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（据报道是一种血管舒张剂）的表达会因缺氧而增强。2)我们发现，将肾上腺髓质素拮抗肽注射到肿瘤组织中，可以通过抑制血管生成来诱导肿瘤消失。3 )我们发现显性失活HIF-1α降低了对低血糖诱导的细胞凋亡的抵抗力。4)我们还发现显性失活HIF-1α降低了肿瘤的致瘤性。 5）我们证明，显性失活的HIF-1α降低了缺氧增强的Glut-1的表达，并且显性失活的HIF-1α降低了肿瘤组织中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。

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。

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)

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)

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

T Ishikawa：“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。