TY - JOUR T1 - Pretreatment with S-1, an Oral Derivative of 5-Fluorouracil, Enhances Gemcitabine Effects in Pancreatic Cancer Xenografts JF - Anticancer Research JO - Anticancer Res SP - 179 LP - 186 VL - 28 IS - 1A AU - SHIN NAKAHIRA AU - SHOJI NAKAMORI AU - MASANORI TSUJIE AU - SETSUO TAKEDA AU - KEISHI SUGIMOTO AU - YUJI TAKAHASHI AU - JIRO OKAMI AU - SHIGERU MARUBASHI AU - ATSUSHI MIYAMOTO AU - YUTAKA TAKEDA AU - HIROAKI NAGANO AU - KEIZO DONO AU - KOJI UMESHITA AU - MASATO SAKON AU - MORITO MONDEN Y1 - 2008/01/01 UR - http://ar.iiarjournals.org/content/28/1A/179.abstract N2 - 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. ER -