国家肝癌诊断治疗规范内科部分的解读.pptVIP

谢谢! * Two principal mechanisms implicated in hepatocarcinogenesis: Liver cirrhosis following tissue damage Mutations occurring in one or more oncogenic or tumor suppressor genes Dysplastic nodule figures adapted from Tornillo L, et al. Explanation: Quadrant 1: Macroscopic dysplastic nodule Quadrant 2: Low-grade dysplastic nodule in cirrhotic liver Quadrant 3: High-grade dysplastic nodule with pseudoglandular pattern and high nuclear/cytoplasmic ratio Quadrant 4: High-grade dysplastic nodule with preserved reticulin pattern. HCC figures adapted from Dysplasia and Neoplasia in the Liver. * HCC的分子发病机制极其复杂，信号传导途径异常导致细胞异常增生和无限制增殖。 异常的生长因子激活 (TGF-β, EGFR)； 细胞分裂信号途径持续活化 (Raf/MEK/ERK, PI3K/AKT/mTOR , Wnt／?-catenin) ； 抗细胞凋亡信号途径失调 (p53, PTEN)。 新生血管异常增生（如VEGF途径）促进HCC生长及进展。 Bisphosphonates Overview * Role of angiogenesis in cancer development, growth and metastasis. A switch to an angiogenic phenotype is a prerequisite for the development from a premalignant stage to an invasive tumor. The neovascularization provides not only nutrients for tumor growth but also a large surface area of leaky vessels with incomplete basement membrane that facilitate intravasation of tumor cells. Tumor cells seeding in distant organs develop initially as avascular dormant micrometastases. Angiogenic switch leads to secondary angiogenesis and tumor growth, resulting in overt metastases (reprinted from Ref. [18] with permission of American Society of Clinical Oncology). Bisphosphonates Overview * HCC is characterized by a high propensity for vascular invasion, and the angiogenic activity of HCC correlates with the risk of vascular invasion[27].Angiogenesis inHCChasalsobeenfoundto correlate with metastasis [28]. The importance of angiogenesis in the progression of HCC implies the potential prognostic significance of assessment of angiogenesis in HCC. Studying the molecular mechanisms regulating angiogenesis in HCC provides insights intomolecular targets for antiangiogen