A predictive factor for the response to S-1 plus cisplatin in gastric cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
Miyazaki
Ikuko
I
Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. yukawaiku@yahoo.co.jp
Kawai
Takashi
T
Harada
Youji
Y
Moriyasu
Fuminori
F
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D010094:Oxonic Acid / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D005641:Tegafur / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000097:blood*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D002945:Cisplatin; D005472:Fluorouracil