Characterization, further analysis and inhibition of the hedgehog signaling pathway during carcinogenesis of cholangiocellular carcinoma, with focus on precursor lesions and identification of tumor-iniating cells.

胆管细胞癌发生过程中hedgehog信号通路的表征、进一步分析和抑制，重点关注前体病变和肿瘤起始细胞的鉴定。

• 批准号: 282668534
• 负责人: Professor Dr. Ruben R. Plentz
• 金额: --
• 依托单位: Klinikum Bremen-Nord gGmbH
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/282668534?language=en
• 关键词: Characterization; further; analysis; inhibition; hedgehog

Cholangiocarcinoma (CC) is the second most common primary liver tumor worldwide. Incidence and mortality are rising. The only curative treatment of CCs is surgical resection, but most patients are not diagnosed until a metastatic stage. Current chemotherapies have only limited advantage and median survival is just slightly improved. The CC carcinogenesis is a multistep process that leads to the ignition and cholestasis to cell damage and the consequent excessive of cell proliferation. Here, the Hedgehog signaling pathway plays an important role. Also, tumor-initiating cells are discussed to be the origin of cancer. So far a detailed characterization and inhibition of the hedgehog signaling pathway during in vivo carcinogenesis of intrahepatic CCs and its precursors has not been carried out. There is alsolacking knowledge of the significance and the inhibition of tumor -initiating cells for this disease. Finally, the influence of a Hedgehog inhibition on therapeutic efficacy under hypoxic conditions has not been adequately studied, and should be the research objectives of this project among others.

胆管癌（CC）是全球第二常见的原发性肝脏肿瘤。发病率和死亡率正在上升。 CC 的唯一治愈方法是手术切除，但大多数患者直到转移期才被诊断出来。目前的化疗优势有限，中位生存期仅略有改善。 CC癌变是一个多步骤的过程，导致细胞损伤的点燃和胆汁淤积以及随后的细胞过度增殖。在这里，Hedgehog信号通路发挥着重要作用。此外，肿瘤起始细胞也被认为是癌症的起源。迄今为止，尚未对肝内CC及其前体体内致癌过程中hedgehog信号通路的详细表征和抑制进行研究。对于肿瘤起始细胞对于这种疾病的重要性和抑制作用也缺乏了解。最后，Hedgehog 抑制对缺氧条件下治疗效果的影响尚未得到充分研究，这应该是该项目的研究目标之一。

项目成果

Sonic hedgehog pathway as a new target in cholangiocarcinoma therapy

Sonic Hedgehog通路作为胆管癌治疗的新靶点

• DOI: 10.1055/s-0038-1668970
• 发表时间: 2018
• 期刊: Zeitschrift für Gastroenterologie
• 作者: V Bhuria;J Xing;T Scholta;KC Bui;MLT Nguyen;L Wilkens;NP Malek;P Bozko;RR Plentz
• 通讯作者: RR Plentz