Effects of a topically applied bioadhesive berry gel on loss of heterozygosity indices in premalignant oral lesions.
OBJECTIVE
The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene-associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties.


METHODS
Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes.


RESULTS
Confirming earlier phase I data, none of the 27 participants developed FBR gel-associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene-associated loci.


CONCLUSIONS
These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.
Shumway
Brian S
BS
Department of Oral and Maxillofacial Surgery, Anesthesiology and Pathology, College of Dentistry, The Ohio State University, Columbus, OH 43210-1241, USA.
Kresty
Laura A
LA
Larsen
Peter E
PE
Zwick
Jared C
JC
Lu
Bo
B
Fields
Henry W
HW
Mumper
Russell J
RJ
Stoner
Gary D
GD
Mallery
Susan R
SR
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005638:Fruit; D005782:Gels; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008517:Phytotherapy; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D005782:Gels