Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy.
Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy.
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DOI：
10.3892/ol.2016.5082
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发表时间：
2016-11
期刊：
影响因子：
2.9
通讯作者：
Mikami M
中科院分区：
文献类型：
--
作者：
Shida M;Yasuda M;Fujita M;Miyazawa M;Kajiwara H;Hirasawa T;Ikeda M;Matsui N;Muramatsu T;Mikami M
胸苷磷酸化酶（TP）在结构上与血小板源性内皮细胞生长因子相似，它能激活5-氟尿嘧啶（5-FU）前药并促进血管生成。在本研究中，在妇科肿瘤患者中研究了使用 TP 表达作为 5-FU 前药生物标志物的可能性，以及 TP 作为血管生成因子的重要性。研究对象为2002年2月至2010年1月期间在东海大学医院妇产科接受肿瘤切除术并知情同意的188名妇科肿瘤患者。采用酶联免疫吸附法测定TP和二氢嘧啶脱氢酶（DPD）的酶活性。此外，还通过单色成像、蛋白质印迹和逆转录聚合酶链反应对微血管进行了免疫组织化学（IHC）分析。与良性肿瘤和其他恶性肿瘤（包括子宫内膜癌、卵巢浆液性腺癌）相比，宫颈鳞状细胞癌（分别为 306.9 和 2.2 U/mg 蛋白）和腺鳞癌（分别为 317.6 和 1.4 U/mg 蛋白）的平均 TP 活性和 TP/DPD 比值升高 和卵巢粘液腺癌。然而，这些参数在其他组织学类型的癌症中也升高，例如卵巢透明细胞腺癌（分别为 115.2 和 2.1 U/mg 蛋白质），其中微血管面积是所有分析的组织学类型中最大的。由于在除宫颈癌之外的其他肿瘤中也发现了高 TP 表达和高 TP/DPD 比值，因此如果在开始治疗之前确定 TP 活性并通过 IHC 分析其 TP 表达，则可以适当选择适用 5-FU 前药的患者。
Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.
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影响因子：
8.4
作者：
Miwa, M;Ura, M;Ishitsuka, H
通讯作者：
Ishitsuka, H
影响因子：
2.4
作者：
Akasu, Takayuki;Moriya, Yoshihiro;Kodaira, Susumu
通讯作者：
Kodaira, Susumu
影响因子：
64.8
作者：
HEIDELBERGER, C;CHAUDHURI, NK;SCHEINER, J
通讯作者：
SCHEINER, J
影响因子：
9.7
作者：
Fujimoto, J;Ichigo, S;Tamaya, T
通讯作者：
Tamaya, T
影响因子：
3.3
作者：
Nakanishi, Yoshie;Kodama, Junichi;Kudo, Takafumi
通讯作者：
Kudo, Takafumi