Metabolomics is the study of cells by measuring profiles of all, or a large number, of their metabolites. Metabolomics was originally proposed as a method of functional genomics but its utility extends well beyond that - it is useful whenever an assessment of changes in metabolite levels is important. Metabolomics as a global approach is especially useful in identifying overall metabolic changes associated with breast cancer development and to identify most affected metabolites and metabolic networks. ? ? In this project the progression of malignancy of breast epithelial cells will be characterized under normal as well as oxidative stress conditions with detailed molecular profiles. Robust molecular signatures that uniquely characterize early stages of malignant transformation will be developed using mathematical, statistical, and machine learning algorithms. ? ? Fully malignant, intermediate and non-malignant breast epithelial cell cultures will be analyzed to obtain detailed molecular fingerprints. These fingerprints are processed with variable selection and discriminant analysis algorithms from which the determinant molecules for each stage of breast cancer development will be identified. To further increase the molecular detail of this approach, the cell cultures will be exposed to an oxidative stress caused by an appropriate concentration of cumene hydroperoxide, and subjected to the same data analysis workflow. The molecules identified as characteristic of each culture type, are important metabolic marker candidates for early stages of cancer development. At the same time they point to the molecular mechanisms of breast cancer origin and will increase our knowledge about the etiology of breast cancer. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA120170-02
Application #
7496158
Study Section
Biomedical Computing and Health Informatics Study Section (BCHI)
Program Officer
Wang, Wendy
Project Start
2007-09-13
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$327,183
Indirect Cost
Name
Virginia Polytechnic Institute and State University
Department
Type
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061
Nesterov, Volodymyr V; Zakharov, Lev N; Nesterov, Vladimir N et al. (2015) Crystal structure of (3E,5E)-3,5-bis-[4-(di-ethyl-aza-nium-yl)benzyl-idene]-1-methyl-4-oxopiperidin-1-ium trichloride dihydrate: a potential biophotonic material. Acta Crystallogr E Crystallogr Commun 71:1513-5
Mittler, Ron; Vanderauwera, Sandy; Suzuki, Nobuhiro et al. (2011) ROS signaling: the new wave? Trends Plant Sci 16:300-9
Cortes, Diego F; Sha, Wei; Hower, Valerie et al. (2011) Differential gene expression in normal and transformed human mammary epithelial cells in response to oxidative stress. Free Radic Biol Med 50:1565-74
Armenta, Jenny M; Cortes, Diego F; Pisciotta, John M et al. (2010) Sensitive and rapid method for amino acid quantitation in malaria biological samples using AccQ.Tag ultra performance liquid chromatography-electrospray ionization-MS/MS with multiple reaction monitoring. Anal Chem 82:548-58
Hower, Valerie; Mendes, Pedro; Torti, Frank M et al. (2009) A general map of iron metabolism and tissue-specific subnetworks. Mol Biosyst 5:422-43
Laubenbacher, Reinhard; Hower, Valerie; Jarrah, Abdul et al. (2009) A systems biology view of cancer. Biochim Biophys Acta 1796:129-39
Shulaev, Vladimir; Cortes, Diego; Miller, Gad et al. (2008) Metabolomics for plant stress response. Physiol Plant 132:199-208