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来阐明炎症与舌癌发生的某些关系。雄性 F344 大鼠（4 周龄）在饮用水中添加 4-硝基喹啉 1-氧化物（4-NQO，20 ppm）8 周，然后在 32 实验周内不进行任何处理。处死时，取出所有动物的舌头并进行组织病理学检查。此外，还检测了各种舌病变（包括非病变区、增生性病变、不典型增生病变和鳞状细胞癌）的基质中的IL-α、IL-β以及肥大细胞和微血管的密度。测量结果如下：IL-α(pg/mg)，非病变区7.8±1.5，增生性病变13.8±4.6，不典型增生病变37.8±7.9，鳞状细胞癌45.1±7.7； IL-β(pg/mg)，非病变区域为0.81±0.18，增生病变区域为1.43±0.48，异常增生病变区域为3.92±0.59。鳞状细胞癌4.62±0.61；类胰蛋白酶阳性肥大细胞密度（… More /mm^2），非病变区6.5±1.6，增生性病变9.9±2.0，不典型增生病变18.4±2.0，鳞状细胞癌28.4±5.2； CD31阳性新生微血管密度(/mm^2)，非病灶区为18.0±1.8，增生病灶为17.8±4.6，不典型增生病灶为28.4±5.8，鳞状细胞癌为51.8±7.2。各值均随舌癌变过程的进展而显着升高（P<0.05）。这些结果可能表明炎症与舌癌的发生有关，特别是恶性转化。此外，还提出了肥大细胞密度的增加与血管生成的相关性。特别是，在癌症侵袭前观察到肥大细胞密度增加。我们的研究结果可能表明，在肿瘤前病变和癌症侵袭前动员的炎性肥大细胞重组其基质以促进血管生成。我们现在正在使用本实验中获得的样本分析PPARs的表达与血管生成之间的关系，以建立针对舌癌发展的化学预防的新策略。较少的

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