominant negative HIF-1α decreased the tumorigenicity of a pancreatic cancer cell line.5)We demonstrated that dominant negative HIF-1α decreased the expression of Glut-1 enhanced by hypoxia and that dominant negative HIF-1α decreased the uptake of FDG in tumor tissues.

1)我们发现，肾上腺髓质素是一种血管扩张剂，它的表达在低氧条件下被增强。2)我们发现，在肿瘤组织中应用肾上腺髓质素拮抗剂多肽可以通过抑制血管生成而导致肿瘤的消失。3)我们发现显性阴性的HIF-1α降低了对低血糖诱导的凋亡的抵抗力。4)我们还发现显性阴性的HIF-1α降低了胰腺癌细胞系的致瘤性。5)我们证明显性阴性的HIF-1α降低了缺氧增强的GLUT-1的表达，显性阴性的HIF-1α降低了肿瘤组织对FDG的摄取。

项目成果

Ishikawa T: "Adrenomedullin antagonist suppresses in vivo growth human Pancreatic cancer cells in SCID mice by suppressing"Oncogene. 22. 1238-1242 (2003)

Ishikawa T：“肾上腺髓质素拮抗剂通过抑制”癌基因来抑制 SCID 小鼠体内人胰腺癌细胞的生长。

J Chen: "Dominant negative HIF-1α reduces tumorigenicity of pancreatic cancer cells through the suppression of hypoxia-inducible anaerobic metabolism"Am J Patol.. 162. 1282-1291 (2003)

J Chen：“显性阴性 HIF-1α 通过抑制缺氧诱导的无氧代谢来降低胰腺癌细胞的致瘤性”Am J Patol.. 162. 1282-1291 (2003)

Jiang Chen, et al.: "Dominant negative HIF-1α reduces tumorigenicity of pancreatic cancer cells through the suppression of hypoxia-inducible anaerobic metabolism"Am J Patol.. 162. 1281-1291 (2003)

Jiang Chen 等人：“显性阴性 HIF-1α 通过抑制缺氧诱导的无氧代谢来降低胰腺癌细胞的致瘤性”Am J Patol.. 162. 1281-1291 (2003)

Niizeki, H.: "Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells"Br. J. Cancer. 86. 1914-1919 (2002)

Niizeki, H.：“缺氧增强自分泌运动因子的表达和人胰腺癌细胞的运动”Br。

Suzuki S: "Autocrine production of epithelial cell-derived neutrophil attractant-78 (ENA-78) induced by G-CSF in neutrophils"Blood. 99. 1863-1865 (2002)

Suzuki S：“中性粒细胞中 G-CSF 诱导的上皮细胞衍生的中性粒细胞吸引剂 78 (ENA-78) 的自分泌产生”血液。