Basic research on antlangiogenic drug to prevent metastasls of gastric cancer

抗血管生成药物预防胃癌转移的基础研究

• 批准号: 14571207
• 负责人: KAKEJI Yoshihiro
• 金额: $ 2.3万
• 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: 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-14571207/
• 关键词: angiogenesis; pastric cancer; hypoxia; p53; metastasis

To investigate the impact of expression of hypoxia-inducible factor (HIF)-1α and p53 on prognosis in human gastric cancer, the clinicopathological characteristics of tumor and clinical outcome were analyzed. Expression of HIF-1α and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer. HIF-1α (+)/p53(+) tumors were more frequently undifferentiated type, infiltrative growth appearance, invasive in lymphatic involvement than could be the HIE-1α (-)1p53(-) ones. HIF-1α (+)/p53(+) tumors also had more lymph node metastasis than did HIF-1α (+)/p53(+) ones. When stratified for HIF-1α and p53 positivity, the patients with p53-negative and HIF-1α -negative had the most favorable prognosis and those with p53-positive and HIF-1α -positive had the worst one (P=0.0018). Using multivariate Cox regression analysis, depth of invasion, lymph node metastasis, and HIF-1α positivity were independent prognostic factors in the patients with gastric cancer. HIF-1α is one of the independent prognostic factors in gastric cancer, and the combination of HIF-1α protein overexpression with nonfunctional p53 indicates a dismal prognosis.

为探讨缺氧诱导因子(HIF)-1α和p53表达对人胃癌预后的影响，分析肿瘤的临床病理特征及临床转归。采用免疫组化方法研究了216例原发性胃癌标本中HIF-1α和p53蛋白的表达。HIF-1α (+)/p53（+）肿瘤较HIE-1α (-) /p53（-）肿瘤多为未分化型、浸润性生长、浸润性淋巴累及。HIF-1α (+)/p53（+）肿瘤的淋巴结转移率高于HIF-1α (+)/p53（+）肿瘤。在HIF-1α和p53阳性分层时，p53阴性和HIF-1α阴性患者预后最好，p53阳性和HIF-1α阳性患者预后最差（P=0.0018）。多因素Cox回归分析显示，浸润深度、淋巴结转移、HIF-1α阳性是影响胃癌患者预后的独立因素。HIF-1α是胃癌的独立预后因素之一，HIF-1α蛋白过表达与无功能p53的结合预示着胃癌预后较差。

项目成果

Maehara Y, et al.: "Therapeutic value of lymph node dissection and the clinical outcome for patients with gastric cancer."Surgery. 131・1 Suppl S. S85-S91 (2002)

Maehara Y 等人：“胃癌患者的淋巴结清扫术的治疗价值和临床结果”。Surgery 131・1 Suppl S. S85-S91 (2002)。

Takahashi I, Emi Y, Hasuda S, Kakeji Y, Maehara Y, Suginiachi K: "Clinical application of hyperthermia combined with anticancer drugs for the treatment of solid tumors."Surgery. 131(1 Suppl S). S78-S84 (2002)

Takahashi I、Emi Y、Hasuda S、Kakeji Y、Maehara Y、Suginiachi K：“热疗联合抗癌药物治疗实体瘤的临床应用。”外科。

Kakeji Y, et al.: "Angiogenesis as a target for gastric cancer."Surgery. 131・1 Suppl S. S48-S54 (2002)

Kakeji Y 等人：“血管生成作为胃癌的靶标。”Surgery 131・1 Suppl S.S48-S54 (2002)。

Ohga T, Tanaka S, Maehara S, Futatsugi M, Ito S, Kiniura Y, Saeki H, Kakeji Y, Maehara Y: "Development of DNA microarray system-From Bench to Bed in Esophageal Cancers."Cytometry Research. 12(2). 121-129 (2002)

Ohga T、Tanaka S、Maehara S、Futatsugi M、Ito S、Kiniura Y、Saeki H、Kakeji Y、Maehara Y：“DNA 微阵列系统的开发 - 从食管癌的工作台到床上。”细胞计数研究。

Masuda T, Inoue H, Nishida K, Sonoda H, Yoshikawa Y, Kakeji Y, Utsunomiya T, Mori M: "Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma."Clin Cancer Res. 9. 5693-5698 (2003)

Masuda T、Inoue H、Nishida K、Sonoda H、Yoshikawa Y、Kakeji Y、Utsunomiya T、Mori M：“细胞周期蛋白依赖性激酶 1 基因表达与胃癌的不良预后相关。”Clin Cancer Res。