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

通过抑制口腔癌细胞增殖和侵袭来开发有效疗法

基本信息

批准号：
16390598
负责人：
FUKUDA Masakatsu
金额：
$ 7.42万
依托单位：
Meikai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390598/
关键词：
oral cancer CYLD NF-κB gene alteration NCAM apoptosis perineural invasion adenoid cystic carcinoma 頭頚部悪性腫瘍 NF-kB

项目摘要

(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

(1)活检标本取自口腔颌面科治疗的17例ACC患者。明海大学外科医院，日本。 17例ACC中，12例（70.6%）癌细胞细胞膜上观察到MAb NCAM阳性反应。免疫组化结果表明，NCAM免疫反应性在ACC组织的筛状和导管样结构中零星和/或聚集性存在，尤其是神经周围浸润性癌细胞。虽然NCAM的表达与临床病理变量之间没有发现显着的相关性，但NCAM可能与ACC肿瘤的发生显着相关。(2)CYLD和NF-κB在HSG细胞中自发表达，并且在TNF-α的刺激下两者均表达增加。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。 4 小时时观察到最大 NF-κB 依赖性转录。从刺激后4 h开始，HSG细胞中的荧光素酶活性在对10^<-4>M西咪替丁的反应中呈时间依赖性下降。(3)西咪替丁以剂量依赖性方式抑制HSG细胞与神经细胞的粘附。(4)经皮接种HSG(1×10^6个细胞)给小鼠。 (5)17例ACC中,10例(58.8%)在癌细胞膜和细胞质中清晰可见CYLD,12例(70.6%)在细胞质中可见RelA。 13例（76.5%）在细胞核内观察到IκBα。 14例（82.4%）癌细胞胞质中强烈观察到IKKα，4例（4例）细胞质中弱观察到IKKβ。在无法检测到 CYLD 的 ACC 病例中，CYLD 可能功能失调，或者尽管有 CYLD 表达，但 NF-κB 仍被激活。截至目前，虽然已完成10例ACC的CYLD基因变异分析，但未发现任何变异。这些发现表明，给予西咪替丁可以通过下调 NCAM 表达以及诱导细胞凋亡来阻断唾液腺肿瘤细胞的生长、发育和神经周围/神经侵袭。较少的

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A case of basal cell adenoma in the parotid gland.

腮腺基底细胞腺瘤一例。

DOI：
发表时间：
2005
期刊：
Jpn J Oral and Maxillofac. Surg. 51 (7)
影响因子：
0
作者：
Terayama;Norie;Fukuda M;南弘子;Fukuda M. et al.;Minami H. et al.;Fukuda M;Fukuda M;Fukuda M;Fukuda M;Fukuda M. et al.;Fukuda M. et al.;Fukuda M. et al.;Fukuda M;Fukuda M;Fukuda M. et al.;Shida H. et al.
通讯作者：
Shida H. et al.

A Patient with Multiple Primary Carcinomas, Including 4 Separate Oral Cancers : Study of p53 Mutations and their Implications for Management.

患有多种原发癌（包括 4 种单独的口腔癌）的患者：p53 突变及其对治疗的影响的研究。

DOI：
发表时间：
2005
期刊：
J Oral Maxillofac Surg (In press)
影响因子：
0
作者：
Terayama;Norie;Fukuda M;南弘子;Fukuda M. et al.;Minami H. et al.;Fukuda M;Fukuda M;Fukuda M;Fukuda M;Fukuda M. et al.;Fukuda M. et al.;Fukuda M. et al.;Fukuda M;Fukuda M;Fukuda M. et al.;Shida H. et al.;Tanaka S. et al.;Kaoru K. et al.;Fukuda M;Fukuda M;志田裕子;Fukuda M
通讯作者：
Fukuda M

唾液腺悪性腫瘍の増殖・進展メカニズムに関する研究-cimetidineの及ぼす影響について-

唾液腺恶性肿瘤生长发育机制研究-关于西咪替丁的作用-

DOI：
发表时间：
2007
期刊：
日本口腔科学会雑誌 (印刷中)
影响因子：
0
作者：
Terayama;Norie;Fukuda M;南弘子
通讯作者：
南弘子

Expression of RCA SI and its function in salivary gland tumor cells and adenoid cystic carcinomas.

RCA SI在唾液腺肿瘤细胞和腺样囊性癌中的表达及其功能。

DOI：
发表时间：
2005
期刊：
Jpn J Oral and Maxillofac. Surg. 51 (1)
影响因子：
0
作者：
Terayama;Norie;Fukuda M;南弘子;Fukuda M. et al.;Minami H. et al.;Fukuda M;Fukuda M;Fukuda M;Fukuda M;Fukuda M. et al.;Fukuda M. et al.;Fukuda M. et al.;Fukuda M;Fukuda M;Fukuda M. et al.;Shida H. et al.;Tanaka S. et al.
通讯作者：
Tanaka S. et al.

Expression of RCASI and its function in human squamous cell carcinoma of the oral cavity.

RCASI在人口腔鳞状细胞癌中的表达及其功能

DOI：
发表时间：
2004
期刊：
Oncol Rep. 12
影响因子：
0
作者：
Terayama;Norie;Fukuda M;南弘子;Fukuda M. et al.;Minami H. et al.;Fukuda M;Fukuda M;Fukuda M;Fukuda M;Fukuda M. et al.;Fukuda M. et al.;Fukuda M. et al.;Fukuda M;Fukuda M;Fukuda M. et al.;Shida H. et al.;Tanaka S. et al.;Kaoru K. et al.;Fukuda M;Fukuda M;志田裕子;Fukuda M;Kaoru K;Fukuda M. et al.
通讯作者：
Fukuda M. et al.