Prostate cancer is the second most common cancer in men, and the second leading cause of cancer death. However, patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when cancer is still confined to the prostate gland). Combined with the digital rectal examination, the prostate specific antigen (PSA) test has been widely used to detect prostate cancer in its early stages. An elevated PSA level may be an indication of prostate cancer. However, various conditions such as enlargement or inflammation of prostate can cause elevated levels of PSA. Conversely, PSA levels may be normal despite the presence of prostate cancer. Thus, the PSA screening method for early detection of prostate cancer is not suitable due to highly prevalent false positive and negative PSA test results. Therefore, a reliable marker for early detection of prostate cancer is urgently needed. Transcriptional silencing of tumor suppressor gene expression due to hypermethylation of the gene promoters is believed to contribute to the neoplastic progression. Thus, methylated DNAs can serve as biomarkers for early detection of cancer. But, the methylation of most genes correlates positively with tumor grade and stage and thus the detection of these methylated DNAs is not necessarily suitable to identify prostate cancer at early stages, especially at stages I and II (the critical stages for effective treatment and cure). A prostate cancer gene (PCG) has recently been found to be heavily methylated in stages I and II tumor compared to the normal and later stages of tumor tissues. The methylation in the PCG allows development of PCR-based sensitive and specific tools that clearly identify the early stages of prostate cancer in tissues as well as in biological fluids such as serum and urine. The goal of the proposed studies is to establish 'proof of concept'using a large number of tissue and urine specimens. Results from these studies will lead to the development of a non-invasive diagnostic tool not only for early detection, but also for therapeutic guidance and recurrence monitoring of prostate cancer in urine.

Public Health Relevance

Ahmed, Hafiz Project Narrative Patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when the cancer is still confined to the prostate gland). The objective of this project is to develop a non-invasive, sensitive and specific method that clearly identifies the early stages of prostate cancer in urine. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA133935-01A2
Application #
7753079
Study Section
Special Emphasis Panel (ZCA1-SRLB-F (M1))
Program Officer
Kagan, Jacob
Project Start
2009-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
1
Fiscal Year
2009
Total Cost
$75,000
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
Ahmed, Hafiz; AlSadek, Dina M M (2015) Galectin-3 as a Potential Target to Prevent Cancer Metastasis. Clin Med Insights Oncol 9:113-21
Ahmed, Hafiz; Bandyopadhyaya, Gargi (2015) Examination of the regulation of galectin-3 expression in cancer. Methods Mol Biol 1207:355-69
Guha, Prasun; Bandyopadhyaya, Gargi; Polumuri, Swamy K et al. (2014) Nicotine promotes apoptosis resistance of breast cancer cells and enrichment of side population cells with cancer stem cell-like properties via a signaling cascade involving galectin-3, ?9 nicotinic acetylcholine receptor and STAT3. Breast Cancer Res Treat 145:5-22
Guha, Prasun; Kaptan, Engin; Bandyopadhyaya, Gargi et al. (2013) Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis. Proc Natl Acad Sci U S A 110:5052-7
Ahmed, Hafiz (2012) Methylated DNA as Promising Marker for Early Diagnosis of Cancer. J Bioanal Biomed 4:
Nallar, Shreeram C; Lin, Limei; Srivastava, Varsha et al. (2011) GRIM-1, a novel growth suppressor, inhibits rRNA maturation by suppressing small nucleolar RNAs. PLoS One 6:e24082
Ahmed, Hafiz; Guha, Prasun; Kaptan, Engin et al. (2011) Galectin-3: a potential target for cancer prevention. Trends Carbohydr Res 3:13-22
Ahmed, Hafiz (2010) Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples. Biomark Cancer 2010:17-33