Effects of Combined Administration of DPD-Inhibitory Oral Fluoropyrimidine, S-1, Plus Paclitaxel on Gene Expressions of Fluoropyrimidine Metabolism-Related Enzymes in Human Gastric Xenografts
| Autor: | Shingo Kamoshida, Yoshiyuki Komori, Yoichi Sakurai, Jun Isogaki, Kazuki Inaba, Yutaka Tsutsumi, Ichiro Uyama, Ikuo Yoshida |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Antimetabolites Antineoplastic Paclitaxel Orotate Phosphoribosyltransferase Gene Expression Pharmacology Thymidylate synthase Mice chemistry.chemical_compound Stomach Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine Dihydropyrimidine dehydrogenase Animals Humans Thymidine phosphorylase Dihydrouracil Dehydrogenase (NADP) Tegafur Cisplatin Mice Inbred BALB C Thymidine Phosphorylase Uridine Phosphorylase Taxane biology business.industry Drug Synergism Thymidylate Synthase Xenograft Model Antitumor Assays Drug Combinations Oxonic Acid Oncology chemistry Uridine phosphorylase Cancer research biology.protein Orotate phosphoribosyltransferase Drug Therapy Combination Female Surgery Fluorouracil business medicine.drug |
| Zdroj: | Annals of Surgical Oncology. 15:2301-2309 |
| ISSN: | 1534-4681 1068-9265 |
| DOI: | 10.1245/s10434-008-9963-5 |
| Popis: | S-1 is the most effective oral fluoropyrimidine derivative widely used for patients with gastric carcinoma in Japan. Although S-1 plus taxane has been a promising candidate as an effective chemotherapeutic regimen, the mechanisms of its additive or synergistic anticancer effects and changes in gene expression after the administration of these agents have not yet been fully elucidated. Experimental chemotherapy was performed using human gastric carcinoma xenografts, MKN-45 and TMK-1, to examine anticancer effects and gene expressions of fluoropyrimidine metabolism-related enzymes including thymidine phosphorylase (TP), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and uridine phosphorylase (UP). Nude mice were treated with S-1, paclitaxel, and their combination. After treatment, in vivo antitumor effects of S-1, paclitaxel alone, and their combination and the effects on gene expressions of enzymes involved in 5-fluorouracil metabolism were examined using the RT-PCR method. The combined use of S-1 and paclitaxel showed additive to synergistic antitumor effects on both gastric cancer xenografts. While consistent upregulation of dThPase and DPD gene expression was exhibited after administration of S-1, no further increase of dThPase gene expression after combined use of S-1 with paclitaxel was observed. There was no increase in TS gene expression after the administration of either S-1 alone or paclitaxel alone. These results provide some insight into the mechanism and/or rationale underlying the additive to synergistic effect of combined administration of S-1 and paclitaxel in gastric carcinoma. |
| Databáze: | OpenAIRE |
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