Sasaki Hidefumi, Fukai Ichiro, Kiriyama Masanobu, Kaji Masahiro, Yano Motoki, Yamakawa Yosuke, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Surg Today. 2003;33(2):83-8. doi: 10.1007/s005950300018.
Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma.
To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard.
In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors.
The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.
胸腺瘤是纵隔最常见的实体瘤之一。然而，对于晚期胸腺瘤的最佳辅助化疗尚无明确共识。
为预测胸腺瘤对5-氟尿嘧啶（5-FU）的肿瘤敏感性，我们研究了胸苷酸合成酶（TS）的mRNA水平，TS是催化脱氧尿苷单磷酸甲基化的关键酶，与5-FU耐药相关，还研究了二氢嘧啶脱氢酶（DPD），其可降解胸腺瘤中的5-FU。我们使用LightCycler实时定量逆转录-聚合酶链反应（RT-PCR）监测患者胸腺瘤组织标本中TS和DPD基因表达水平，并与作为内参的甘油醛-3-磷酸脱氢酶（GAPDH）共同扩增。
在切除的肿瘤标本中，TS和DPD的mRNA水平分别为3.876和14.651。肿瘤组织标本中TS和DPD的mRNA水平均显著高于相邻正常胸腺组织标本。未观察到TS或DPD水平与其他临床病理因素之间存在显著相关性。
使用实时RT-PCR分析联合检测TS和DPD的mRNA水平可能提示5-FU对胸腺瘤的选择性细胞毒性。一般而言，5-FU本身不被认为是治疗胸腺瘤的有效药物。因此，应进一步考虑DPD抑制性氟嘧啶（DIF）药物对胸腺瘤的有效性。
