胃癌における血管新生と腫瘍の進展・転移および制癌剤効果に関する研究

胃癌血管生成、肿瘤进展/转移及抗癌药物作用研究

• 批准号: 09770941
• 负责人: 掛地 吉弘
• 金额: $ 1.79万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 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/en/grant/KAKENHI-PROJECT-09770941/
• 关键词: dThdPase; 血管新生; 胃癌; 転移; 化学療法; 脈管侵襲; 浸潤・転移

1. 胃癌におけるdThdPase活性と腫瘍内血管新生との関連切除胃癌42例を対象とし、dThdPase活性を高速液体クロマトグラフィー法(HPLC法)で定量的に測定した。正常胃粘膜部の平均dThdPase活性は49、腫瘍中心部139、腫瘍辺縁部106であり、正常組織に比べて腫瘍組織ではdThdPase活性が有意に高く、さらに腫瘍内では辺縁部よりも中心部で有意に高い値を示した。dThdPase活性が高い症例は腫瘍内血管密度も高い値を示して有意に相関し、dThdPaseの血管新生作用がうかがわれた。組織型でみると分化型でdThdPase活性が高く、静脈侵襲陽性例、肝転移陽性症例で高い値を示した。2. dThdPase活性とdThdPase蛋白の相関と臨床的意義切除胃癌101例を対象とし、dThdPase抗体を用いた染色を行った。dThdPaseの酵素活性は蛋白の発現と相関していた。dThdpsae陽性例は陰性例に比べて腫瘍径が大きく、深達度が深く、脈管侵襲陽性例、リンパ節転移陽性例が多く、進行したものが有意に多く認められた。dThdPase陰性例の5年生存率は95%と良好であるのに対して、陽性例では69%と有意に予後不良であった。stage別にみると、stageIII,IVで、dThdPaseによる予後の差がみられた。以上より、胃癌においてdThdPaseは血管新生を誘導し、dThdPase腸性例は侵潤・転移しやすく、予後不良となる傾向がみられた。dThdPaseによる予後の差はstageIII,IVの症例で明らかであり、臨床的にはstageIIIのdThdPase陽性症例で5'-DFURを用いた化学療法の有効性が期待される。

1. 42 cases of gastric cancer were resected by dThdPase activity, internal angiogenesis and dThdPase activity. High-speed liquid chromatography, HPLC method and quantitative assay. The average dThdPase activity in the normal gastric mucous membrane was 49, the central part was 139, the normal tissue was higher than the normal tissue, the dThdPase activity in the normal tissue was higher than that in the normal tissue, and the central part of the normal gastric mucous membrane was intentionally high. DThdPase activity high blood vessel density in patients with high blood vessel density indicates intentional angiogenesis and dThdPase angiogenesis. High dThdPase activity, static invasion and liver metastases were found in tissue type, differentiated type, and liver metastatic type. 2. The significance of dThdPase activity and dThdPase protein phase in the bed of gastric cancer 101cases of gastric cancer were resected, and dThdPase antibodies were stained with anti-gastric cancer. The activity of dThdPase enzyme and the activity of protein were different from each other. The sexual cases of dThdpsae are larger, deeper, more invasive, more invasive, more frequent, and more intentional than those of other patients. The 5-year survival rate of dThdPase sexual cases was 95%, good sexual cases and 69% sexual cases, respectively. Stage, stageIII,IV, dThdPase, please do not know what to do in the future. The above diseases, gastric cancer, dThdPase angiogenesis guidance, dThdPase cases of invasion and migration, and adverse reactions in the future. After dThdPase treatment, the symptoms of poor stageIII,IV were clearly diagnosed, and the sexual symptoms of patients with 5'-DFUR were expected by chemical method.

项目成果

Yoshihiro Kakeji,et al.: "Long-term survival of patients with stage IV gastric cancer." Cancer. 82(12). 2307-2311 (1998)

Yoshihiro Kakeji 等人：“IV 期胃癌患者的长期生存。”

Yoshihiko Maehara et al.: "Tumor angiogenesis and micrometastasis in bone marrow of patients with early gastric cancer." Clin.Cancer Res. 4. 2129-2134 (1998)

Yoshihiko Maehara 等人：“早期胃癌患者骨髓中的肿瘤血管生成和微转移。”

Yoshihiro Kakeji,et al.: "Preclinical studies of the combination of angiogenic inhibitors with cytotoxic agents" Investigational New Drugs. 15. 39-48 (1997)

Yoshihiro Kakeji 等人：“血管生成抑制剂与细胞毒性药物组合的临床前研究”研究新药。

Yoshihiro Kakeji,et al.: "Dymanics of tumor oxygenation.CD31 staining and transforming growth factor-β levels after treatment with radiation or cyclophosphamide in the rat 13762 mammary carcinoma" Int.J.Radiation Oncology Biol.Phys.37. 1115-1123 (1997)

Yoshihiro Kakeji 等人：“大鼠 13762 乳腺癌中放射或环磷酰胺治疗后肿瘤氧合的动态。CD31 染色和转化生长因子-β 水平”Int.J.Radiation Oncology Biol.Phys.37。 (1997)