RRC ID 42598
著者 Koga Y, Kitajima Y, Miyoshi A, Sato K, Sato S, Miyazaki K.
タイトル The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer.
ジャーナル J Gastroenterol
Abstract BACKGROUND:We studied the correlations between CHFR (checkpoint with FHA and RING finger) gene methylation and responses to microtubule inhibitors (MI) in gastric cancer.
METHODS:We examined 9 gastric cancer cell lines and 46 gastric cancer specimens from patients who underwent surgical resection. Promoter methylation was determined by methylation-specific polymerase chain reaction (MSP). CHFR mRNA expression was estimated by quantitative reverse transcription-PCR. The MI-induced growth inhibition was assayed by a standard MTT method.
RESULTS:CHFR expression was silenced by aberrant promoter methylation in 3 of 9 gastric cancer cell lines. The level of CHFR mRNA expression was closely correlated with IC(50) in the MI-treated cells (R=0.889, P=0.005). In 46 patients with gastric cancers, 24 (52%) presented aberrant CHFR methylation. Among them, 12 patients had received treatment with MI because of advanced-stage tumor or tumor recurrence after surgery. The responders to the MI treatment were 29% in patients with CHFR methylation and 20% in those without the methylation. However, 6 (86%) of 7 patients with methylated CHFR tumor showed some regression or no progression, whereas 4 (80%) of 5 patients with unmethylated CHFR tumor manifested progressive deterioration.
CONCLUSIONS:These observations indicated that CHFR methylation may be a clinically useful approach to predict the responsiveness of gastric cancers to treatment with MI.
巻・号 41(2)
ページ 133-9
公開日 2006-2-1
DOI 10.1007/s00535-005-1732-7
PMID 16568372
MeSH Adult Aged Cell Cycle Proteins / genetics* Cell Line, Tumor Female Gene Expression Humans In Vitro Techniques Male Methylation Middle Aged Neoplasm Proteins / genetics* Poly-ADP-Ribose Binding Proteins Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics Stomach Neoplasms / surgery Tubulin Modulators / pharmacology* Ubiquitin-Protein Ligases
IF 6.132
引用数 45
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 MKN1(RCB1003) MKN7(RCB0999) MKN45(RCB1001) Kato III(RCB2088)