Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.
Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.
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DOI：
10.1054/bjoc.2001.2193
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发表时间：
2001-11-30
影响因子：
8.8
通讯作者：
Taylor I
中科院分区：
文献类型：
--
作者：
Asham E;Shankar A;Loizidou M;Fredericks S;Miller K;Boulos PB;Burnstock G;Taylor I
内皮素-1 (ET-1) 是一种血管收缩肽，可刺激不同细胞类型（包括结直肠癌细胞）的体外增殖。在癌症患者的组织样本和血浆中都检测到了升高的 ET-1 水平。为了研究 ET-1 在结直肠癌中的作用：（i）通过放射免疫测定法测量结直肠癌患者的 ET-1 血浆水平：第 1 组 = 对照组（n = 22），第 2 组 = 仅原发性结直肠癌（n = 39），第 3 组 = 仅肝转移（n = 26）； (ii) 通过免疫组织化学法测定原发性结直肠癌标本 (n =10) 中的 ET-1 表达，(iii) 评估门静脉内输注两种 ET-1 受体 (ET A 和 ET B) 拮抗剂对大鼠模型肝转移瘤生长的影响。与对照组相比，原发肿瘤患者和转移瘤患者的 ET-1 血浆水平均显着升高（分别为 P<0.01、3.9±1.4、4.5±1.5 和 2.75±1.37 pg/ml）。免疫组织化学显示，ET-1在癌症的细胞质、间质和血管中强表达，与正常结肠不同，正常结肠仅上皮的顶层、血管内皮细胞和周围间质呈阳性染色。在大鼠模型中，在门静脉内接种肿瘤细胞30分钟后用ETA拮抗剂(BQ123)治疗后，与对照组相比，肝脏肿瘤重量显着减少(P < 0.05)。这些结果表明 ET-1 由结直肠癌产生，并可能通过 ET A 受体在结直肠癌的生长中发挥作用。 ETA拮抗剂被认为是潜在的抗癌剂。 © 2001 癌症研究运动 http://www.bjcancer.com
Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET A and ET B, on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 ± 1.4, 4.5 ± 1.5, vs. 2.75 ± 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET A antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET A receptors. ET A antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.com
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DOI：
10.1111/j.1349-7006.1989.tb02310.x
发表时间：
1989-04
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Kusuhara M;Yamaguchi K;Ohnishi A;Abe K;Kimura S;Oono H;Hori S;Nakamura Y
通讯作者：
Nakamura Y
影响因子：
4
作者：
Ashraf, S;Loizidou, M;Burnstock, G
通讯作者：
Burnstock, G
影响因子：
20.1
作者：
CLOZEL, JP;CLOZEL, M
通讯作者：
CLOZEL, M
影响因子：
4
作者：
LOIZIDOU, MC;LAWRANCE, RJ;TAYLOR, I
通讯作者：
TAYLOR, I
影响因子：
82.9
作者：
NELSON, JB;HEDICAN, SP;SIMONS, JW
通讯作者：
SIMONS, JW