Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Sinensetin attenuates oxygen–glucose deprivation/reperfusion-induced neurotoxicity by MAPK pathway in human cerebral microvascular endothelial cells

Sinensetin is a polymethoxylated flavone with anti-inflammatory and anti-oxidative activities. This work aimed to explore the function and mechanism of sinensetin in oxygen and glucose deprivation/reperfusion (OGD/R)-induced neurotoxicity. The overlapping target genes of cerebral stroke and sinensetin were determined according to GeneCards and ParmMapper tools and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Human cerebral microvascular endothelial cells (HCMECs) were stimulated with OGD/R. Neurotoxicity was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, qRT-PCR, and TUNEL analysis. The proteins (p38, JNK, and ERK) in mitogen-activated protein kinase (MAPK) signaling were measured using Western blotting. Total of 50 overlapping target genes of cerebral stroke and sinensetin were predicted. Pathway analysis showed they might be involved in the MAPK pathway. Sinensetin attenuated OGD/R-induced neurotoxicity by mitigating viability reduction, LDH release, ROS generation, inflammatory response, and apoptosis in HCMECs. Sinensetin weakened OGD/R-induced activation of the MAPK pathway via decreasing the phosphorylation of p38, JNK, and ERK. The pathway inhibitors mitigated the activation of the MAPK signaling, and sinensetin exacerbated this effect. The inhibitors reversed OGD/R-induced neurotoxicity in HCMECs, and sinensetin contributed to this role. Overall, sinensetin prevents OGD/R-induced neurotoxicity through decreasing the activation of MAPK pathway.     

Association between R1 resection and oncological outcome in resectable gastrointestinal stromal tumors without tumor rupture: A systematic review and meta-analysis

BackgroundThe influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly associated with the occurrence of R1 resection and may be a confounder of R1 resection in GISTs. The present meta-analysis evaluated the real influence of R1 resection on the prognosis of GISTs by excluding the confounding effect of tumor rupture.MethodsThe PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were searched. Studies that compared R1 with negative microscopic margin (R0) resection in GIST patients and reported the time-to-event data of recurrence-free survival (RFS) or disease-free survival (DFS) were eligible for inclusion. The quality of the observational studies was assessed using the Newcastle–Ottawa scale.ResultsOf the 4896 records screened, 23 retrospective studies with 6248 participants were selected. In the overall analysis, R1 resection resulted in a significantly shorter RFS/DFS than R0 resection for GISTs (HR = 1.80, 95% CI = 1.54–2.10, P < 0.001, I² = 14%). However, the inferior RFS/DFS vanished when tumor rupture cases were excluded (HR = 1.34, 95% CI = 0.98–1.83, P = 0.07, I² = 33%). Sensitivity analysis by high-quality studies brought about a more robust HR of 1.15 (95% CI = 0.88–1.50, P = 0.29), with low heterogeneity (I² = 0%). The qualities of evidence for the outcomes were high.ConclusionsThis meta-analysis shows that R1 resection did not influence the survival outcome of GISTs. Reresection may not be necessary when positive microscopic margins exist. This analysis could provide high-quality evidence for the development of guidelines.     

LINC00649通过miR-424-5p/IGF1R轴调控内质网应激介导的宫颈癌细胞凋亡

目的探讨LINC00649/miR-424-5p/IGF1R对内质网应激(ERs)介导的宫颈癌(CC)细胞凋亡的影响。方法从GEO数据库中获取CC相关的数据,并分析差异表达的miRNAs。利用生物信息学数据库预测miR-424-5p的上、下游靶点,将LINC00649和IGF1R纳入研究,随后双荧光素酶实验进一步验证靶向关系。qRT-PCR检测LINC00649、miR-424-5p和IGF1R在CC组织和细胞中的表达水平。CCK-8和流式细胞术分别评估CC细胞增殖和凋亡变化。Western blot检测ERs相关蛋白GRP78、CHOP和Caspase-12的表达。结果与癌旁组织和H8细胞相比,LINC00649和IGF1R在CC组织和细胞中表达上调,而miR-424-5p下调(均P<0.05)。LINC00649的异常高表达与CC患者的预后不良有关,敲减LINC00649可通过促进ERs来抑制CC细胞活力,诱导细胞凋亡(均P<0.05)。LINC00649吸附miR-424-5p上调IGF1R的表达。miR-424-5p抑制剂或过表达IGF1R均可部分逆转敲减LINC00649对CC细胞的影响(均P<0.05)。结论 LINC00649能够通过miR-424-5p/IGF1R抑制CC细胞的ERs过程进而减少细胞凋亡,提高细胞活力。     

医科达数字化电子直线加速器控制软件IPV基本原理与应用解读

目的 介绍医科达数字化医用电子直线加速器控制软件里子项目和项目成分值(IPV)的工作原理,并具体说明控制软件通过三类子项目及其项目分项实时监测、控制子系统的运行状态。方法 首先介绍医科达数字化医用电子直线加速器的控制系统组成,然后介绍控制软件里子项目和项目分项的定义和分类,以及各类子项目的基本原理,最后通过分析高功率移相器的运动控制具体说明控制软件的子项目在实时监测、控制子系统运行状态的应用。结果 通过分析原理和举例详细、具体说明了控制软件IPV的工作原理及其应用,使用户尤其是维修人员能掌握相应理论知识,在日常使用和维修时能通过软件快速准确地查找运行参数,并根据相关子系统的控制原理分析问题和解决故障。结论 用户尤其是维修人员掌握这些子项目及其项目分项的工作原理,就能在日常使用或维修、校准时,快速准确地通过控制软件查看、校准运行参数,解决设备故障,并避免错误操作引起事故。     

三维可视化技术在胰头癌胰腺全系膜切除术中应用研究

目的 探讨三维可视化技术在胰头癌胰腺全系膜切除术中的应用价值。方法 回顾性分析2013年1月至2017年6月在上海交通大学医学院附属新华医院普外科行胰腺全系膜切除的105例胰头癌病人资料，采用三维可视化技术对胰头肿瘤的部位、大小、与周围血管的毗邻关系进行观察，完成术前可切除性的评估，共施行胰腺全系膜切除术105例。结果 平均手术时间239 min，平均术中出血409 mL。29例（27.6%）发生术后并发症，无围手术期死亡病例。74例标本三维空间切缘病理学检查达到R0切除，R0切除率为70.5%。结论 三维可视化技术在胰头癌全系膜切除术前规划中的应用，可以更好地指导胰头癌的精准手术，提高了术前评估的准确率与手术的R0切除率，降低手术并发症发生率。