Hedgehog signaling pathway is a possible therapeutic target for gastric cancer
Hedgehog signaling pathway is a possible therapeutic target for gastric cancer
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DOI：
10.1002/jso.20606
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发表时间：
2007-01-01
影响因子：
2.5
通讯作者：
Katano, Mitsuo
中科院分区：
文献类型：
--
作者：
Yanai, Kosuke;Nagai, Shuntaro;Katano, Mitsuo
背景与目的：研究表明，hedgehog （Hh）信号通路在胃癌中被激活。为了研究Hh通路作为治疗靶点的可行性，我们分析了Hh通路在胃癌中的激活情况。方法：对手术切除的胃癌标本及淋巴结进行免疫组织化学分析。我们使用Gli - 1核易位的癌细胞百分比作为Hh通路激活的标志。结果：28例未分化型肿瘤Gli - 1的核定位高于30例分化型肿瘤。58例肿瘤标本中有18例由组织学上占优势的部分和具有不同组织学的小区域组成。在这18例肿瘤中，未分化型部分显示Gli - 1核染色的细胞比例高于分化型部分。原发性肿瘤中Gli - 1核染色与淋巴结转移呈正相关。转移淋巴结的Gli - 1核染色百分率与各原发癌的Gli - 1核染色百分率密切相关。Hh通路抑制剂环巴胺体外抑制胃癌细胞生长。结论：Hh通路可能是未分化型胃癌伴淋巴结转移的有效治疗靶点。
Background and Objectives: It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.Methods: Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli 1 as a marker of Hh pathway activation.Results: Nuclear localization of Gli 1 was higher in 28 undifferentiated-type tumors than in 30 differentiated-type tumors. Eighteen of the fifty-eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli 1 was higher in the undifferentiated-type part than in the differentiated-type part. Nuclear staining of Gli 1 in primary tumors was positively correlated with lymph node metastasis. The Gli 1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.Conclusions: The Hh pathway may be a useful therapeutic target for such as undifferentiated-type gastric cancer with lymph node metastasis.