Development of a novel combined chemotherapy in head and neck cancer-combination of a DNA demethylating agent and an anticancer agent-

开发头颈癌新型联合化疗——DNA去甲基化剂和抗癌剂的组合——

基本信息

批准号：
15390617
负责人：
AZUMA Masayuki
金额：
$ 8.13万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

1.Cisplatin treatment affected neither NF-κB activity nor the expression levels of antiapoptotic proteins, including TRAF-1,TRAF-2, and cFLIP, in oral cancer cells. However, two apoptosome molecules, cytochrome c and Apaf-1, were significantly augmented in the cytoplasm by cisplatin treatment. Thus, cisplatin exerts its apoptotic action by the mitochondria-mediated activation of caspases but not by the activation of caspases due to the inhibition of NF-κB activity.2.Introduction into human oral squamous carcinoma cells of a super-repressor form of IκB-α cDNA causes a drastic decrease in tumorigenicity in nude mice due to down-regulation of the expression of IL-1α,IL-6,IL-8,VEGF, and MMP-9.3.Irradiation- and 5-FU-induced production of IL-6 and IL-8 was significantly suppressed in IκB-α cDNA-transfected cell clones, leading to a marked inhibition of the tumorigenic ability in IκB-α cDNA-transfectedcell clones as compared to that in parental cellc or empty vector-transfected cell clones.4.Cepharanthin suppressed the NF-κB activity in oral squamous carcinoma cells and concomitantly enhanced radiosensitization in vitro and in vivo, therefore, leading to the possibility that combination of radiotherapy with cepharanthin could lead to the enhancement of radiosensitization in the treatment of oral cancer.5.Immortalized normal human salivary gland ductal cells, expressing aquaporin (AQP)-3 but not AQP5, acquired the ability to express AQP-5 and secrete fluid in response 5-aza-2'-deoxycytidine. Demethylation at CG sites, both in the second consensus Sp1-binding site and outside of the third consensus Sp1-binding site of the AQP-5 promoter region, directly activated the transcription of the AQP-5 gene in ductal cells.

1. cIsplatin治疗既不影响NF-κB活性，也没有影响口腔癌细胞中抗凋亡蛋白的表达水平，包括TRAF-1，TRAF-2和CFLIP。然而，通过顺铂处理，在细胞质中显着增强了两个细胞色素C和APAF-1。这是，顺铂通过线粒体介导的胱天蛋白酶激活的激活来发挥其凋亡作用，而不是由于NF-κB活性的抑制而引起的胱天蛋白酶的激活。2。对人类口腔鳞状癌细胞的侵蚀，导致IMB-αcdna的超级抑制作用导致thamorigy prrection prone的人性化形式的人性化形式，从而导致thyorigy pression persional perrrece persional perrrecienty perrreg降低。 IL-1α，IL-6，IL-8，VEGF和MMP-9.3.3.3.3.irradiation-和5-Fu诱导的IL-6和IL-8的产生在IκB-αcDNA转染的细胞克隆中被显着抑制载体转染的细胞克隆。4。头头霉素抑制口腔鳞状癌细胞中NF-κB活性，并抑制体内和体内的放射敏感性增强，因此导致了放射治疗与头脑植物中放射疗法的结合的可能性，可能会导致肾小球术中的肾小球疗法的治疗癌症。表达水通道蛋白（AQP）-3但非AQP5的细胞获得了表达AQP-5和秘密流体以响应5-aza-2'-脱氧胞丁胺的能力。在第二个共识SP1结合位点和AQP-5启动子区域的第三共识SP1结合位点外，CG位点的去甲基化直接激活了导管细胞中AQP-5基因的转录。

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）

Masayuki Azuma: "Potentiation of induction of apoptosis by sequential treatment with cisplatin followed by 5-fluorouracil in human oral cancer cells"Int J Oncol. (in press).

Masayuki Azuma：“在人口腔癌细胞中顺铂和 5-氟尿嘧啶连续治疗可增强细胞凋亡的诱导作用”Int J Oncol。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Enhanced radiosensitization and chemosensitization in NF-кB-suppressed human oral cancer via the inhibition of γ-irradiation-and 5-FU-indued production of IL-6 and IL-8.

通过抑制 γ 辐射和 5-FU 诱导的 IL-6 和 IL-8 产生，增强 NF-кB 抑制的人类口腔癌的放射增敏和化学增敏。

DOI：
发表时间：
2004
期刊：
International Journal of Cancer 108・6
影响因子：
0
作者：
Susumu Hashitani;et al.;Masayuki Azuma;Katsumi Motegi;Katsumi Motegi;Katsumi Motegi;玉谷哲也;東雅之;玉谷哲也;Katsumi Motegi;Tetsuya Tamatani
通讯作者：
Tetsuya Tamatani

Therapy of patients with oral cancer based on the regulation of a transcription factor, NF-κB

基于转录因子 NF-κB 调节的口腔癌患者治疗

DOI：
发表时间：
2003
期刊：
Head and Neck Cancer 29(1)
影响因子：
0
作者：
Susumu Hashitani;et al.;Masayuki Azuma;Katsumi Motegi;Katsumi Motegi;Katsumi Motegi;玉谷哲也;東雅之;玉谷哲也;Katsumi Motegi;Tetsuya Tamatani;Masayuki Azuma;Yrjo Konttinen;Tetsuya Tamatani;Masayuki Azuma;Yrjo Konttinen;Tetsuya Tamatani;Yrjo T Konttinen;東雅之;Masayuki Azuma;東雅之;Masayuki Azuma;Masayuki Azuma
通讯作者：
Masayuki Azuma

転写因子NF-кBの制御に基づいた口腔癌治療

基于转录因子NF-кB调控的口腔癌治疗

DOI：
发表时间：
2003
期刊：
頭頸部腫瘍 29・1
影响因子：
0
作者：
Susumu Hashitani;et al.;Masayuki Azuma;Katsumi Motegi;Katsumi Motegi;Katsumi Motegi;玉谷哲也;東雅之;玉谷哲也;Katsumi Motegi;Tetsuya Tamatani;Masayuki Azuma;Yrjo Konttinen;Tetsuya Tamatani;Masayuki Azuma;Yrjo Konttinen;Tetsuya Tamatani;Yrjo T Konttinen;東雅之;Masayuki Azuma;東雅之
通讯作者：
東雅之

Tetsuya Tamatani: "Enhanced radiosensitization and chemosensitization in NF-κB-suppressed human oral cancer cells via the inhibition of γ-irradiation-and 5-FU-induced production of IL-6 and IL-8"Int J Cancer. 108(6). 912-921 (2004)

Tetsuya Tamatani：“通过抑制 γ 照射和 5-FU 诱导的 IL-6 和 IL-8 产生，增强 NF-κB 抑制的人类口腔癌细胞的放射增敏和化学增敏”Int J Cancer 108(6)。 .912-921 (2004)