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

为了阐明炎症与舌癌发生的一定关系，我们进行了体内实验。4周龄雄性F344大鼠在饮水中添加4-硝基喹啉1-氧化物（4- nqo, 20 ppm） 8周后，不给药至32周。在献祭时，所有动物的舌头都被切除并进行组织病理学检查。此外，我们还检测了各种舌病变（包括非病变区、增生病变、发育不良病变和鳞状细胞癌）间质中IL-α、IL-β、肥大细胞和微血管的密度。测量结果如下：IL-α (pg/mg)，非病变区为7.8±1.5，增生区为13.8±4.6，发育不良区为37.8±7.9，鳞状细胞癌为45.1±7.7；IL-β (pg/mg)，非病变区为0.81±0.18，增生区为1.43±0.48，发育不良区为3.92±0.59。鳞状细胞癌为4.62±0.61；胰蛋白酶阳性肥大细胞密度（…More /mm^2），非病变区为6.5±1.6，增生性病变为9.9±2.0，发育不良病变为18.4±2.0，鳞状细胞癌为28.4±5.2；cd31阳性新生微血管密度（/mm^2），非病变区18.0±1.8，增生性病变区17.8±4.6，发育不良区28.4±5.8，鳞状细胞癌区51.8±7.2。随着舌癌进程的发展，各项指标均显著升高（P <0.05）。这些结果可能表明炎症与舌癌的发生，特别是恶性转化有关。此外，肥大细胞密度的增加与血管生成也存在相关性。特别是，肥大细胞密度的增加被观察到在癌症侵袭前。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。我们正在利用本实验获得的样本分析PPARs表达与血管生成之间的关系，以建立一种新的化学预防舌癌发展的策略。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