Stem Cells and Perinatal Factors for Breast Cancer Risk

干细胞和乳腺癌风险的围产期因素

• 批准号: 6702303
• 负责人: CHUNG-CHENG HSIEH
• 金额: $ 35.68万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6702303
• 关键词: BCL2 gene /protein; apoptosis; binding proteins; breast neoplasms; cancer risk; clinical research; cord blood; estradiol; estriol; female; gene induction /repression; hormone binding protein; hormone related neoplasm /cancer; human birth weight; human subject; insulinlike growth factor; neoplasm /cancer genetics; perinatal; progesterone; prolactin; stem cells; testosterone; women' s health

DESCRIPTION (provided by applicant): This study proposes to examine whether hormone levels in human umbilical cord blood are associated with measurements of stem cell potential and expression of Bcl-2 family proteins indicating levels of apoptotic activity. Measurements of stem cells and Bcl-2 apoptosis will be further examined to see if they correlate with birth weight as an indicator of fetal growth. The study is based on the hypothesis that cancer risk can be influenced in part by the hormonal environment in utero and that cancer risk is proportional to the number of primitive proliferating stem cells. Umbilical cord blood from 300 donors will be obtained from singleton birth, full-term, and low-risk deliveries at hospitals affiliated with the American Red Cross Cord Blood Program. Hormones and other growth factors including estradiol, estriol, progesterone, prolactin, sex-hormone binding globulin (SHIBG), testosterone, insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3) will be assayed in cord blood samples. We will measure the total number of nucleated cells, number of cells per volume expressing CD34 protein on the cell surface as well as CD34+/CD38, CD34+/c-kit, and CD45/GlyA sub-population cells, and the number of colony-forming-unit granulocytes and macrophages (CFU-GM) as laboratory parameters for primitive proliferating stem cells. Among Bcl-2 family proteins we will measure the expression of Bcl-2, Bcl-xL, Bax, and Bad to construct an overall apoptotic index. We will apply regression analysis treating as outcome variables each measurement of stem cell potential and Bcl-2 apoptotic index and as predictor variables hormone levels, controlling for maternal and neonatal characteristics. Stem cell measurements and index of Bcl-2 apoptotic expressions will be further examined as predictors of birth weight. The study seeks to obtain information on parameters of perinatal cell proliferation relevant to intervening steps between intrauterine hormone exposure and subsequent cancer risk.

描述（由申请人提供）：本研究建议检查是否是否 人脐带血中的激素水平与测量有关 Bcl-2家族蛋白的干细胞电位和表达的表达 凋亡活性的水平。干细胞和BCL-2凋亡的测量 将进一步检查，以查看它们是否与出生体重相关 胎儿生长的指标。该研究基于癌症的假设 风险可能部分受子宫的荷尔蒙环境的影响， 癌症风险与原始增生茎的数量成正比 细胞。将从Singleton获得300个捐助者的脐带血 隶属于医院的出生，充实和低风险分娩 美国红十字脐带血计划。激素和其他增长因素 包括雌二醇，雌二醇，孕酮，催乳素，性激素结合 球蛋白（湿布），睾丸激素，胰岛素样生长因子1（IGF-1）和IGF 结合蛋白3（IGFBP-3）将在脐带血样品中分析。我们将 测量核细胞的总数，每体积的细胞数量 在细胞表面以及CD34+/CD38，CD34+/C-KIT上表达CD34蛋白 和CD45/Glya子群体，以及集型形成单元的数量 粒细胞和巨噬细胞（CFU-GM）作为原始参数 增殖的干细胞。在Bcl-2家族蛋白中，我们将测量 构建总体凋亡的Bcl-2，Bcl-XL，BAX和不良 指数。我们将应用回归分析，将每个结果视为结果变量 干细胞电位和Bcl-2凋亡指数的测量和预测指数 变量激素水平，控制母亲和新生儿 特征。 Bcl-2凋亡的干细胞测量和索引 表达式将进一步研究为出生体重的预测指标。研究 寻求获取有关围产期细胞增殖参数的信息 与宫内激素暴露和 随后的癌症风险。