CD133和CD90在肝细胞癌中的表达及其意义

存在于肿瘤组织中的少数具有干细胞性质的细胞群体被称为肿瘤干细胞(CSCs),可促进肿瘤的发生和发展,也是肿瘤耐药性、复发及转移的根源.有报道CD133和CD90可能为肿瘤干细胞表面标志物,但CD133和CD90在肝癌中的表达及其意义报道尚少.本研究采用免疫组织化学方法检测不同肝组织中CD133及CD90蛋白的表达水平,探讨其在肝癌中的表达情况及其与肝癌生物学特性及预后的关系.     

CD133和CD90在肝细胞癌中的表达及其意义

存在于肿瘤组织中的少数具有干细胞性质的细胞群体被称为肿瘤干细胞(CSCs),可促进肿瘤的发生和发展,也是肿瘤耐药性、复发及转移的根源.有报道CD133和CD90可能为肿瘤干细胞表面标志物,但CD133和CD90在肝癌中的表达及其意义报道尚少.本研究采用免疫组织化学方法检测不同肝组织中CD133及CD90蛋白的表达水平,探讨其在肝癌中的表达情况及其与肝癌生物学特性及预后的关系.     

CD133+肺癌细胞的干细胞特性研究

目的 收获CD133+肺腺癌细胞并评估其肿瘤干细胞特性.方法 从13例新鲜肺腺癌组织中收获CD133+和CD133-肺腺癌细胞,并进行Transwell侵袭实验、裸鼠成瘤实验等对比研究,观察CD133+和CD133-肺腺癌细胞的差异.结果 13例中有10例发现CD133表达,其阳性表达率最高为13.12%,CD133+和CD133-细胞在侵袭性、致瘤能力上有明显区别.结论 CD133在人肺腺癌组织细胞中广泛表达,CD133+较CD133-人肺腺癌细胞具有更强的侵袭性和致瘤能力.     

Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease

AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver diseases were randomized into two groups.Group 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous CD34 + and CD133 + stem cell infusion in the portal vein.Group 2,comprising 50 patients,received regular liver treatment only and served a...     

CD133 and membrane microdomains: old facets for future hypotheses

Understanding all facets of membrane microdomains in normal and cancerous cells within the digestive tract is highly important,not only from a clinical point of view,but also in terms of our basic knowledge of cellular transformation.By studying the normal and cancer stem cell-associated molecule CD133 (prominin-1),novel aspects of the organization and dynamics of polarized epithelial cells have been revealed during the last decade.Its association with particular membrane microdomains is highly relevant in ...     

Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors

Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133-based selection method in 10 paediatric patients with matched unrelated (n = 2) or mismatched-related donors (n = 8). These patients received a combination of stem cells (median = 29.3 x 10(6)/kg), selected with either anti-CD34 or anti-CD133 coated microbeads. The proportion of CD133+ selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133+ and CD34+ separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133+ selection (3.7 log vs. 4.1 log, P < 0.001). Both separation procedures produced >90% CD34+/CD133+ double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) >/= grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13.5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow-up of 10 months. Our data demonstrates the feasibility of CD133+ selection for transplantation from alternative donors and encourages further trials with total CD133+ separated grafts.     

肝癌细胞株SMMC7721中CD133＋和CD133-亚群生物学特性的比较

背景：肝癌是常见的恶性肿瘤之一,易复发、转移,术后5年生存率较低。目前肿瘤干细胞学说已成为肿瘤研究的热点．CD133是一种肿瘤干细胞的标记物。目的：比较肝癌细胞株SMMC7721中CD133＋和CD133一亚群的生物学特性差异．并初步探讨CD133＋亚群的干细胞特性。方法：采用免疫磁珠法（MACS）分选SMMC7721细胞中CD133＋和CD133一亚群．以流式细胞术检测CD133表达量,平板克隆形成实验检测CDl33体外增殖能力,裸鼠成瘤实验检测体内致瘤性．CCK-8法检测对5-氟尿嘧啶（5-Fu）的敏感性。结果：MACS分选并培养1周后,CD133＋亚群中CD133表达量明显下降。与CD133-亚群相比．CD133＋亚群的体外克隆形成率明显增高,裸鼠肿瘤的体积明显升高,对5-Fu的敏感性降低．差异均有统计学意义（P〈0．05）。结论：肝癌SMMC7721细胞中CD133＋亚群较CD133-亚群更具有肿瘤干细胞的特性．     

CD133在人肺腺癌组织中的表达及其临床关系

目的研究CD133在肺腺癌中的表达,探讨CD133表达与患者临床信息的相关性。方法取83例肺腺癌组织石蜡标本,用免疫组化法检测CD133的表达,结合患者年龄、性别、吸烟指数等信息进行统计分析,探讨CD133的表达与患者相关资料的关系。结果 83例中CD133阳性率为81.9%,同时具有表达的不均一性。结论 CD133在肺腺癌中广泛表达,表达强度具有不均一性,其表达与患者淋巴转移及病理分化程度相关,与年龄、性别、吸烟指数未见相关性。     

Performance of serum CD163 as a marker of fibrosis in patients with NAFLD

Background and aimsCD163, a surface hemoglobin-haptoglobin scavenger receptor, is expressed on macrophages and monocytes and up-regulated during macrophage activation. This study aimed to evaluate CD163 in nonalcoholic steatohepatitis patients as a diagnostic and prognostic marker in such patients. Methods: Serum samples were collected from 41 NAFLD patients and 14 healthy controls. All cases were subjected to clinical assessment, abdominal ultrasound examination, laboratory assessment including liver function and enzymes, kidney function, and lipid profile. Fib-4 and NAFLD fibrosis score were calculated for all patients. Also, serum levels of CD163 were detected by ELISA technique. Results: The present study showed that BMI, NAFLD fibrosis score (NFS), uric acid, cholesterol, and triglyceride levels were significantly elevated in the NAFLD cases compared with healthy controls (P < 0.05). The serum level of sCD163 was considerably higher in NAFLD cases (9.97 ± 9.97 ng/ml) vs. healthy controls (1.87 ± 0.83 ng/ml) (p < 0.001). Circulating level of sCD163 was significantly higher in the obese-diabetic subjects and diabetic non-obese patients as compared with the lean healthy subjects (11.15 ± 7.69 ng/ml) and 11.46 ± 13.83 ng/ml vs. 1.87 ± 0.83 ng/ml, P < 0.05; respectively. The sensitivity and specificity of this marker was 85.4%, and 92.9 for distinguishing patients with NAFLD in obese and/or diabetic subjects from healthy controls. Conclusion: serum level of CD163 can be used as a diagnostic marker for individuals with NAFLD. However, it didn’t correlate with NAFLD fibrosis score of those patients and thus couldn’t predict the severity of disease.     

CD133、Ki-67在胃癌的表达及临床病理意义

目的:研究CDl33和Ki-67在胃癌中的表达,并探讨其与肿瘤生物学特征及患者术后生存时间的关系.方法:应用组织芯片技术,采用PV6000二步法检测有完整随访资料的336例胃癌及60例癌旁正常组织是CD133和Ki-67表达的差异.结果:胃癌CDl33和Ki-67的阳性率为57.4%.5[8]3%.CD133和Ki-67的表达均与肿瘤大小、分化程度、浸润深度、淋巴结转移数目、TNM分期和出现腹腔及远处转移相关(均P<0.05).CD133和Ki-67阳性组患者的5年生存率均低于阴性组(均P<0.05).CD133和Ki-67在胃癌的表达呈正相关(r=0.188,P<0.05).CD133和Ki-67在胃癌组织中的表达显著高于在癌旁正常组织中的表达(57.4% VS 28.6%.58.3% VS 18.6%,均P<0.05).CDl33和Ki-67均是患者术后生存时间的独立预后因子.结论:CD133和Ki-67在胃癌的发生、发展、转移及预后中发挥重要作用,可考虑作为胃癌临床评价肿瘤生物学行为及评估预后的指标.     

Enhanced functional response of CD133+ circulating progenitor cells in patients early after acute myocardial infarction

Aims: Circulating progenitor cells (PC) may contribute to myocardialrecovery following infarction. Growth factors including VEGFare produced during ischaemia and stimulate PC release and activation.In this study, we focused on the functional chemotactic responseof PC to VEGF in subjects early after myocardial ischaemia. Methods and results: Number and phenotype of PC were characterized using flow-cytometry.CD133⁺PC were isolated from peripheral blood using positiveMACS isolation. The chemotactic response towards members ofthe VEGF family (VEGF-A, PlGF-1, and VEGF-E) was analysed inthree groups: (i) early period following acute myocardial infarction(days 2–4) treated with primary PCI (AMI) (n = 35), (ii)stable coronary artery disease (CAD) (n = 35), and (iii) controls(CTR) (n = 20). CD133⁺PC number was 2-fold higher in AMI whencompared with CAD and CTR (P = 0.0001), whereas CAD was notdifferent from CTR. The chemotactic response of CD133⁺PC toVEGF-A, PlGF-1, and VEGF-E was significantly enhanced (2-fold)in AMI when compared with CAD (P = 0.0001). While the increaseof the VEGFR-1-mediated/PlGF-triggered response was rapid (2days following infarction), the VEGFR-2-mediated/VEGF-E-triggeredresponse was maximally increased on day 4 post-AMI, thus correlatingwith the kinetics of maximal inflammatory activation reflectedby increased CRP levels (P = 0.019). Conclusion: The enhanced chemotactic response of CD133⁺PC following myocardialinfarction represents a novel principle potentially involvedin cardiovascular repair early after myocardial infarction.Acute inflammatory processes are closely associated with thisincreased cellular function.     

CD133在肺癌中的研究与进展

肺癌是世界范围内死亡率最高的恶性肿瘤之一,也是我国常见的恶性肿瘤之一,恶性程度高,发展迅速,治疗困难,总体疗效不理想。肿瘤干细胞是肿瘤组织中一小部分具有自我更新、无限增殖和多向分化能力的肿瘤细胞,它在肿瘤组织中所占比例虽然很少,却与肿瘤起源、发展与转移关系密切,因此肿瘤干细胞被看作是一个根除癌症的潜在目标。CD133是...     

细胞外囊泡与肝脏疾病发生发展的关系

细胞外囊泡(EV)是细胞释放到细胞外环境中的膜结合小泡,能够选择性地富集特定蛋白和RNA,介导细胞间通讯。因此,EV具有作为疾病的生物标志物、治疗靶标和传递载体的潜力。总结了EV在病毒性肝炎、肝纤维化和肝癌中的研究进展,探讨其在肝脏疾病中所发挥的作用,以强调EV在未来肝脏疾病研究中的应用前景。     

Bulk immunoassays for analysis of extracellular vesicles

There is increasing clinical interest in extracellular vesicles (EV) for diagnostic and treatment purposes. This review provides an overview of bulk immunoassays to analyse EV. Western blot and enzyme-linked immunosorbent assay are still the two predominant bulk immunoassays. Recently, new assays have become available that can detect exposure to EV concentrations that are up to 10,000-fold lower. This is advantageous for applications that detect rare EV. Other important parameters are the detectable concentration range, the required sample volume, whether simultaneous presence of different antigens on a single EV can be detected, size selectivity of each assay and practical considerations. In this review, we will explain the working principles of the traditional and novel assays together with their performance parameters. The most sensitive assays are micro-nuclear magnetic resonance, surface plasmon resonance, and time-resolved fluorescent immunoassay.     

Extracellular vesicles in fatty liver disease and steatohepatitis: Role as biomarkers and therapeutic targets

Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) are characterized by lipid deposition in hepatocytes in the absence or presence of excessive alcohol consumption, respectively, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) or alcoholic hepatitis (AH) and from mild fibrosis to cirrhosis. Fatty liver disease and steatohepatitis similarly occur in individuals who have both metabolic syndrome and excessive alcohol intake; therefore, the single overarching term metabolic associated fatty liver disease (MAFLD) has been proposed to better reflect these risk factors and the continuity of disease progression. Extracellular vesicles (EVs) are membrane-bound endogenous nanoparticles released into the extracellular space by a majority of cell types. Liver disease-related EVs contain a variety of cellular cargo and are internalized into target cells resulting in the transfer of bioinformation reflecting the state of the donor cell to the recipient. Furthermore, EV composition can be used to identify the degree and type of liver disease, suggesting that EV composition may be a useful biomarker. With regard to MAFLD, the presence of metabolic risk factors, such as insulin resistance, will be indicated by adipose tissue-derived EVs and with that comes the potential to use as a clinical monitor of overall metabolic status. However, the inhibition of specific EV composition may be difficult to implement as a real-world therapeutic approach. Current global evidence shows that mesenchymal stem cell (MSCs)-derived EVs (MSC-EVs) play an important role in regulating the immune response, which has spawned a clinical trial to treat liver disease.     

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells

Background: The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy.Methods: The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot.Results: Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK.Conclusion: Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.     

Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

BACKGROUNDOxidized low-density lipoprotein (ox-LDL), which is abnormally increased in the serum of colorectal cancer (CRC) patients consuming a high-fat diet (HFD), may be one of the risk factors for the development of CRC. Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment. The role of ox-LDL in CRC remains unclear.AIMTo investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODSThe expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence. We stimulated the macrophages with 20 μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction. We further knocked down LOX-1, the surface receptor of ox-LDL, to confirm the function of ox-LDL in macrophages. Then, LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTSThe expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia, and also upregulated in the HFD-fed mice. Moreover, an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation. Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages. Ox-LDL could induce CD206+ macrophages, which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSIONOx-LDL stimulates CD206+ macrophages to upregulate CD44 and CD133 expression in HFD related CRC.     

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Preeclampsia (PE), defined as new-onset hypertension and multi-organ systemic complication during pregnancy, is the leading cause of maternal and neonatal mortality and morbidity. With extracellular vesicles research progresses, current data refers to the possibility that ferroptosis may play a role in exosomal effects. Evidence has suggested that ferroptosis may contribute to the pathogenesis of preeclampsia by bioinformatics analyses. The purpose of the current study is to identify the potential ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles (STB-EVs) of preeclampsia using bioinformatics analyses. Clinical characteristics and gene expression data of all samples were obtained from the NCBI GEO database. The differentially expressed mRNAs (DE-mRNAs) in STB-EVs of preeclampsia were screened and then were intersected with ferroptosis genes. Functional and pathway enrichment analyses of ferroptosis-related DE-mRNAs in STB-EVs were performed. Ferroptosis-related hub genes in STB-EVs were identified by Cytoscape plugin CytoHubba with a Degree algorithm using a protein-protein interaction network built constructed from the STRING database. The predictive performance of ferroptosis-related hub genes was determined by a univariate analysis of receiver operating characteristic (ROC). The miRNA-hub gene regulatory network was constructed using the miRwalk database. A total of 1976 DE-mRNAs in STB-EVs were identified and the most enriched item identified by gene set enrichment analysis was signaling by G Protein-Coupled Receptors (normalized enrichment score = 1.238). These DE-mRNAs obtained 26 ferroptosis-related DE-mRNAs. Ferroptosis-related DE-mRNAs of gene ontology terms and Encyclopedia of Genes and Genomes pathway enrichment analysis were enriched significantly in response to oxidative stress and ferroptosis. Five hub genes (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) were found in the constructed protein-protein interaction network with ferroptosis-related DE-mRNAs and the areas under the ROC curves for ALB, NOX4, CDKN2A, TXNRD1, and CAV1 were 0.938 (CI: 0.815−1.000), 0.833 (CI: 0.612−1.000), 0.875 (CI: 0.704−1.000), 0.958 (CI: 0.862−1.000), and 0.854 (CI: 0.652−1.000) in univariate analysis of ROC. We constructed a regulatory network of miRNA-hub gene and the findings demonstrate that hsa-miR-26b-5p, hsa-miR-192-5p, hsa-miR-124-3p, hsa-miR-492, hsa-miR-34a-5p and hsa-miR-155-5p could regulate most hub genes. In this study, we identified several central genes closely related to ferroptosis in STB-EVs (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) that are potential biomarkers related to ferroptosis in preeclampsia. Our findings will provide evidence for the involvement of ferroptosis in preeclampsia and improve the understanding of ferroptosis-related molecular pathways in the pathogenesis of preeclampsia.