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Zhang Shaolong,Zhou Jingping,Shang Pengzhao,Zhao Guomeng,Wang Anlei,Mao Jinlei,Tao Yuhang,Chen Ziyi,Wang Xuehao,Guo Changying 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Tumor-associated macrophages (TAMs) are one of the main cellular components in the tumor microenvironment (TME). In many types of solid tumors, TAMs tend to accumulate in hypoxic areas and are intimately related to poor patient prognosis. However, the underlying mechanisms by which TAMs infiltrate hypoxic tumor regions remain unclear. In this study, we report that genetic deletion of SE translocation (SET) in myeloid cells inhibited the entry of TAMs into the hypoxic tumor region and abated their proangiogenic and immunosuppressive functions, ultimately inhibiting tumor growth. Mechanistically, in response to hypoxic tumor supernatant stimulation, SET in macrophages shuttled between the nucleus and cytoplasm via the PKC-CK2α signaling axis. Cytoplasmic retention of SET increased ERK and P38 signaling by inhibiting PP2A, which promoted TAM migration into the hypoxic area and polarization toward the M2 phenotype. Therefore, we conclude that SET modulates tumor immunity by acting as a key regulator of macrophage positioning and function in the tumor.
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Zhou Hekai,Liu Houcong,Li Jun,Wang Jidong,Fu Xiaohong,Li Yingqiang,Mao Shaolong,Du Jihui 한국유전학회 2023 Genes & Genomics Vol.45 No.8
Background Several studies have demonstrated that circulating tumor DNA (ctDNA) can be used to predict the postoperative recurrence of several cancers. However, there are few studies on the use of ctDNA as a prognosis tool for gastric cancer (GC) patients. Objective This study aims to determine whether ctDNA could be used as a prognostic biomarker in GC patients through multigene-panel sequencing. Methods Using next-generation sequencing (NGS) Multigene Panels, the mutational signatures associated with the prognosis of GC patients were identified. We calculated the survival probability with Kaplan–Meier and used the Log-rank test to compare survival curves between ctDNA-positive and ctDNA-negative groups. Potential application of radiology combined with tumor plasma biomarker analysis of ctDNA in GC patients was carried out. Results Disease progression is more likely in ctDNA-positive patients as characterized clinically by a generally higher T stage and a poorer therapeutic response (P < 0.05). ctDNA-positive patients also had worse overall-survival (OS: P = 0.203) and progression-free survival (PFS: P = 0.037). The combined analysis of ctDNA, radiological, and serum biomarkers in four patients indicated that ctDNA monitoring can be a good complement to radiological and plasma tumor markers for GC patients. Kaplan–Meier analysis using a cohort of GC patients in the TCGA database showed that patients with CBLB mutations had shorter OS and PFS than wild-type patients (OS: P = 0.0036; PFS: P = 0.0027). Conclusions This study confirmed the utility and feasibility of ctDNA in the prognosis monitoring of gastric cancer.
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