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Possibility of GVT effects on oral malignant nepolasms

GVT 对口腔恶性瘤的影响的可能性

基本信息

批准号：
13671977
负责人：
OHNO Jun
金额：
$ 1.73万
依托单位：
Fukuoka Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

The results obtained were divided into three parts ; 1) effects of MCP-1 producing macrophages on the development of local GVH reactions in the oral mucosa, 2) GVT effects on oral melanoma in mice, and 3) biosynthesis of sialic acid on the terminal portion of glycoconjugates can affect effects of GVT against oral melanoma in mice. First, in local GVH reaction of the oral mucosa, macrophages infiltrate into the upper region of lamina propria after an expression of ICAM-1 in epithelial cells. We suggest that MCP-1, produced by macrophages, may be responsible for the chemotactic factor of CTL into surface epithelia of the oral mucosa. Second, GVT effects may depend on degree of systemic GVH reaction. In advanced stages of systemic GVHD, CTL infiltrated directly into nests of melanoma cells (B16 ; C57BL/6-origin), whereas less infiltration of CTL was noted in the early phase. We suggested that GVT effects were induced by immunological pathway of acute oral mucosal GVHD. However, CTL reaction against tumor cells were not specific, because they also attacked oral mucosa, ispecially epithelial cells. Third, the cell surface glycoconjugates of melanoma cells injected were modified during their development in the oral mucosa. We examined histochemically an attachment of sialic acid on the terminal portion of glycoconjugates in melanoma cells. Binding of sialic acid on the cell surface may responsible for susceptibleness of metastasis into submandibular lymph nodes and for difficulties of GVT effects.

结果分为三部分：1)产生MCP-1的巨噬细胞对口腔黏膜局部GVH反应的影响；2)GVT对小鼠口腔黑色素瘤的作用；3)糖结合物末端唾液酸的生物合成影响GVT对小鼠口腔黑色素瘤的作用。首先，在口腔粘膜的局部GVH反应中，巨噬细胞在上皮细胞表达ICAM-1后，渗入固有层上部。我们认为巨噬细胞产生的单核细胞趋化蛋白-1可能与CTL进入口腔粘膜表面上皮细胞的趋化因子有关。其次，GVT效应可能取决于全身GVH反应的程度。在全身性移植物抗宿主病的晚期，CTL直接渗入黑色素瘤细胞巢(B16；C57BL/6来源)，而早期CTL的渗入较少。我们认为GVT效应是通过急性口腔粘膜移植物抗宿主病的免疫途径诱导的。然而，CTL对肿瘤细胞的反应不是特异性的，因为它们也攻击口腔粘膜，特别是上皮细胞。第三，注射的黑色素瘤细胞的细胞表面糖偶联物在口腔粘膜中的发育过程中被修饰。我们用组织化学方法检测了黑色素瘤细胞中唾液酸在糖偶联物末端的附着。唾液酸在细胞表面的结合可能是导致颌下淋巴结转移的易感性和GVT效应困难的原因。