G1/S REGULATION AND RADIATION SENSITIVITY

G1/S 调节和辐射灵敏度

• 批准号: 2517537
• 负责人: Francisco S Pardo
• 金额: $ 8.88万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517537
• 关键词: DNA binding protein; cell growth regulation; cyclins; glioma; laboratory rat; protein kinase; radiation sensitivity; transfection

Recent developments in molecular biology have stimulated general interest in the genetic determinants of radiation sensitivity. Since late S phase is the most radiation resistant portion of the cell cycle to ionizing radiation, elucidation of the genetic regulatory mechanisms of the G1/S cell cycle transition would likely be fundamental to an understanding of cellular radiation sensitivity. Both the putative tumor suppressor gene, p53 and the G1/S cyclin, cyclin D1 or PRAD-1, serve as genetic regulatory elements at the G1/S boundary. Potential associations among cell cycle alterations, periodic changes in levels of expression of these genes, and phenotypic changes in cellular radiation sensitivity remain poorly characterized. Transfection studies of both primary rat embryo cells (REC) and human glioblastoma cell lines will reveal how p53 and PRAD-1 affect the phenotypes of cellular radiation sensitivity, cell cycle kinetics, and in vivo tumorigenicity. Cell kinetic analyses of transfected cells will lead to a better understanding of basic mechanisms of cell cycle control, both prior to as well as following irradiation. The role that WAF-1(CIP-1), -a gene regulated by both p53 and cyclin D1, plays in the modulation of the intrinsic radiation sensitivity and cell cycle kinetics of transfected cellular populations will be examined. The proposed program of investigation should thus not only lead to a better understanding of cellular radiation sensitivity, as it relates to basic mechanisms of cell cycle regulation, but may serve to unify concepts in radiation biology and molecular biology.

分子生物学的最新发展激发了人们的普遍兴趣 在辐射敏感性的遗传决定因素中。S晚期以来 是细胞周期中抗辐射能力最强的电离部分 辐射，阐明G1/S的基因调控机制 细胞周期转变很可能是理解 细胞辐射敏感性。既有可能的肿瘤抑制基因， P53和G1/S细胞周期蛋白，细胞周期蛋白D1或PRAD-1起基因调控作用 位于G1/S边界的元素。细胞周期之间的潜在联系 这些基因表达水平的周期性变化，以及 细胞辐射敏感性的表型变化仍然很差 特色化的。 原代大鼠胚胎细胞(REC)和人胚胎细胞的转基因研究 胶质母细胞瘤细胞系将揭示P53和PRAD-1如何影响 细胞辐射敏感性的表型，细胞周期动力学，以及 体内致瘤性。对转基因细胞的细胞动力学分析将导致 为了更好地理解细胞周期控制的基本机制， 在照射之前以及之后。WAF-1(CIP-1)，-a 受P53和细胞周期蛋白D1共同调控的基因在细胞周期调控中发挥作用 转基因细胞的本征辐射敏感性和细胞周期动力学 将对细胞种群进行检查。 因此，拟议的调查方案不仅应导致更好的 了解细胞辐射敏感性，因为它与基础知识有关 细胞周期调节的机制，但可以用来统一 辐射生物学和分子生物学。

项目成果

Correlation of FDG-PET interpretation with survival in a cohort of glioma patients.

FDG-PET 解读与神经胶质瘤患者队列生存率的相关性。

• 发表时间: 2004
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Pardo,FranciscoS;Aronen,HannuJ;Fitzek,Markus;Kennedy,DavidN;Efird,James;Rosen,BruceR;Fischman,AlanJ
• 通讯作者: Fischman,AlanJ