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。发病率和死亡率都在上升。CC的唯一治愈性治疗是手术切除，但大多数患者直到转移阶段才被诊断。目前的化疗只有有限的优势，中位生存期只是略有改善。CC的癌变是一个多步骤的过程，导致点燃和胆汁淤积，细胞损伤和随之而来的细胞过度增殖。在这里，Hedgehog信号通路起着重要的作用。此外，肿瘤起始细胞被讨论为癌症的起源。到目前为止，在肝内CC及其前体的体内致癌过程中，hedgehog信号通路的详细表征和抑制尚未进行。对于肿瘤起始细胞的重要性以及抑制肿瘤起始细胞在这种疾病中的作用也缺乏认识.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，应成为本项目的研究目标。

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