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Grant Details

Grant Number: 5R01CA090902-02 Interpret this number
Primary Investigator: Hsieh, Chung-Cheng
Organization: Univ Of Massachusetts Med Sch Worcester
Project Title: Stem Cells and Perinatal Factors for Breast Cancer Risk
Fiscal Year: 2003


Abstract

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.



Publications

Prenatal Maternal Physical Activity And Stem Cells In Umbilical Cord Blood
Authors: Onoyama S. , Qiu L.I. , Low H.P. , Chang C.I. , Strohsnitter W.C. , Norwitz E.R. , Lopresti M. , Edmiston K. , Lee I.M. , Trichopoulos D. , et al. .
Source: Medicine And Science In Sports And Exercise, 2016 Jan; 48(1), p. 82-9.
PMID: 26197028
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Effect Of Preeclampsia On Umbilical Cord Blood Stem Cells In Relation To Breast Cancer Susceptibility In The Offspring
Authors: Qiu L. , Onoyama S. , Low H.P. , Chang C.I. , Strohsnitter W.C. , Norwitz E.R. , Lopresti M. , Edmiston K. , Lambe M. , Trichopoulos D. , et al. .
Source: Carcinogenesis, 2015 Jan; 36(1), p. 94-8.
PMID: 25398884
Related Citations

Screening Preeclamptic Cord Plasma For Proteins Associated With Decreased Breast Cancer Susceptibility
Authors: Low H.P. , Tiwari A. , Janjanam J. , Qiu L. , Chang C.I. , Strohsnitter W.C. , Norwitz E.R. , Tam S.W. , Evans J.E. , Green K.M. , et al. .
Source: Genomics, Proteomics & Bioinformatics, 2013 Dec; 11(6), p. 335-44.
PMID: 24296084
Related Citations

Novel Measurements Of Mammary Stem Cells In Human Umbilical Cord Blood As Prospective Predictors Of Breast Cancer Susceptibility In Later Life
Authors: Qiu L. , Low H.P. , Chang C.I. , Strohsnitter W.C. , Anderson M. , Edmiston K. , Adami H.O. , Ekbom A. , Hall P. , Lagiou P. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2012 Jan; 23(1), p. 245-50.
PMID: 21515664
Related Citations

Prenatal Modulation Of Breast Density And Breast Stem Cells By Insulin-like Growth Factor-1
Authors: Chang C.I. , Low H.P. , Qiu L. , Strohsnitter W.C. , Hsieh C.C. .
Source: American Journal Of Stem Cells, 2012; 1(3), p. 239-52.
PMID: 23671811
Related Citations

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk.
Authors: Strohsnitter W.C. , Savarese T.M. , Low H.P. , Chelmow D.P. , Lagiou P. , Lambe M. , Edmiston K. , Liu Q. , Baik I. , Noller K.L. , et al. .
Source: British Journal Of Cancer, 2008-02-12 00:00:00.0; 98(3), p. 660-3.
EPub date: 2008-02-12 00:00:00.0.
PMID: 18256588
Related Citations

Correlation Of Umbilical Cord Blood Hormones And Growth Factors With Stem Cell Potential: Implications For The Prenatal Origin Of Breast Cancer Hypothesis
Authors: Savarese T.M. , Strohsnitter W.C. , Low H.P. , Liu Q. , Baik I. , Okulicz W. , Chelmow D.P. , Lagiou P. , Quesenberry P.J. , Noller K.L. , et al. .
Source: Breast Cancer Research : Bcr, 2007; 9(3), p. R29.
PMID: 17501995
Related Citations

Reproducibility Of Assays For Steroid Hormones, Prolactin And Insulin-like Growth Factor-1 In Umbilical Cord Blood
Authors: Baik I. , Liu Q. , Sturgeon S. , Stanek E.J. , Okulicz W. , Hsieh C.C. .
Source: Paediatric And Perinatal Epidemiology, 2006 Jan; 20(1), p. 79-86.
PMID: 16420345
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Normal Breast Stem Cells, Malignant Breast Stem Cells, And The Perinatal Origin Of Breast Cancer
Authors: Savarese T.M. , Low H.P. , Baik I. , Strohsnitter W.C. , Hsieh C.C. .
Source: Stem Cell Reviews, 2006; 2(2), p. 103-10.
PMID: 17237548
Related Citations

Association Of Fetal Hormone Levels With Stem Cell Potential: Evidence For Early Life Roots Of Human Cancer
Authors: Baik I. , Devito W.J. , Ballen K. , Becker P.S. , Okulicz W. , Liu Q. , Delpapa E. , Lagiou P. , Sturgeon S. , Trichopoulos D. , et al. .
Source: Cancer Research, 2005-01-01 00:00:00.0; 65(1), p. 358-63.
PMID: 15665314
Related Citations

Stem Cells And Prenatal Origin Of Breast Cancer
Authors: Baik I. , Becker P.S. , DeVito W.J. , Lagiou P. , Ballen K. , Quesenberry P.J. , Hsieh C.C. .
Source: Cancer Causes & Control : Ccc, 2004 Jun; 15(5), p. 517-30.
PMID: 15286472
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