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）在其饮用水中给予4-硝基喹啉1-氧化物（4-NQO，20 ppm）8周，然后在32个实验周内不进行处理。处死时，取出所有动物的舌头并进行组织病理学检查。此外，IL-α、IL-β以及肥大细胞和微血管密度在各种舌病变包括非病变区、增生性病变、不典型增生性病变和鳞状细胞癌的间质中进行测定。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37.8±7.9，鳞癌45.1±7.7; IL-β（pg/mg），非病变区0.81±0.18，增生性病变1.43±0.48，不典型增生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（ ...更多信息 /mm ~ 2），非病变区6.5±1.6，增生性病变9.9±2.0，不典型增生性病变18.4±2.0，鳞癌28.4±5.2; CD 31阳性新生微血管密度（/mm^2），非病变区为18.0±1.8，增生病变区为17.8±4.6，不典型增生为28.4±5.8，鳞癌为51.8±7.2。随着舌癌变进程的进行，上述各值均显著增高（P <0.05）。这些结果可能表明，炎症与舌癌的发展，特别是恶变。此外，肥大细胞密度的增加与血管生成的相关性被提出。特别是在癌前浸润区肥大细胞密度增加，提示癌前病变和癌前浸润区的炎性肥大细胞通过重组间质促进血管生成。我们正在分析PPARs的表达与血管生成的关系，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