alone (conventional 70Gy/35fr/7weeks) or concurrent cisplatin(CDDP) CTRT or AFRT (70Gy/35fr/6weeks) or use of both (CT+AFRT).

Results: Between January 1995 and December 2005, 347 patientswere registered. The median age of this group was 50 years (range-22–85); 83% were males. Eighty three percent belonged to stage III/IV, of which, 57% were unresectable. Three thirty eight cases re-ceived radical treatment and 9 received palliative RT (±CT). These9 patients were excluded from the analysis. Of 338, 127 receivedpostoperative RT (±CT), 84 cases received radical RT alone, 66 CTRT,18 AFRT and 43 CT+AFRT. The Median follow up of this study groupwas 35 months. For the purpose of comparison, 4 subgroups weremade i.e CTRT versus RT alone and intensification (i.e AFRT/CTRT/CT+AFRT) versus no intensification. The 5-year survival rates withthese protocols i.e CTRT vs. RT alone was 16% vs. 13% (p = 0.67)and intensification versus no intensification group was 11% vs. 16%(p = .14).

Conclusion: There was no improvement in survival by eitheradding CT or accelerating the RT in oral cancers in the present audit.

doi:10.1016/j.oos.2009.06.489

P2.86. Apoptotic effect of CKD-602(Camtobell�) on oral squa-mous cell carcinoma cell linesP.Y. Yun a,*, Y.J. Ok b, J.H. Kang c, H. Myoung b, J.H. Lee b, M.J. Kim b

a Seoul National University Bundang Hospital, Republic of Koreab Seoul National University, Republic of Koreac Hallym University, Republic of Korea

The purposes of this study were to measure the cytotoxic effect ofCKD-602 on oral squamous cell carcinoma (OSCC) cell lines, to eval-uate the apoptotic aspect of dead cells, and to identify the signalingmolecules involved in apoptosis. The human OSCC cell lines A253,HSC-3 and KB were treated with CKD-602. The apoptotic proportionof the cells was analyzed using flow cytometry. The expression ofBax, Bcl-2, and p53 were detected by western blotting analysis.CKD-602 showed excellent cytotoxicity to the OSCC cell lines. Mostcell death was attributed to apoptosis rather than necrosis. CKD-602 induced the down-regulation of Bcl-2 in A253 and HSC-3 cells,and p53 was expressed in the KB cell line after treatment withCKD-602.

doi:10.1016/j.oos.2009.06.490

P2.87. Combined effect of cisplatin and herpes simplex virus onoral cancer cellsE.J. Shillitoe*

SUNY Upstate Medical University, United States

Introduction: Viruses such as Herpes simplex virus type-1 (HSV-1), have been investigated for a therapeutic effect against oral can-cer, but the benefits have been incomplete. It has been proposed thata combination of a virus with a cytotoxic drug would be more potentthan the virus alone, but the mechanism of interaction is unknown.

Methods: The SCC-25 oral cancer cell line was used. The growthof the cells was determined by an MTT assay, with an optical absor-bance at A560–690 value expressed as the % of an untreated controlculture. The final stages of apoptosis were measured by the CellDeath Detection ELISA method (Roche) with values expressed asA405–490. The dose of cisplatin that reduced the growth of the cellsby around 50% after a 6-h exposure was determined to be 50 lM

and the concentration of virus (HSV-1strain KOS) that reduced thegrowth of cells by around 50% was 103 pfu/ml. These concentrationswere used in all experiments.

Results: When cells were grown in the presence of virus and cis-platin, growth was completely inhibited, compared to a reduction to26.5 ± SE3.1% of the control in the presence of cisplatin alone and59.1 ± 9.3% with the virus alone. If the cells were exposed to cisplatinfor 6 h only, and then infected with the virus, growth was reduced to18.3 ± 10.3%, compared with 55.6 ± 9.3% with drug alone and44.1 ± 5.6% with virus alone. If the cells were exposed to cisplatinfor only 1 h, the virus had no additional effect. The level of apoptosisin camptothecin-treated cells was detected at an A405 level of0.52 ± 0.08, and cisplatin reduced this to 0.39 ± 0.05.

Discussion: Cisplatin makes oral cancer cells more susceptible togrowth-inhibition by HSV-1 within 6 h of exposure. One mechanismby which this occurs may be the blocking of late stages of apoptosis.

Supported by: NIH Grant R21DE017611

doi:10.1016/j.oos.2009.06.491

P2.88. Enhanced susceptibility to TRAIL-mediated apoptosis inoral squamous cell carcinoma cells through down-regulation ofcellular FLIPM. Iwase*, S. Takaoka, M. Uchida, S. Yoshiba, T. Shirota, M. Hatori

Showa University, Japan

In general, oral squamous cell carcinoma (OSCC) cells are relativelyresistant to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis during culture in vitro. In this study, weinvestigated the roles of phosphatidylinositol 3-kinase (PI 3-K), epi-dermal growth factor receptor (EGFR), proteasome, and histone deace-tylase (HDAC) in TRAIL-mediated apoptosis of OSCC cells. The PI 3-Kinhibitors wortmannin and LY294002, EGFR inhibitors AG1478 andC225, proteasome-inhibitor MG132, and HDAC inhibitors suberoylan-ilide hydroxamic acid (SAHA) and trichostatin A (TSA) markedly accel-erated TRAIL-mediated apoptosis in OSCC cells. The addition of TRAILto these inhibitor-treated cells resulted in caspase-8 activation and theloss of mitochondrial membrane potential. Furthermore, the inhibi-tors of caspase-3, �8, and �9 reduced the acceleration effect of theseinhibitors on TRAIL-mediated apoptosis. These results suggest that thepro-apoptotic effect of these inhibitors on TRAIL-mediated apoptosismay contribute to both the extrinsic and intrinsic pathways of apopto-sis. Although the PI 3-K and EGFR inhibitors did not affect expressionsof the TRAIL receptors DR4 and DR5, the proteasome and HDAC inhib-itors enhanced the expressions of these receptors. Furthermore, weobserved a marked reduction in the expression of cellular FLICE inhib-itory protein (c-FLIP) with these inhibitors. The knockdown of c-FLIP inOSCC cells with a small interfering RNA (siRNA) strongly enhancedTRAIL-mediated apoptosis. Although these inhibitors also modulatedthe expressions of members of the Bcl-2 and inhibitor of apoptosisprotein (IAP) family, common mechanisms of modulation were notobserved. These results suggest that the down-regulation of c-FLIPmay represent a novel strategy for overcoming resistance to TRAIL-mediated apoptosis in OSCC cells.

doi:10.1016/j.oos.2009.06.492

P2.89. Optimizing the 4NQO oral carcinogenesis model for rapa-mycin chemopreventionR.C. Czerninski a,*, P. Amornphimoltham b, V. Patel b, A.A. Molinolo b,S.J. Gutkind b

Poster session II / Oral Oncology Supplement 3 (2009) 162–200 189

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