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.
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.
Authors: M Esteller; J Garcia-Foncillas; E Andion; S N Goodman; O F Hidalgo; V Vanaclocha; S B Baylin; J G Herman Journal: N Engl J Med Date: 2000-11-09 Impact factor: 91.245
Authors: A S Fleisher; M Esteller; S Wang; G Tamura; H Suzuki; J Yin; T T Zou; J M Abraham; D Kong; K N Smolinski; Y Q Shi; M G Rhyu; S M Powell; S P James; K T Wilson; J G Herman; S J Meltzer Journal: Cancer Res Date: 1999-03-01 Impact factor: 12.701
Authors: Rathi N Pillai; Seth A Brodie; Gabriel L Sica; You Shaojin; Ge Li; Dana C Nickleach; Liu Yuan; Vijay A Varma; Dacian Bonta; James G Herman; Malcom V Brock; Maria J A Ribeiro; Suresh S Ramalingam; Taofeek K Owonikoko; Fadlo R Khuri; Johann C Brandes Journal: Clin Cancer Res Date: 2013-02-05 Impact factor: 12.531
Authors: Yazhuo Li; Yunsheng Yang; Youyong Lu; James G Herman; Malcolm V Brock; Po Zhao; Mingzhou Guo Journal: Gastric Cancer Date: 2014-04-21 Impact factor: 7.370