The long-term objective of this research plan is to understand the molecular events at the protein level of cellular changes that drive the evolution of neoplastic disease. The focus is on the development and implementation of laser capture micro-dissection and mass spectrometry technologies for the screening of prostate and ovarian cancer and/or tissue-specific protein markers for early diagnosis, risk assessment, and 2anticancer drug evaluation. The methodology involves the isolation of cancer cells from human tissues by laser capture micro-dissection, protein separation by high-resolution 2D-gel electrophoresis, and identification of target proteins by mass spectrometry.
The specific aims of this research: 1. To use a combination of modern techniques to analyze proteins and protein profiles directly from premalignant and malignant subpopulations of cells selected under microscopic visualization of actual cancer tissue specimens. 2. To define the protein changes that occur in prostate and ovary cancer progression which correlate with disease stage and arise at the earliest premalignancies. 3. To identify specific proteins and protein profiles from patient sample study sets for further analysis in patient-matched body fluid for marker identification. The initial utility of these studies will be to aid clinicians in early diagnosing prostate and ovarian cancer patients at an early stage of the diseases. These studies will also provide means to accurately predict prognosis and help clinicians recommend the most appropriate treatment and follow up strategies for their patients. Thus, this research will contribute to prolonging survival and reducing mortality of prostate and ovarian cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA085146-06
Application #
6663278
Study Section
Special Emphasis Panel (ZCA1-SRRB-3 (O1))
Program Officer
Srivastava, Sudhir
Project Start
1999-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
6
Fiscal Year
2003
Total Cost
$224,426
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Chan Kim, Sung; Kho, Yoonjung; Barma, Deb et al. (2006) A tagging-via-substrate technology for genome-wide detection and identification of farnesylated proteins. Methods Enzymol 407:629-37
Demou, Zoe N; Awad, Michael; McKee, Trevor et al. (2005) Lack of telopeptides in fibrillar collagen I promotes the invasion of a metastatic breast tumor cell line. Cancer Res 65:5674-82
Bockhorn, Maximilian; Roberge, Sylvie; Sousa, Cristina et al. (2004) Differential gene expression in metastasizing cells shed from kidney tumors. Cancer Res 64:2469-73
Zhao, Yingming; Kwon, Sung Won; Anselmo, Anthony et al. (2004) Broad spectrum identification of cellular small ubiquitin-related modifier (SUMO) substrate proteins. J Biol Chem 279:20999-1002
Zhao, Yingxin; Zhang, Wei; Kho, Yoonjung et al. (2004) Proteomic analysis of integral plasma membrane proteins. Anal Chem 76:1817-23
Kho, Yoonjung; Kim, Sung Chan; Jiang, Chen et al. (2004) A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. Proc Natl Acad Sci U S A 101:12479-84
Geiman, Theresa M; Sankpal, Umesh T; Robertson, Andrea K et al. (2004) Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery. Nucleic Acids Res 32:2716-29
Geiman, Theresa M; Sankpal, Umesh T; Robertson, Andrea K et al. (2004) DNMT3B interacts with hSNF2H chromatin remodeling enzyme, HDACs 1 and 2, and components of the histone methylation system. Biochem Biophys Res Commun 318:544-55
Roose, Tiina; Netti, Paolo A; Munn, Lance L et al. (2003) Solid stress generated by spheroid growth estimated using a linear poroelasticity model small star, filled. Microvasc Res 66:204-12
Zhang, Wei; Zhou, Ge; Zhao, Yingxin et al. (2003) Affinity enrichment of plasma membrane for proteomics analysis. Electrophoresis 24:2855-63

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