The aim of this study is to improve the molecular analysis of pre- neoplastic and neoplastic tissue obtained by endoscopic biopsy. The long- term goal of this study is to develop a method of performing molecular analysis of lesions from which only limited sized specimens can be sampled. Endoscopic biopsies are routinely obtained from gastrointestinal neoplasms but two major problems have prevented their utilization for molecular analysis. The primary problem with existing technology has been the need to rely solely on visual inspection to determine which tissue can be used for molecular analysis. The second is the inability to perform genetic testing on the small size of tissue specimens that are obtained from endoscopic biopsies. This proposal will assess the ability of two techniques to improve the detection of mutations in neoplastic tissues using endoscopic biopsy material. The first technique is an """"""""optical biopsy"""""""" using laser induced fluorescence (LIF) and diffuse reflectance spectroscopy that allows the selection the appropriate neoplastic tissue for analysis. This device allows immediate localization of the neoplastic tissue with a high level of accuracy, which permits the sampling of the most appropriate tissue for molecular analysis. The samples will be processed using a new technique termed Denaturing High Pressured Liquid Chromatography (DHPLC) which is a rapid, sensitive, and automated technique for screening genetic abnormalities. We would propose to test these techniques in Barrett's esophagus, a pre-malignant epithelial tissue of the distal esophagus. These patients have common well-characterized molecular abnormalities that can be examined with these techniques. We will compare the rests of molecular analysis of tissue obtained with optical biopsy compared with obtained with standard techniques. In addition, we will assess the ability of DHPLC followed by direct gene sequencing to rapidly screen and identify mutations. It is anticipated that the combination of these techniques can substantially increase the ability to detect molecular abnormalities from limited tissue samples obtained through endoscopy. These techniques have the potential to advance the molecular analysis of any tissue samples of limited size.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA078870-02
Application #
6124643
Study Section
Special Emphasis Panel (ZCA1-RLB-Y (M1))
Program Officer
Wu, Roy S
Project Start
1998-12-18
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
2
Fiscal Year
2000
Total Cost
$138,373
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Pacifico, Rodney J; Wang, Kenneth K (2002) Nonsurgical management of Barrett's esophagus with high-grade dysplasia. Surg Oncol Clin N Am 11:321-36
Buttar, Navtej S; Wang, Kenneth K; Leontovich, Olga et al. (2002) Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus. Gastroenterology 122:1101-12
Wang, Kenneth K (2002) Multimodality therapy for gastroesophageal cancers. J Gastrointest Surg 6:527-31
Buttar, Navtej S; Wang, Kenneth K; Anderson, Marlys A et al. (2002) The effect of selective cyclooxygenase-2 inhibition in Barrett's esophagus epithelium: an in vitro study. J Natl Cancer Inst 94:422-9
Pacifico, Rodney J; Wang, Kenneth K (2002) Role of mucosal ablative therapy in the treatment of the columnar-lined esophagus. Chest Surg Clin N Am 12:185-203
Buttar, N S; Wang, K K; Lutzke, L S et al. (2001) Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus. Gastrointest Endosc 54:682-8
Buttar, N S; Wang, K K; Sebo, T J et al. (2001) Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma. Gastroenterology 120:1630-9
Krishnadath, K K; Reid, B J; Wang, K K (2001) Biomarkers in Barrett esophagus. Mayo Clin Proc 76:438-46
Wang, K K; Sampliner, R E (2001) Mucosal ablation therapy of barrett esophagus. Mayo Clin Proc 76:433-7
Wang, K K; Nijhawan, P K (2000) Complications of photodynamic therapy in gastrointestinal disease. Gastrointest Endosc Clin N Am 10:487-95

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