Cyclooxygenase-2 inhibitor is a possible new drug for treatment of gastrointestinal cancers

考克斯-2在胃肠道肿瘤中的表达：<Study1>我们研究了考克斯-2和Lox在大肠癌中的表达。在91例原发性大肠癌中，Loxs mRNA阳性率为72.5%。免疫组化检测Loxs和考克斯-2蛋白的高表达率分别为68.7%和79.1%。Loxs蛋白的高表达与考克斯-2蛋白的高表达相关。花生四烯酸通过Lox或考克斯代谢。该研究表明Loxs在结直肠癌中上调，抑制Loxs和考克斯-2可以预防结直肠癌的发展。<Study2>本文对169例胃癌组织中VEGF、考克斯-2和CD 34的表达与微血管密度的关系进行了研究。考克斯-2和VEGF的高表达率分别为36.7%和50.3%。VEGF与考克斯-2、CD 34的表达呈正相关。VEGF表达与肿瘤浸润深度、淋巴结转移、淋巴结和静脉浸润及TNM分期有关。VEG阳性患者 ...更多信息 F染色显示无病生存率和总生存率低于VGEF染色阴性者。多因素分析显示，肿瘤部位、浸润深度和淋巴结转移是独立的预后因素。VEGF的表达可能是一个有价值的胃癌预后因素。考克斯-2抑制剂和抑制肿瘤生长：<Study1>我们研究了小肺转移的微血管结构和JTE-522，一种选择性考克斯-2抑制剂，对大鼠结直肠癌肺转移的血管生成的影响。向20只大鼠的尾静脉注射大鼠结肠癌细胞系的肿瘤悬浮液。3周后取肺血管树脂铸型，用体视显微镜和扫描电镜观察肺转移瘤的血管分布。此外，我们研究了0、10和30 mg/kg/天的JTE-522对3组5只大鼠肺转移瘤血管生成的影响。35例肺转移瘤血管直径和肺转移灶大小与新生血管形成呈显著正相关。JTE-522缩小了转移性肿瘤的大小和肿瘤血管的直径。选择性考克斯-2抑制剂可通过破坏新生血管形成来干扰血行转移性肿瘤的生长。<Study2>我们研究了大鼠转移性肝肿瘤的肿瘤血管和选择性考克斯-2抑制剂美洛昔康对小转移性肝肿瘤生长和微血管的影响。40只大鼠门静脉接种RCN-H_4细胞，建立转移性肝肿瘤模型。应用扫描电镜和体视显微镜观察肝转移瘤的微血管。在肿瘤接种后14天通过腹主动脉灌注产生微血管铸型。从接种RCN-H4细胞之日起，每周5天，以0、0.6、1.0、3.0 mg/kg/天的剂量经口给予4组美洛昔康，持续2周。美洛昔康治疗组的转移性肿瘤数量较少，呈剂量依赖性。根据这些观察结果，美洛昔康通过抗血管生成活性干扰转移性肝肿瘤的生长。美洛昔康可能对结直肠癌肝肿瘤有治疗潜力。少

COX-2 expression of gastrointestinal cancers: <Study1> We investigate COX-2 and Loxs of colorectal cancer. Of 91 primary colorectal cancers, Loxs mRNA was found in 72.5%. High expression of Loxs and COX-2 protein were found by immunohistochemical staining in 68.7% and 79.1%, respectively. The high expression of Loxs protein was correlated with that of COX-2 protein. Arachdonic acid is metabolized either by Loxs or COX. This study showed Loxs is up-regulated in colorectal cancer, and inhibition of Loxs as well as COX-2 may prevent development of colorectal cancer. <Study2> Expression of VEGF, COX-2 and CD34 for microvessel density was investigated in 169 gastric cancers. COX-2 and VEGF were highly expressed in 36.7% and 50.3%, respectively. Positive relation was found between VEGF and COX-2 expression and between VEGF and CD34 expression. VEGF expression was correlated with depth of invasion, metastatic lymph nodes, lymphatic and venous invasion and TNM stage. Patients with positive VEG … More F staining showed lower disease free survival and overall survival than those with negative VGEF staining. In multivariate analysis, tumor location, depth of invasion and lymph node metastasis were shown to be independent prognostic factor. VEGF expression may be a valuable prognostic factor in gastric cancer.COX-2 inhibitors and suppression of tumor growth: <Study1> We investigate the microvascular structure of small lung metastases and the effect of JTE-522, a selective COX-2 inhibitor, on the angiogenesis of pulmonary metastases from colorectal cancer in rats. The tail veins of 20 rats were injected with a tumor suspension of a rat colon cancer cell line. Three weeks later, pulmonary vascular resin corrosion casts were taken and the vascularity of metastases was studied with using stereo and scanning electron microscopes. In addition, we investigated the effect of 0, 10 and 30 mg/kg/day of JTE-522 on the angiogenesis of pulmonary metastases in 3 groups of 5 rats. The diameter of tumor vessels and the size of lung metastases significantly and positively correlated with neovascularization in 35 metastatic tumors. JTE-522 reduced the size of metastatic tumors and the diameter of tumor vessels. Selective COX-2 inhibitors may interfere the growth of hematogenous metastatic tumors by disrupting neovascularization. <Study2> We investigated the tumor vessel of metastatic liver tumors and the effect of Meloxicam, a selective COX-2 inhibitor, on growth and microvasculature of small metastatic liver tumors in rats. Metastatic liver tumors were produced by intraportal inoculation of RCN-H4 cells in 40 rats. Microvasculature of liver metastasis was studied by scanning electron microscopy and stereomicroscopy. Microvascular casts were produced by perfusion via the abdominal aorta 14 days after tumor inoculation. Meloxicam was administered in four groups with a dose of 0, 0.6, 1.0, 3.0 mg/kg/day orally 5 days per week from the day of inoculation of RCN-H4 cells for 2 weeks. The number of metastatic tumors and was less in the Meloxicam-treated groups in comparison with dose dependent fashion. From these observations, Meloxicam interfered growth of metastatic liver tumors through anti-angiogenic activity. Meloxicam may have therapeutic potential for liver tumors of colorectal carcinoma. Less