Selection of drucrs against ovarian cancer and trial of discovering new molecular targets using gene expression profiles
卵巢癌药物的选择和利用基因表达谱发现新分子靶点的试验
基本信息
- 批准号:13671690
- 负责人:
- 金额:$ 1.15万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To clarify genes that play critical roles for carcinogenesis steps and acquisition of drug resistance of ovarian cancer, we studies approximately 6,000 gene expressions using an oligonucleotide microarray system. Gene expression patterns were analyzed by clustering technique, which standardized the gene expression level in normal ovarian tissues. With written informed consent, ovarian cancer tissues from surgical specimens were frozen at-80 C and mRNA was extracted from the tissues. Clustered gene expression profiles of ovarian cancer tissues were clearly different from those of normal tissues. However. there were no significant differences among each histological subtype of cancers. The expression levels of 97 genes were commonly up-regulated in cancer tissues and those of 227 genes were down-regulated. Among these genes, cytokeratin18, Am-1=Evil, HER3, keratin19, ear-2, βtubulin, GSTπ, c-erb-B2, nm23, BRCA2, p57, IGFBP5.6, Brush-1 and TGFB1BP were thought to become a molecular target … More of developng new anti-cancer drugs. One of highly effective drugs against ovarian cancer, paclitaxel, acts as a mitotic spindle poison, i.e., paclitaxel promotes assembly of tubulins and stabilizes them, preventing depolymerization. Our results that βtsubulin was up-regulated in all cancer specimens gave a theoretical evidence to the application of paclitaxel against ovarian cancer treatment. Then, we studied gene expression profiles of human ovarian cancer cell, KF28, Drug-resistant subclones of KF2B were prepared, KFr13, which is resistant to cis-platinum and, KF28TX and KFr13TX, which are resistant to paclitaxel. The cis-platinum-resistant clone showed the high expression of genes related with depoisoning pathway through glutathione, with glycolysis/ glycogenesis, with transketolase and with polyamine synthesis enzymes. The paclitaxel-resistant clones highly expressed multiple drug resistant genes, MDR and semaphorinE, etc. Comparison of clinical factors with expression levels of genes identified in this study will help to develop new molecular target drugs and to clarify mechanism of the acquisition of drug resistance. Less
为了阐明在卵巢癌的致癌步骤和获得耐药性中起关键作用的基因,我们使用寡核苷酸微阵列系统研究了大约6,000个基因的表达。采用聚类分析技术分析基因表达模式,标准化正常卵巢组织中的基因表达水平。在书面知情同意的情况下,将来自手术标本的卵巢癌组织冷冻在-80 ℃,并从组织中提取mRNA。卵巢癌组织与正常卵巢组织的基因表达谱明显不同。然而.各组织学亚型之间无显著差异。97个基因在癌组织中普遍表达上调,227个基因表达下调。在这些基因中,细胞角蛋白18、Am-1=Evil、HER 3、keratin 19、ear-2、βtubulin、GSTπ、c-erb-B2、nm 23、BRCA 2、p57、IGFBP5.6、Brush-1和TGFB 1BP被认为是分子靶点 ...更多信息 开发新的抗癌药物。紫杉醇是抗卵巢癌的高效药物之一,其作为有丝分裂纺锤体毒物,即,紫杉醇促进微管蛋白的组装并稳定它们,防止解聚。β-tsubulin在卵巢癌组织中表达上调的结果为紫杉醇治疗卵巢癌提供了理论依据。然后,我们研究了人卵巢癌细胞KF 28的基因表达谱,制备了KF 2B的耐药亚克隆KFr 13(对顺铂耐药)和KF 28 TX和KFr 13 TX(对紫杉醇耐药)。顺铂抗性克隆显示与谷胱甘肽解毒途径、糖酵解/糖原生成、转酮醇酶和多胺合成酶相关的基因高表达。紫杉醇耐药克隆高表达MDR和semaphorinE等多个耐药基因。比较临床因素与本研究中鉴定的基因表达水平,将有助于开发新的分子靶向药物,并阐明耐药获得的机制。少
项目成果
期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Murakami T., Terada Y., Sugawara J., Yaegashi N., Okamura K.: "The current status of gynecological laparoscopic surgery in educational facilities in Japan."Tohoku Journal of Experimental Medicine. 193. 175-180 (2001)
Murakami T.、Terada Y.、Sukawara J.、Yaeashi N.、Okamura K.:“日本教育机构中妇科腹腔镜手术的现状。”东北实验医学杂志。
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Yokomizo R, Matsuzaki S, Uehara S, Murakami T, Yaegashi N, Okamura K.: "Erythropoietin and erythropoietin receptor expresiion in human endometrium throughout the menstrual cyst"Molecular Human Reproduction. 8. 441-446 (2002)
Yokomizo R、Matsuzaki S、Uehara S、Murakami T、Yaegashi N、Okamura K.:“整个月经囊肿中人类子宫内膜中促红细胞生成素和促红细胞生成素受体的表达”人类分子生殖。
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Akahira J., Suzuki T., Ito K., Kaneko C., Darnel AD., Moriya T., Okamura K., Yaegashi N., Sasano H.: "Differential expression of progesteron receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors."Japanese J
Akahira J.、Suzuki T.、Ito K.、Kaneko C.、Darnel AD.、Moriya T.、Okamura K.、Yaegashi N.、Sasano H.:“正常卵巢中孕激素受体亚型 A 和 B 的差异表达
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- 影响因子:0
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Akahira J, Suzuki T, Ito K, Kaneko C, Darnet AD, Moriya T, Okamura K, Yaegashi N, Sasano H.: "Differential expression of progesteron receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors"Japanese Journal of
Akahira J、Suzuki T、Ito K、Kaneko C、Darnet AD、Moriya T、Okamura K、Yaegashi N、Sasano H.:“孕激素受体亚型 A 和 B 在正常卵巢以及良性、交界性和恶性卵巢中的差异表达
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Ito K., Suzuki T., Akahira J., Moriya T., Kaneko C., Utsunomiya H., Yaegashi N., Okamura K., Sasano H.: "Expression of androgen receptor and 5a-reductases in the human normal endometrium and its disorders."International Journal of Cancer. 99. 652-657 (200
Ito K.、Suzuki T.、Akahira J.、Moriya T.、Kaneko C.、Utsunomiya H.、Yaeashi N.、Okamura K.、Sasano H.:“人类正常子宫内膜中雄激素受体和 5a-还原酶的表达
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YAEGASHI Nobuo其他文献
YAEGASHI Nobuo的其他文献
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{{ truncateString('YAEGASHI Nobuo', 18)}}的其他基金
Comprehensive genomic and transcriptome analyses to clarify molecular mechanisms contributing to chemoresistance in gynecologic cancer
全面的基因组和转录组分析,以阐明导致妇科癌症化疗耐药的分子机制
- 批准号:
19H03795 - 财政年份:2019
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Integrated analysis of circulating tumor cells and DNA toward clinical application of liquid biopsy.
循环肿瘤细胞和 DNA 的综合分析,用于液体活检的临床应用。
- 批准号:
16K15697 - 财政年份:2016
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Clarification of genetic factors of endometriosis onset using Japanese standard genome reference and Japonica array
使用日本标准基因组参考和 Japonica 芯片阐明子宫内膜异位症发病的遗传因素
- 批准号:
15H04978 - 财政年份:2015
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Pathological examination of tubal fimbria and blood circulating DNA measurement toward the ultra-early detection of fallopian tubal cancer
输卵管伞病理检查及血循环DNA检测超早期发现输卵管癌
- 批准号:
26670710 - 财政年份:2014
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
The therapeutic strategy toward overcoming drug resistance of gynecologic cancers utilizing high throughput screening.
利用高通量筛选克服妇科癌症耐药性的治疗策略。
- 批准号:
24390375 - 财政年份:2012
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The regulatory factor to aberrant epigenetic state in ovarian cancer and target molecule.
卵巢癌表观遗传异常状态的调控因子及靶分子。
- 批准号:
23659769 - 财政年份:2011
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
A fundamental research for developing ubiquitin-targeted cancer therapies utilizing vesicular transport related molecules Hrs knocked-out mice.
利用囊泡运输相关分子 Hrs 基因敲除小鼠开发泛素靶向癌症疗法的基础研究。
- 批准号:
20390428 - 财政年份:2008
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel mass-screening methods by three-dimension microarray for endometrial cancer
子宫内膜癌三维微阵列大规模筛查新方法的开发
- 批准号:
17390444 - 财政年份:2005
- 资助金额:
$ 1.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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