AIM： To investigate the prognostic role of thymidylate synthase （TS） and thymidine phosphorylase （TP） mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS： Fifty...AIM： To investigate the prognostic role of thymidylate synthase （TS） and thymidine phosphorylase （TP） mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS： Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS： The median disease-free survival （DFS） time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS （14.4 mo vs 8.3 mo, P = 0.017）. The median overall survival （OS） time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP （for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009）. Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION： Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.展开更多
The mRNA and protein expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and their relationship with prognosis were investigated. Real-time quantitative RT-P...The mRNA and protein expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and their relationship with prognosis were investigated. Real-time quantitative RT-PCR (Taqman) was used to detect the mRNA expression of TS, TP and DPD in formalin-fixed and paraffin-embedded 106 samples of epithelial ovarian cancer and 29 normal ovaries. A TATA box-binding protein (TBP) was used as an endogenous reference gene. A relationship between TS, TP, DPD expression and clinicopathologic features was investigated. The protein location and expression of TS, TP and DPD was examined in the same patients by an avidin-biotin-peroxidase immunohistochemistry. TS and TP mRNA expression levels were significantly higher in tumor group than in normal controls, with the average value of TS and TP mRNA being 6.14±0.62 and 0.59±0.06 in tumor tissue, and 0.71±0.14 and 0.16±0.04 in normal tissue, respectively. DPD mRNA expression levels were significantly lower in tumor group (0.11±0.02) than in normal controls (0.38±0.05). There was statistically significant difference in TS and TP mRNA expression levels among different pathological grades and clinical stages (P<0.05), but histological subtype was not significantly associated with TS and TP mRNA expression. DPD gene expression was not significantly associated with any clinicopathological parameters. Immunohistochemistry revealed that TP protein was mainly distributed in nucleus, and TS and DPD mainly in cytoplasm. The protein expression intensity of TS, TP and DPD was coincided with the mRNA expression levels. It was concluded that TS, TP mRNA and protein expression levels were significantly higher in epithelial ovarian cancer, and DPD mRNA and protein expression levels were significantly lower. The expression levels of TS and DPD were related to the patients’ prognosis and survival. Combined gene expression levels of TS, TP and DPD represent a new variable to predict the clinical outcome in ovarian cancer. The association of TS, TP and DPD expression levels with survival suggests an importance of these genes for tumor occurrence and progression.展开更多
AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of ...AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.展开更多
背景与目的：胸苷酸合成酶（thymidylate synthetase，TS）和胸苷酸磷酸化酶（thymidine phosphorylase，TP）是氟尿嘧啶类药物在体内代谢的关键酶，与胃癌患者接受氟尿嘧啶药物化疗疗效和预后密切相关。本研究旨在探讨晚期胃癌患者血清...背景与目的：胸苷酸合成酶（thymidylate synthetase，TS）和胸苷酸磷酸化酶（thymidine phosphorylase，TP）是氟尿嘧啶类药物在体内代谢的关键酶，与胃癌患者接受氟尿嘧啶药物化疗疗效和预后密切相关。本研究旨在探讨晚期胃癌患者血清中TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性。方法：收集2006年1月-2008年10月于北京大学肿瘤医院消化肿瘤内科治疗的109例一线接受氟尿嘧啶类药物为基础化疗的晚期胃癌患者化疗前的血清标本，运用酶联免疫吸附试验（ELISA）方法检测血清中Ts、TP表达水平，分析TS、TP表达水平与化疗疗效及患者预后的相关性。结果：近端胃癌患者的TS表达水平高于远端胃癌患者（P=0．035），腹膜转移患者的TP表达水平明显低于无腹膜转移患者（P〈0．001）。TS高表达患者临床获益率（clinical benefitrate，CBR）高于低表达患者（68．75％vs47．1％，P=0．029），与患者生存无明显相关。TP高表达患者的中位无进展生存期（progression—free survival，PFS）与总生存期（overall survival，0S）均长于低表达患者（PFS：177d vs 113d，P=0．018：OS：399d vs 234d，P=0．227）。联合分析TS、TP表达发现，TS低表达且TP高表达患者的中位PFS和0S明显长于TS、TP均低表达患者（PFS：182d vs 87d，P=0．042：OS：429d vs 223d，P=0．019）。Cox多因素生存分析表明，在TS低表达时，TP表达水平是预后的独立影响因素（HR=I．913，95％CI：1．027-3．564，P=0．041）。结论：在接受氟尿嘧啶为基础化疗的晚期胃癌患者中，TS高表达患者的疗效较好，TP高表达患者的生存期较长，特别是TS低表达且TP高表达患者的生存期明显延长。展开更多
文摘AIM： To investigate the prognostic role of thymidylate synthase （TS） and thymidine phosphorylase （TP） mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS： Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS： The median disease-free survival （DFS） time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS （14.4 mo vs 8.3 mo, P = 0.017）. The median overall survival （OS） time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP （for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009）. Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION： Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30973184)
文摘The mRNA and protein expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and their relationship with prognosis were investigated. Real-time quantitative RT-PCR (Taqman) was used to detect the mRNA expression of TS, TP and DPD in formalin-fixed and paraffin-embedded 106 samples of epithelial ovarian cancer and 29 normal ovaries. A TATA box-binding protein (TBP) was used as an endogenous reference gene. A relationship between TS, TP, DPD expression and clinicopathologic features was investigated. The protein location and expression of TS, TP and DPD was examined in the same patients by an avidin-biotin-peroxidase immunohistochemistry. TS and TP mRNA expression levels were significantly higher in tumor group than in normal controls, with the average value of TS and TP mRNA being 6.14±0.62 and 0.59±0.06 in tumor tissue, and 0.71±0.14 and 0.16±0.04 in normal tissue, respectively. DPD mRNA expression levels were significantly lower in tumor group (0.11±0.02) than in normal controls (0.38±0.05). There was statistically significant difference in TS and TP mRNA expression levels among different pathological grades and clinical stages (P<0.05), but histological subtype was not significantly associated with TS and TP mRNA expression. DPD gene expression was not significantly associated with any clinicopathological parameters. Immunohistochemistry revealed that TP protein was mainly distributed in nucleus, and TS and DPD mainly in cytoplasm. The protein expression intensity of TS, TP and DPD was coincided with the mRNA expression levels. It was concluded that TS, TP mRNA and protein expression levels were significantly higher in epithelial ovarian cancer, and DPD mRNA and protein expression levels were significantly lower. The expression levels of TS and DPD were related to the patients’ prognosis and survival. Combined gene expression levels of TS, TP and DPD represent a new variable to predict the clinical outcome in ovarian cancer. The association of TS, TP and DPD expression levels with survival suggests an importance of these genes for tumor occurrence and progression.
基金Supported by The Thailand Research Fund through The Royal Golden Jubilee PhD Program Grant No. PHD/0037/2544 for Thanasai J and Limpaiboon T and grants-in-aid from the Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand, and from the Ministry of Education, Sports, Science, Culture and Technology, Japan
文摘AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.
文摘背景与目的：胸苷酸合成酶（thymidylate synthetase，TS）和胸苷酸磷酸化酶（thymidine phosphorylase，TP）是氟尿嘧啶类药物在体内代谢的关键酶，与胃癌患者接受氟尿嘧啶药物化疗疗效和预后密切相关。本研究旨在探讨晚期胃癌患者血清中TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性。方法：收集2006年1月-2008年10月于北京大学肿瘤医院消化肿瘤内科治疗的109例一线接受氟尿嘧啶类药物为基础化疗的晚期胃癌患者化疗前的血清标本，运用酶联免疫吸附试验（ELISA）方法检测血清中Ts、TP表达水平，分析TS、TP表达水平与化疗疗效及患者预后的相关性。结果：近端胃癌患者的TS表达水平高于远端胃癌患者（P=0．035），腹膜转移患者的TP表达水平明显低于无腹膜转移患者（P〈0．001）。TS高表达患者临床获益率（clinical benefitrate，CBR）高于低表达患者（68．75％vs47．1％，P=0．029），与患者生存无明显相关。TP高表达患者的中位无进展生存期（progression—free survival，PFS）与总生存期（overall survival，0S）均长于低表达患者（PFS：177d vs 113d，P=0．018：OS：399d vs 234d，P=0．227）。联合分析TS、TP表达发现，TS低表达且TP高表达患者的中位PFS和0S明显长于TS、TP均低表达患者（PFS：182d vs 87d，P=0．042：OS：429d vs 223d，P=0．019）。Cox多因素生存分析表明，在TS低表达时，TP表达水平是预后的独立影响因素（HR=I．913，95％CI：1．027-3．564，P=0．041）。结论：在接受氟尿嘧啶为基础化疗的晚期胃癌患者中，TS高表达患者的疗效较好，TP高表达患者的生存期较长，特别是TS低表达且TP高表达患者的生存期明显延长。
