Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: Role of p53 expression

Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: Role of p53 expression
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胸苷磷酸化酶在人结直肠粘膜、腺瘤和癌中的表达:p53 表达的作用

DOI:
10.1046/j.1440-1827.1999.00897.x
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发表时间:
1999
影响因子:
2.2
通讯作者:
Hisao Ito
Hisao Ito
中科院分区:
医学4区
文献类型:
--
作者:
K. Shomori;T. Sakatani;A. Goto;T. Matsuura;H. Kiyonari;Hisao Ito

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胸苷磷酸化酶(dThdlase)与血小板衍生的内皮细胞生长因子(PD-ECGF)相同,后者是一种有效的血管生成因子。本研究以肿瘤内微血管密度(IMVD)和P53表达为指标,采用免疫组化方法检测了dThdR在人结直肠粘膜、腺瘤和癌以及6种培养的结直肠癌细胞系中的表达。胸苷磷酸化酶在淋巴细胞、成纤维细胞和巨噬细胞以及周围神经纤维中的平滑肌细胞和雪旺细胞中观察到。dThd 3阳性基质细胞明显多于正常上皮细胞、腺瘤和癌细胞。弱,但明显的细胞质免疫反应,注意到在一些正常的结肠上皮,主要是上表面区域,而一些腺瘤细胞表现出弱的核免疫染色dThdR在6(24%)的25个结肠腺瘤。45例Dukes A、B、27例Dukes C、25例Dukes D癌中dThd 3阳性表达率分别为73.3%、51.9%、56.0%。36例dThd 3阴性癌的平均IMVD为84.0 ± 26.2,61例dThd 3阳性癌的平均IMVD为97.9 ± 31.6,后者的IMVD值显著高于前者(P< 0.05)。P53阴性癌中dThd 4蛋白表达率明显低于阳性癌(P< 0.05)。Western blot分析显示,在携带野生型p53基因的LoVo中,dThdR的表达最高,其次是携带突变基因的Colo 201、Colo 320、DLD-11和WiDr。这些结果表明:(i)dThdR的主要来源是基质细胞,包括结直肠正常组织和癌组织中的淋巴细胞和巨噬细胞;(ii)dThdR可能参与肿瘤内微血管的诱导,而与肿瘤阶段无关;(iii)表达可能不仅受P53调节,还受其他分子调节。
The enzyme, thymidine phosphorylase (dThdPase) is identical to platelet‐derived endothelial cell growth factor (PD‐ECGF), which acts as a potent angiogenic factor. The present study immunohistochemically examined the expression of dThdPase in human colorectal mucosa, adenomas and carcinomas, as well as six cultured colorectal carcinoma cell lines, in terms of intratumoral microvessel density (IMVD) and P53 expression. Thymidine phosphorylase was observed in lymphocytes, fibroblasts and macrophages, as well as smooth muscle cells and Schwann cells in the peripheral nerve fibers. The dThdPase‐positive stromal cells apparently outnumbered the normal epithelial cells, adenoma and carcinoma cells with dThdPase. Weak but obvious cytoplasmic immunoreactivity was noted in a few normal colonic epithelia, predominantly the upper surface area, while a few adenoma cells showed weak nuclear immunostaining for dThdPase in six (24%) of the 25 colonic adenomas. Expression of dThdPase was noted in 33 (73.3%) of the 45 Dukes A and B, 14 (51.9%) of the 27 Dukes C and 14 (56.0%) of the 25 Dukes D carcinomas. The mean IMVD was 84.0 ± 26.2 in the 36 dThdPase‐negative carcinomas and 97.9 ± 31.6 in the 61 dThdPase‐positive carcinomas, the value being significantly higher in the latter group (P< 0.05). The frequency of dThdPase expression was significantly lower in the P53‐negative carcinomas than in the positive carcinomas (P< 0.05). Western blot analysis showed the highest expression of dThdPase in LoVo carrying the wild‐type p53 gene, followed by Colo201, Colo320, DLD‐11 and WiDr carrying the mutated gene. These results indicate that: (i) the main source of dThdPase is stromal cells, including lymphocytes and macrophages in both colorectal normal and carcinoma tissues; (ii) dThdPase may take part in the induction of intratumoral microvessels, regardless of tumor stage; and (iii) expression might be modulated by not only P53 but also other molecules.
DOI: 10.1056/nejm199101033240101
发表时间: 1991-01-03
影响因子: 158.5
作者:
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
通讯作者: FOLKMAN, J
DOI: --
发表时间: 1998-05
期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子: --
作者:
H. Lenz;K. Hayashi;D. Salonga;K. Danenberg;P. Danenberg;R. Metzger;D. Banerjee;J. Bertino;S. Groshen;L. Leichman;C. Leichman
通讯作者: H. Lenz;K. Hayashi;D. Salonga;K. Danenberg;P. Danenberg;R. Metzger;D. Banerjee;J. Bertino;S. Groshen;L. Leichman;C. Leichman
DOI: 10.1021/bi00345a011
发表时间: 1985-01-01
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
ILTZSCH, MH;ELKOUNI, MH;CHA, S
通讯作者: CHA, S