Hepatocellular carcinoma is the one of most frequent causes of death by cancer in the world. There is no reliable diagnosis prior to late stages of disease and no hope for cure except surgery. The overall goal of the proposal is to discover and identify distinctive alterations of protein expression in early precancerous lesions isolated from their physiological microenvironment. The data obtained will provide early molecular markers with diagnostic and therapeutic potential for early intervention in human liver cancer. We propose to apply innovative proteomics and laser capture microdissection microscopy (LCM) to study a well-characterized animal model of liver carcinogenesis (RH) that exhibits well-defined, synchronous stages of initiation and progression of liver cancer that are strikingly similar to those in liver cancer in humans. In the R21 phase, we will focus on demonstrating our ability to generate useful patterns/profiles with combined LCM and protein technologies using control tissue/serum and one preneoplastic stage of the biological model system. In the R33 phase, we will apply the pattern/profile generation technologies to the cells and sera of each of the early stages and control paradigms so that we can identify candidate markers and targets. We will use both global and targeted proteomics strategies to: 1) identify difference proteins in cells early in the development of liver cancer; 2) identify unique serum markers at early stages; 3) determine progressive changes in tubulin isotype composition, which is associated with development of drug resistance; and 4) identify changes in proteins associated with the cytoskeletal scaffold.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA101150-03
Application #
6950360
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (J1))
Program Officer
Knowlton, John R
Project Start
2003-06-16
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$644,829
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Nika, Heinz; Angeletti, Ruth Hogue; Hawke, David H (2016) Phosphopeptide Enrichment by Covalent Chromatography After Solid Phase Derivatization of Protein Digests on Reversed Phase Supports. Methods Mol Biol 1355:31-50
Nika, Heinz; Angeletti, Ruth Hogue; Hawke, David H (2014) N-terminal protein characterization by mass spectrometry using combined microscale liquid and solid-phase derivatization. J Biomol Tech 25:77-86
Nika, Heinz; Hawke, David H; Angeletti, Ruth Hogue (2014) N-terminal protein characterization by mass spectrometry after cyanogen bromide cleavage using combined microscale liquid- and solid-phase derivatization. J Biomol Tech 25:19-30
Nika, Heinz; Hawke, David H; Angeletti, Ruth Hogue (2014) C-terminal protein characterization by mass spectrometry: isolation of C-terminal fragments from cyanogen bromide-cleaved protein. J Biomol Tech 25:1-18
Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band et al. (2014) Proteomics of cancer cell lines resistant to microtubule-stabilizing agents. Mol Cancer Ther 13:260-9
Nika, Heinz; Nieves, Edward; Hawke, David H et al. (2013) Phosphopeptide enrichment by covalent chromatography after derivatization of protein digests immobilized on reversed-phase supports. J Biomol Tech 24:154-77
Nika, Heinz; Nieves, Edward; Hawke, David H et al. (2013) Optimization of the ?-elimination/michael addition chemistry on reversed-phase supports for mass spectrometry analysis of O-linked protein modifications. J Biomol Tech 24:132-53
Nika, Heinz; Nieves, Edward; Hawke, David H et al. (2013) C-terminal protein characterization by mass spectrometry using combined micro scale liquid and solid-phase derivatization. J Biomol Tech 24:17-31
Nika, Heinz; Lee, JaeHoon; Willis, Ian M et al. (2012) Phosphopeptide characterization by mass spectrometry using reversed-phase supports for solid-phase ?-elimination/Michael addition. J Biomol Tech 23:51-68
Albrethsen, Jakob; Miller, Leah M; Novikoff, Phyllis M et al. (2011) Gel-based proteomics of liver cancer progression in rat. Biochim Biophys Acta 1814:1367-76

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