Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Tsujie, M. et al.

Schedule-dependent therapeutic effects of gemcitabine combined with uracil-tegafur in a human pancreatic cancer xenograft model.

OBJECTIVES: Gemcitabine is taken up by cells mainly via human equilibrative nucleoside transporter 1 (hENT1). Pretreatment of cancer cell lines with 5-fluorouracil (5-FU) leads to an increase in the expression of hENT1 and augments the effect of single-agent gemcitabine treatment in vitro. The purpose of the present study was to evaluate the relationship between the schedules of gemcitabine/uracil-tegafur (UFT) combination therapy and their effects in pancreatic cancer in vivo. METHODS: The expression level of hENT1 mRNA was examined using 6 types of human pancreatic cancer cell lines treated with 5-FU and MiaPaCa-2 xenograft tumors in BALB/c nu/nu mice treated with UFT. A [H] gemcitabine cellular uptake assay was performed using MiaPaCa-2 cells treated with 5-FU. We compared the effects of 6 different schedules of treatment using UFT and/or gemcitabine on MiaPaCa-2 xenograft tumors. RESULTS: MiaPaCa-2 cell line was one of the lines that showed the highest rate of 5-FU-induced increase in the hENT1 mRNA level. Gemcitabine uptake was significantly increased when cells were treated with 5-FU. Treatment with UFT significantly increased the hENT1 mRNA expression in MiaPaCa-2 tumors. A significant growth inhibition of MiaPaCa-2 tumors was observed in the mice treated with UFT followed by gemcitabine as compared with either untreated mice or UFT alone-treated mice. CONCLUSIONS: Our results suggest that the schedule in which the gemcitabine is administered after UFT may be the optimal combination for gemcitabine/UFT treatment in pancreatic cancer.[1]

References

Schedule-dependent therapeutic effects of gemcitabine combined with uracil-tegafur in a human pancreatic cancer xenograft model. Tsujie, M., Nakamori, S., Nakahira, S., Takeda, S., Takahashi, Y., Hayashi, N., Okami, J., Nagano, H., Dono, K., Umeshita, K., Sakon, M., Monden, M. Pancreas (2006) [Pubmed]

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