Melanoma is the most serious form of skin cancer and early diagnosis is the best way to combat it. Distinguishing benign pigmented lesions from early melanomas can be difficult. Smell or odor has been used as a symptom of disease for centuries. The evidence for the extreme olfactory ability of canines, both in terms of detection threshold and in terms of ability to detect cancer has been documented. The goal of this project is to directly demonstrate that canine olfactory receptors respond to melanoma tumor markers (volatile compounds). The central hypothesis is that melanoma tissue contains unique volatiles - biomarkers that can be recognized by olfactory receptors. Melanoma volatiles from human biopsy samples will be profiled by gas chromatography and mass spectrometry. The major innovation of this proposal is to lay foundation for the clinical diagnosis of melanoma based on volatile by-products of altered metabolism. The bilaterally symmetrical olfactory epithelium will be divided into subsections. Membrane sheets containing receptors isolated from the left side of the epithelium will be injected into Xenopus oocytes and tested by high throughput electrophysiology against isolated melanoma biomarkers. The genetic identify of the canine olfactory receptors will be determined using microarray analysis of mRNA isolated from the parallel subsections on the right side. After identification, candidate canine olfactory receptors will be pharmacologically characterized in heterologous expression system. Identification of the specific canine olfactory receptors that recognize melanoma markers will enable pursuit of our long-term objective: the development of a safe and non-invasive diagnostic tool - a biosensor for the early detection of melanoma.

Public Health Relevance

Melanoma is the most serious form of skin cancer, and early diagnosis is the best strategy to combat it. The goal of this project is to identify canine olfactory receptors that recognize volatile compounds - biomarkers present is human melanoma in order to develop diagnostic screen assay - a biosensor, for its early detection. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA132046-01A1
Application #
7530661
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Thurin, Magdalena
Project Start
2008-09-29
Project End
2010-08-31
Budget Start
2008-09-29
Budget End
2009-08-31
Support Year
1
Fiscal Year
2008
Total Cost
$206,550
Indirect Cost
Name
University of Miami School of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Abaffy, T; Möller, M G; Riemer, D D et al. (2013) Comparative analysis of volatile metabolomics signals from melanoma and benign skin: a pilot study. Metabolomics 9:998-1008
Abaffy, Tatjana; Moller, Mecker; Riemer, Daniel D et al. (2011) A case report - Volatile metabolomic signature of malignant melanoma using matching skin as a control. J Cancer Sci Ther 3:140-144
Abaffy, Tatjana; Duncan, Robert; Riemer, Daniel D et al. (2010) Differential volatile signatures from skin, naevi and melanoma: a novel approach to detect a pathological process. PLoS One 5:e13813