Involvement of inflammation-related enzymes and PPARs in tongue carcinogenesis and inhibition of tongue carcinogenesis by their inhibition

我们进行了体内实验，以阐明炎症与舌癌发生的某些关系。雄性F344大鼠(4周龄)饮用4-硝基喹啉-1-氧化物(4-NQO，20ppm)8周，然后不处理至32周。处死动物时，取出所有动物的舌头，并进行组织病理学检查。同时检测非皮损区、增生性病变、异常增生性病变和鳞癌等不同舌体病变间质中IL-α、IL-β及肥大细胞和微血管密度。IL-α(pg/mg)非病变区为13.8±4.6pg/mg，非病变区为37.8±7.9pg/mg，鳞癌为45.1±7.7pg/mg，非病变区IL-β为0.81±0.18pg/mg，增生性皮损为1.43±0.48，不典型增生性皮损为3.92±0.59。鳞癌组织中类胰蛋白酶阳性肥大细胞密度(…)为4.62±0.6CD31阳性新生微血管密度(/mm^2)，非病变区18.0±1.8，增生区17.8±4.6，增生区28.4±5.8，鳞癌51.8±7.2。随着舌癌进程的进展，上述各值均显著升高(P&lt；0.05)。这些结果可能提示炎症与舌癌的发生发展有关，尤其是恶变。此外，还提出了肥大细胞密度增加与血管生成的关系。结果提示，癌前病变和癌前病变中动员的炎性肥大细胞重组其间质，以促进血管生成。我们正在利用本实验中获得的样本分析PPAR的表达与血管生成的关系，以期建立一种新的预防舌癌发展的化学预防策略。较少

We conducted an in vivo experiment to clarify certain relation of inflammation and tongue carcinogenesis. Male F344 rats (4 weeks of age) were given 4-nitroquinoline 1-oxide (4-NQO, 20 ppm) in their drinking water for 8 weeks, and then they were untreated up to 32 experimental weeks. At sacrifice, tongues of all animals were removed and histopathologically examined. Also, IL-α, IL-β, and the densities of mast cells and microvessels were assayed in the stroma of various tongue lesions including non-lesional areas, hyperplastic lesions, dysplastic lesions, and squamous cell carcinomas. The measurements are as follows : IL-α (pg/mg), 7.8±1.5 in the non-lesional areas 13.8±4.6 the hyperplastic lesions, 37.8±7.9 in the dysplastic lesion, 45.1±7.7 in the squamous cell carcinomas ; IL-β (pg/mg), 0.81±0.18 in the non-lesional areas 1.43±0.48 in the hyperplastic lesions, 3.92±0.59 in the dysplastic lesions. 4.62±0.61 in the squamous cell carcinomas ; density of the tryptase-positive mast cell ( … More /mm^2), 6.5±1.6 in the non-lesional areas, 9.9±2.0 in the hyperplastic lesions, 18.4±2.0 in the dysplastic lesions, 28.4±5.2 in the squamous cell carcinomas ; density of the CD31-positive neogenesis microvessel (/mm^2), 18.0±1.8 in the non-lesional areas, 17.8±4.6 in the hyperplastic lesions, 28.4±5.8 in the dysplastic lesions, 51.8±7.2 in the squamous cell carcinomas. All the values significantly increased with development of tongue carcinogenesis process (P <0.05). These results may indicate that inflammation was associated with development of tongue carcinogenesis, particularly malignant conversion. In addition, the correlation of the increase in the density of the mast cell and angiogenesis were suggested. In particular, an increase in mast cell density was observed in the front of cancer invasion.Our findings may suggest that inflammatory mast cell mobilized in the preneoplastic lesions and front of the cancer invasion reorganize their stroma in order to promote angiogenesis. We are now analyzing relationship between PPARs' expression and angiogenetic using samples obtained in this experiment in order to establish a novel strategy of chemoprevention against tongue cancer development. Less