The development of effective therapy by the inhibition of cell proliferation and invasion in oral cancer

(1)对17例在口腔颌面内科治疗的ACC患者进行活检。外科医生，日本明治大学医院。17例ACC患者中有12例（70.6%）在癌细胞细胞膜上观察到MAb - NCAM阳性反应。免疫组化结果显示，在ACC组织的筛状和导管样结构中，特别是神经周围浸润性癌细胞中，NCAM的免疫反应性是零星和/或聚集的。虽然NCAM的表达与临床病理变量之间没有明显的相关性，但NCAM可能与ACC的肿瘤发展有显著的相关性。(2)CYLD和NF-κB在HSG细胞中自发表达，且均在TNF-α刺激下升高。虽然西咪替丁抑制了NF-κB和NCAM的表达，但CYLD的表达并未降低。HSG细胞荧光素酶活性在刺激后4 h呈时间依赖性下降，刺激后4 h达到10^<-4>M西咪替丁。(3)西咪替丁抑制HSG细胞对神经细胞的粘附，并呈剂量依赖性。(4)小鼠经皮接种HSG （1 × 10^6个细胞）。西咪替丁抑制HSG肿瘤块的生长呈剂量依赖性。(5) 17例ACC患者中有10例（58.8%）在细胞膜和细胞质中可见CYLD， 12例（70.6%）在细胞质中可见RelA。13例（76.5%）核内可见IκBα。14例（82.4%）癌细胞细胞质中存在IKKα强表达，4例细胞细胞质中存在IKKβ弱表达。在未检测到CYLD的ACC病例中，CYLD可能功能失调，或者尽管CYLD表达，NF-κB仍被激活。到目前为止，虽然完成了10例ACC的CYLD基因改变分析，但未发现任何改变。提示西咪替丁可通过下调NCAM表达和诱导细胞凋亡抑制唾液腺肿瘤细胞的生长发育和周围神经/神经侵袭。少

(1)Biopsy specimens were obtained from 17 patients with ACC treated in the Dept. of Oral and Maxillofac. Surg., Meikai Univ. Hospital, Japan. The positive reaction for MAb NCAM was observed on the cell membrane of cancer cells in 12 of 17 cases of ACC (70.6%). The immunohistochemical findings showed that NCAM immunoreactivity was sporadically and/or aggregately found in the cribriform and duct-like structure, especially perineural invasive cancer cells of ACC tissues. Although no significant association was found between expression of NCAM and clinicopathological variables, NCAM might be significantly associated with tumor development of ACC.(2)CYLD and NF-κB were spontaneously expressed in HSG cells and both were increased by stimulation of TNF-α. Although the expression of NF-κB and NCAM was inhibited by cimetidine, CYLD expression was not decreased. Maximum NF-κB -dependent transcription was observed at 4 h. Luciferase activities in HSG cells were time-dependently decreased in respo … More nse to 10^<-4>M cimetidine from 4 h after stimulation.(3)The adhesion of HSG cells to neural cells was inhibited by cimetidine in a dose-dependent manner.(4)Mice were inoculated with HSG (1 × 10^6 cells) percutaneously. Cimetidine prevented the growth of HSG tumor mass in a dose-dependent manner.(5)CYLD was clearly observed on the membrane and in the cytoplasm of cancer cells in 10 of 17 cases (58.8%) of ACC, whereas RelA was observed in the cytoplasm in 12 cases (70.6%). IκBα was observed in the nucleus in 13 cases (76.5%). IKKα was strongly observed in the cytoplasm of cancer cells in 14 cases (82.4%), and IKKβ was weakly observed in the cytoplasm in 4 cases. CYLD may be dysfunctional in ACC cases where CYLD is not detectable, or that NF-κB is activated despite the expression of CYLD. Up to date, although the analysis of CYLD gene alteration in 10 cases of ACC was finished, there was no alteration. These findings suggest that the growth, development and perineural/neural invasion of salivary gland tumor cells can be blocked by cimetidine administration through down-regulation of NCAM expression as well as by induction of apoptosis. Less