Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a type of malignant and heterogeneous tumor in premenopausal females with ineffective therapeutic targets. IL-8 is one of the earliest discovered chemotaxis cytokines which expression is closely related to the progress of various cancers. Previous studies showed that IL-8 determines the prognosis of TNBC patients, nevertheless how IL-8 influences the progress of TNBC is unclear. In our studies, we discovered that overexpression of IL-8 promotes TNBC cells (TNBCs) migration and tumor growth via the PI3K-Akt and MAPK signaling pathway. Cell-cycle of TNBCs arrest at S phase by overexpression of IL-8, however, there is no significant variation on the cell viability and cell apoptosis of TNBCs. Besides, overexpression of IL-8 result in the downregulation of E-cadherin and the upregulation of Cyclin B1 in MDA-MB-231 cells. Taken together, our results suggest that IL-8 performs a crucial role in the progress of TNBC, and it could be a novel therapeutic target of TNBC.     

STEAP1 Inhibits Breast Cancer Metastasis and Is Associated With Epithelial–Mesenchymal Transition Procession

Purpose

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The aims of this study were to evaluate STEAP1 expression in breast cancer and to determine the mechanisms involved.

Silencing of miRNA-218 promotes migration and invasion of breast cancer via Slit2-Robo1 pathway

MiRNAs play an important role in regulating tumor migration and invasion, and abnormal expression of miRNAs occurs in various kinds of human cancers. In this essay, it is reported that the level of miRNA-218 decreases in metastatic breast cancer cells, moreover, miRNA-218 suppresses breast cancer cells migration and invasion through binding Robo1 (one of Slit receptors) to its 3′UTR. MiRNA-218 restoration suppresses Robo1 expression and inhibits breast cancer cells invasion and migration. What the results describe is that the function of Robo1 regulated by miRNA-218 may provide a new strategy for inhibiting migration and invasion of breast cancer cells.     

Questioning the failure of neural crest cell migration theory in Hirschsprung’s disease: A case report and literature review

IntroductionSegmental aganglionosis (the absence of ganglions) is a rare presentation of Hirschsprung’s disease, whereby only limited segment/segments of aganglionic bowel is interposed between segments of innervated bowel, or “skip’’ area of normal innervations is present within an area of aganglionosis.Presentation of caseWe reported a case of a 3 day old male newborn who presented with failure to pass meconium along with progressive abdominal distension. There were skip lesions present in between. Mikulicz double barrel enterostomy was carried out, which was followed by an uneventful postoperative period. Four months later, the patient was admitted for levelling biopsies which revealed the absence of ganglions in the terminal ileum as well as in the rectosigmoid junction. But the ganglions were present in between and proximal to the terminal ileum where the previously dilated small bowel segment was resected. This presentation was contradicted the most accepted migration theory of Hirschsprung’s disease.DiscussionAs seen in our case, and in21 other cases published between 1954–2016, we highly recommend that leveling/mapping biopsies should definitely include the cecal pole and the small bowel segments proximal to the ileocecal valve as well as the multilevel colonic biopsies down till the rectum.ConclusionReporting of these cases brings out interesting questions with respect to the pathogenesis and serves to highlight the existence of several variants within the spectrum of Hirschsprung’s disease.     

Wound healing potential of a dimeric InlB variant analyzed by in vitro experiments on re-epithelialization of human skin models

A constitutively dimeric truncated variant of internalin B (InlB₃₂₁-CD), acting as stimulator of the receptor tyrosine kinase MET, was tested for dermal wound-healing potential. Due to a lack of the endogenous MET agonist HGF/SF in chronic wounds, HGF/SF substitution by an InlB₃₂₁-CD-loaded hydrogel might be beneficial in chronic wound therapy.In this study, InlB₃₂₁-CD in solution and incorporated in a hydrogel was tested for mitogenic effects on immortalized human dermal keratinocytes (HaCaT) with an MTT assay. Cell migration was investigated with a scratch assay on primary keratinocytes (PHK) and on HaCaT. For the latter, scratching needed to be mitomycin C-controlled. InlB₃₂₁-CD effects on a model of human skin were analyzed histologically with respect to viability.InlB₃₂₁-CD led to dose-dependent proliferative effects on HaCaT cells whereas the equimolar dose of monomeric InlB₃₂₁ did not. Upon hydrogel incorporation of InlB₃₂₁-CD its mitogenic activity for HaCaT cells was maintained thus confirming the hydrogel as a promising drug delivery system. Motogenic effects were shown on both HaCaT and PHK cells. InlB₃₂₁-CD neither possesses cytotoxic effects on the viability of a human skin model nor alters its organotypic cell morphology.     

白头翁皂苷 B4调控去乙酰化酶 6对胃癌细胞转移和放疗敏感性的影响

目的探讨白头翁皂苷 B4(AB4)对胃癌细胞增殖、迁移、侵袭及放疗敏感性的影响及其分子机制。方法该研究起止时间为 2018年 4月至 2019年 10月。体外培养人正常胃黏膜上皮细胞 GES-1与胃癌细胞 HGC-27，采用不同浓度( 25、50、100 μmol/L)的 AB4处理 24 h，通过 MTT法检测细胞存活率并筛选 AB4适宜浓度用于后续研究。 Transwell实验检测 HGC-27细胞迁移及侵袭能力。细胞克隆形成实验检测 AB4对 HGC-27细胞放射敏感性的影响；蛋白质印迹法检测 AB4对 HGC-27细胞中去乙酰化酶 6(SIRT6)蛋白表达的影响；干扰 SIRT6表达联合 AB4处理后，采用上述检测方法检测 HGC-27细胞增殖、迁移、侵袭及放射敏感性；蛋白质印迹法检测 DNA激活蛋白激酶催化亚基( DNA-PKcs)、 DNA双链修复蛋白 Rad51、DNA修复酶 Ku80、基质金属蛋白酶 -2(MMP-2)、基质金属蛋白酶 -9(MMP-9)蛋白表达水平。结果与 NC组相比， AB4处理后 HGC-27细胞存活率［( 100.01±9.57)%比( 86.57±6.58)%、(65.45±8.45)%、(49.58±7.96)%］显著降低( P<0.05)，迁移细胞数［( 98.47±8.79)个比(43.57±6.53)个］与侵袭细胞数［(88.42±9.32)个比( 45.56±5.13)个］显著减少( P<0.05)MMP-2、MMP-9蛋白表达水平显著降低(P<0.05)，SIRT6蛋白表达水平(0.42±0.03比 1.03±0.15)显著升高( P<0.05)；细胞克隆形成，实验显示 AB4可降低 HGC-27细胞存活分数( P<0.05)增加增敏比，降低 Rad51、DNA-PKcs、Ku80的表达水平( P<0.05)；干扰 SIRT6表达联合 AB4处理后，迁移细胞数［(44.25±5.52)个，比( 86.47±11.16)个］与侵袭细胞数［(48.56±6.29)个比( 90.17±12.13)个］显著增多( P<0.05)，MMP-2、MMP-9 蛋白相对表达量显著升高( P<0.05)细胞存活分数显著升高( P<0.05)Rad51、DNA-PKcs、Ku80蛋白表达水平明显升高( P<0.05)。结论促进 SIRT6的表达进而发挥抑癌细胞 HGC-27增殖、迁移及侵袭的作用，并增加胃癌细胞的放射敏感性。     

人脐静脉内皮细胞损伤后迁移能力的变化与血管内皮钙黏蛋白和连环蛋白p120的关系

目的初步探讨人脐静脉内皮细胞(HUVEC)损伤之后迁移能力的变化与血管内皮钙黏蛋白(VE-cad)和连环蛋白p120(p120ctn)的关系。方法 DMEM培养基培养HUVEC,将HUVEC分为对照组和损伤组。Transwell实验检测HUVEC迁移能力的变化。Western blot测定p120ctn与VE-cad蛋白表达水平。免疫荧光实验检测VEcad的定位表达变化。免疫共沉淀法检测p120ctn与VE-cad的相互结合。结果 Transwell实验发现HUVEC经损伤刺激6、8 h后迁移能力最强(P0.05)。Western blot结果显示HUVEC损伤6、8 h后p120ctn及VE-cad表达水平明显上调。免疫荧光实验显示HUVEC经损伤刺激后,VE-cad的定位由细胞膜转到细胞浆。免疫共沉淀证实p120ctn可以与VE-cad相互结合。结论 HUVEC损伤刺激后迁移能力增强,其机制可能与升高的p120ctn将VEcad由细胞膜携带入细胞浆导致VE-cad膜表达缺失有关。     

The downregulation of ANGPTL4 inhibits the migration and proliferation of tongue squamous cell carcinoma

ObjectiveTongue squamous cell carcinoma (TSCC) is the most common malignant cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be novel indicators for tumor metastasis. The aim of the present study was to investigate the expression and function of ANGPTL4 in TSCC and the relationship between ANGPTL4 and MVD.MethodsThe expression levels of ANGPTL4 and MVD (CD34) were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using immunohistochemistry (IHC). siRNA was delivered into TSCCA cells to downregulate ANGPTL4 expression. Subsequently, validation with real-time RT-PCR and western blot analyses was performed to analyze ANGPTL4 expression levels. In addition, a proliferation assay, migration and invasion assays were carried out.ResultsANGPTL4 expression was associated with tumor stage, lymph node metastasis and MVD expression. Cox regression analysis showed that high levels of ANGPTL4 expression were closely associated with poor survival time. In vitro analyses using qRT-PCR and western blot confirmed that ANGPTL4 was successfully inhibited in TSCCA cells. Suppressing ANGPTL4 resulted in the inhibition of cell proliferation and migration, but neither invasion nor cisplatin resistance was significantly affected.ConclusionHigh expression levels of ANGPTL4 are associated with the T stage, lymphatic metastasis, angiogenesis and poor overall survival in TSCC patients. The downregulation of ANGPTL4 inhibits the migration and proliferation of cells in TSCC. Taken together, ANGPTL4 may serve as a novel biomarker and therapeutic target for TSCC.     

Cyclic voltammetry in weakly supported media: The reduction of the cobaltocenium cation in acetonitrile – Comparison between theory and experiment

Experimental cyclic voltammetry at a hemispherical mercury microelectrode in acetonitrile solution, containing 3 mM cobaltocenium hexafluorophosphate and different concentrations of supporting electrolyte, is compared with theoretical simulations using the Nernst–Planck–Poisson system of equations, without the assumption of electroneutrality, and is found in to be in good agreement. Deviations from diffusion-only theory are analyzed in terms of migration and potential drop in the solution as a function of the concentration of supporting electrolyte. We are unaware of previous reports in which non-steady-state cyclic voltammetry without supporting electrolyte has been quantitatively and fully simulated, so this work opens up a new area for voltammetry.