PT  - JOURNAL ARTICLE
AU  - NAKAHIRA, SHIN
AU  - NAKAMORI, SHOJI
AU  - TSUJIE, MASANORI
AU  - TAKEDA, SETSUO
AU  - SUGIMOTO, KEISHI
AU  - TAKAHASHI, YUJI
AU  - OKAMI, JIRO
AU  - MARUBASHI, SHIGERU
AU  - MIYAMOTO, ATSUSHI
AU  - TAKEDA, YUTAKA
AU  - NAGANO, HIROAKI
AU  - DONO, KEIZO
AU  - UMESHITA, KOJI
AU  - SAKON, MASATO
AU  - MONDEN, MORITO
TI  - Pretreatment with S-1, an Oral Derivative of 5-Fluorouracil, Enhances Gemcitabine Effects in Pancreatic Cancer Xenografts
DP  - 2008 Jan 01
TA  - Anticancer Research
PG  - 179--186
VI  - 28
IP  - 1A
4099  - http://ar.iiarjournals.org/content/28/1A/179.short
4100  - http://ar.iiarjournals.org/content/28/1A/179.full
SO  - Anticancer Res2008 Jan 01; 28
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.