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GCKR MEDIATED SIGNAL TRANSDUCTION AND LEUKEMIC TRANSFORM

GCKR MEDIATED SIGNAL TRANSDUCTION AND LEUKEMIC TRANSFORM
GCKR 介导的信号转导和白血病转化
批准号:
6173226
负责人:
JOSEPH M TUSCANO
金额:
$8.48万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-09-30 至 2001-09-29

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中文摘要
翻译
描述(申请人描述): 慢性粒细胞白血病(CML)是一种克隆性骨髓增生性疾病 原始的造血干细胞。 CML约占 占所有成人白血病的25% BCR-ABL癌基因可能代表了 在几乎所有的CML中启动事件,尽管额外的遗传事件 完全恶性表型所需的。 最近描述的 已知丝氨酸-苏氨酸激酶GCK和GCKR激活 被认为介导BCR-ABL的转化能力。具体地说, 根据将在初步研究中提出的工作, 申请人假设GCKR特异性地与 由BCR-ABL激活,可能是BCR-ABL的关键因素 转化潜力 在此基础上,他们建议:1)检查 协调GCKR之间关联的基本要素和要求 和BCR-ABL; 2)检查BCR-ABL的功能后果 GCK与GCKR的关系; 3)评估GCK的体内转化潜力 和GCKR。 阐明GCKR在BCR-ABL介导的转化中的作用 这将有助于更好地了解致癌的机制。 改造,从而允许开发更好的治疗方法, 慢性粒细胞白血病的诊断策略。 申请人在分子生物学方面的培训 生物学,免疫学和临床肿瘤学,除了他的直接 最初克隆GCKR的经验使他处于独特的位置, 进行这里提出的研究。
英文摘要
DESCRIPTION (Applicant's Description): Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of the primitive hematopoietic stem cell. CML accounts for approximately 25% of all adult leukemia. The BCR-ABL oncogene probably represents the initiating event in nearly all CML, although additional genetic events are required for the full malignant phenotype. The recently described serine-threonine kinases GCK and GCKR are known to activate the pathway that is thought to mediate the transforming ability of BCR-ABL. Specifically, based on work that is to be presented under Preliminary Studies, the applicants hypothesize that GCKR specifically associates with, and is activated by, BCR-ABL and is likely a critical element in BCR-ABL's transforming potential. Based on this they propose to: 1) examine the basic elements and requirements that mediate the association between GCKR and BCR-ABL; 2) examine the functional consequences of the BCR-ABL relationship with GCKR; 3) assess the in vivo transforming potential of GCK and GCKR. Elucidating the role of GCKR in BCR-ABL mediated transformation will allow for a better understanding of the mechanism of oncogenic transformation, and thus allow for the development of improved treatment and prognostication strategies for CML. The applicant's training in molecular biology, immunology, and clinical oncology, in addition to his direct experience with the initial cloning of GCKR put him in the unique position to pursue the studies proposed here.
期刊论文(1)
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会议论文
cis-1,4-diaminocyclohexane-Pt(II) and -(IV) adducts with DNA bases and nucleosides.
cis-1,4-二氨基环己烷-Pt(II) 和-(IV) 与DNA碱基和核苷的加合物。
DOI: 10.1016/s0162-0134(03)00262-9
发表时间: 2003
期刊: Journal of inorganic biochemistry
影响因子: 3.9
作者: [Ali,MohammadS, Khokhar,AbdulR]
通讯作者: Khokhar,AbdulR
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