Thyroid Cancer Gene Therapyt with Molecular Targeting by Radio-responsing genes
放射反应基因分子靶向的甲状腺癌基因治疗
基本信息
- 批准号:12470221
- 负责人:
- 金额:$ 8.06万
- 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:2000
- 资助国家:日本
- 起止时间:2000 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Thyroid follicular cell-derived carcinomas are classified pathologically as differentiated (papillary and follicular) and undifferentiated (anaplastic) carcinoma. Although differentiated carcinoma have relatively good prognosis, anaplastic thyroid carcinoma are highly aggressive and extremely lethal, with poor therapeutic response. External beam radiotherapy with chemotherapy would provide the chance for relative long-terrm survival of patients in thyroid anaplastic carcinoma. The discovery of new potent therapy is urgently warranted. A candidate of this strategy is gene therapy that will be selectively cytotoxic or will increase sensitivity to the ionizing radiationo for anaplastic thyroid cancer. To search the cancer-specific targets, we challenged SAGE screening (DNA Sequence 2000) and PCR-based subtraction (BBCR2001). Among the candidate genes that we found, we focused on radio-inducible hSNK gene which is transcriptionally regulated by p53 binding homology element (BBRC 2001). Next we elucidated a signal transduction pathway specifically induced by ionizing radiation in thyroid cells. It involved PKC-delta that mediates ionizing radiation-induced activation of c-Jun kinase through MKK7 (Oncogene 2001). Finally, we have demonstrated the potential gene therapy approachs in experimental model (Cancer Gene Therapy 2001, Human Gene Therapy 2000).
甲状腺滤泡细胞来源的癌在病理学上分为分化(乳头状和滤泡状)和未分化(间变性)癌。分化型甲状腺癌预后较好,但未分化型甲状腺癌侵袭性强、致死率高,治疗效果差。外照射加化疗可为甲状腺未分化癌患者提供相对长期生存的机会。迫切需要发现新的有效疗法。这一策略的一个候选者是基因治疗,它将选择性地具有细胞毒性或将增加对未分化甲状腺癌的电离辐射的敏感性。为了寻找癌症特异性靶点,我们挑战了SAGE筛选(DNA Sequence 2000)和基于PCR的减法(BBCR 2001)。在我们发现的候选基因中,我们集中于受p53结合同源元件转录调控的放射诱导hSNK基因(BBRC 2001)。接下来,我们阐明了电离辐射在甲状腺细胞中特异性诱导的信号转导途径。它涉及通过MKK 7介导电离辐射诱导的c-Jun激酶活化的PKC-δ(Oncogene 2001)。最后,我们在实验模型中展示了潜在的基因治疗方法(Cancer Gene Therapy 2001,Human Gene Therapy 2000)。
项目成果
期刊论文数量(138)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
T. Nakayama, et al: "Expression of the ets-1 proto-oncogene in human colorectal carcinoma"Mod Pathol. 14(5). 415-422 (2001)
T. Nakayama 等人:“人结直肠癌中 ets-1 原癌基因的表达”Mod Pathol。
- DOI:
- 发表时间:
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- 影响因子:0
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- 通讯作者:
Y. Nagayama, et al: "Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53 regulated Cre/loxP system"Cancer Gene Ther. 8. 36-44 (2001)
Y. Nagayama 等人:“利用 p53 调节的 Cre/loxP 系统将腺病毒复制靶向 p53 缺陷型甲状腺癌”Cancer Gene Ther。
- DOI:
- 发表时间:
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- 影响因子:0
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E. Nishihara, et al: "Ontogenetic changes in the expression of estrogen receptor alpha and beta in rat pituitary gland detected by immunohistochemistry"Endocrinology. 141. 615-620 (2000)
E. Nishihara 等人:“通过免疫组织化学检测大鼠垂体中雌激素受体α和β表达的个体发生变化”内分泌学。
- DOI:
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- 影响因子:0
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N.Mitsutake, et al.: "PKC δ mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through Mkk7 in human thyroid cells"Oncogene. 20. 989-996 (2001)
N. Mitsutake 等人:“PKC δ 在人甲状腺细胞中通过 Mkk7 介导电离辐射诱导的 c-Jun NH2 末端激酶的激活”Oncogene。20. 989-996 (2001)
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- 影响因子:0
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V.Braiden, et al.: "Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter"Human Gene Therapy. 11. 2453-2463 (2000)
V.Braiden 等人:“在热休克蛋白启动子的控制下通过高温自杀基因疗法根除乳腺癌异种移植物”人类基因疗法。
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YAMASHITA Shunichi其他文献
YAMASHITA Shunichi的其他文献
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{{ truncateString('YAMASHITA Shunichi', 18)}}的其他基金
Molecular epidemiological study of thyroid cancers by international collaboration
国际合作的甲状腺癌分子流行病学研究
- 批准号:
16H02774 - 财政年份:2016
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Morphological analysis of mitochondria during mitophagy
线粒体自噬过程中线粒体的形态学分析
- 批准号:
15K18501 - 财政年份:2015
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Elucidation of Prognostic Markers and their Molecular Mechanism for Thyroid Cancer
甲状腺癌预后标志物及其分子机制的阐明
- 批准号:
26293222 - 财政年份:2014
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Provocative epidemiological study on identification of factor of thyroid carcinogenesis
甲状腺癌发生因素鉴定的前瞻性流行病学研究
- 批准号:
26670460 - 财政年份:2014
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Molecular Epidemiological Study on Risk of Radiation-associated Cancer after the Chernobyl Nuclear Power Plant accident
切尔诺贝利核电站事故后辐射相关癌症风险的分子流行病学研究
- 批准号:
25257508 - 财政年份:2013
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Large-scale cohort molecular epidemiological study after the Chernobyl accident
切尔诺贝利事故后大规模队列分子流行病学研究
- 批准号:
22256004 - 财政年份:2010
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Elucidation of molecular mechanism on thyroid carcinogenesis anddevelopmental application of molecular targeting therapy
甲状腺癌发生分子机制阐明及分子靶向治疗的发展应用
- 批准号:
22390189 - 财政年份:2010
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Long-term molecular epidemiological studies on thyroid cancers around Chernobyl
切尔诺贝利周围甲状腺癌的长期分子流行病学研究
- 批准号:
19256003 - 财政年份:2007
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Elucidation of thyroid carcinogenesis and clinical application of molecular targeting therapy
甲状腺癌发生机制的阐明及分子靶向治疗的临床应用
- 批准号:
19390253 - 财政年份:2007
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular Epidemiology of Thyroid Diseases around Semiparatinsk, Kazakhstan and Altai region, Russia
哈萨克斯坦塞米帕拉金斯克和俄罗斯阿尔泰地区甲状腺疾病的分子流行病学
- 批准号:
12576020 - 财政年份:2000
- 资助金额:
$ 8.06万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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