• 【NF45作为新型细胞周期蛋白在食管鳞状细胞癌(ESCC)中的表达及其临床作用。】 复制标题 收藏 收藏
    DOI:10.1007/s13277-014-2683-5 复制DOI
    作者列表:Ni S,Zhu J,Zhang J,Zhang S,Li M,Ni R,Liu J,Qiu H,Chen W,Wang H,Guo W
    BACKGROUND & AIMS: :NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression.
    背景与目标: :NF45(也称为ILF2),作为NF-AT(活化的T细胞的核因子)的一个亚基,修复DNA断裂,抑制病毒复制,并与NF90一起在microRNA加工途径中起负调控作用。最近,发现牵涉HeLa细胞的有丝分裂控制和内源性NF45的缺失降低HeLa细胞的生长。尽管NF45在癌症生物学中的作用仍在争论中。在这项研究中,我们分析了NF45在食管鳞状细胞癌ESCC中的表达及其临床意义。通过Western印迹法在8对配对的ESCC组织中对NF45的表达进行了评估,并在105个石蜡包埋的切片上进行了免疫组织化学分析。 NF45在ESCC中高表达,并与ESCC细胞的肿瘤分期和Ki-67显着相关。此外,NF45高表达是ESCC患者生存不良的独立预后因素。为了确定NF45是否能调节ESCC细胞的增殖,我们增加了内源性NF45并使用Western blot,CCK8,流式细胞术和集落形成分析来分析TE1 ESCC细胞的增殖,这共同表明NF45的过表达有利于NF45的细胞周期进程。 TE1 ESCC细胞。而敲低NF45导致细胞周期停滞在G0 / G1期,从而废除了细胞生长。这些发现表明NF45可能在促进ESCC的肿瘤发生中起重要作用,因此是预防ESCC进展的有希望的治疗靶标。
  • 【通过EP2对EGFR的反式激活,研究PGE2对ESCC细胞的调控作用及其机制。】 复制标题 收藏 收藏
    DOI:10.26355/eurrev_201712_14011 复制DOI
    作者列表:Cui FB,Huang DF,Zhang FL,Gao EY,Zhang Y,Cao YM,Ding S,Wang Y,Cao QS,Cao XM
    BACKGROUND & AIMS: OBJECTIVE:To determine whether the combination of prostaglandin E2 (PGE2) and EP2, the subtype receptor of PGE2, could trans-activate the epidermal growth factor receptor (EGFR). PATIENTS AND METHODS:In this experiment, we selected epithelial cells from normal esophageal mucosa as the negative control group, and the ESCC EC109 and TE-1 cell strain as the observation group. Real-time PCR and Western-blotting were used to detect the expression of EP2, EGFR and phosphorylated EGFR (p-EGFR). The pre-treatment of ESCC cell strains was carried out using Butaprost (special agonist of PGE2 and EP2) and RNAi of EP2, and we observed the expression of EP2, EGFR, and p-EGFR. WST-8 (CCK-8) was applied for the detection of the cell proliferation rate. The transwell invasion experiment was conducted for the detection of the invasion capability of cells. The expression of MMP-9 (matrix metalloproteinase-9), VEGF (vascular endothelial growth factor), pro-inflammatory factors (IL-6 and TNF-α) in the cell supernatant were detected using ELISA. RESULTS:The high mRNA and protein expression of EP2, EGFR, and p-EGFR were found in the EC109 and TE-1 cell strains in the observation group, which were higher than those in the control group (p < 0.05). After the intervention of PGE2, EP2 expression was decreased and the p-EGFR expression was increased (p < 0.05). There was no variation found in the expression of EGFR (p > 0.05). After cells were intervened using Butaprost, the expressions of EP2 and p-EGFR were increased (p < 0.05), and there were no changes identified in the expression of EGFR (p > 0.05). After the intervention of RNAi, the expression of EP2 and p-EGFR was decreased (p < .05), and no changes were identified in the expression of EGFR (p > 0.05). After the intervention of PGE2 and Butaprost, great increases were seen in the cell proliferation rate, invasion capability, and the expression of MMP-9, VEGF, IL-6, and TNF-α in EC109 and TE-1 cell strains (p < 0.05), however, the intervention of RNAi could reduce above indexes (p < 0.05). CONCLUSIONS:Through cell experiments, we verified that the combination of prostaglandin E2 (PGE2) and EP2, the subtype receptor of PGE2, could trans-activate the epidermal growth factor receptor (EGFR) to regulate the proliferation and invasion capability of esophageal squamous cell carcinoma (ESCC) cells, and secrete and express multiple cytokines, thus discovering the pathological mechanism of inflammation to carcinoma transition in the occurrence of ESCC, and providing the experimental evidence for the search of new target in the treatment of ESCC. ESCC cells can highly express the receptor subtype EP2 of PGE2 that can transactivate the EGFR, through which PGE2 is involved in the transition mechanism from inflammation to cancer.
    背景与目标: 目的:确定前列腺素E2(PGE2)和EP2(PGE2的亚型受体)的组合是否可以反激活表皮生长因子受体(EGFR)。
    病人与方法:本实验以正常食管粘膜上皮细胞为阴性对照组,以ESCC EC109和TE-1细胞株为观察组。实时PCR和Western-blotting用于检测EP2,EGFR和磷酸化EGFR(p-EGFR)的表达。使用Butaprost(PGE2和EP2的特殊激动剂)和EP2的RNAi进行ESCC细胞株的预处理,我们观察到EP2,EGFR和p-EGFR的表达。 WST-8(CCK-8)用于检测细胞增殖率。进行transwell侵袭实验以检测细胞的侵袭能力。使用ELISA检测细胞上清液中MMP-9(基质金属蛋白酶-9),VEGF(血管内皮生长因子),促炎因子(IL-6和TNF-α)的表达。
    结果:观察组EC109和TE-1细胞株中EP2,EGFR和p-EGFR的mRNA和蛋白表达较高,高于对照组(p <0.05)。在PGE2干预后,EP2表达降低,而p-EGFR表达升高(p <0.05)。在EGFR的表达中没有发现变化(p> 0.05)。用Butaprost干预细胞后,EP2和p-EGFR的表达增加(p <0.05),而EGFR的表达没有变化(p> 0.05)。 RNAi干预后,EP2和p-EGFR的表达降低(p <.05),而EGFR的表达未见变化(p> 0.05)。在PGE2和Butaprost的干预下,EC109和TE-1细胞株的细胞增殖速率,侵袭能力以及MMP-9,VEGF,IL-6和TNF-α的表达均显着增加(p < 0.05),但是,RNAi的干预可以降低上述指标(p <0.05)。
    结论:通过细胞实验,我们证实前列腺素E2(PGE2)和EP2(PGE2的亚型受体)的组合可以反激活表皮生长因子受体(EGFR)来调节食管鳞状细胞癌的增殖和侵袭能力。 (ESCC)细胞,并分泌和表达多种细胞因子,从而发现了发生ESCC时炎症向癌变的病理机制,为寻找ESCC的新靶标提供了实验依据。 ESCC细胞可以高表达PGE2的受体亚型EP2,该亚型可以使EGFR活化,PGE2可以通过该亚型参与从炎症到癌症的转变机制。
  • 【EphA5沉默通过依赖ATM的途径增加ESCC细胞的放射敏感性。】 复制标题 收藏 收藏
    DOI:10.2147/CMAR.S261182 复制DOI
    作者列表:Zhang R,Han D,Li L,Luo W,Liu J,Qian L
    BACKGROUND & AIMS: Background:Radiotherapy is one of the most important treatments for esophageal squamous cell carcinoma (ESCC). Previously, we found that EphA5 expression was increased in ESCC cells and tumor tissues. Studies from other groups reported that EphA5 is abnormally expressed in numerous malignant tumors and may be involved in the radiosensitivity of lung cancer. However, the role of EphA5 in radiotherapy for ESCC remains unclear. Methods:The siRNA sequences against human EPHA5 were transfected to the ESCC cells (KYSE150 and KYSE450). After ionizing radiation (IR), cell viability and colony formation assays were used to test the changes of cell proliferation in EphA5-silenced cells. Flow cytometry analysis was performed to investigate the cell apoptosis and cycle in the irradiated cells interfered by siRNA. The key molecules involved in cell cycle checkpoints and DNA damage repair were evaluated by Western blot and immunofluorescence. Results:CCK8 assay and clonogenic assay showed that the proliferation of EphA5-silenced ESCC cells was inhibited after IR. At 24 h post-IR treatment, we found that the G1/S checkpoint triggered by DNA damage in EphA5-silenced cells was defective. γ-H2AX foci in the irradiated EphA5-silenced cells were impaired at 0.5 h post-IR treatment as well as ATM activation. The defective activation of ATM resulted in a decrease of p-Chk2, p-p53 and p21 expression. Conclusion:In conclusion, these results indicate that EphA5 silencing increases radiosensitivity in ESCC cells through ATM-dependent pathway, which provides a potential target for the radiotherapy in ESCC.
    背景与目标: 背景:放射治疗是食管鳞状细胞癌(ESCC)的最重要治疗方法之一。以前,我们发现EphA5表达在ESCC细胞和肿瘤组织中增加。其他研究表明,EphA5在许多恶性肿瘤中异常表达,可能与肺癌的放射敏感性有关。然而,EphA5在ESCC放射治疗中的作用尚不清楚。
    方法:将针对人类EPHA5的siRNA序列转染至ESCC细胞(KYSE150和KYSE450)。电离辐射(IR)后,细胞活力和集落形成测定法用于测试EphA5沉默的细胞中细胞增殖的变化。进行流式细胞术分析以研究被siRNA干扰的被照射细胞的细胞凋亡和周期。通过蛋白质印迹和免疫荧光评估了参与细胞周期检查点和DNA损伤修复的关键分子。
    结果:CCK8法和克隆形成法显示,IR后,EphA5沉默的ESCC细胞的增殖受到抑制。红外线治疗后24小时,我们发现由EphA5沉默的细胞中的DNA损伤触发的G1 / S检查点存在缺陷。照射后的EphA5沉默的细胞中的γ-H2AX焦点在IR处理以及ATM激活后0.5小时受到损害。 ATM激活缺陷导致p-Chk2,p-p53和p21表达降低。
    结论:总之,这些结果表明,EphA5沉默可通过ATM依赖性途径提高ESCC细胞的放射敏感性,这为ESCC放射治疗提供了潜在的靶标。
  • 【肿瘤相关巨噬细胞数量的增加与VEGF-C的过度表达有关,在哈萨克斯坦ESCC的侵袭和转移中起着重要的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.yexmp.2016.12.001 复制DOI
    作者列表:Hu JM,Liu K,Liu JH,Jiang XL,Wang XL,Yang L,Chen YZ,Liu CX,Li SG,Cui XB,Zou H,Pang LJ,Zhao J,Qi Y,Liang WH,Yuan XL,Li F
    BACKGROUND & AIMS: :Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.
    背景与目标: :肿瘤相关的巨噬细胞(TAM)在肿瘤的生长,进展和转移中起重要作用。在哈萨克人食管鳞状细胞癌(ESCC)中TAM的分布尚未确定。我们旨在调查TAM在哈萨克ESCC发生和发展中的作用。 CD163用作TAM标记,免疫组化(IHC)计数用于量化肿瘤巢和周围基质中TAM的密度。 IHC染色用于评估哈萨克斯坦ESCC和癌旁正常组织(CAN)中血管内皮生长因子C(VEGF-C)的表达。哈萨克ESCCs肿瘤巢和基质中TAMs的密度显着高于CAN组织中的TAMs的密度。肿瘤巢和肿瘤基质中CD163阳性TAM数量的增加与哈萨克斯坦ESCC淋巴结转移和临床分期进展呈正相关。同时,哈萨克人食管鳞癌中VEGF-C的表达明显高于CAN组织。哈萨克人食管鳞癌中VEGF-C的过度表达与性别,肿瘤浸润深度,淋巴结转移和肿瘤临床分期显着相关。无论是在肿瘤巢中还是在肿瘤基质中,TAM的数量增加都与VEGF-C的过表达呈正相关,这可能促进淋巴管生成,并在哈萨克ESCC的侵袭和转移中起重要作用。
  • 【荟萃分析和图聚类相结合,以鉴定ESCC的预后指标。】 复制标题 收藏 收藏
    DOI:10.1590/S1415-47572012000300021 复制DOI
    作者列表:Gao H,Wang L,Cui S,Wang M
    BACKGROUND & AIMS: :Esophageal squamous cell carcinoma (ESCC) is one of the most malignant gastrointestinal cancers and occurs at a high frequency rate in China and other Asian countries. Recently, several molecular markers were identified for predicting ESCC. Notwithstanding, additional prognostic markers, with a clear understanding of their underlying roles, are still required. Through bioinformatics, a graph-clustering method by DPClus was used to detect co-expressed modules. The aim was to identify a set of discriminating genes that could be used for predicting ESCC through graph-clustering and GO-term analysis. The results showed that CXCL12, CYP2C9, TGM3, MAL, S100A9, EMP-1 and SPRR3 were highly associated with ESCC development. In our study, all their predicted roles were in line with previous reports, whereby the assumption that a combination of meta-analysis, graph-clustering and GO-term analysis is effective for both identifying differentially expressed genes, and reflecting on their functions in ESCC.
    背景与目标: 食管鳞状细胞癌(ESCC)是最恶性的胃肠道癌之一,在中国和其他亚洲国家以很高的频率发生。最近,鉴定了几种分子标志物来预测ESCC。尽管如此,仍然需要其他的预后指标,并清楚地了解其潜在作用。通过生物信息学,使用DPClus的图聚类方法检测共表达的模块。目的是确定一组可用于通过图聚类和GO项分析预测ESCC的区分基因。结果表明,CXCL12,CYP2C9,TGM3,MAL,S100A9,EMP-1和SPRR3与ESCC的发展高度相关。在我们的研究中,它们的所有预测作用均与以前的报告一致,因此,假设荟萃分析,图聚类和GO项分析相结合可有效识别差异表达的基因并反映其在ESCC中的功能。
  • 【与CCNH / CDK7的相互作用可通过上调上皮-间质转化(EMT)进程促进CtBP2促进食管鳞状细胞癌(ESCC)转移。】 复制标题 收藏 收藏
    DOI:10.1007/s13277-015-3354-x 复制DOI
    作者列表:Zhang J,Zhu J,Yang L,Guan C,Ni R,Wang Y,Ji L,Tian Y
    BACKGROUND & AIMS: :CtBP2, as a transcriptional corepressor of epithelial-specific genes, has been reported to promote tumor due to upregulating epithelial-mesenchymal transition (EMT) in cancer cells. CtBP2 was also demonstrated to contribute to the proliferation of esophageal squamous cell carcinoma (ESCC) cells through a negative transcriptional regulation of p16(INK4A). In this study, for the first time, we reported that CtBP2 expression, along with CCNH/CDK7, was higher in ESCC tissues with lymph node metastases than in those without lymph node metastases. Moreover, both CtBP2 and CCNH/CDK7 were positively correlated with E-cadherin, tumor grade, and tumor metastasis. However, the concrete mechanism of CtBP2's role in enhancing ESCC migration remains incompletely understood. We confirmed that CCNH/CDK7 could directly interact with CtBP2 in ESCC cells in vivo and in vitro. Furthermore, our data demonstrate for the first time that CtBP2 enhanced the migration of ESCC cells in a CCNH/CDK7-dependent manner. Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of ESCC.
    背景与目标: :CtBP2,作为上皮特异性基因的转录共抑制子,由于在癌细胞中上皮-间质转化(EMT)上调而促进了肿瘤。还证明了CtBP2通过对p16(INK4A)的负转录调节来促进食管鳞状细胞癌(ESCC)细胞的增殖。在本研究中,我们首次报道,在有淋巴结转移的ESCC组织中,CtBP2表达以及CCNH / CDK7高于无淋巴结转移的ESCC组织。此外,CtBP2和CCNH / CDK7与E-钙粘蛋白,肿瘤等级和肿瘤转移均呈正相关。但是,对CtBP2在增强ESCC迁移中作用的具体机制尚不完全了解。我们证实,CCNH / CDK7可以在体内和体外直接与ESCC细胞中的CtBP2相互作用。此外,我们的数据首次证明CtBP2以CCNH / CDK7依赖性方式增强了ESCC细胞的迁移。我们的研究结果表明CCNH / CDK7-CtBP2轴可能会增加ESCC细胞的迁移,并且靶向两者的相互作用可能会提供ESCC的新型治疗靶点。
  • 【新疆食管鳞状细胞癌(ESCC)中VEGF,EGFR和HER-2 mRNA的表达与新疆各族群临床病理特征的关系。】 复制标题 收藏 收藏
    DOI:10.1007/s13277-015-3656-z 复制DOI
    作者列表:Zhang L,Wang Y,Bai G,Zhang J,Yang M,Ma X
    BACKGROUND & AIMS: :The purpose of this study was to explore the relationship between the expression of vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER-2), and epidermal growth factor receptor (EGFR) mRNA in esophageal squamous cell carcinoma (ESCC) and the clinicopathological characteristics of the Han, Uyghur, and Kazakh in Xinjiang. Real-time quantitative polymerase chain reaction technology (RT-PCR) was used to detect the expression of VEGF, HER-2, and EGFR mRNA in esophageal squamous cancer tissue of 60 cases and 30 cases of VEGF, HER-2, and EGFR mRNA in esophageal cancer adjacent tissues, and analyze its relationship with clinicopathological features. The results were as follows: (1) There was no statistically significant difference in esophageal tissue VEGF, HER-2, and EGFR mRNA gene expression levels of the Han, Uyghur, and Kazakh patients (P > 0.05). (2) The expression levels of VEGF, HER-2, and EGFR mRNA in ESCC group were higher than those in adjacent esophageal tissue group (P < 0.05). (3) The expression levels of VEGF and HER-2 mRNA in ESCC of the Han patients were higher than those of the Uyghur and Kazakh patients (P < 0.05). (4) The expression levels of VEGF, HER-2, and EGFR mRNA in lymph node metastases were higher than those without lymph node metastasis (P < 0.05). (5) The expression level of HER-2 mRNA was related with the degrees of pathological differentiation, and the higher pathologic degree, the lower expression level in HER-2 mRNA (P < 0.05). Therefore, the following conclusions were drawn: (1) There were ethnic differences in the VEGF and HER-2 gene mRNA expression levels of the Uyghur, Han, and Kazakh patients in Xinjiang. (2) The expressions of VEGF, HER-2, and EGFR mRNA were related to the lymph node metastasis in ESCC and pathologic differentiation degree.
    背景与目标: :本研究旨在探讨食管鳞状细胞癌中血管内皮生长因子(VEGF),人表皮生长因子受体2(HER-2)和表皮生长因子受体(EGFR)mRNA的表达之间的关系( ESCC)和新疆汉族,维吾尔族和哈萨克族的临床病理特征。采用实时定量聚合酶链反应技术(RT-PCR)检测60例食管鳞癌组织和30例VEGF,HER-2和EGFR mRNA的食管鳞癌组织中VEGF,HER-2和EGFR mRNA的表达。在食管癌附近组织中,并分析其与临床病理特征的关系。结果如下:(1)汉族,维吾尔族和哈萨克族患者食管组织VEGF,HER-2和EGFR mRNA基因表达水平差异无统计学意义(P> 0.05)。 (2)食管鳞癌组VEGF,HER-2和EGFR mRNA的表达水平高于邻近食管组织组(P <0.05)。 (3)汉族人食管鳞癌中VEGF和HER-2 mRNA的表达水平高于维吾尔族和哈萨克族人(P <0.05)。 (4)淋巴结转移中VEGF,HER-2,EGFR mRNA的表达水平高于无淋巴结转移者(P <0.05)。 (5)HER-2 mRNA的表达水平与病理分化程度有关,病理程度越高,HER-2 mRNA的表达水平越低(P <0.05)。因此,得出以下结论:(1)新疆维吾尔族,汉族和哈萨克族患者的VEGF和HER-2基因mRNA表达水平存在种族差异。 (2)VEGF,HER-2,EGFR mRNA的表达与ESCC淋巴结转移及病理分化程度有关。
  • 【LncRNA TUG1通过在体外调节miR-148a-3p / MCL-1 / Wnt /β-catenin轴来促进ESCC进程。】 复制标题 收藏 收藏
    DOI:10.1111/1759-7714.13236 复制DOI
    作者列表:Tang Y,Yang P,Zhu Y,Su Y
    BACKGROUND & AIMS: BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Latest studies report that long noncoding RNAs (LncRNAs) play an essential role in diversified pathological processes of ESCC, although the mechanism by which they do so remains unknown. This study aimed to explore the parts of lncRNA taurine upregulated gene 1 (TUG1) in ESCC tissues and cells, its biofunctional effect and its underlying regulatory mechanism in ESCC. METHODS:The levels of TUG1 and miR-148a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in ESCC cells and tissues. The biofunctional effects were examined by MTT, flow cytometry, and transwell assay. The protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins and MCL-1 were determined by western blot analysis. The binding sites between miR-148a-3p and TUG1 or MCL-1 were predicted by online software starBase and confirmed by dual luciferase reporter assay. RESULTS:The mRNA expression of TUG1 was significantly upregulated in ESCC tissues or cells, and was negatively correlated to miR-148a-3p expression in tissues. Knockdown of TUG1 inhibited the proliferation, migration, and invasion, promoted apoptosis, and relieved the EMT progression in EC9706 and OE19 cells. Besides, knockdown of miR-148a-3p inverted positive effects from TUG1 deletion on ESCC cells. Besides, MCL-1 reversed the inhibitive effects from TUG1 deletion on expression of EMT-associated proteins (Wnt1, C-myc, CyclinD1, and β-catenin) above subsequently. CONCLUSION:TUG1 regulated the biofunction and EMT progression of ESCC by mediating miR-148a-3p/MCL-1/Wnt/β-catenin axis in vitro.
    背景与目标: 背景:食管鳞状细胞癌(ESCC)是最致命的恶性肿瘤之一。最新研究报道,长的非编码RNA(LncRNA)在ESCC的多种病理过程中起着至关重要的作用,尽管其作用机理尚不清楚。这项研究旨在探讨ESCC组织和细胞中lncRNA牛磺酸上调基因1(TUG1)的部分,其生物功能作用及其在ESCC中的潜在调控机制。
    方法:采用定量实时聚合酶链反应(qRT-PCR)检测ESCC细胞和组织中TUG1和miR-148a-3p的水平。通过MTT,流式细胞术和transwell测定法检查生物功能作用。通过蛋白质印迹分析确定上皮-间质转化(EMT)相关蛋白和MCL-1的蛋白表达水平。通过在线软件starBase预测了miR-148a-3p与TUG1或MCL-1之间的结合位点,并通过双重荧光素酶报告基因测定法进行了确认。
    结果:在食管鳞癌组织或细胞中TUG1的mRNA表达明显上调,与组织中miR-148a-3p的表达呈负相关。敲低TUG1抑制EC9706和OE19细胞的增殖,迁移和侵袭,促进细胞凋亡,并缓解EMT进展。此外,敲除miR-148a-3p可以逆转TUG1缺失对ESCC细胞的积极作用。此外,MCL-1随后逆转了TUG1缺失对上述EMT相关蛋白(Wnt1,C-myc,CyclinD1和β-catenin)表达的抑制作用。
    结论:TUG1通过介导miR-148a-3p / MCL-1 / Wnt /β-catenin轴调控ESCC的生物学功能和EMT进程。
  • 【大环内酯类似物F806通过阻断β1整合素激活来抑制食管鳞状细胞癌(ESCC)。】 复制标题 收藏 收藏
    DOI:10.18632/oncotarget.3612 复制DOI
    作者列表:Li LY,Jiang H,Xie YM,Liao LD,Cao HH,Xu XE,Chen B,Zeng FM,Zhang YL,Du ZP,Chen H,Huang W,Jia W,Zheng W,Xie JJ,Li EM,Xu LY
    BACKGROUND & AIMS: :The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.
    背景与目标: :食管鳞状细胞癌(ESCC)的新药匮乏,限制了治疗方案的选择。这项研究的特点是新型的天然大环内酯化合物F806在人类ESCC异种移植模型和细胞系中的治疗功效和作用机理。 F806抑制了ESCC的生长,最重要的是,它在两种人类ESCC异种移植模型中对正常组织的不良副作用更少。 F806抑制了6种ESCC细胞系的增殖,最大抑制浓度(IC50)的一半在9.31至16.43μM之间。此外,F806诱导ESCC细胞凋亡,有助于其生长抑制作用。同样,F806抑制细胞粘附,导致阳极失调。机理研究表明,F806部分通过与β1整合素的新位点Arg610结合而抑制β1整合素的活化,抑制了粘着斑的形成,减少了细胞对细胞外基质的粘附,并最终触发了细胞凋亡。我们得出的结论是,通过靶向β1整联蛋白,F806可能是一种耐受良好的抗癌药物,从而导致ESCC细胞失衡。
  • 【循环CD14()HLA-DR(-/低)髓样来源的抑制细胞是ESCC患者预后不良的指标。】 复制标题 收藏 收藏
    DOI:10.1007/s13277-015-3426-y 复制DOI
    作者列表:Huang H,Zhang G,Li G,Ma H,Zhang X
    BACKGROUND & AIMS: :Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low) cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA-DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.
    背景与目标: :越来越多的证据表明,称为髓样抑制细胞(MDSC)的抑制细胞群是抑制抗肿瘤免疫力的关键免疫调节剂。在这项研究中,我们发现患者中循环CD14()HLA-DR(-/ low)细胞的水平显着高于健康供体,并且与肿瘤负荷,淋巴结转移以及肿瘤,淋巴结转移有关。转移(TNM)临床阶段。更重要的是,通过3年总生存期的分析,我们首次发现CD14()HLA-DR(-/低)的水平是预后不良的生物学指标。此外,我们证明在肿瘤转移性肿瘤引流淋巴结(TDLNs)中的CD14()HLA-DR(-/ low)细胞所占的比例明显高于无肿瘤的TDLNs。此外,与健康对照组相比,食管鳞癌(ESCC)患者的CD14()HLA-DR(-/ low)细胞表达的程序性死亡配体1(PD-L1)显着增加。随后,通过抗体阻断PD-L1途径可有效逆转体外对CD14()HLA-DR(-/ low)细胞介导的自体T细胞增殖的抑制作用。总之,我们的数据显示,在ESCC患者中CD14()HLA-DR(-/低)MDSCs增加是一种新的不良预后指标,并且可能通过PD-L1 / PD-1途径发挥免疫抑制作用。
  • 【中国北方高发区两个DNA修复基因的多态性及其对ESCC和GCA的易感性研究。】 复制标题 收藏 收藏
    DOI:10.1007/s11033-007-9187-y 复制DOI
    作者列表:Wang N,Dong XJ,Zhou RM,Guo W,Zhang XJ,Li Y
    BACKGROUND & AIMS: AIM:To investigate the possible association of three SNPs, XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of northern China. METHODS:XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G SNP were genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 583 cancer patients (329 ESCC and 254 GCA) and 614 healthy controls. RESULTS:The genotype distribution of the XRCC2 C41657T in ESCC and GCA patients were significantly different from that in healthy controls (P values = 0.04 and 0.04 respectively). And a significant difference was found in the allele distribution of GCA patients from that in controls (P = 0.01). The XRCC2 C41657T polymorphism was associated with a modest enhancement in ESCC risk and GCA risk: OR for C/T genotype was 1.38 (1.01-1.89) in GCA risk and for T/T genotype was 2.24 (1.10-4.57) in ESCC risk. When stratified for age, smoking status and family history of UGIC, the C/T genotype showed a modest significant trend on the risk of GCA patients in the groups of age < or =50 years and non-smokers, the adjusted OR were 2.84 (1.21-6.66) and 1.62 (1.06-2.49). The T/T genotype significantly increased the susceptibility of GCA patients in negative family history of UGIC (3.04, 1.02-8.32) and to ESCC patients in the group of age >50 years (3.03, 1.31-6.98), Negative family of UGIC (3.03, 1.12-7.07) and smokers (2.64, 1.02-6.83). The genotype and allele distribution of XRCC2 G4234C and XRCC3 A17893G in ESCC and GCA patients were not significantly different from that in healthy controls (all P values were above 0.05). CONCLUSION:In this study, we found that the C41657T polymorphism of XRCC2 genes might modify the risk of ESCC and GCA development.
    背景与目标: 目的:研究在中国北方人群中三种SNPs XRCC2 C41657T,XRCC2 G4234C和XRCC3 A17893G与食管鳞状细胞癌(ESCC)和胃门腺癌(GCA)的易感性之间的关系。
    方法:采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)分析法对583例癌症患者(329例ESCC和254例GCA)和614例健康对照者的XRCC2 C41657T,XRCC2 G4234C和XRCC3 A17893G SNP进行基因分型。
    结果:ESCC和GCA患者中XRCC2 C41657T的基因型分布与健康人相比有显着差异(P值分别为0.04和0.04)。 GCA患者的等位基因分布与对照组相比有显着差异(P = 0.01)。 XRCC2 C41657T多态性与ESCC风险和GCA风险的适度提高相关:GCA风险的C / T基因型为1.38(1.01-1.89),ESCC风险的T / T基因型为2.24(1.10-4.57)。当按年龄,吸烟状况和UGIC家族史进行分层时,C / T基因型在年龄小于或等于50岁且不吸烟的人群中显示出GCA患者风险的适度显着趋势,校正后的OR为2.84( 1.21-6.66)和1.62(1.06-2.49)。 T / T基因型显着增加了UGIC阴性家族史(3.04,1.02-8.32)中的GCA患者的敏感性,以及UGIC阴性家族(> 503岁的人群)(3.03,1.31-6.98)对ESCC患者的敏感性。 3.03、1.12-7.07)和吸烟者(2.64、1.02-6.83)。 ESCC和GCA患者中XRCC2 G4234C和XRCC3 A17893G的基因型和等位基因分布与健康对照组无显着差异(所有P值均高于0.05)。
    结论:在本研究中,我们发现XRCC2基因的C41657T多态性可能会改变ESCC和GCA发生的风险。
  • 【MCP2激活NF-κB信号通路,促进ESCC细胞的迁移和侵袭。】 复制标题 收藏 收藏
    DOI:10.1002/cbin.10909 复制DOI
    作者列表:Zhou J,Zheng S,Liu T,Liu Q,Chen Y,Tan D,Ma R,Lu X
    BACKGROUND & AIMS: :Synchronous lung and esophageal cancers are rare but represent a unique challenge to thoracic surgeons. The literature is limited but series describe long-term survival with curative surgery for concomitant esophageal and lung cancer. Preoperative risk assessment is critical because surgical resection of both cancers requires adequate cardiopulmonary function and performance status. Chemotherapy and radiation are used as adjuvant therapy or as primary treatment of unresectable lesions. Although long-term survival for patients with concomitant lung and esophageal cancer is lower than that of patients with either one alone, survival with curative surgery is higher than that of patients with metastatic disease of either primary.
    背景与目标: :肺癌和食道癌是罕见的,但对胸外科医生来说是一个独特的挑战。文献有限,但系列文章描述了伴随食管癌和肺癌的根治性手术的长期生存。术前风险评估至关重要,因为两种癌症的手术切除都需要足够的心肺功能和表现状态。化学疗法和放射疗法被用作辅助疗法或不可切除病变的主要疗法。尽管伴发肺癌和食管癌的患者的长期生存率低于任何一个单独接受治疗的患者,但根治性手术的生存率高于任何一个患有转移性疾病的患者。
  • 【通过ESCC microRNA和Polycomb复合物双重抑制内吞性细胞,调节小鼠胚胎干细胞的多能性。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-17828-7 复制DOI
    作者列表:Mote RD,Mahajan G,Padmanabhan A,Ambati R,Subramanyam D
    BACKGROUND & AIMS: :Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that Osteocalcin (Bglap) can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that Bglap-expressing cells in adult sheath tissues possess clonogenic and multipotent properties comparable to those of stem/progenitor cells isolated from tendon fibers. Transplantation of sheath tissues improves tendon repair. Mechanistically, Hh signaling in sheath tissues is necessary and sufficient to promote the proliferation of Mkx-expressing cells in sheath tissues, and its action is mediated through TGFβ/Smad3 signaling. Furthermore, co-localization of GLI1+ and MKX+ cells is also found in human tendinopathy specimens. Our work reveals the molecular function of Hh signaling in extrinsic sheath tissues for tendon repair.
    背景与目标: :外在和内在组织都有助于肌腱修复,但外在组织在肌腱修复中的起源和分子功能尚不完全清楚。在这里,我们显示肌腱鞘细胞具有干/祖细胞特性,并通过激活刺猬信号来促进肌腱修复。我们发现骨钙蛋白(Bglap)可以用作小鼠中成年肌腱鞘的特异性标志物。谱系追踪实验表明,成年鞘组织中表达Bglap的细胞具有克隆形成和多能性的特性,与从肌腱纤维中分离的干/祖细胞的特性相当。鞘组织的移植改善了肌腱的修复。从机理上讲,鞘内组织中的Hh信号对于促进鞘组织中表达Mkx的细胞的增殖是必要和充分的,并且其作用是通过TGFβ/ Smad3信号介导的。此外,在人类肌腱病标本中还发现了GLI1和MKX细胞的共定位。我们的工作揭示了Hh信号在外在鞘组织中用于肌腱修复的分子功能。
  • 【丙酮酸激酶(PKM2)的M2亚型在哈萨克斯坦的ESCC中被上调,并促进ESCC细胞的增殖和迁移。】 复制标题 收藏 收藏
    DOI:10.1007/s13277-015-4073-z 复制DOI
    作者列表:Liu Q,Liang M,Liu T,Vuitton L,Zheng S,Gao X,Lu M,Li X,Sheyhidin I,Lu X
    BACKGROUND & AIMS: :The objectives of the present study are to explore role of pyruvate kinase isoenzyme type M2 (PKM2) in progression of Kazakh's esophageal squamous cell carcinoma (ESCC) in Xinjiang, China, and to clarify mechanism of PKM2 in malignant phenotype. PKM2 expression was examined using immunohistochemistry (IHC) in 101 matched pairs of ESCC and normal adjacent tissues (NATs) and using enzyme-linked immunosorbent assay (ELISA) in 35 serum samples of Kazakh's ESCC and 8 serum samples of healthy subjects. To investigate mechanism, small interfering RNA (siRNA)-PKM2 was transfected into ESCC cells. Cell migration and invasion were evaluated by wound healing and Transwell assays. Apoptosis and cell cycle were analyzed by flow cytometry (FCM). PKM2 expression was significantly higher in ESCC tissues (77.2 %, 78/101) compared with matched NAT (P = 0.003) and also higher in serum samples of Kazakh's ESCC patients (78.84 ng/mL) compared with healthy subjects (13.55 ng/mL) (P = 0.001). Patients with overexpression of PKM2 had a poor prognosis (P = 0.032). After knockdown of PKM2, cell proliferation, migration, and invasion were significantly reduced (P = 0.001), apoptosis increased (P = 0.001), and cell cycle was arrested at G1 phase. PKM2 overexpression was significantly correlated with the worse outcome of Kazakh's ESCC. Furthermore, PKM2 was involved in progression of ESCC by promoting proliferation and suppressing apoptosis, accelerating invasion, and influencing cell cycle. PKM2 could be a potential biomarker for molecular classification of ESCC.
    背景与目标: :本研究的目的是探讨M2型丙酮酸激酶同工酶(PKM2)在中国新疆哈萨克族食管鳞状细胞癌(ESCC)进展中的作用,并阐明PKM2在恶性表型中的作用机制。使用免疫组化(IHC)在101对匹配的ESCC和正常相邻组织(NAT)中检测PKM2的表达,并使用酶联免疫吸附测定(ELISA)在35个哈萨克人ESCC血清样品和8个健康受试者血清样品中检测PKM2的表达。为了研究机制,将小干扰RNA(siRNA)-PKM2转染到ESCC细胞中。通过伤口愈合和Transwell测定法评估细胞迁移和侵袭。通过流式细胞仪(FCM)分析细胞凋亡和细胞周期。与匹配的NAT(P = 0.003)相比,ESCC组织中的PKM2表达显着更高(77.2%,78/101),与健康受试者(13.55 ng / mL)相比,哈萨克斯坦ESCC患者的血清样品中的PKM2表达也更高(78.84 ng / mL)。 )(P = 0.001)。 PKM2过表达的患者预后较差(P = 0.032)。敲除PKM2后,细胞增殖,迁移和侵袭显着降低(P = 0.001),细胞凋亡增加(P = 0.001),细胞周期被阻滞在G1期。 PKM2的过表达与哈萨克斯坦ESCC的不良结局显着相关。此外,PKM2通过促进增殖和抑制凋亡,加速侵袭并影响细胞周期而参与ESCC的发展。 PKM2可能是ESCC分子分类的潜在生物标志物。
  • 【CTLA-4和PLR联合分析在食管鳞状细胞癌(ESCC)患者中的预后价值。】 复制标题 收藏 收藏
    DOI:10.1155/2019/1601072 复制DOI
    作者列表:Zhang CY,Zhang J,Ma YF,Zhe H,Zhao R,Wang YY
    BACKGROUND & AIMS: Objective:The purpose of this study was to evaluate the prognostic role of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression level and the platelet lymphocyte ratio (PLR) level in esophageal squamous cell carcinoma (ESCC) patients. Methods:84 ESCC patients who received surgical treatment in our hospital were enrolled in the study. The correlation of each biomarker's level with ESCC patients' clinicopathological characteristics and overall survival (OS) was assessed. Results:The elevated expression rate of T-CTLA-4 (tumor cell CTLA-4) and I-CTLA-4 (interstitial lymphocyte CTLA-4) was 48.8% and 44.0%, respectively. The number of enrolled patients with a higher PLR level (≥119) was 48. The prognostic value of T-CTLA-4, I-CTLA-4, and PLR in ESCC patients was not detected. However, patients with both a low T-CTLA-4 expression level and a low PLR level that had longer OS (p = 0.023) were found. The prognostic role of T-CTLA-4(-) +PLR (-) status in ESCC patients was also confirmed in multivariate analyses (p = 0.027). Conclusion:These results demonstrated the potential prognostic value of combined analysis of CTLA-4 and PLR in ESCC patients.
    背景与目标: 目的:本研究旨在评估食管鳞状细胞癌(ESCC)细胞毒性T淋巴细胞相关抗原4(CTLA-4)表达水平和血小板淋巴细胞比率(PLR)水平的预后作用。
    方法:选择84例在我院接受外科手术治疗的ESCC患者作为研究对象。评估了每种生物标志物水平与ESCC患者的临床病理特征和总生存期(OS)的相关性。
    结果:T-CTLA-4(肿瘤细胞CTLA-4)和I-CTLA-4(间质淋巴细胞CTLA-4)的表达率分别为48.8%和44.0%。 PLR水平较高(≥119)的入组患者为48名。未检测到ESCC患者中T-CTLA-4,I-CTLA-4和PLR的预后价值。但是,发现同时具有较低的T-CTLA-4表达水平和较低的PLR水平且OS较长的患者(p = 0.023)。多因素分析也证实了T-CTLA-4(-)PLR(-)状态在ESCC患者中的预后作用(p = 0.027)。
    结论:这些结果证明了CTLA-4和PLR联合分析在ESCC患者中的潜在预后价值。

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