突变体p53能够通过内源性PDGFRb促进胰腺癌转移.ppt

Journal: Cell Reporter: XuWang IF: 33.116 RESULTS DISCUSSION 肺转移 肺组织病理切片 Result 5： Modulation of PDGFRb Expression Levels Mediates the Phenotypic Effects of Mutant p53 Depletion In Vivo 转移灶大小 免疫组化 whether pharmacologic inhibition of the PDGFRb pathway recapitulates the effects of PDGFRb or mutant p53 depletion? 时效关系实验 量效关系实验 Crenolanib两种细胞IC50 whether crenolanib can suppress metastasis? Crenolanib处理与DMSO处理 荧光和免疫组化 细胞凋亡 KPflC 细胞 pancreatic cancer cells can provide a source of PDGF ligand that could trigger autocrine activation of PDGFRb 条件培养 Summary 5 abrogation of autocrine activation signaling of PDGFRb leads to a significant reduction of invasion and metastasis driven by mutant p53 . whether PDGFRb inhibition prevents the development of metastasis in KPC mice? Question 量效关系 抑制细胞增殖所需IC50 体外KPC 细胞侵袭实验 Imatinib处理KPC的肺转移 Result 5： Imatinib Inhibits the Development of Metastases in a PDAC Mouse Model by Targeting PDGFRb the high disease burden in the pancreas was the primary cause of death 肿瘤体积 总体存活率 92% 15% 其他器官转移情况 不同器官HE染色 DAPI, blue; CK8, red; pPDGFRb, green imatinib was able to effectively inhibit PDGFRb activity in primary tumors based on reduced levels of phospho-PDGFRb in the tumor cells pPDGFRb强度 imatinib对体内PDGFRb的影响 Summary 6 by inhibiting the kinase activity of PDGFRb, imatinib significantly diminishes the metastatic potential of pancreatic cancer cells. whether upregulation of PDGFRb is correlated with prognosis or with the clinicopathological characteristics of PDACs in patients. Question 无病存活率 不同阶段PDGFRb表达 血管内渗 whether PDGFRb levels correlate with the status of p53 ? Result 7： PDGFRb Expression Correlates with Disease-free Survival in Human Pancreatic, Colorectal, and Ovarian Cancer Patients 磷酸化PDGFRb强度 p53积累 结直肠癌无病生存率 As in PDAC, a significant increase in PDGFRb expression was observed in higher-stage colorectal 不同分期PDGFRb的表达水平 结直肠癌 卵巢癌 * Abstract Mutant p53 metastasis antiproliferative prometastatic phenotype PDGFRb p73/NF-Y metastasis invasi