Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU.
Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU.
复制标题
DOI：
10.1007/s101470200051
复制
发表时间：
2002-12-01
影响因子：
3.3
通讯作者：
Maekawa, Yoshimi
中科院分区：
文献类型：
--
作者：
Isshi, Kimio;Sakuyama, Toshikazu;Maekawa, Yoshimi
背景：在肿瘤细胞中，羊角酸磷酸核糖基转移酶（OPRT）有助于5-氟尿嘧啶（5-FU）的磷酸化，而另一种酶，二氢嘧啶脱氢酶（DPD），与5-FU的分解代谢作用有关。我们测量了OPRT和DPD活性，并确定它们的水平是否可以作为5-FU敏感性的指标，同时测定了对5-FU的体外化学敏感性。方法：取结直肠癌患者组织标本，采用双醋酸荧光素法（FDA）或组织培养药物反应法（HDRA）检测体外化疗敏感性。用放射法测定DPD和OPRT活性。结果：对62例结直肠癌标本进行了化疗敏感性试验。30例FDA患者中有29例（96.7%）可评估，32例HDRA患者中有30例（98.3%）可评估。FDA法和HDRA法的阳性敏感性分别为37.9%和30%。阳性标本平均DPD活性为44.9 +/- 32.6 pmol/min / mg蛋白，阴性标本平均DPD活性为53.8 +/- 33.7 pmol/min / mg蛋白（P= 0.875）。阳性标本的平均OPRT值（0.418 +/- 0.180 nmol/min / mg protein）显著高于阴性标本（0.325 +/- 0.153 nmol/min / mg protein, P < 0.05）。ORPT活性在0.413或以上的标本中，60%呈阳性，DPD活性在30或以下的标本中，50%呈阳性。在OPRT活性0.413及以上、DPD活性30及以下的患者标本中，88.9%的患者5-FU敏感性阳性，提示这两种水平的结合可能预测5-FU阳性敏感性。结论：肿瘤细胞内DPD和OPRT活性可预测5-FU的阳性敏感性。
BACKGROUND: In tumor cells, the enzyme orotate phosphoribosyl transferase (OPRT) contributes to 5-fluorouracil (5-FU) phosphorylation and another enzyme, dihydropyrimidine dehydrogenase (DPD), is associated with 5-FU catabolic action. We measured OPRT and DPD activities and, to determine whether their levels might serve as indicators of 5-FU sensitivity, simultaneously assayed in vitro chemosensitivity to 5-FU.METHODS: Tissue specimens were obtained from colorectal cancer patients and in vitro chemosensitivity was tested using fluorescein diacetate assay (FDA) or histoculture drug response assay (HDRA). DPD and OPRT activities were measured by radioassay.RESULTS: The chemosensitivity assay was performed on 62 colorectal cancer specimens. Results were evaluable in 29 of 30 cases (96.7%) for FDA and 30 of 32 cases (98.3%) for HDRA. The positive sensitivity rate was 37.9% by FDA assay and 30% by HDRA assay. In positive specimens, the mean DPD activity was 44.9 +/- 32.6 pmol/min per mg protein, and in negative specimens, it was 53.8 +/- 33.7 pmol/min per mg protein ( P= 0.875). In contrast, the mean OPRT value was significantly higher in positive specimens (0.418 +/- 0.180 nmol/min per mg protein) than in negative specimens (0.325 +/- 0.153 nmol/min per mg protein; P < 0.05). The chemosensitivity test proved positive in 60% of the specimens with ORPT activity of 0.413 or above and 50% of those with DPD activity of 30 or below. Of the patient specimens showing OPRT activity of 0.413 or above and DPD activity of 30 or below, 88.9% were positive for 5-FU sensitivity, suggesting the possibility that the combination of these two levels may be predictive of 5-FU positive sensitivity.CONCLUSION: DPD and OPRT activities within cancer cells may predict positive sensitivity to 5-FU.