Trial of novel thermo-gene therapy for malignant brain tumors-Aiming for enhancement of hyperthermia using p53 introduction-
恶性脑肿瘤新型热基因疗法的试验-利用p53导入增强热疗效果-
基本信息
- 批准号:15390430
- 负责人:
- 金额:$ 9.02万
- 依托单位:
- 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 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We evaluated combination effect of p53 introduction and hyperthermia on malignant glioma cells. Cell lines used are U251-MG, U373-MG (mutant p53), and D54, U87-MG (wild-type p53). 1)First, optimal MOl of Ad/p53 vector was determined. 2)Heat shock was applied at 43℃ for 2h using liquid incubator. 3)In in vitro experiment, additive effect of both treatments was observed in all the cell lines used. 4)In cell cycle analysis, no change of distribution was observed by heat shock alone in either U373-MG or D54 cells. However, there was an increase in both sub-G1 and G1 by p53 introduction alone. The effect of combination treatment was similar to that of p53 introduction alone. 5)In DNA fragmentation assay, apoptosis was induced by p53 introduction alone but not by heat shock alone. Higher percentage of apoptosis was induced by the combination treatment, which was likely to be caused by heat shock. This enhancing effect by heat shock was observed regardless of p53 status of tumor cells. 6)Apoptosis induction was caspase-dependent in U373-MG and U251-MG cells, but was caspase-independent in D54 cells. 7)p21 protein was over-expressed only after p53 introduction. 8)As in vivo experiment, we established U373-MG subcutaneous tumor model using nude mice. 9)Treatments were given to the following four groups. A)control-vector(CTR) and 37℃ heat shock(HS), b)CTR and 43℃ HS, c)p53-vector(p53V) and 37℃ HS, d)p53V and 43℃ HS. Results showed that no significant inhibitory effect on tumor growth was observed in groups (b),(c),and (d)compared with control-group (a).For future experiments, to achieve more efficient hyperthermia, A)repeating of heat shock, and B)heating with needle electrode, should be considered. Regarding gene transfer, C)gene expression under the control of tetracycline, and D) use of liposome with higher transfer efficiency, should be also be considered.
我们评估了p53导入和热疗对恶性胶质瘤细胞的联合作用。使用的细胞系是U251-MG、U373-MG(突变型p53)和D54、U87-MG(野生型p53)。1)首先,确定Ad/p53载体的最佳MOl。2)使用液体培养箱在43℃下施加热休克2 h。3)在体外实验中,两种处理对所用细胞系均表现出相加效应。4)细胞周期分析中,单独热休克对U373-MG和D54细胞的分布无明显影响。然而,单独引入p53,亚G1和G1均增加。联合治疗的效果与单独导入p53的效果相似。5)在DNA片段化实验中,单独导入p53可诱导细胞凋亡,而单独热休克则不能诱导细胞凋亡。联合处理可诱导较高比例的细胞凋亡,这可能是热休克所致。无论肿瘤细胞的p53状态如何,都观察到热休克的这种增强作用。6)U373-MG和U251-MG细胞的凋亡诱导依赖于caspase,而D54细胞的凋亡诱导不依赖于caspase。7)p53基因导入后p21蛋白表达增加。8)作为体内实验,我们建立了U373-MG裸鼠皮下移植瘤模型。9)治疗分为以下四组。A)对照载体(CTR)和37℃热休克(HS),B)CTR和43℃ HS,c)p53载体(p53 V)和37℃ HS,d)p53 V和43℃ HS。结果表明,与对照组(a)相比,(B)、(c)、(d)组对肿瘤生长无明显抑制作用,为进一步提高热疗效果,应考虑采用热休克重复和针电极加热。关于基因转移,还应考虑C)四环素控制下的基因表达,以及D)使用具有更高转移效率的脂质体。
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Komata T: "Mild heat shock induces autophagic growth arrest, but not apoptosis in U251-MG and U87-MU human malignant glioma cells"J Neuro-Oncol. (in press).
Komata T:“轻度热休克会诱导 U251-MG 和 U87-MU 人类恶性神经胶质瘤细胞自噬生长停滞,但不会导致细胞凋亡”J Neuro-Oncol。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8-dependent but not caspase-9-dependent apoptosis in human malignant glioma cells
组蛋白脱乙酰酶抑制剂 N-丁酸和曲古抑菌素 A 可诱导人恶性胶质瘤细胞中 caspase-8 依赖性而非 caspase-9 依赖性细胞凋亡
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:Nakagawa A;Sato J;Hirano T;Ohki T;Saito T;Takayama K;Tominaga T.;Komata T
- 通讯作者:Komata T
Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8-dependent but not caspase-9-dependent apoptosis in human malignant glioma cells.
组蛋白脱乙酰酶抑制剂 N-丁酸和曲古抑菌素 A 可诱导人恶性胶质瘤细胞中 caspase-8 依赖性细胞凋亡,但不诱导 caspase-9 依赖性细胞凋亡。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:Nishimura M;et al.;Tanaka T;Komata T
- 通讯作者:Komata T
田中 隆一: "脳腫瘍の温熱治療-最近の進歩"Annual Review 神経 2003. 163-168 (2003)
Ryuichi Tanaka:“脑肿瘤的热治疗 - 最新进展”年度神经病学评论 2003. 163-168 (2003)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Mild heat shock induces autophagic growth arrest, but not apoptosis in U251-MG and U87-MG human malignant glioma cells
- DOI:10.1023/b:neon.0000027739.33842.6c
- 发表时间:2004-06-01
- 期刊:
- 影响因子:3.9
- 作者:Komata, T;Kanzawa, T;Tanaka, R
- 通讯作者:Tanaka, R
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TANAKA Ryuichi其他文献
TANAKA Ryuichi的其他文献
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{{ truncateString('TANAKA Ryuichi', 18)}}的其他基金
On the Relationship between Human Resource Allocation and Macroeconomic Productivity : An Educational Economic Approach
论人力资源配置与宏观经济生产率的关系:一种教育经济学方法
- 批准号:
20730128 - 财政年份:2008
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Investigation of noninvasive heating system using re-entrant type applicator for malignant brain tumor
使用可再入式涂抹器的无创加热系统治疗恶性脑肿瘤的研究
- 批准号:
13557115 - 财政年份:2001
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel heat-induced cytokine gene therapy against malignant gliomas
针对恶性胶质瘤的新型热诱导细胞因子基因疗法的开发
- 批准号:
12470286 - 财政年份:2000
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
A new chemothermotherapy focusing to the tumor invading zone of malignant glioma by thermosensitive liposome
热敏脂质体针对恶性胶质瘤肿瘤侵袭区的新型化疗
- 批准号:
09557115 - 财政年份:1997
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
DEVELOPMENT OF COMPUTER TEMPERATURESIMULATION FOR RFINETRSTITIAL HYPERTHERMIA
射频热疗计算机温度模拟的研制
- 批准号:
08457358 - 财政年份:1996
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
New chemo-thermotherapy for malignant brain tumor using 40゚CC thermosensitive liposome
40゚CC热敏脂质体治疗恶性脑肿瘤的新型化疗热疗法
- 批准号:
08557081 - 财政年份:1996
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Development of RF interstitial capacitive hyperthermic system for malignant brain tumor.
恶性脑肿瘤射频间质电容热疗系统的研制。
- 批准号:
06557077 - 财政年份:1994
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
Targeting thermo-chemotherapy for malignant brain tumor using thermosensitive liposome and local hyperthermia
使用热敏脂质体和局部热疗进行恶性脑肿瘤的靶向热化疗
- 批准号:
05454394 - 财政年份:1993
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
IMMUNOLOGICAL ANALYSIS OF THE RATS WITH ANTERIOR HYPOTHALAMIC LESIONS
下丘脑前部病变大鼠的免疫学分析
- 批准号:
02454335 - 财政年份:1990
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
CULTURE OF CEREBRAL MICROVASCULAR ENDOTHELIAL CELL AND APPLICATION FOR THE ANALYSIS OF THE CEREBRAL ISCHEMIA
脑微血管内皮细胞的培养及其在脑缺血分析中的应用
- 批准号:
63480326 - 财政年份:1988
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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将创新的分子佐剂方法与新型腺病毒载体递送相结合以产生通用流感疫苗
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