? ? Lung cancer is the number one cancer killer for men and women in the USA. The ability to detect lung cancer at its early, curable stages will reduce the mortality and is thus an important clinical goal. Toward this goal, using genome-wide microarray-based comparative genomic hybridization analysis of primary lung tumors, we have identified a set of genetic signatures that can be detected in sputum and provided potential biomarkers for the early detection of lung cancer (Clin Cancer Res, 2007, 15 and AACR breaking News). We have also developed an in situ mini-chip consisting of a panel of probes for simultaneously measuring multiple genetic changes in a single test. However, the application of the potential genetic biomarkers and test in the clinical settings is limited by the probes that are labeled with organic dyes, because the conventional fluorochromes fade fast and show blurry signals, and thus reduce the sensitivity of the biomarkers in the detection of cancer cells. The newly developed quantum dots (QDs) feature intense and stable fluorescence, and provide a promising approach for effectively detecting molecular genetic targets. The objective of this R03 exploratory study is to develop a diagnostic test that can reliably detect genetic biomarkers using sputum for the early detection of lung cancer. We propose to 1) develop a nanogenetic test by incorporating the most optimum fluorescent QDs into the probes of the genetic signatures and integrating the nanoprobes into the in situ mini-chip, 2) determine diagnostic utility of the nanogenetic test for the early detection of lung cancer in sputum samples from 83 patients with stage I lung cancer and 83 cancer-free heavy smokers and 83 nonsmokers. At the conclusion of this study, we expect to develop a genetic approach for effectively detecting the biomarker panel in sputum that can be used for the early detection of lung cancer with high sensitivity. This exploratory R03 grant will set the stage for future large-scale cohort studies designed to validate its utility for adoption in routine clinical settings. Resources that will contribute towards our objective include a bank of well-characterized sputum samples with comprehensive clinical and cytopathologic database. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA133956-01
Application #
7475337
Study Section
Special Emphasis Panel (ZCA1-SRRB-F (J1))
Program Officer
Krueger, Karl E
Project Start
2008-04-04
Project End
2010-03-31
Budget Start
2008-04-04
Budget End
2009-03-31
Support Year
1
Fiscal Year
2008
Total Cost
$75,000
Indirect Cost
Name
University of Maryland Baltimore
Department
Pathology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Mei, Y-P; Liao, J-P; Shen, J et al. (2012) Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene 31:2794-804
Mannoor, Kaiissar; Liao, Jipei; Jiang, Feng (2012) Small nucleolar RNAs in cancer. Biochim Biophys Acta 1826:121-8
Shen, Jun; Jiang, Feng (2012) Applications of MicroRNAs in the Diagnosis and Prognosis of Lung Cancer. Expert Opin Med Diagn 6:197-207
Shen, Jun; Liu, Ziling; Todd, Nevins W et al. (2011) Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer 11:374
Jiang, Feng; Todd, Nevins W; Li, Ruiyun et al. (2010) A panel of sputum-based genomic marker for early detection of lung cancer. Cancer Prev Res (Phila) 3:1571-8
Li, Ting; Su, Yun; Mei, Yuping et al. (2010) ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest 90:234-44
Zhang, Jian; Fu, Yi; Jiang, Feng et al. (2010) Metal Nanoshell - Capsule for Light-Driven Release of Small Molecule. J Phys Chem C Nanomater Interfaces 114:7635-7659
Liao, Jipei; Yu, Lei; Mei, Yuping et al. (2010) Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer. Mol Cancer 9:198
Zhang, Jian; Fu, Yi; Mei, Yuping et al. (2010) Fluorescent metal nanoshell probe to detect single miRNA in lung cancer cell. Anal Chem 82:4464-71
Yu, Lei; Todd, Nevins W; Xing, Lingxiao et al. (2010) Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer 127:2870-8

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