Cyclooxygenase-2 in development of colorectal neoplasia and effect of cyclooxyhgenase-2 inhbitor on colorectal neoplasia

环氧合酶2在结直肠肿瘤发生过程中的作用及环氧合酶2抑制剂对结直肠肿瘤的影响

• 批准号: 12470253
• 负责人: SUGIHARA Kenichi
• 金额: $ 7.81万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470253/
• 关键词: Cyclooxygenase-2; NSAIDs; COX-2 Inhibitor; colorectal adenoma; Colorectal cancer; familial nolyposis coli; 大腸腺腫; 大腸腺腫症; COX2; 動物実験; 癌; 治療; サイクロオキシゲナーゼ; COX-2; 大腸腺種; NSAID

1 COX-2protein is induced in the polyp stroma near the intestinal luminal surface in the APC^<Δ716> and stimulate tumor angiogenesis. By immunohistochemical analysis, we showed that majority of COX-2 expressing cells in the intestinal polyps of mice are fibroblasts and endotherial cells. Can Res 2002;62:6846-6849.2 COX-2 expression was evaluated by immunohistochemical staining in 95 colorectal adenomas. Expression was significantly related to grade of dysplasia and tumor size, but multivariate analysis showed COX-2 expression to be independently associated with grade of dysplasia. (Dis Colon Rectum 2003;46:786-792.3 Immunohistochemical staining for Ki-67 antigen and COX-2 was performed on 95 colorectal adenomas. The Ki-67 labeling index was significantly higher in the high-COX-2 group than in the low-COX-2 and negative group in adenoma with sever and moderate dysplasia. Ther was no correlation between Ki-67 labeling index and COX-2 expression in mild dysplasia. (Jpn J Clin Oncol 2003;33:631-635.4 A total of 48 T1 colorectal cancers were classified into polypoid or non-polypoid. COX-2 expression was determined immunohistochmically and PCR-RFLP was used to detecte a K-ras mutation. COX-2 expression was significantly higher in polypoid tha in non-polypoid. The K-ras mutation was associated higher levels of COX-2 expression. (Dis Colon Rectum 2004;47: in press)5 A total of 21 patients with familial adenomatous polyposis coli were assigned randomly to receive either 25 mg of rofecoxib or placebo for '9 months. The number and size of the rectal polyps were evaluated by colonoscopy. The number and size of the polyps of patients who had rofecoxib were significantly decreased at 9 months. (Clin Can Res 2003:9:4756-4760)

1考克斯-2蛋白在大肠息肉间质中被诱导表达于APC^<Δ716>中，并刺激肿瘤血管生成。免疫组化结果显示，小鼠肠息肉中表达考克斯-2的细胞主要为成纤维细胞和内皮细胞。Can Res 2002;62：6846- 6849。2通过免疫组织化学染色评价了95例结直肠腺瘤中考克斯-2的表达。COX-2的表达与异型增生的分级和肿瘤大小显著相关，但多因素分析显示考克斯-2的表达与异型增生的分级独立相关。(Dis结肠直肠2003;46：786-792.3对95例结肠直肠腺瘤进行Ki-67抗原和考克斯-2的免疫组织化学染色。在腺瘤伴重度和中度异型增生中，高COX-2组Ki-67标记指数显著高于低COX-2组和阴性组。轻度异型增生中Ki-67标记指数与考克斯-2表达无相关性。(Jpn J Clin Oncol 2003;33：631-635.4将总共48例T1结肠直肠癌分类为息肉样或非息肉样。采用酶联免疫吸附法检测考克斯-2表达，PCR-RFLP法检测K-ras基因突变。考克斯-2在息肉样病变中的表达明显高于非息肉样病变。K-ras基因突变与考克斯-2高表达相关。(Dis结肠直肠2004;47：出版中）5共有21名家族性腺瘤性结肠息肉病患者被随机分配接受25 mg罗非昔布或安慰剂治疗9个月。通过结肠镜检查评估直肠息肉的数量和大小。服用罗非昔布的患者息肉的数量和大小在9个月时显著减少。(Clin Can Res 2003：9：4756-4760）

项目成果

Ohno R, et al.: "Depth of invasion parallels increased cyclooxygenese-2 levels in patients with gastric carcinoma"Cancer. 91. 1876-1881 (2001)

Ohno R 等人：“胃癌患者的侵袭深度与环氧合酶 2 水平升高相似”。

Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, Sugihara K.: "A randomized, double-blind, placebo-controlled trial of the effects of Rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients."Oli

Higuchi T、Iwama T、Yoshinaga K、Toyooka M、Taketo MM、Sugihara K.：“一项随机、双盲、安慰剂对照试验，研究罗非昔布（一种选择性环氧合酶 2 抑制剂）对家族性腺瘤直肠息肉的影响

Sato T, Yoshinaga K, Okabe T, Okawa T, Enomoto M, Sugihara K: "Cyclooxygenase-2 expression in colorectal adenoma"Diseases of the Colon and Rectum. 46(6). 786-792 (2003)

Sato T、Yoshinaga K、Okabe T、Okawa T、Enomoto M、Sugihara K：“结直肠腺瘤中环氧化酶 2 的表达”结肠和直肠疾病。

Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, Sugihara K: "A randomized, double-blind, palacebo-controlled trial of the effects of Rogecoxib, and a selective cyclooxygenase-2 inhibitor, on rectal polyp"Clinical Cancer Research. 15(9). 4756-4760 (

Higuchi T、Iwama T、Yoshinaga K、Toyooka M、Taketo MM、Sugihara K：“一项关于罗吉昔布和选择性环氧合酶 2 抑制剂对直肠息肉影响的随机、双盲、palabo 对照试验”临床癌症

Tsunozaki H, Yoshinaga K, Kumagai J, Sugihara K: "Cyclooxygenase-2 overexpresion in colorectal cancer is associated with non-polypoid growth."Jpn J Clin Oncol. 32(5). 167-171 (2002)

Tsunozaki H、Yoshinaga K、Kumagai J、Sugihara K：“结直肠癌中环加氧酶 2 的过度表达与非息肉样生长相关。”Jpn J Clin Oncol。