RRC ID 61585
著者 Kamoshida S, Suzuki M, Sakurai Y, Ochiai M, Kimura F, Kuwao S, Sakamoto K, Sugimoto Y, Fukushima M, Tsutsumi Y.
タイトル Expression of chemoresistance-related proteins in alpha-fetoprotein-producing adenocarcinoma of the digestive organs.
ジャーナル Oncol Rep
Abstract alpha-fetoprotein-producing adenocarcinoma of the digestive organs (APAD) is known to show a poor prognosis. To clarify the characteristics of chemoresistance in APAD, three proteins of fluoropyrimidine chemotherapy association [dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and thymidylate synthase (TS)] and one protein of cisplatin association [metallothionein (MT)] were immunohistochemically evaluated. Tissue samples were taken from 12 AFP-positive gastric cancers and 94 AFP-negative gastric cancers. Four AFP-positive cancer xenografts (one colonic, two pancreatic, and one biliary tract) and 17 AFP-negative cancer xenografts were also examined. In gastric cancers, high expression of TP was observed in 30% of AFP-negative tumors but in none of AFP-positive tumors (p=0.03). High expression of MT was found in 30% of AFP-negative tumors but in only one of the AFP-positive tumors. The TP-low and MT-low phenotype was noted in 92% of AFP-positive tumors and in 46% of AFP-negative tumors (p=0.004). None of the AFP-positive cancer xenografts revealed high TP expression and only one showed high MT expression. In the cellular level, TP and MT were scarcely co-expressed with AFP in either gastric cancer or xenograft series, using double immunostaining and serial sectioning techniques. There were no significant differences in the expression of DPD and TS between AFP-positive group and -negative group. However, DPD was frequently co-expressed with AFP in poorly differentiated medullary areas of the AFP-positive gastric cancers. The data presented herein suggest that APAD should be sensitive to cisplatin, but resistant to capecitabine and 5'-deoxyfluorouridine, fluoropyrimidines which are converted to 5-fluorouracil by TP. S-1, a fluoropyrimidine containing a strong DPD inhibitor, may be effective for AFP-positive gastric cancers with poorly differentiated medullary growth pattern.
巻・号 16(4)
ページ 721-7
公開日 2006-10-1
PMID 16969485
MeSH Adenocarcinoma / metabolism* Animals Cell Line, Tumor Dihydrouracil Dehydrogenase (NADP) / biosynthesis Drug Resistance, Neoplasm* Gastrointestinal Neoplasms / metabolism* Gene Expression Regulation, Neoplastic* Humans Metallothionein / biosynthesis Mice Mice, Nude Neoplasm Transplantation Thymidine Phosphorylase / biosynthesis Thymidylate Synthase / biosynthesis alpha-Fetoproteins / metabolism*
IF 3.417
リソース情報
ヒト・動物細胞 TGBC14TKB(RCB1186)