Brief Article
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World J Gastroenterol. Sep 28, 2010; 16(36): 4575-4582
Published online Sep 28, 2010. doi: 10.3748/wjg.v16.i36.4575
A predictive factor for the response to S-1 plus cisplatin in gastric cancer
Ikuko Miyazaki, Takashi Kawai, Youji Harada, Fuminori Moriyasu
Ikuko Miyazaki, Fuminori Moriyasu, Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
Takashi Kawai, Endoscope Center, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
Youji Harada, Department of Gastroenterology, Toda Chuo General Hospital, 1-19-3 Honcho, Toda-shi, Saitama 335-1132, Japan
Author contributions: Miyazaki I designed this study, performed all the experiments, analyzed and interpreted the data, and wrote the manuscript under the supervision of Moriyasu F; Harada Y, Kawai T and Moriyasu F approved the final version of the manuscript.
Correspondence to: Dr. Ikuko Miyazaki, Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. yukawaiku@yahoo.co.jp
Telephone: +81-3-33426111 Fax: +81-3-53816654
Received: April 26, 2010
Revised: June 23, 2010
Accepted: June 30, 2010
Published online: September 28, 2010
Abstract

AIM: To prove that the protein expression level of thymidylate synthase is a predictive factor for the response to S-1/cisplatin (CDDP) chemotherapy in gastric cancer.

METHODS: We measured the protein expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in advanced gastric cancer. Before S-1/CDDP chemotherapy, tumor specimens from primary sites were obtained by endoscopic biopsy and analyzed by enzyme-linked immunosorbent assay. The chemotherapeutic effects on the primary sites were evaluated by endoscopic biopsy performed more than once after S-1/CDDP chemotherapy. The effects are a predictive factor for the response to S-1/CDDP chemotherapy in patients with advanced gastric cancer, as evaluated by endoscopic biopsy over time.

RESULTS: The protein expression level of TS was significantly higher (P < 0.05) in the tumor than in the normal tissue, and significantly lower (P < 0.05) in the responders than in the non-responders. We were able to evaluate the correlation between changes in the protein expression levels of TS, DPD and OPRT and chemotherapeutic responses in 7 patients by assessing tumor tissues more than twice. In the responders, the protein expression level of TS was < 40 ng/mg protein. However, there were significant increases in the protein expression levels of TS (P < 0.01) and DPD (P < 0.05) after chemotherapy in 3 patients. In these cases, the patient assessment changed from “responder” to “non-responder”. In the non-responders, the protein expression level of TS was > 40 ng/mg protein.

CONCLUSION: We have confirmed that the protein expression level of TS is a predictive factor for the response to S-1/CDDP chemotherapy in patients with advanced gastric cancer.

Keywords: Gastric cancer; Thymidylate synthase; Dihydropyrimidine dehydrogenase; Orotate phosphoribosyltransferase; Biopsy