adenovirus-delivered herpes simplex virus thymidine kinase suicidegene using translational control. J Gene Med 2006

Sorrells DL Jr., Ghali, GE, De Benedetti A, Nathan CA, Li BD. Pro-gressive amplification and overexpression of the eukaryotic initiationfactor 4E gene in different zones of head and neck cancers. J OralMaxillofacial Surg. 1999 Mar; 57(3): 294-9

4-Hexylresorcinol Induced an Apoptosisand Differentiation of Oral Cancer CellsSeong-Gon Kim, DDS, PhD, Dept. of OMFS, SacredHeart Hospital, Hallym University, #896 Pyungchon-Dong, Dongan-Gu, Anyang, 431-070, Korea (Chae CH;Mulyukin A; Choi JY; Kim SG)

Statement: A chemical analog of natural alkylresorcin-ols, 4-hexylresorcinol (4-HR), is known to induce dor-mancy in bacteria for survival under extreme environ-ments. However, it is not known if 4-HR has an anti-tumor effect. This study examined whether or not 4-HRhas anti-tumor effect through apoptosis.

Materials and Methods: SCC-9 was used for the cellculture and xenograft model. The effects of 4-HR onthe cellular proliferation were examined by a MTTassay, TUNNEL assay, and immunocytochemistry. Inthe case of a xenograft model, SCC-9 was implantedsubcutaneously, and 4-HR was administered by anintraperitoneal injection. The tumor size was mea-sured periodically and the mass was examined byimmunohistochemistry.

Method of Data Analysis: n/aResults: 4-HR significantly suppressed the prolifera-

tion of SCC-9 cells in a dose-dependent manner alongwith the inhibition of respiratory activity (p�0.05). Italso caused prominent morphological changes includingsize reduction and a rounding of the SCC-9 cells. Inter-estingly, 4-HR increased the expression of various differ-entiation markers, which was confirmed by proteomicsanalysis and RT-PCR. The 4-HR-mediated effects weredue in part to an increase of intracellular calcium, whichwas demonstrated by confocal microscopy and immuno-cytochemistry. This might be a key mechanism for cel-lular apoptosis. An intraperitoneal injection of 4-HR sub-stantially and dose-dependently reduced the tumor massafter the implantation of SCC-9 cells into the nude micemodel (p�0.05). Immunochemical analysis showed in-creased cytokeratin expression, a well-known marker ofepithelial cell differentiation. However, the level of Ki67expression, a cellular proliferation marker, was de-creased after the administration of 4-HR compared withthe control.

Conclusion: Overall, these results suggest that 4-HRhas an anti-tumor effect through apoptosis and the re-version of de-differentiated tumor cells into more differ-entiated cells.

Presence of Dominant-Negative p53Mutation Is a Risk of Early Recurrencein Oral Squamous Cell CarcinomaHaruhiko Kashiwazaki, DDS, PhD, Kita-13 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8586, Japan (Yamazaki Y;Tei K; Kitagawa Y; Totsuka Y; Inoue N; Hassan N)

Statement: Genetic alteration of p53 is a significantdetermining factor in the carcinogenesis. In addition tothe loss of function, mutant p53 can possess a dominant-negative effect that suppresses wild-type p53, and mayalso exert gain-of-function activity of malignancy. It is,however, not clear whether the functional status of p53mutation contributes to clinical outcome of patientswith oral cancer. In order to elucidate the prognosticsignificance of p53 mutations, particularly their func-tional status in oral cancer, we examined p53 expressedin oral squamous cell carcinomas (OSCC) using a yeastp53 functional assay and a transdominance assay.

Materials and Methods: A total of 47 oral SCC sampleswere subjected to yeast functional assay that screenshuman p53 function in yeast, and subsequent sequenc-ing for determination of p53 mutations. The detectedp53 genes were further investigated for their dominantactivity using a yeast based transdominance assay.

Method of Data Analysis: Disease-free survival curveswere obtained by the Kaplan-Meier method and thedifferences between curves were examined by the log-rank test and the generalized Wilcoxon test. p� 0.05was considered statistically significant. Statistical analy-ses were performed using the Statview 5.0 softwarepackage (SAS Institute, Cary, NC).

Results: p53 mutation was found in 33 out of 47(70.2%), of which 9 (27.3%) exhibited dominant nega-tive activity and 24 (72.7%) without dominant activity(recessive mutation). The remaining 14 (29.8%) wereconsidered to have wild type p53. The patients withdominant-negative mutation had significantly shorter re-lapse-free survival than patients with no mutation(p�0.002) and those with a recessive mutation(p�0.04) assessed by log-rank test and generalized Wil-coxon test.

Conclusion: The presence and absence of a dominant-negative p53 mutation may thus provide a predictor ofearly recurrence in oral SCC patients.

References

Kashiwazaki H, Tonoki H, Tada M, Chiba I, Shindoh M, Totsuka Y,Iggo R, Moriuchi T. High frequency of p53 mutations in human oralepithelial dysplasia and primary squamous cell carcinoma detected byyeast functional assay. Oncogene 1997; 15: 2667-74

Sakuragi, N., Watari, H., Ebina, Y., Yamamoto, R., Steiner,E., Koelbl,H., Yano M., Tada, M., Moriuchi, T. Functional analysis of p53 gene andthe prognostic impact of dominant-negative p53 mutation in endome-trial cancer. Int J Cancer 2005; 11: 514-19

Marutani M, Tonoki H, Tada M, Takahashi M, Kashiwazaki H, Hida Y,Hamada J, Asaka M, Moriuchi T. Dominant-negative mutations of the

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AAOMS • 2007 41.e3