BACKGROUND: Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects. METHODS: We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging. RESULTS: FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mg kg À1; 30 mg kg À1 once a week or 15 mg kg À1 twice a week for 4 weeks) and siFASN (1.4 mg kg À1 every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control. CONCLUSION:The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.

13582 Background: This prospective, nonrandomized study was conducted to compare the efficacy and toxicity of postoperative concurrent chemoradiation therapy (CCRT) using daily oral uracil-tegafur plus leucovorin (UFUR/LV) vs. weekly intravenous fluorouracil plus leucovorin (5-FU/LV) in patients with locally advanced rectal cancer. Methods: From November 1996 through December 2004, 30 patients with stage II or III rectal cancer were enrolled. Seventeen received oral UFUR/LV regiment and thirteen with intravenous 5-FU/LV regiment during CCRT. A weekly infusion of 400 to 450 mg/m2 of 5-FU plus a bolus injection of 80 to 100 mg/m2 of LV and 250 to 300 mg/m2/d of oral UFUR plus 30 to 45 mg /m2/d of oral LV were given separately during RT and for an additional 42 weeks thereafter. Forty-five Gy of whole-pelvis irradiation was followed by a local boost of 5.4 to 14.4 Gy to the tumor bed delivered in 33 fractions. Analytical method was Kaplan-Meier method. Results: Mean survival in the UFUR/LV group was 36 months compare with 30 months in the 5-FU/LV group. The 2-year OS, DFS and LCR were 68.1% vs. 65.8%, 54.9% vs. 50.4%, and 79.4% vs. 83.9%, (p > 0.05), respectively. There were no treatment-related deaths and grade 4 toxicity in both groups. Grade 3 of dermatitis, gastrointestinal, and hematologic toxicity was noted in the 5-FU/LV group. Conclusions: Postoperative CCRT with oral UFUR/LV in locally advanced rectal cancer provides an alternative way for those who have difficulty with an intravenous regimen due to it was more tolerable and less toxicity and has similar survival rate. No significant financial relationships to disclose.

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