胃癌淋巴结微转移的临床研究进展

胃癌是我国目前最常见的恶性肿瘤之一,微转移是恶性肿瘤在发展过程中所形成的尚处于临床不可探测阶段的微小转移灶,播散并存活于淋巴系统、血液循环、骨髓、肝、肺等组织器官中,是恶性肿瘤复发和转移的根源。目前对胃癌淋巴结微转移的深入研究主要集中在通过寻找不同的检测方法、途径和特异性肿瘤标志物,对常规检查淋巴结为阴性的胃癌,微转移检测可能对准确地确定临床分期、指导治疗、判断预后有积极临床意义。现就胃癌微转移检测研究的现状和存在的问题予以综述。     

Toward a post‐conflict Colombia: restoring to the future

At an historic moment, when Colombia is emerging from 60 years of armed conflict, the 7‐year‐old Colombian Network for Ecological Restoration (Red Colombiana de Restauración Ecológica [REDCRE]) has created four subnational nodes, and is actively developing several more. All of this is taking place in the context of the Ibero‐American and Caribbean Society for Ecological Restoration (Sociedad Ibero‐Americana y del Caribe de la Restauración Ecológica [SIACRE]). In mid‐November 2014, over 200 representatives of government agencies, academia, private enterprises, and nongovernmental organizations (NGOs) from the entire country attended a symposium to launch the Antioquia Province node, and take stock and plan the way forward. There are bright prospects of transdisciplinary and public–private collaborations in Colombia for ecological restoration and restoration of natural capital as part of a strategy to transition smoothly to a post‐conflict era. We suggest some goals and guidelines to help move forward an ambitious agenda to mainstream ecological restoration.     

大豆苗期茎秆相关性状对荫蔽的响应

通过设置自然光照和遮荫环境2个处理,对51份大豆种质资源的苗期茎秆相关性状进行研究。结果表明:大豆茎秆相关性状在自然光照和遮荫环境下的变异系数分别为8.40%~78.06%和11.27%~84.68%,除第1、2节节间长度外,其他各性状在荫蔽环境下的变异系数均高于在自然光照下的变异系数。苗期荫蔽胁迫导致大豆株高、最低分枝高度、各节间长度极显著增加(P0.01),而茎粗、分枝数、主茎节数极显著降低。对2种光照环境下的株高指数进行分析发现,株高指数IL以及I2、I4和I6在2种光照环境下差异达到显著水平(P0.05)。相关分析表明,在荫蔽环境下,除第1节外,大豆株高与各节间长度呈显著或极显著正相关,与主茎节数相关性不显著。通径分析表明,自然光照下,第10(0.752)、11(0.736)节对株高的正向作用最大,而在荫蔽环境下,第7(0.752)、10(0.732)节对株高的正向效应较大。在筛选的材料中,有6份材料的株高在2种光照环境下差异不显著,可为套作大豆品种选育奠定基础。     

Reorganization of metastamiRs in the evolution of metastatic aggressive neuroblastoma cells

Background

MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes.

Results

Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs’ targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKβ, Birc1, Birc2, Bric5, β-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3β, IL1α, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1β, SEMA3D, SELE, STAT3, TLR3, TNFα, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. miRNA mimic (hsa-miR-125b, hsa-miR-27b, hsa-miR-93, hsa-miR-20a) and inhibitor (hsa-miR-1224-3p, hsa-miR-1260) approach for select miRNAs revealed the direct influence of the altered metastamiRs in the regulation of identified protein targets. Clinical outcome association analysis with the validated metastamiRs’ targets corresponded strongly with poor overall and relapse-free survival.

Conclusions

For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1642-x) contains supplementary material, which is available to authorized users.     

Single-cell analysis reveals metastatic cell heterogeneity in clear cell renal cell carcinoma

Renal cell carcinoma (RCC) is one of the leading causes of cancer-related death worldwide. Tumour metastasis and heterogeneity lead to poor survival outcomes and drug resistance in patients with metastatic RCC (mRCC). In this study, we aimed to assess intratumoural heterogeneity (ITH) in mRCC cells by performing a combined analysis of bulk data and single-cell RNA-sequencing data, and develop novel biomarkers for prognosis prediction on the basis of the potential molecular mechanisms underlying tumorigenesis. Eligible single-cell cohorts related to mRCC were acquired using the Gene Expression Omnibus (GEO) dataset to identify potential mRCC subpopulations. We then performed gene set variation analysis to understand the differential function in primary RCC and mRCC samples. Subsequently, we applied weighted correlation network analysis to identify coexpressing gene modules that were related to the external trait of metastasis. Protein-protein interactions were used to screen hub subpopulation-difference (sub-dif) markers (ACTG1, IL6, CASP3, ACTB and RAP1B) that might be involved in the regulation of RCC metastasis and progression. Cox regression analysis revealed that ACTG1 was a protective factor (HR < 1), whereas the other four genes (IL6, CASP3, ACTB and RAP1B) were risk factors (HR > 1). Kaplan-Meier survival analysis suggested the potential prognostic value of these sub-dif markers. The expression of sub-dif markers in mRCC was further evaluated in clinical samples by immunohistochemistry (IHC). Additionally, the genetic features of sub-dif marker expression patterns, such as genetic variation profiles, correlations with tumour-infiltrating lymphocytes (TILs), and targeted signalling pathway activities, were assessed in bulk RNA-seq datasets. In conclusion, we established novel subpopulation markers as key prognostic factors affecting EMT-related signalling pathway activation in mRCC, which could facilitate the implementation of a treatment for mRCC patients.     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

CHFR binds to and regulates MAD2 in the spindle checkpoint through its cysteine-rich domain

Recent studies have revealed that various neurotransmitters regulate the immune system via their receptors expressed on the immune cells. Calcitonin gene-related peptide (CGRP), a sensory nerve C-fiber neuropeptide, is also known to have the ability to modulate the functions of immune cells in vitro. However, the contribution of CGRP to the immune regulation in vivo remains to be fully elucidated. Here we report that mice deficient in receptor activity-modifying protein 1 (RAMP1), which is a subunit of the CGRP receptor, showed a significantly lower incidence of diarrhea compared with wild-type (WT) mice in the ovalbumin (OVA)-induced food allergic model. Serum OVA-specific IgE levels and the differentiation of T helper cells was comparable in WT mice and RAMP1-deficient mice. Moreover, there were no significant differences between recruitment and degranulation of mast cells in the small intestine of these mice. In contrast, significantly diminished intestinal peristalsis was observed by the allergy induction in RAMP1-deficient mice compared with WT mice. These results suggest that this suppression of allergic diarrhea is due to the diminished intestinal peristalsis in RAMP1-deficient mice.     

Proteomic analysis of porcine mesenteric lymph-nodes after Salmonella typhimurium infection

In this study we employed for the first time an in vivo approach coupled to DIGE-based proteomics to explore the response of porcine mesenteric lymph nodes (MLN) to Salmonella typhimurium infection. MLN samples were collected from four control and twelve infected pigs (at 1, 2 and 6 days post infection) for histological analysis, protein and RNA purification. Afterwards, expressed proteins were screened by differential in gel analysis and data were analyzed by bioinformatic tools to generate interaction networks, and identify enriched signaling pathways and biological annotations. S. typhimurium labeling in tissue and phagocyte infiltration were analyzed by immunohistochemistry and RNA was employed to determine the relative expression of immune-related genes by quantitative RNA analysis. The proteome response of porcine MLN to infection was associated to the induction of processes such as phagocyte infiltration, cytoskeleton remodeling and pyroptosis. Moreover, our results suggest that S. typhimurium antigens are cross-presented via MHC-I in a proteasome-dependent manner in porcine MLN. Since pathogen burden in tissue was noticeably reduced at the end of the time course, we infer that host innate and adaptive immunity act in association in MLN to control S. typhimurium dissemination in swine infections.     

Noding of Cyprideis torosa valves (Ostracoda) – a proxy for salinity? New data from field observations and a long‐term microcosm experiment

Cyprideis torosa (Jones , 1850) (Ostracoda, Crustacea) is one of the most common marginal marine ostracod species in the Northern hemisphere. We investigate the relationship between variable noding of its valves and salinity as well as Ca²⁺ concentration in the ambient water, analysing populations from an in vitro experiment and field data from the southern Baltic Sea coast. There is a clear negative linear correlation between the proportion of noded individuals from our microcosms and salinity. Deficiency of Ca²⁺ causes heavier noding in laboratory cultures. The same effect can be seen in the field, however, the increase of noded individuals with falling salinity appears to be stepped, not linear. This pattern probably reflects the ability of the animals to wait some time until better salinity conditions occur within the highly variable conditions of estuaries and lagoons. At the southern Baltic Sea coast, proportions of more than 20% noded valves within a C. torosa population indicates salinities of up to 2 psu, up to 10% noded valves indicate salinities between 2 and 7 psu, and the lack of noded valves salinities > 7 psu. Stable salinity conditions as in the studied microcosms cause a shift of these salinity limits to 5 and 14 psu approximately but in a linear relationship between salinity and proportion of noded individuals. Hence, athalassic populations from more stable water bodies should be used for continuous and more detailed salinity trend reconstructions. Deficiency of Ca²⁺ (approximately < 120 mg/l) effects up to about 20% more noded individuals than in water with same salinity but with higher Ca²⁺ concentrations. The reproduction rates within the microcosms indicate a salinity optimum of C. torosa eggs of 8 psu whereas the optimum of the adults seems to be at least 14 psu (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

全胸腔镜肺叶切除联合淋巴结清扫术治疗高龄非小细胞肺癌患者的疗效观察

目的:研究全胸腔镜肺叶切除联合淋巴结清扫术治疗高龄非小细胞肺癌(NSCLC)患者的临床疗效。方法:回顾性分析108例我院2009年2月到2013年2月接受全胸腔镜肺叶切除联合淋巴结清扫术治疗的老年NSCLC患者的临床病历,记录患者的基本资料及相关手术指标(手术时间、术中出血量、术后输血量、术后住院时间、胸管放置时间、胸液总量、止痛药使用次数、术后并发症、清除淋巴结情况),随访两年,了解其生存情况。结果:≥70岁患者30例(高龄组),70岁患者78例(非高龄组),两组患者年龄及术前肺功能差异均有统计学意义(P0.05),但两组患者性别、病理类型、病理分期和基础疾病均无统计学意义(P0.05)。两组相关手术指标比较差异均无统计学差异(P0.05)。高龄患者与非高龄患者的中位生存时间(30.5月vs36月)、1年生存率(96.9%vs98.1%),2年生存率(75.2%vs80.3%)比较差异无统计学意义(P0.05)。结论:高龄NSCLC患者与非高龄者的手术指标及两年预后大致相同,因此采用全胸腔镜肺叶切除联合淋巴结清扫术治疗高龄非小细胞癌患者并不会增加手术风险。