The research to establish the orader-made therapy system for hepatocellular carcinoma patients by use of genome-wide microarray database

利用全基因组芯片数据库建立肝癌患者定制治疗体系的研究

基本信息

  • 批准号:
    13357013
  • 负责人:
  • 金额:
    $ 30.45万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
  • 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

项目摘要

Results 1Through a genome-wide cDNA microarray of hepatocellular carcinomas (HCCs), we identified a number of genes associated with tumor progression. Thus, to analyze expression profiles more precisely and to establish a predictive system of intrahepatic recurrence after surgery, we performed second screening of 47 HCCs by TaqMan PCR consisting of 120 genes. Then we divided 47 HCCs into two groups, 25 HCCs are for training and 22 HCCs are blinded sets for validation. We identified 27 genes that associated with intrahepatic recurrence within 1 year after curative resection. A predictive score, based on expression profiles of 15 of the genes, correctly predicted the recurrent status in 16 of 22 HCCs in the blinded sets. A positive predictive value was 75% and negative predictive value was 71.4%. Accumulation of such data will make it possible to define the nature of individual tumors, to provide clues for identifying new therapeutic targets, and ultimately to optimize treatment of each … More patient.Results 2In a previous study, we observed a high frequency of LOH on chromosome 16, which correlated with vascular invasiveness of tumors. We performed deletion mapping of chromosome 16 and then identified SIAHI as a putative tumor suppressor gene for HCC and found a correlation between its suppressed expression and tumor size and differentiation, suggesting an important role of SIAHI in the development of HCC. Through a genome-wide cDNA microarray, we identified that the paternally expressed gene 10 (PEG10) was highly expressed in a great majority of HCCs. Exogenous expression of PEG 10 conferred oncogenic activity and transfection of hepatoma cells with antisense S-oligonucleotides **ppressing PEG10 resulted in their growth inhibition. Additional experiments revealed that PEG10 protein associated with SIAHI and **erexpression of PEG 10 decreased the cell death mediated by SIAH1. These findings suggested that development of drug(s) inhibiting PEG10 activity could be a novel approach for the treatment of HCCs.Results 3We analyzed expression profiles of 20 intestinal type gastric tumors by a cDNA microarray and identified a number of genes that are commonly up-regulated or down-regulated in the cancer tissues. A predictive score, based on expression profiles of 5 genes, correctly diagnosed the lymph node status of 9 additional gastric cancers. It may help clinicians predict metastasis to lymph nodes and assist researchers in understanding molecular changes during the development of intestinal type gastric cancers and identifying novel therapeutic targets for this type of cancer. VEGF-C/D Al VEGFR-3 pathway is said to play an important role in tumor lymphangiogenesis and lymphatic metastasis. We identified that by administrating anti-VEGFR-3 blocking antibodies in murine orthotopic gastric cancer models, regional lymph node metastasis and lymphatic vessel density in the primary tumors are reduced. In addition, increased density of LYVE-1-positive lymphatic vessels of primary tumors was closely correlated with lymph node metastasis in human samples of gastric cancer. Anti-lymphangiogenesis by inhibiting VEGFR-3 signaling could provide a potential strategy for the prevention of lymph node metastasis in gastric cancer. Less
结果1通过全基因组的肝细胞癌基因芯片,我们发现了一些与肿瘤进展相关的基因。因此,为了更准确地分析表达谱并建立术后肝内复发的预测系统,我们用包含120个基因的TaqMan PCR对47例肝癌进行了二次筛查。然后,我们将47个样本分为两组,其中25个样本用于训练,22个样本作为盲集进行验证。我们确定了27个与根治性切除后1年内肝内复发相关的基因。基于15个基因表达谱的预测分数正确地预测了盲组中22个肝癌中的16个的复发状态。阳性预测值为75%,阴性预测值为71.4%。这些数据的积累将使确定单个肿瘤的性质成为可能,为确定新的治疗靶点提供线索,并最终优化每个…的治疗结果2在先前的研究中,我们在16号染色体上观察到了高频率的LOH,它与肿瘤的血管侵袭性相关。我们对16号染色体进行了缺失定位,发现SIAHI是一个可能的肝癌抑癌基因,其表达受抑与肿瘤大小和分化程度有关,提示SIAHI在肝癌的发生发展中起重要作用。通过全基因组的基因芯片,我们发现父系表达的基因10(PEG10)在绝大多数的肝癌细胞中高表达。外源表达的PEG10具有致癌活性,反义S寡核苷酸对肝癌细胞的生长有抑制作用。进一步的实验表明,与SIAHI相关的PEG10蛋白和PEG10的表达可以减少SIAH1介导的细胞死亡。这些结果表明,开发抑制PEG10活性的药物(S)可能是治疗肝癌的一种新途径。结果3利用基因芯片分析了20例肠型胃肿瘤的表达谱,发现了一些在癌组织中普遍上调或下调的基因。基于5个基因表达谱的预测性评分,正确诊断了另外9例胃癌的淋巴状态。它可以帮助临床医生预测淋巴结转移,帮助研究人员了解肠型胃癌发生发展过程中的分子变化,并寻找治疗该类型癌症的新靶点。血管内皮生长因子C/D A1 VEGFR-3通路在肿瘤淋巴管生成和淋巴转移中起重要作用。我们在小鼠原位胃癌模型中发现,通过给予抗VEGFR-3封闭抗体,原发肿瘤的区域淋巴转移和淋巴管密度降低。此外,在人的胃癌标本中,原发肿瘤LYVE-1阳性淋巴管密度的增加与淋巴结转移密切相关。通过抑制VEGFR-3信号通路来抑制淋巴管生成,为预防胃癌的淋巴转移提供了一种潜在的策略。较少

项目成果

期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
  • DOI:
  • 发表时间:
    2003-06
  • 期刊:
  • 影响因子:
    11.2
  • 作者:
    H. Okabe;S. Satoh;Y. Furukawa;Tatsushi Kato;Suguru Hasegawa;Y. Nakajima;Y. Yamaoka;Yusuke Nakamura-Yusuke
  • 通讯作者:
    H. Okabe;S. Satoh;Y. Furukawa;Tatsushi Kato;Suguru Hasegawa;Y. Nakajima;Y. Yamaoka;Yusuke Nakamura-Yusuke
Involvement of PEG10 in Human Hepatocellular Carcinogenesis through Interaction with SIAM.
PEG10 通过与 SIAM 相互作用参与人类肝细胞癌变。
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Okabe H.
  • 通讯作者:
    Okabe H.
松尾 宏一, 佐藤 誠二, 他: "SIAH1 Inactivation Correlates With Tumor Progression in Hepatocellular Carcinomas"GENES, CHROMOSOMES&CANCER. 36. 283-291 (2003)
Koichi Matsuo、Seiji Sato 等人:“SIAH1 失活与肝细胞癌中的肿瘤进展相关”GENES,CHROMOSOMES&CANCER 36. 283-291 (2003)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Suppression of VEGFR‐3 signaling inhibits lymph node metastasis in gastric cancer
  • DOI:
    10.1111/j.1349-7006.2004.tb03211.x
  • 发表时间:
    2004-04
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    K. Shimizu;H. Kubo;K. Yamaguchi;K. Kawashima;Y. Ueda;Koichi Matsuo;M. Awane;Y. Shimahara;
  • 通讯作者:
    K. Shimizu;H. Kubo;K. Yamaguchi;K. Kawashima;Y. Ueda;Koichi Matsuo;M. Awane;Y. Shimahara;
SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas.
SIAH1 失活与肝细胞癌的肿瘤进展相关。
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YAMAOKA Yoshio其他文献

YAMAOKA Yoshio的其他文献

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{{ truncateString('YAMAOKA Yoshio', 18)}}的其他基金

Biological searches for factors interacted with Helicobacter pylori virulence factor OipA
幽门螺杆菌毒力因子 OipA 相互作用因子的生物学搜索
  • 批准号:
    24659200
  • 财政年份:
    2012
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Clarification of mechanisms how H. pylori virulence factor OipA produces cytokines
阐明幽门螺杆菌毒力因子 OipA 产生细胞因子的机制
  • 批准号:
    22390085
  • 财政年份:
    2010
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular Epidemiological Studies using Helicobacter pylori
使用幽门螺杆菌进行分子流行病学研究
  • 批准号:
    22659087
  • 财政年份:
    2010
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Activation of regeneration capacity of the cirrhotic livers based on the molecular and genetic biology
基于分子和遗传生物学的肝硬化肝脏再生能力的激活
  • 批准号:
    11307022
  • 财政年份:
    1999
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Availability of interlrulkin 12 for gene therapy of hepatoma
Interlrulkin 12用于肝癌基因治疗的可用性
  • 批准号:
    09044294
  • 财政年份:
    1997
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Moduration of the molecular chaperone activity to increase the safety of extended liver surgery in the damaged liver patients -- challenge by the induction of stress response and heat shock gene transfection --
调节分子伴侣活性以提高肝损伤患者扩大肝脏手术的安全性——诱导应激反应和热休克基因转染的挑战——
  • 批准号:
    09307026
  • 财政年份:
    1997
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Comparative study of immunological tolerance in the liver transplantation from cadaver and living donor
尸体肝移植与活体肝移植免疫耐受的比较研究
  • 批准号:
    08044278
  • 财政年份:
    1996
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Non-touch isolation hepatectomy and extra-corporeal anticancer therapy for liver tumors-Feedback of surgical technique in living-related partial liver transplantation to liver surgery-
非接触隔离肝切除及肝脏肿瘤体外抗癌治疗-活体部分肝移植手术技术对肝脏手术的反馈-
  • 批准号:
    07407035
  • 财政年份:
    1995
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Comperative study in the viability of the liver graft harvested from cadaver and living donor, evaluated by assessment of tissue oxygenation in sinusoid and oxidation of hepatocyte
通过评估肝窦组织氧合和肝细胞氧化来评估从尸体和活体供体中获取的肝移植物的活力的比较研究
  • 批准号:
    06044127
  • 财政年份:
    1994
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Perioperative management in clinical liver traus plantation
临床肝外伤种植术的围手术期处理
  • 批准号:
    04044098
  • 财政年份:
    1992
  • 资助金额:
    $ 30.45万
  • 项目类别:
    Grant-in-Aid for international Scientific Research

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Attempt to stratify gastric cancer patients by AI using general clinical information
尝试利用一般临床信息通过人工智能对胃癌患者进行分层
  • 批准号:
    23K08102
  • 财政年份:
    2023
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    $ 30.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
stablishment of non-invasive DNA methylation panel for peritoneal metastasis of gastric cancer patients
胃癌腹膜转移非侵入性DNA甲基化检测试剂盒的建立
  • 批准号:
    23K08210
  • 财政年份:
    2023
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Development a novel immnunotherapy for gastric cancer by targeted SMARCA4
通过靶向 SMARCA4 开发一种新型胃癌免疫疗法
  • 批准号:
    23K15047
  • 财政年份:
    2023
  • 资助金额:
    $ 30.45万
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    Grant-in-Aid for Early-Career Scientists
Prospective metabolomics investigation of gastric cancer risk in African Americans and European Whites with a low socioeconomic status
社会经济地位较低的非裔美国人和欧洲白人胃癌风险的前瞻性代谢组学调查
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    10912190
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    2023
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    $ 30.45万
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Development of Gastric Cancer Therapy Targeting Pyruvate Metabolism
针对丙酮酸代谢的胃癌治疗的进展
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    22KJ1826
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    $ 30.45万
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The clinical impact of drug holiday in treatment of metastatic gastric cancer
药物假期对转移性胃癌治疗的临床影响
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    23K09533
  • 财政年份:
    2023
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    $ 30.45万
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Computational imaging approaches to personalized gastric cancer treatment
个性化胃癌治疗的计算成像方法
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    10585301
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Prospective study on the diagnostic accuracy of early gastric cancer by serum methylated RUNX3
血清甲基化RUNX3诊断早期胃癌准确性的前瞻性研究
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    23K06910
  • 财政年份:
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Effect of ant-claudin antibody against peritoneal metastasis from gastric cancer
抗密蛋白抗体对抗胃癌腹膜转移的作用
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    23K19642
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    $ 30.45万
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Development of a Novel Cancer Therapy Strategy Targeting TGFBI in Gastric Cancer Stroma
开发针对胃癌基质中 TGFBI 的新型癌症治疗策略
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