論文 - 詳細
RRC ID | 42598 |
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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) |