Relation of abnormal expression of cell cycle regulating factor and outcome of patients with COX-2 expression in the progression of oral carcinoma
Relation of abnormal expression of cell cycle regulating factor and outcome of patients with COX-2 expression in the progression of oral carcinoma
批准号:
15592148
负责人:
SAKURAI KAZUNARI
金额:
$2.11万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2005
中文摘要
在对200例口腔鳞癌(OSCC)组织中COX-2的表达与增殖活性的分析中,发现COX-2在早期有转移的病例中,高表达患者预后较差(74%)。此外,COX-2在预后较差的口腔鳞癌患者的侵袭灶顶部极高表达。因此,认为COX-2与口腔鳞癌的侵袭性有关,COX-2的表达可能成为口腔鳞癌患者预后的一个指标。接下来,我们研究了与COX-2表达相关的P53-Rb通路以及细胞周期调节基因群的趋势。其中环氧合酶-2表达阳性45例,其中HPV16型阳性率为78%,COX-2阳性表达阳性率为69%。…时,82例口腔鳞癌中HPV16型阳性,COX-2阳性,18型阳性,Rb各基因预期HPVE6、E7基因表达阳性。更多的是我们表演的。综合上述结果,两例阳性病例均有高水平的TopollαLI表达,Rb蛋白高表达,p21/p53、cyClinB、D1、E高表达,而p27蛋白未见表达。结果表明,在P53-Rb途径中,COX-2过表达的调控基因失效,细胞周期快速推进,并引起口腔鳞癌的增加,但在检测到HPV16/18型COX-2低表达的例子中,我们可能恢复了p27基因的异常,并通过E6、E7基因的参与来规避。口腔鳞癌进展加快,在COX-2过表达的情况下,认为我们通过连接显著表达缺失的p27蛋白参与了恢复期的功能缺陷。另一方面,HPV16/18型的高表达和p27蛋白水平相对稳定,在COX-2低表达的例子中,在有限的范围内阻止了癌症的增加,并提示了保持较好的恢复期的可能性。综上所述,COX-2与多种细胞周期调控基因的异常有关,与口腔鳞癌的侵袭、转移和侵袭有关,并可能与预后因素有关。此外,当我们检测COX-2和LN-5-伽马2时,发现COX-2有多种癌基因异常,并且COX-2和层粘连蛋白-5-伽马2的共同表达,整合素α的表达与肿瘤侵袭和转移的相关性,并考虑了获得侵袭活性和促进转移的可能性。我们希望通过对口腔鳞状细胞癌侵袭转移作用的研究、环氧合酶-2调控因子的鉴定、环氧合酶-2通路的参与等方面的研究,为今后口腔鳞癌的研究奠定基础。较少
英文摘要
In the analysis of COX-2 expression with proliferaive activity in 200 oral squamous carcinoma (OSCC), COX-2 was guided on the occasion of metastasis early, and found that there were poor prognosis in patients in overexpression (74% of high-expression). In addition, COX-2 extremely high expressed in the top of an invasive foci in OSCC patients with poor outcome. Therefore, it was considered that the COX-2 related to tumor invasiveness, and was suggested that the COX-2 expression become a possible indicator in the outcome in patients with OSCC. We investigated p53-Rb pathway related to COX-2 expression and a trend of cell cycle regulator gene group to the subject next. Among of this analysis, HPV16 type was detected to 78%, and HPV18 type to 69% among COX-2 expression 45 examples again by p53 related to COX-2 expression and Brigati labelled in situ hybridization method for HPV16 type in 82 OSCC, COX-2 expression and 18 type about expected HPV-E6,E7 gene expression to each gene of Rb when … More we performed it. As a result of having examined the above generally, linked a high level of Topoll alpha LI in all both positive examples, overexpression of Rb protein, and p21/p53, cyclinB, D1,E overexpression were revealed, but the expression of p27 protein was not shown. As the result, cell cycle rapidly progress by failure of a regulator gene with COX-2 overexpression in a p53-Rb pathway through COX-2 pathway and raised an increase in OSCC than the above, but, in the example that HPV16/18 type was detected with COX-2 underexpression, possibility we restored p27 gene abnormality, and to evade was suggested by participation of an E6, E7 gene. Progress of OSCC accelerated, in COX-2 overexpression, it was considered that we participated in convalescence defectiveness by linking a significant expression lack of p27 protein. On the other hand, overexpression of HPV16/18 type and a p27 protein level were comparatively stable and, in COX-2 underexpression example, stopped an increase of cancer in a limited part, and possibility to keep convalescence comparatively well was suggested. From the above mentioned research results, COX-2 linked abnormality of a regulator gene in various cell cycles and was related to permeation of OSCC and metastasis and invasiveness, and it was thought that it could be it with a prognostic factor. Furthermore, it was recognized, and COX-2 received various oncogene abnormality, and mutual expression of COX-2 and Laminin-5 gamma 2 expression in 73% when we examined COX-2 and laminin-5 gamma 2, relevance of Integrin alpha expression with tumor invasiveness and metastasis, and possibility to acquisition of invasive activity and promotion of metastatic character was thought about. We want to go ahead through investigation about the role of invasiveness and metastasis of OSCC, identification of a COX-2 instruction factor, participation in COX-2 pathway in future. Less
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Apoptosis induction and enhancement of anticancer drugs by celecoxib, a selective cyclooxygenase-2 inhibitor, in human head and neck carcinoma cell lines.
塞来昔布(一种选择性环氧合酶 2 抑制剂)在人头颈癌细胞系中诱导细胞凋亡并增强抗癌药物的作用。
DOI:
--
发表时间:
2003
期刊:
International Journal of Oncology 23
影响因子:
--
作者:
[Hashitani S., Urade M., Nishimura N., Maeda T., Takaoka K., Noguchi K., Sakurai K.]
通讯作者:
Sakurai K.
Prognostic significance of cyclooxygenase-2 and DNA topoisomerase II α expression in head and neck carcinoma.
头颈癌中环氧合酶-2 和 DNA 拓扑异构酶 II α 表达的预后意义。
DOI:
--
发表时间:
期刊:
Head and Neck (in press)
影响因子:
--
作者:
[Sakurai K., Urade M., Noguchi K., Hashitani S., Takaoka K., Segawa E., Kishimoto H.]
通讯作者:
Kishimoto H.
Promotion of cell differentiation, and suppression of cell growth and cyclooxy-genase-2 expression by differentiation inducing agent in human oral squamous carcinoma SCC25 cells.
分化诱导剂促进人口腔鳞癌SCC25细胞的细胞分化、抑制细胞生长和环氧合酶2表达。
DOI:
--
发表时间:
2005
期刊:
International Journal of Oncology 26
影响因子:
--
作者:
[Kuroda J., Urade M., Kishimoto H., Noguchi K., Hashitani S., Sakurai K., Nishimura N., Hashimoto-Tamaoki T.]
通讯作者:
Hashimoto-Tamaoki T.
Increased expression of cyclooxygenase (COX) -2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor.
DMBA 诱导的仓鼠颊囊癌发生中环氧合酶 (COX) -2 表达增加以及选择性 COX-2 抑制剂的化学预防作用。
DOI:
--
发表时间:
2004
期刊:
Journal of Oral Pathology and Medicine 66
影响因子:
--
作者:
[Nishimura N., Urade M., Hashitani S., Noguchi K., Mannno Y., Takaoka K., Sakurai K.]
通讯作者:
Sakurai K.
海外基金