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.

胆管癌（CC）是世界上第二常见的原发性肝脏肿瘤。发病率和死亡率都在上升。唯一的治疗方法是手术切除，但大多数患者直到转移期才被诊断出来。目前的化疗只有有限的优势，中位生存期只是略有改善。CC癌的发生是一个多步骤的过程，从着火和胆汁淤积到细胞损伤，进而导致细胞过度增殖。在这里，Hedgehog信号通路起着重要的作用。同时，肿瘤起始细胞也被认为是癌症的起源。到目前为止，在肝内cc及其前体的体内癌变过程中，刺猬信号通路的详细表征和抑制尚未进行。关于肿瘤起始细胞在本病中的作用和抑制作用的知识也很少。最后，在缺氧条件下，Hedgehog基因抑制对治疗效果的影响尚未得到充分的研究，这应该是本项目的研究目标之一。

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.