Lung cancer is the leading cause of death in men and women in the United States (160,000 new cases and 157,400 deaths in 2001). Although the relative risk of developing lung cancer declines in smokers who quit, former smokers remain at high risk for at least 5 years. Since smoking cessation is a major public health initiative, former smokers will increasingly account for a high percentage of lung cancer. A potential important approach to reduce the large number of tobacco caused cancer deaths is chemoprevention. The long-term goal o f our Chemoprevention of Lung Cancer Program Project is to develop chemopreventive strategies to reduce the incidents of lung cancer in high-risk current and former smokers. The Program Project will focus its chemoprevention strategies on Budesonide (a glucocorticoid agonist), green tea extracts (Polyphenon E), Myo-inositol, and difiuoromethylornithine (DFMO) for three reasons: i) they exhibit high chemopreventive efficacy in rodent models; ii) they are effective in the post-initiation period of carcinogenesis; and iii) they have a previous history of therapeutic or dietary administration to humans. Our Program Project consists of four research projects designed by a group of lung cancer scientists to address our primary hypothesis--selective combination of chemoprevention agents can prevent the progression and formation ofpreneoplastic lesions in the respiratory epithelium. In summary, the Program Project will (1) conduct a Phase II trial to determine the efficacy and safety of green tea, the second most commonly consumed beverage after water for chemoprevention of lung cancer (Project I); (2) generate new information on the use of markers in cell survival pathways as intermediate endpoint biomarkers for chemoprevention trials (Project I-III); (3) facilitate a major new initiative to develop confocal miscroendoscopy as a non-biopsy method to assess the effect ofchemopreventive agents (Project I); (4) determine the scientific basis for combining chemopreventive agents in future Phase II trials by examining their ability to inhibit progression of preneoplasia to more advanced lesions in a mouse model for adenocarcinoma and a hamster model for upper respiratory squamous cell carcinoma (Project II-IV) and by clinical trials with single agents (Project I).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA096964-03
Application #
6909883
Study Section
Subcommittee G - Education (NCI)
Program Officer
Seifried, Harold E
Project Start
2003-05-23
Project End
2008-04-30
Budget Start
2005-06-22
Budget End
2006-04-30
Support Year
3
Fiscal Year
2005
Total Cost
$2,721,020
Indirect Cost
Name
University of Cincinnati
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
McWilliams, Annette; Tammemagi, Martin C; Mayo, John R et al. (2013) Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 369:910-9
Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan et al. (2013) A dynamic bronchial airway gene expression signature of chronic obstructive pulmonary disease and lung function impairment. Am J Respir Crit Care Med 187:933-42
Li, Gerald; Guillaud, Martial; LeRiche, Jean et al. (2012) Automated sputum cytometry for detection of intraepithelial neoplasias in the lung. Anal Cell Pathol (Amst) 35:187-201
Rice, Carol; Jin, Na; Cocco, P et al. (2011) The exposure metric: does including time since exposure in the calculation of working lifetime exposure provide a better understanding of disease risk than the cumulative exposure? Med Lav 102:343-9
Tichelaar, Jay W; Yan, Ying; Tan, Qing et al. (2010) A dominant-negative c-jun mutant inhibits lung carcinogenesis in mice. Cancer Prev Res (Phila) 3:1148-56
Yee, John; Sadar, Marianne D; Sin, Don D et al. (2009) Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection. J Clin Oncol 27:2787-92
Lane, Pierre M; Lam, Stephen; McWilliams, Annette et al. (2009) Confocal fluorescence microendoscopy of bronchial epithelium. J Biomed Opt 14:024008
Lane, Pierre M; MacAulay, Calum E (2009) Reflection-contrast limit of fiber-optic image guides. J Biomed Opt 14:064028
Yuan, R; Hogg, J C; Paré, P D et al. (2009) Prediction of the rate of decline in FEV(1) in smokers using quantitative Computed Tomography. Thorax 64:944-9
Lam, Stephen; Standish, Beau; Baldwin, Corisande et al. (2008) In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res 14:2006-11

Showing the most recent 10 out of 26 publications