As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for ca...As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for cancer treatment.Errors in cytokinesis increase CIN,so cytokinesis components are valuable targets for treating cancer.However,due to the short time span and confined space of cytokinesis bridges,profiling cytokinesis fac-tors is challenging.Taking advantage of engineered ascorbate peroxidase(APEX2),we established a cytokinesis bridge-APEX reaction in living cells.A total of 218 cytokinesis bridge proteins were identified with high relia-bility.Knockdown of cytokinesis bridge genes generated micronuclei that activate the cGAS-pathway and cause apoptosis in cancer cells bearing high CIN rather than low CIN.Thus,our study proposes a strategy for killing high-CIN tumors regardless of tumor type,and provides a proteome resource of cytokinetic bridges for future research.展开更多
目的探讨阴道镜表现与宫颈上皮内瘤变(CIN)进展的关系及对高级别病变评估漏诊的因素。方法选取2020年1月-2023年11月于该院行阴道镜下活检且存在CIN的患者304例。根据阴道镜活检结果,将CIN分为CINⅠ级(103例)、CINⅡ级(137例)、CINⅢ级...目的探讨阴道镜表现与宫颈上皮内瘤变(CIN)进展的关系及对高级别病变评估漏诊的因素。方法选取2020年1月-2023年11月于该院行阴道镜下活检且存在CIN的患者304例。根据阴道镜活检结果,将CIN分为CINⅠ级(103例)、CINⅡ级(137例)、CINⅢ级(59例)及早期浸润癌(5例)。通过对比宫颈环形电切术(LEEP of cervix)术后病理结果,将高级别病例(CINⅡ级及以上)进一步分为检出组和漏诊组。采用Logistic回归模型,分析影响阴道镜漏诊高级别CIN的危险因素。结果阴道镜下异常血管和醋酸白上皮的表现有助于区分不同级别CIN;阴道镜活检对于CIN的诊断符合率较高,但仍有21例高级别CIN漏诊(CINⅡ级14例,CINⅢ级5例,早期浸润癌2例)。分娩、绝经、碘不着色区<2 cm、细胞学检查为低级别磷状上皮内病变(LSIL)、宫颈病变面积<1/2、活检标本为1个和阴道镜图像模糊是影响阴道镜检查漏诊高级别CIN的独立危险因素(P<0.05)。结论阴道镜活检对不同级别CIN病例的诊断符合率均较高。分娩、绝经、碘不着色区<2 cm、细胞学检查为LSIL、宫颈病变面积<1/2、活检标本为1个和阴道镜图像模糊是影响阴道镜检查漏诊高级别CIN的独立危险因素。展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(Grants No.81672610,81521002,81871160)to ML,and by the“Clinic+X”program(to ML)of Peking University.
文摘As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for cancer treatment.Errors in cytokinesis increase CIN,so cytokinesis components are valuable targets for treating cancer.However,due to the short time span and confined space of cytokinesis bridges,profiling cytokinesis fac-tors is challenging.Taking advantage of engineered ascorbate peroxidase(APEX2),we established a cytokinesis bridge-APEX reaction in living cells.A total of 218 cytokinesis bridge proteins were identified with high relia-bility.Knockdown of cytokinesis bridge genes generated micronuclei that activate the cGAS-pathway and cause apoptosis in cancer cells bearing high CIN rather than low CIN.Thus,our study proposes a strategy for killing high-CIN tumors regardless of tumor type,and provides a proteome resource of cytokinetic bridges for future research.
文摘目的探讨阴道镜表现与宫颈上皮内瘤变(CIN)进展的关系及对高级别病变评估漏诊的因素。方法选取2020年1月-2023年11月于该院行阴道镜下活检且存在CIN的患者304例。根据阴道镜活检结果,将CIN分为CINⅠ级(103例)、CINⅡ级(137例)、CINⅢ级(59例)及早期浸润癌(5例)。通过对比宫颈环形电切术(LEEP of cervix)术后病理结果,将高级别病例(CINⅡ级及以上)进一步分为检出组和漏诊组。采用Logistic回归模型,分析影响阴道镜漏诊高级别CIN的危险因素。结果阴道镜下异常血管和醋酸白上皮的表现有助于区分不同级别CIN;阴道镜活检对于CIN的诊断符合率较高,但仍有21例高级别CIN漏诊(CINⅡ级14例,CINⅢ级5例,早期浸润癌2例)。分娩、绝经、碘不着色区<2 cm、细胞学检查为低级别磷状上皮内病变(LSIL)、宫颈病变面积<1/2、活检标本为1个和阴道镜图像模糊是影响阴道镜检查漏诊高级别CIN的独立危险因素(P<0.05)。结论阴道镜活检对不同级别CIN病例的诊断符合率均较高。分娩、绝经、碘不着色区<2 cm、细胞学检查为LSIL、宫颈病变面积<1/2、活检标本为1个和阴道镜图像模糊是影响阴道镜检查漏诊高级别CIN的独立危险因素。
