RT Journal Article SR Electronic T1 Pretreatment with S-1, an Oral Derivative of 5-Fluorouracil, Enhances Gemcitabine Effects in Pancreatic Cancer Xenografts JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 179 OP 186 VO 28 IS 1A A1 SHIN NAKAHIRA A1 SHOJI NAKAMORI A1 MASANORI TSUJIE A1 SETSUO TAKEDA A1 KEISHI SUGIMOTO A1 YUJI TAKAHASHI A1 JIRO OKAMI A1 SHIGERU MARUBASHI A1 ATSUSHI MIYAMOTO A1 YUTAKA TAKEDA A1 HIROAKI NAGANO A1 KEIZO DONO A1 KOJI UMESHITA A1 MASATO SAKON A1 MORITO MONDEN YR 2008 UL http://ar.iiarjournals.org/content/28/1A/179.abstract AB Background: The systemic administration of gemcitabine (GEM) has been accepted as a standard treatment for patients with advanced pancreatic cancer. The major mediator of cellular uptake of GEM is the human equilibrative nucleoside transporter 1 (hENT1) whose expression is up-regulated by thymidylate synthase inhibitors, such as 5-fluorouracil (5-FU). S-1 is a novel oral derivative of the 5-FU prodrug tegafur combined with two modulators. Recent clinical trials have reported the promising effect of S-1 in pancreatic cancer. The purpose of this study was to evaluate the relationship between different schedules and the effects of GEM/S-1 combination therapy on pancreatic cancer xenograft models. Materials and Methods: Human pancreatic tumor xenografts were prepared by subcutaneous implantation of MiaPaCa-2 into nude mice. Expression of hENT1 was determined by quantitative RT-PCR. GEM cellular uptake was determined using [3H] GEM. Results: Significant increases in hENT1 expression and GEM cellular uptake were observed after S-1 treatment. Six different treatment schedules (no treatment, single agent of GEM or S-1, combination treatment with GEM either before, simultaneously or following administration of S-1) were compared. Significant tumor growth inhibition was observed in the mice treated with S-1 followed by GEM compared to either untreated mice or the mice treated with the other schedules. Conclusion: Based on the effects of S-1 on the uptake of GEM, S-1 should be used before GEM treatment. The GEM/S-1 combination therapy in patients with pancreatic cancer may be promising and should be tested in clinical trials.