colorectal cancer

结直肠癌
  • 文章类型: Journal Article
    目的:本研究的目的是比较结肠镜(CS)和CT结肠造影(CTC)在以病理大小为参考的结直肠息肉测量中的准确性。
    方法:分析包括在我们机构接受术前CTC的28例患者的61例结直肠息肉。所有息肉均经内镜切除。通过CS和CTC测量息肉大小。从两位内窥镜医师之一撰写的内窥镜检查记录中提取内窥镜息肉大小(A为11,B为6年内窥镜检查经验,分别),谁在没有任何测量设备的情况下视觉/分类地估计尺寸。匹配位置后,在CTC上使用工作站上的手动三维(3D)测量息肉大小.病理检查后,还测量了切除的息肉的大小。CTC和组织学之间息肉大小的差异,使用配对t检验比较CS和组织学之间的差异。还分析了两位内窥镜医师之间的测量差异。
    结果:使用CS测量的息肉的平均直径,反恐委员会,病理为10.5毫米,9.2mm,和8.4毫米,分别。CS与病理有显著的相关性,以及CTC和病理之间(均P<0.0001)。CS的相关系数(r=0.86)低于CTC的相关系数(r=0.96)。内窥镜医师A和B的CS与病理之间的相关性分别为0.90和0.89。
    结论:与CS相比,使用CTC测量的息肉大小更接近病理测量,表现出更大的变异性。这表明,如果患者同时接受CTC和结肠镜检查,则CTC可能更适合于临床环境中的息肉大小测量。
    OBJECTIVE: The aim of this study was to compare the accuracy of colonoscopy (CS) and CT colonography (CTC) in the measurement of colorectal polyps using pathological size as a reference.
    METHODS: The analysis included 61 colorectal polyps in 28 patients who underwent preoperative CTC at our institution. All polyps were endoscopically resected. Polyp sizes were measured by CS and CTC. Endoscopic polyp size was extracted from endoscopy records written by one of two endoscopists (A with 11 and B with 6 years of endoscopic experience, respectively), who estimated the size visually/categorically without any measuring devices. After matching the location, the polyp size was measured on CTC using manual three-dimensional (3D) measurement on a workstation. The sizes of resected polyps were also measured after pathological inspection. Differences of the polyp size between CTC and histology, and between CS and histology were compared using paired t tests. Differences in measurement between the two endoscopists were also analyzed.
    RESULTS: The mean diameters of polyps measured using CS, CTC, and pathology were 10.5 mm, 9.2 mm, and 8.4 mm, respectively. There was a significant correlation between CS and pathology, as well as between CTC and pathology (both P < 0.0001). The correlation coefficient for CS (r = 0.86) was lower than that for CTC (r = 0.96). The correlations between CS and pathology for endoscopists A and B were 0.90 and 0.89, respectively.
    CONCLUSIONS: Measurements of polyp size using CTC were closer to the pathological measurements compared to those by CS, which exhibited greater variability. This suggests that CTC may be more suitable for polyp size measurements in the clinical setting if patients undergo CTC concurrently with colonoscopy.
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  • 文章类型: Journal Article
    目的:大肠癌(CRC)的随访需要在医院定期监测癌胚抗原(CEA)。毛细管家庭采血,包括微创技术,如刺血针取样或自动上臂装置(TAP-II),有可能取代医院血液采样的很大一部分,从而提高自力更生和生活质量。这项研究的目的是评估可行性,CEA采血的可靠性和偏好。
    方法:收集102名参与者的基线静脉和毛细血管(通过刺血针和TAP-II)血样,包括20例CEA水平升高的CRC患者,60例接受术后门诊监测的CRC患者和20例健康志愿者。第二组连续两次随访在家中进行毛细血管采血,随后将其送往医院。满意度通过患者报告的疼痛结局指标进行评估,负担,易用性和偏好。
    结果:对所有可用样品进行Pearson相关性检验后,TAP-II法的线性系数为0.998(95%CI0.997-0.998),刺血针法的线性系数为0.997(95%CI0.996-0.998),两者都与静脉穿刺相比。在最初的血液采集之后,86%的参与者(n=102)赞成TAP-II,将其评为最不痛苦和最繁重的选择。在做了两份家庭血样后,对TAP-II方法的偏好持续存在,64%的患者认可其使用。
    结论:这项研究证明了以家庭为基础的CEA毛细管采样的可行性。TAP-II采血是最可靠的方法,患者比静脉穿刺和刺血针取样更喜欢这种方法。
    OBJECTIVE: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection.
    METHODS: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference.
    RESULTS: The Pearson\'s correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use.
    CONCLUSIONS: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.
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  • 文章类型: Journal Article
    目的:自2015年12月以来,已向NHSTayside的初级保健提供了粪便免疫化学测试(FIT),作为评估新发肠道症状的临床敏锐性的辅助手段。这项工作的目的是评估这种方法对结直肠癌(CRC)诊断时间的影响。
    方法:对2013年1月至2019年12月的NHSTayside癌症审计数据进行了审查,以确定在引入FIT之前和之后通过初级保健转诊途径诊断的所有CRC患者。访问了他们的电子患者记录,并记录了转诊日期以及任何同期的FIT和全血计数(FBC)结果。计算每位患者从转诊到诊断CRC的时间,并在亚组之间进行比较。
    结果:研究队列由959名患者组成:引入FIT前后的378名和581名患者,分别。FIT前的中位诊断时间为30天[四分位距(IQR)16-57天],而引入FIT后为25天(IQR14-47天)(p=0.006)。在介绍FIT之后,完成FIT的患者的中位诊断时间为23天(IQR14~43天),而未完成FIT的患者的中位诊断时间为30天(IQR16~62天)(p=0.019).97.5%的FIT患者可获得FBC结果,以帮助粪便血红蛋白浓度低或无法检测到的患者的安全网。
    结论:在初级护理中引入基于FIT的新肠道症状分类作为临床诊断的辅助手段与减少CRC诊断时间相关。
    OBJECTIVE: Since December 2015, a faecal immunochemical test (FIT) has been provided to primary care in NHS Tayside as an adjunct to clinical acumen in the assessment of new-onset bowel symptoms. The aim of this work was to assess the impact of this approach on time to diagnosis of colorectal cancer (CRC).
    METHODS: NHS Tayside Cancer audit data from January 2013 to December 2019 were reviewed to identify all CRC patients diagnosed via the primary-care referral pathway for a period before and after the introduction of FIT. Their electronic patient records were accessed and date of referral and any contemporaneous FIT and full blood count (FBC) result were recorded. Time from referral to diagnosis of CRC was calculated for each patient and compared between subgroups.
    RESULTS: The study cohort consisted of 959 patients: 378 and 581 from the time periods before and after the introduction of FIT, respectively. The median time to diagnosis before FIT was 30 days [interquartile range (IQR) 16-57 days] versus 25 days (IQR 14-47 days) following the introduction of FIT (p = 0.006). Following the introduction of FIT, patients who completed a FIT had a median of time to diagnosis of 23 days (IQR 14-43 days) compared with 30 days (IQR 16-62 days) for patients not completing a FIT (p = 0.019). FBC results were available for 97.5% of FIT patients to aid safety-netting of patients with a low or undetectable faecal haemoglobin concentration.
    CONCLUSIONS: The introduction of FIT-based triage of new bowel symptoms in primary care as an adjunct to clinical acumen is associated with a reduced time to CRC diagnosis.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    内镜梗阻(eOB)与结直肠癌(CRC)的不良预后相关。我们的研究旨在探讨肿瘤位置与eOB之间的关系,以及非内镜梗阻(N-EOB)之间的预后差异,eOB,肿瘤大小≤5cm,非老年患者肿瘤大小>5cm的eOB。
    我们回顾性回顾了230例接受根治性手术的CRC患者的临床病理变量。采用多变量logistic回归模型识别eOB的危险因素。使用多变量cox回归分析评估肿瘤大小≤5cm的eOB与无病生存期(DFS)之间的相关性。
    共有87名患者患有eOB,而143名患者患有N-eOB。在多变量分析中,术前癌胚抗原(p=0.014),肿瘤大小(p=0.010),肿瘤位置(左侧结肠;p=0.033;直肠;p<0.001),和pT分期(T3,p=0.009;T4,p<0.001)是eOB的重要因素。在生存分析中,肿瘤大小≤5cm的eOB的DFS率显着降低(p<0.001)。肿瘤大小≤5cm(p=0.012)的eOB是DFS的一个不利的独立因素。
    与左侧结肠癌和直肠癌相比,eOB患者与右侧结肠癌显著相关。肿瘤大小≤5cm的eOB是一个独立的预后不良因素。需要进一步的研究来针对这些高危人群。
    UNASSIGNED: Endoscopic obstruction (eOB) is associated with a poor prognosis in colorectal cancer (CRC). Our study aimed to investigate the association between tumor location and eOB, as well as the prognostic differences among non-endoscopic obstruction (N-eOB), eOB with tumor size ≤ 5 cm, and eOB with tumor size > 5 cm in non-elderly patients.
    UNASSIGNED: We retrospectively reviewed the clinicopathological variables of 230 patients with CRC who underwent curative surgery. The multivariable logistic regression model was used to identify risk factors for eOB. The association between eOB with tumor size ≤ 5 cm and disease-free survival (DFS) was evaluated using multivariate cox regression analysis.
    UNASSIGNED: A total of 87 patients had eOB while 143 had N-eOB. In multivariate analysis, preoperative carcinoembryonic antigen (p = 0.014), tumor size (p = 0.010), tumor location (left-side colon; p = 0.033; rectum; p < 0.001), and pT stage (T3, p = 0.009; T4, p < 0.001) were significant factors of eOB. The DFS rate for eOB with tumor size ≤ 5 cm was significantly lower (p < 0.001) in survival analysis. The eOB with tumor size ≤ 5 cm (p = 0.012) was an unfavorable independent factor for DFS.
    UNASSIGNED: The patients with eOB were significantly associated with right-side colon cancer as opposed to left-side colon cancer and rectal cancer. The eOB with tumor size ≤ 5 cm was an independent poor prognostic factor. Further studies are needed to target these high-risk groups.
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  • 文章类型: Journal Article
    本研究旨在构建基于机器学习算法的预测模型,以评估结直肠癌患者术后住院时间延长的风险,并分析与住院时间延长相关的术前和术后因素。
    我们前瞻性收集了83例结直肠癌患者的临床数据。该研究包括40个变量(包括39个预测变量和1个目标变量)。重要变量通过Lasso回归算法选择变量来识别,并使用十种机器学习模型构建预测模型,包括Logistic回归,决策树,随机森林,支持向量机,轻型梯度增压机,KNN,和极端梯度提升,分类提升,人工神经网络与深层森林.使用BootstrapROC曲线和校准曲线评估模型性能,选择最优模型,并使用SHAP可解释性算法进一步解释。
    通过Lasso回归确定了十个显著相关的重要变量,由1000个Bootstrap重采样验证,并通过BootstrapROC曲线表示。Logistic回归模型获得最高的AUC(AUC=0.99,95%CI=0.97-0.99)。可解释的机器学习算法显示,手术后第三天行走的距离是LR模型最重要的变量。
    本研究利用患者临床数据成功构建了预测术后住院时间的模型。该模型有望在临床实践中为医疗保健专业人员提供更精确的预测工具,为个性化护理干预提供基础,改善患者预后和生活质量,提高医疗资源利用效率。
    UNASSIGNED: This study aims to construct a predictive model based on machine learning algorithms to assess the risk of prolonged hospital stays post-surgery for colorectal cancer patients and to analyze preoperative and postoperative factors associated with extended hospitalization.
    UNASSIGNED: We prospectively collected clinical data from 83 colorectal cancer patients. The study included 40 variables (comprising 39 predictor variables and 1 target variable). Important variables were identified through variable selection via the Lasso regression algorithm, and predictive models were constructed using ten machine learning models, including Logistic Regression, Decision Tree, Random Forest, Support Vector Machine, Light Gradient Boosting Machine, KNN, and Extreme Gradient Boosting, Categorical Boosting, Artificial Neural Network and Deep Forest. The model performance was evaluated using Bootstrap ROC curves and calibration curves, with the optimal model selected and further interpreted using the SHAP explainability algorithm.
    UNASSIGNED: Ten significantly correlated important variables were identified through Lasso regression, validated by 1000 Bootstrap resamplings, and represented through Bootstrap ROC curves. The Logistic Regression model achieved the highest AUC (AUC=0.99, 95% CI=0.97-0.99). The explainable machine learning algorithm revealed that the distance walked on the third day post-surgery was the most important variable for the LR model.
    UNASSIGNED: This study successfully constructed a model predicting postoperative hospital stay duration using patients\' clinical data. This model promises to provide healthcare professionals with a more precise prediction tool in clinical practice, offering a basis for personalized nursing interventions, thereby improving patient prognosis and quality of life and enhancing the efficiency of medical resource utilization.
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  • 文章类型: Journal Article
    背景:代谢重编程在结直肠癌(CRC)的发生发展中起着至关重要的作用。影响肿瘤异质性,肿瘤微环境,和转移。虽然代谢和CRC之间的相互作用对于开发个性化治疗至关重要,在了解肿瘤细胞代谢如何影响预后方面仍存在空白.我们的研究通过整合单细胞和批量转录组分析来探索CRC细胞内的代谢景观及其影响疾病进展的机制,引入了新的见解。这种方法使我们能够发现代谢异质性并确定影响转移的特定代谢基因。在以前的研究中没有进行过彻底的检查。方法:我们从基因表达综合(GEO)获得微阵列和单细胞RNA测序数据集,并从癌症基因组图谱(TCGA)获得CRC的批量测序数据。我们采用基因集变异分析(GSVA)来评估代谢途径的活性,共识聚类以识别bulkseq中的CRC特异性转录组亚型,严格的质量控制,包括在scRNAseq中排除具有高线粒体基因表达的细胞。高级分析,如AUCcell,地狱CNV,非负矩阵分解(NMF),和CytoTRACE用于解剖细胞景观并评估途径活性和肿瘤细胞干细胞性。hdWGCNA算法有助于识别与预后相关的枢纽基因,使用随机森林机器学习模型整合这些发现。结果:Kaplan-Meier存活曲线确定了21条与预后相关的重要代谢途径,在基于代谢活动定义三个CRC亚型(C3、C2、C1)的共识聚类中,这与不同的临床结果相关。13个细胞亚群的代谢活性,特别是具有活跃代谢水平的上皮细胞亚群,在scRNAseq中使用AUCcell进行评估。为了进一步分析肿瘤细胞,NMF将这些细胞分解成10个细胞亚群。其中,与C6和C0相比,C2亚群表现出较高的干性,并且预后较差。相反,C8、C3和C1亚群表现出更高水平的五种代谢途径,C3和C8亚群往往具有更良好的预后。hdWGCNA确定了20个模块,我们从中选择主要在高代谢肿瘤亚组中表达且与临床信息高度相关的模块,包括蓝色和青色。通过将RF的可变降尺度应用于总共50个集线器基因,获得了七个基因签名。此外,与相关分子一起筛选在GEO中被验证为保护性的分子,导致鉴定预后相关分子,如UQCRFS1和GRSF1。此外,使用qPCR检查了GRSF1在结肠癌细胞系中的表达,并通过体外实验进行了表型验证。结论:我们的发现强调了特定代谢途径的高活性,包括丙酮酸代谢和三羧酸循环,与结肠癌预后改善相关,为代谢疗法提供新的途径。GRSF1和UQCRFS1等hub基因的鉴定及其与有利代谢谱的联系为肿瘤新血管形成和转移提供了新的见解。对于在CRC治疗中靶向代谢途径具有重要的临床意义。
    Background: Metabolic reprogramming plays a crucial role in the development of colorectal cancer (CRC), influencing tumor heterogeneity, the tumor microenvironment, and metastasis. While the interaction between metabolism and CRC is critical for developing personalized treatments, gaps remain in understanding how tumor cell metabolism affects prognosis. Our study introduces novel insights by integrating single-cell and bulk transcriptome analyses to explore the metabolic landscape within CRC cells and its mechanisms influencing disease progression. This approach allows us to uncover metabolic heterogeneity and identify specific metabolic genes impacting metastasis, which have not been thoroughly examined in previous studies. Methods: We sourced microarray and single-cell RNA sequencing datasets from the Gene Expression Omnibus (GEO) and bulk sequencing data for CRC from The Cancer Genome Atlas (TCGA). We employed Gene Set Variation Analysis (GSVA) to assess metabolic pathway activity, consensus clustering to identify CRC-specific transcriptome subtypes in bulkseq, and rigorous quality controls, including the exclusion of cells with high mitochondrial gene expression in scRNA seq. Advanced analyses such as AUCcell, infercnvCNV, Non-negative Matrix Factorization (NMF), and CytoTRACE were utilized to dissect the cellular landscape and evaluate pathway activities and tumor cell stemness. The hdWGCNA algorithm helped identify prognosis-related hub genes, integrating these findings using a random forest machine learning model. Results: Kaplan-Meier survival curves identified 21 significant metabolic pathways linked to prognosis, with consensus clustering defining three CRC subtypes (C3, C2, C1) based on metabolic activity, which correlated with distinct clinical outcomes. The metabolic activity of the 13 cell subpopulations, particularly the epithelial cell subpopulation with active metabolic levels, was evaluated using AUCcell in scRNA seq. To further analyze tumor cells using infercnv, NMF disaggregated these cells into 10 cellular subpopulations. Among these, the C2 subpopulation exhibited higher stemness and tended to have a poorer prognosis compared to C6 and C0. Conversely, the C8, C3, and C1 subpopulations demonstrated a higher level of the five metabolic pathways, and the C3 and C8 subpopulations tended to have a more favorable prognosis. hdWGCNA identified 20 modules, from which we selected modules primarily expressed in high metabolic tumor subgroups and highly correlated with clinical information, including blue and cyan. By applying variable downscaling of RF to a total of 50 hub genes, seven gene signatures were obtained. Furthermore, molecules that were validated to be protective in GEO were screened alongside related molecules, resulting in the identification of prognostically relevant molecules such as UQCRFS1 and GRSF1. Additionally, the expression of GRSF1 was examined in colon cancer cell lines using qPCR and phenotypically verified by in vitro experiments. Conclusion: Our findings emphasize that high activity in specific metabolic pathways, including pyruvate metabolism and the tricarboxylic acid cycle, correlates with improved colon cancer outcomes, presenting new avenues for metabolic-based therapies. The identification of hub genes like GRSF1 and UQCRFS1 and their link to favorable metabolic profiles offers novel insights into tumor neovascularization and metastasis, with significant clinical implications for targeting metabolic pathways in CRC therapy.
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  • 文章类型: Journal Article
    目的:白术是一种广泛使用的传统中药,在癌症中显示出显著的疗效。结直肠癌是全球最常见的恶性肿瘤。干扰素(IFN)-γ,一种参与抗肿瘤免疫的重要细胞因子,具有细胞抑制作用,促凋亡,以及用于检测和去除转化细胞的免疫刺激特性。白术-II(AT-II)属于衍生自具有抗癌活性的白术的内酯化合物。然而,AT-II联合IFN-γ是否能调节CRC进展及其潜在机制尚不清楚.本研究旨在阐明AT-II联合IFN-γ通过调节NF-kBp65/PD-L1信号通路协同对抗CRC的功效和作用机制。方法:用AT-Ⅱ和IFN-γ单独或联合处理HT29和HCT15细胞,迁移,然后使用细胞计数试剂盒-8(CCK-8)和Transwell测定法分析侵袭,分别。此外,通过westernblot分析研究了潜在的机制。在体内评估AT-II与IFN-γ组合对肿瘤生长和肺转移的作用。最后,通过流式细胞术和酶联免疫吸附试验(ELISA)证实了肺转移C57BL/6小鼠肿瘤组织中淋巴细胞的数量和血浆细胞因子的水平。结果:AT-II或联合IFN-γ在体外和体内均显着抑制CRC细胞的生长和迁移能力。还测量了AT-II与IFN-γ联合的有益作用背后的生物学机制,并抑制了p38MAPK,FAK,Wnt/β-catenin,Smad,观察到NF-kBp65/PD-L1通路。此外,AT-II联合IFN-γ能显著抑制C57BL/6小鼠HCT15移植瘤生长和肺转移,伴随淋巴细胞浸润进入肿瘤组织和炎症反应失活。结论:AT-II联合IFN-γ可作为结直肠癌肿瘤免疫治疗的潜在策略。更重要的是,AT-II抑制CRC进展的机制是通过抑制NF-kBp65/PD-L1信号通路.
    Purpose: Atractylodes macrocephala Koidz is a widely used classical traditional Chinese herbal medicine, that has shown remarkable efficacy in cancers. Colorectal cancer (CRC) is the most common malignant tumor globally. Interferon (IFN)-γ, a prominent cytokine involved in anti-tumor immunity that has cytostatic, pro-apoptotic, and immune-stimulatory properties for the detection and removal of transformed cells. Atractylenolides-II (AT-II) belongs to the lactone compound that is derived from Atractylodes macrocephala Koidz with anti-cancer activity. However, whether AT-II combined with IFN-γ modulates CRC progression and the underlying mechanisms remain unclear. The present study aimed to elucidate the efficacy and pharmaceutical mechanism of action of AT-II combined with IFN-γ synergistically against CRC by regulating the NF-kB p65/PD-L1 signaling pathway. Methods: HT29 and HCT15 cells were treated with AT-II and IFN-γ alone or in combination and cell viability, migration, and invasion were then analyzed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Furthermore, the underlying mechanism was investigated through western blot assay. The role of AT-II combined with IFN-γ on tumor growth and lung metastases was estimated in vivo. Finally, the population of lymphocytes in tumor tissues of lung metastatic C57BL/6 mice and the plasma cytokine levels were confirmed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Results: AT-II or the combination IFN-γ significantly inhibited the growth and migration abilities of CRC cells in vitro and in vivo. The biological mechanisms behind the beneficial effects of AT-II combined with IFN-γ were also measured and inhibition of p38 MAPK, FAK, Wnt/β-catenin, Smad, and NF-kB p65/PD-L1 pathways was observed. Moreover, AT-II combined with IFN-γ significantly inhibited HCT15 xenograft tumor growth and lung metastases in C57BL/6 mice, which was accompanied by lymphocyte infiltration into the tumor tissues and inflammatory response inactivation. Conclusions: The results showed that the AT-II in combination with IFN-γ could be used as a potential strategy for tumor immunotherapy in CRC. More importantly, the mechanism by which AT-II suppressed CRC progressions was by inhibiting the NF-kB p65/PD-L1 signal pathway.
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  • 文章类型: Journal Article
    白细胞介素-17(IL-17)家族细胞因子促进保护性炎症抵抗病原体,而且还促进自身免疫和肿瘤的发展。IL-17对调节性T细胞(Tregs)的直接信号尚未报道,可能有助于解释这些二分法反应。
    我们通过将Foxp3-YFP-Cre小鼠与Il17ra-flox小鼠(Il17raΔTreg小鼠)杂交,在Treg中产生了Il17ra的条件性敲除。随后,我们将Il17raΔTreg小鼠的骨髓细胞过继转移到散发性结直肠癌的小鼠模型(Cdx2-Cre/ApcF/),在结直肠癌中选择性消融IL-17对Tregs的直接信号传导。对来自小鼠结肠直肠肿瘤的纯化Treg进行单细胞RNA测序和批量RNA测序,并与人类肿瘤浸润的Treg细胞进行比较。
    IL-17受体A(IL-17RA)在存在于小鼠肠系膜淋巴结和结肠肿瘤中的Treg中表达。IL-17RA消融,特别是在Tregs中,导致Th17细胞增加,并加剧了肿瘤的发展。机械上,肿瘤浸润性Tregs表现出与其激活相关的独特基因特征,成熟,和抑制函数,并且该签名部分由IL-17向Tregs的直接信号传导支持。为了研究Treg编程的途径,我们发现肿瘤Tregs中IL-17RA的缺失导致RNA剪接减少,和下调几种RNA结合蛋白,已知这些蛋白可以调节可变剪接并促进Treg功能。
    IL-17直接向Tregs发出信号,并促进其成熟和功能。该信号传导途径构成了一个负反馈回路,可控制CRC中的促癌炎症。
    UNASSIGNED: Interleukin-17 (IL-17) family cytokines promote protective inflammation for pathogen resistance, but also facilitate autoimmunity and tumor development. A direct signal of IL-17 to regulatory T cells (Tregs) has not been reported and may help explain these dichotomous responses.
    UNASSIGNED: We generated a conditional knockout of Il17ra in Tregs by crossing Foxp3-YFP-Cre mice to Il17ra-flox mice (Il17ra ΔTreg mice). Subsequently, we adoptively transferred bone marrow cells from Il17ra ΔTreg mice to a mouse model of sporadic colorectal cancer (Cdx2-Cre +/Apc F/+), to selectively ablate IL-17 direct signaling on Tregs in colorectal cancer. Single cell RNA sequencing and bulk RNA sequencing were performed on purified Tregs from mouse colorectal tumors, and compared to those of human tumor infiltrating Treg cells.
    UNASSIGNED: IL-17 Receptor A (IL-17RA) is expressed in Tregs that reside in mouse mesenteric lymph nodes and colon tumors. Ablation of IL-17RA, specifically in Tregs, resulted in increased Th17 cells, and exacerbated tumor development. Mechanistically, tumor-infiltrating Tregs exhibit a unique gene signature that is linked to their activation, maturation, and suppression function, and this signature is in part supported by the direct signaling of IL-17 to Tregs. To study pathways of Treg programming, we found that loss of IL-17RA in tumor Tregs resulted in reduced RNA splicing, and downregulation of several RNA binding proteins that are known to regulate alternative splicing and promote Treg function.
    UNASSIGNED: IL-17 directly signals to Tregs and promotes their maturation and function. This signaling pathway constitutes a negative feedback loop that controls cancer-promoting inflammation in CRC.
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  • 文章类型: Editorial
    在这篇社论中,我们评论了Agatsuma等人发表在《世界胃肠病学杂志》上的文章。他们提出了更有效的结直肠筛查政策。筛查是导致有资格进行筛查的人群中晚年死亡率降低的主要政策。结肠镜检查是筛查的金标准工具,通过去除癌前或早期恶性息肉具有预防作用。然而,结肠镜检查是一个侵入性过程,并开发了粪便测试,例如当前的血红蛋白免疫检测,然后是内窥镜检查,作为人群筛查的通用工具,避免后勤和经济问题。即便如此,参与率和依从率很低。正在开发不同的筛查选项,其想法是,如果人们可以在最适合自己的选择之间进行选择,参与基于人群的筛查计划将会增加.验血,例如最近的一种检测肿瘤脱落的无细胞DNA的方法,称为循环肿瘤DNA,显示出与癌症粪便测试相似的准确率,但对晚期癌前病变的敏感性较低。当免疫系统和癌症之间的串扰被确立为癌症的新标志时,新型免疫系统相关生物标志物和患者免疫参数信息,例如不同免疫群体的细胞计数,被研究用于早期发现结直肠癌,因为它们对无症状的人有效,与粪便血液的存在相比,在腺瘤-癌的发展中出现得更早。sCD26,例如,检出80.37%的晚期腺瘤。为了接触到尽可能多的合格人员,从比当前项目更早的年龄开始,方向可能是应用基于血液的测试,在常规访问初级卫生系统期间采集的尿液或唾液。
    In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology. They suggest policies for more effective colorectal screening. Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening. Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps. However, colonoscopy is an invasive process, and fecal tests such as the current hemoglobin immunodetection were developed, followed by endoscopy, as the general tool for population screening, avoiding logistical and economic problems. Even so, participation and adherence rates are low. Different screening options are being developed with the idea that if people could choose between the ones that best suit them, participation in population-based screening programs would increase. Blood tests, such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA, showed a similar accuracy rate to stool tests for cancer, but were less sensitive for advanced precancerous lesions. At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer, novel immune system-related biomarkers and information on patients\' immune parameters, such as cell counts of different immune populations, were studied for the early detection of colorectal cancer, since they could be effective in asymptomatic people, appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood. sCD26, for example, detected 80.37% of advanced adenomas. To reach as many eligible people as possible, starting at an earlier age than current programs, the direction could be to apply tests based on blood, urine or salivary fluid to samples taken during routine visits to the primary health system.
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