Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: possible predictor for sensitivity to 5-fluorouracil.
Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: possible predictor for sensitivity to 5-fluorouracil.
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DOI：
10.1111/j.1349-7006.2000.tb00866.x
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发表时间：
2000-01
期刊：
影响因子：
--
通讯作者：
Kitajima M
中科院分区：
文献类型：
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作者：
Ishikawa Y;Kubota T;Otani Y;Watanabe M;Teramoto T;Kumai K;Takechi T;Okabe H;Fukushima M;Kitajima M
我们研究了人胃癌标本中肿瘤对5-氟尿嘧啶（5-FU）的敏感性与胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）的酶活性之间的相关性。41例晚期胃癌患者提供了知情同意书并入组研究。术前通过胃镜活检获得胃癌组织标本，并用于检测TS和DPD信使RNA（mRNA）的水平。TS和DPD酶活性和mRNA水平也测量手术切除后获得的切除肿瘤组织样品。分别使用TS结合试验和放射酶试验测量TS和DPD活性，同时通过半定量逆转录聚合酶链反应（RT-PCR）测量mRNA水平，并以甘油醛-3-磷酸脱氢酶（GAPDH）的共扩增作为内标。通过基于四唑的比色测定法（MTT测定法）测量切除肿瘤标本的5-FU敏感性。TS和DPD mRNA水平相关性良好活检和切除肿瘤标本。一个统计学上显着的相关性，也观察到活检标本中的mRNA水平和酶的活性在切除标本。DPD水平与5-FU敏感性显著相关，因此高DPD活性和高DPD mRNA水平导致对5-FU的低敏感性。相反，TS活性或TS mRNA水平与5-FU敏感性之间未观察到相关性。我们的结论是，肿瘤DPD mRNA水平，从活检标本通过胃镜检查获得的评估，可能是一个有用的指标，预测肿瘤敏感性5-FU胃癌患者。
We investigated the correlation between tumor sensitivity to 5‐fluorouracil (5‐FU) and enzymatic activities of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in human gastric cancer specimens. Forty‐one patients with advanced gastric cancer gave informed consent and were enrolled in the study. Biopsy specimens of gastric cancer were obtained preoperatively through gastrofiberscopy and used to determine TS and DPD messenger RNA (mRNA) levels. TS and DPD enzyme activity and mRNA levels were also measured in resected tumor tissue samples obtained after surgical resection. TS and DPD activity were measured using the TS‐binding assay and a radioenzymatic assay, respectively, while mRNA levels were measured by semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR), with co‐amplification of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) as an internal standard. 5‐FU sensitivity of resected tumor specimens was measured by the tetrazolium‐based colorimetric assay (MTT assay). Both TS and DPD mRNA levels correlated well between biopsied and resected tumor specimens. A statistically significant correlation was also observed between mRNA levels in biopsied specimens and enzymatic activities in resected specimens. DPD levels significantly correlated with 5‐FU sensitivity, such that high DPD activity and high DPD mRNA levels resulted in low sensitivity to 5‐FU. In contrast, no correlation was observed between TS activity or TS mRNA levels and 5‐FU sensitivity. We conclude that tumor DPD mRNA level, as assessed from biopsy specimens obtained by gastrofiberscopy, may be a useful indicator in predicting tumor sensitivity to 5‐FU in patients with gastric cancer.
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影响因子：
45.3
作者：
ETIENNE, MC;CHERADAME, S;MILANO, G
通讯作者：
MILANO, G
影响因子：
45.3
作者：
Baker, SD;Khor, SP;Rowinsky, EK
通讯作者：
Rowinsky, EK
影响因子：
8.4
作者：
BECK, A;ETIENNE, MC;MILANO, G
通讯作者：
MILANO, G
影响因子：
45.3
作者：
Leichman, CG;Lenz, HJ;Danenberg, PV
通讯作者：
Danenberg, PV
影响因子：
8.8
作者：
通讯作者：
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