Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
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结直肠癌中核胸苷酸合酶表达、p53 表达和 5FU 反应
DOI：
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发表时间：
2001
影响因子：
8.8
通讯作者：
D. I. Jodrell
中科院分区：
文献类型：
--
作者：
N. Wong;L. Brett;M. Stewart;A. Leitch;D. Longley;D. Longley;Malcolm G. Dunlop;P. G. Johnston;P. G. Johnston;A. Lessells;D. I. Jodrell
胸苷酸合成酶（TS）是DNA合成的关键酶，可被化疗药物5-氟尿嘧啶（5 FU）的代谢产物抑制。TS在体内人体组织中的核表达尚未得到表征，其在恶性肿瘤中的临床病理学相关性尚不清楚。应用单克隆抗体TS 106对52例原发性结直肠癌和24例转移癌进行免疫组化研究。核TS免疫染色的程度密切相关的TS mRNA表达水平之间的10个研究的CRC。在正常基底隐窝结肠细胞和生发中心细胞以及不同比例的腺癌细胞中观察到强烈的核免疫染色。在原发癌中，较高的TS核表达与突出的细胞外粘蛋白产生和右侧位置相关。较高的TS核表达也显示出与对长期静脉输注5 FU治疗的反应较差显著相关。免疫组化检测TS核表达与Ki 67或p53表达之间无明显相关性。原发性和转移性CRC中TS核表达之间存在强正相关，但后者通常表现出比匹配的原发性肿瘤组织更高的表达。这些发现证实了TS蛋白在体内人细胞中的核表达，并为这种表达如何与CRC的行为相关提供了新的见解。© 2001年癌症研究运动http://www.bjcancer.com
Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of primary colorectal carcinoma (CRC) and 24 cases of matched metastatic carcinoma were studied immunohistochemically using the monoclonal antibody TS106. The degree of nuclear TS immunostaining correlated closely with levels of TS mRNA expression amongst 10 CRCs studied. Strong nuclear immunostaining was seen in normal basal crypt colonocytes and germinal centre cells, and in a varying proportion of adenocarcinoma cells. Amongst the primary carcinomas, higher TS nuclear expression was associated with prominent extracellular mucin production and right-sided location. Higher TS nuclear expression also showed a significant association with poorer response to protracted venous infusional 5FU therapy. There was no clear association between TS nuclear expression and Ki67 or p53 expression assessed immunohistochemically. There was a strong positive correlation between TS nuclear expression in primary and metastatic CRC but the latter generally showed higher expression than matched primary tumour tissue. These findings confirm the nuclear expression of TS protein in human cells in vivo and provide new insight into how such expression may relate to the behaviour of CRCs. © 2001 Cancer Research Campaign http://www.bjcancer.com
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DOI：
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发表时间：
2000-12
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
C. Aschele;D. Debernardis;G. Tunesi;F. Maley;A. Sobrero
通讯作者：
C. Aschele;D. Debernardis;G. Tunesi;F. Maley;A. Sobrero
影响因子：
11.2
作者：
P. Johnston;H. Lenz;C. Leichman;K. Danenberg;C. Allegra;P. Danenberg;L. Leichman
通讯作者：
P. Johnston;H. Lenz;C. Leichman;K. Danenberg;C. Allegra;P. Danenberg;L. Leichman
影响因子：
8.4
作者：
BIKFALVI, A
通讯作者：
BIKFALVI, A
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
影响因子：
45.3
作者：
Aschele, C;Debernardis, D;Sobrero, A
通讯作者：
Sobrero, A