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【Clin Cancer Res】接受非氟尿嘧啶治疗的结直肠癌
Purpose: K-Ras mutations predict resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies. Because combinations of anti-EGFR with 5-fluorouracil (5-FU)-based chemotherapy are promising treatments, we analyzed the effect of K-Ras mutations in patients having received exclusive 5-FU therapy.
Experimental Design: This study was conducted on 93 stage IV colorectal cancer patients with unresectable measurable liver metastasis receiving 5-FU-leucovorin (56 men and 37 women; 77 cancer deaths). Liver metastases (n = 93) along with primary tumors (n = 48) were analyzed for K-Ras mutations (codons 12 and 13), p53 mutations (exons 4-9), p53 polymorphism (codon 72), thymidylate synthase (TS) polymorphism (28-bp repeats including G>C mutation), methylenetetrahydrofolate reductase polymorphism (677C>T, 1298A>C), thymidylate synthase (TS) activity, dihydropyrimidine dehydrogenase activity, folylpolyglutamate synthase activity, and p53 protein expression.
Results: Thirty-six of 93 (38.7%) metastases were K-Ras mutated (30 at codon 12 and 6 at codon 13). Mutated primary tumors (16 of 48) matched perfectly with mutated metastases. The additional analyzed tumor markers were not different between K-Ras mutated and wild-type tumors. The objective response rate was 37%: 44.4% in K-Ras mutated versus 32.1% in wild-type K-Ras metastasis (P = 0.27). Low TS activity in metastasis was the only significant predictor of tumor response (P = 0.047). K-Ras status did not influence specific survival.
Conclusions: The present data indicate a perfect concordance of K-Ras mutations between primary and liver metastasis and suggest that any predictive and/or prognostic value of K-Ras mutations in treatments combining anti-EGFR monoclonal antibodies with 5-FU should be exclusively linked to the anti-EGFR agent.
http://clincancerres.aacrjournals.org/cgi/content/abstract/14/15/4830 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy
接受氟脲嘧啶的结直肠癌患者其K-Ras突变与治疗结局的关系
Purpose: K-Ras mutations predict resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies. Because combinations of anti-EGFR with 5-fluorouracil (5-FU)-based chemotherapy are promising treatments, we analyzed the effect of K-Ras mutations in patients having received exclusive 5-FU therapy.
目的：K-Ras突变预示着对于内皮生长因子受体(EGFR)单抗出现拮抗作用。因为抗EGFR单抗和以5-FU为基础的化疗相结合是一种很有前景的治疗方法，我们对K-Ras突变对接受单独5-FU化疗患者的影响进行了研究。
Experimental Design: This study was conducted on 93 stage IV colorectal cancer patients with unresectable measurable liver metastasis receiving 5-FU-leucovorin (56 men and 37 women; 77 cancer deaths). Liver metastases (n = 93) along with primary tumors (n = 48) were analyzed for K-Ras mutations (codons 12 and 13), p53 mutations (exons 4-9), p53 polymorphism (codon 72), thymidylate synthase（胸腺嘧啶） (TS) polymorphism (28-bp repeats including G>C mutation), methylenetetrahydrofolate reductase（亚甲基四氢叶酸还原酶） polymorphism (677C>T, 1298A>C), thymidylate synthase (TS) activity, dihydropyrimidine dehydrogenase（二氢嘧啶脱氢酶） activity, folylpolyglutamate synthase（叶酰聚谷氨酸合酶）activity, and p53 protein expression.
实验设计：本次研究对象为93名IV期结直肠癌伴有不可切除的肝转移患者（男性56人，女性37人，77人死于肿瘤），全部患者接受了5-FU甲酰四氢叶酸化疗。我们对93例患者的肝转移灶和48例患者的原发肿瘤K-Ras突变(密码子12，13)，p53突变（外显子4-9），p53多态性（密码子72），胸腺嘧啶多形性(28-bp repeats including G>C mutation)，亚甲基四氢叶酸还原酶多形性 (677C>T, 1298A>C), 胸腺嘧啶活性,二氢嘧啶脱氢酶活性, 叶酰聚谷氨酸合酶活性和p53蛋白表达的情况进行了分析.
Results: Thirty-six of 93 (38.7%) metastases were K-Ras mutated (30 at codon 12 and 6 at codon 13). Mutated primary tumors (16 of 48) matched perfectly with mutated metastases. The additional analyzed tumor markers were not different between K-Ras mutated and wild-type tumors. The objective response rate was 37%: 44.4% in K-Ras mutated versus 32.1% in wild-type K-Ras metastasis (P = 0.27). Low TS activity in metastasis was the only significant predictor of tumor response (P = 0.047). K-Ras status did not influence specific survival.
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作者:admin@医学,生命科学 2011-02-27 17:14
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