Cyr61在单纯及放创复合伤愈合过程中的表达及其临床意义

目的研究Cyr61在单纯和放创复合伤愈合过程中的表达变化,对伤口愈合和组织改建的影响,及其在创伤实验室诊断中的意义。方法制备单纯及放创复合伤动物模型,采用光镜、免疫组化、RT-PCR等方法,动态观察伤口愈合过程中Cyr61mRNA及蛋白表达变化规律。结果5Gy(γ射线)全身照射后对伤口愈合有明显的损害作用。在伤后第3、6、9、15天,Cyr61表达量均随创伤愈合时间延长而增加;但在同一时间点,放创复合伤组Cyr61蛋白和mRNA的表达量均低于单纯创伤组,第21天放创复合伤组表达继续升高,而单纯创伤组表达下降。Cyr61表达时相拖后与辐射所致伤口愈合延迟一致。结论Cyr61在放创复合伤肉芽组织中表达较单纯创伤组明显降低,影响细胞迁移、新生血管形成和组织改建等重要过程,这可能是辐射所致伤口难愈的重要原因之一,认识Cyr61在创伤愈合过程的表达规律有助于创伤的预后判断和治疗。     

富含半胱氨酸蛋白61在结直肠癌中的应用

目的通过测定结直肠癌(colorectal cancer,CRC)患者血清富含半胱氨酸蛋白61(cysteine-rich Protein 61,Cyr61)水平,分析其用于结直肠癌诊断和病理评估的价值。方法用ELISA方法检测血清Cyr61浓度,再用ROC曲线计算最佳灵敏度和特异性,比较Cyr61在诊断结直肠癌的效果;分析Cyr61水平与结直肠癌TNM分期及淋巴结转移的关系,探究血清Cyr61水平与结直肠癌临床病理分期的关系。结果 CRC患者的血清Cyr61水平明显高于健康对照组(P<0.05),血清Cyr61、CEA和CA19-9检测对诊断结直肠癌的灵敏度分别为70.2%、48.2%和48.9%,Ⅲ-Ⅳ期血清Cyr61表达高于Ⅰ-Ⅱ期,有淋巴结转移的血清Cyr61表达高于无淋巴结转移。结论血清Cyr61水平可作为CRC诊断的潜在标志物,且与肿瘤分期和淋巴结转移有关,血清Cyr61水平对结直肠癌的监测有重要意义。     

Effect of (NH4)2ZrF6, Voltage and Treating Time on Corrosion Resistance of Micro-Arc Oxidation Coatings Applied on ZK61M Magnesium Alloys

The effects of (NH₄)₂ZrF₆ concentration, voltage and treating time on the corrosion resistance of ZK61M magnesium alloy micro-arc oxidation coatings were studied by orthogonal experiments. The SEM result shows that the surface roughness and porosity of MAO coatings increased with (NH₄)₂ZrF₆ concentration, voltage and treating time as a whole, except the porosity decreased with treating time. EDS, XRD and XPS analysis show that (NH₄)₂ZrF₆ was successfully incorporated into coatings by reactive incorporation, coatings are dominantly composed of ZrO₂, MgO, MgF₂ and amorphous phase Mg phosphate. Potentiodynamic polarization was used to evaluate the corrosion property of coatings. When the concentration of (NH₄)₂ZrF₆ is 6 g/L, the voltage is 450 V, and the treating time is 15 min, the coating exhibits the best corrosion resistance which corrosion current density is four magnitudes lower than substrate attributed to the incorporation of ZrO₂ and the deposition of MgF₂ in the micropores.     

GLI inhibitors overcome Erlotinib resistance in human pancreatic cancer cells by modulating E-cadherin

Inhibition of hedgehog (Hh) signalling pathway, including its end effector GLI1, can reverse epithelial-to-mesenchymal transition (EMT) which plays an important role in drug resistance of pancreatic cancer cells to Erlotinib (ETB). This study investigated the effect of GLI inhibitors Forskolin (FSK), GANT-61 (GNT), and Arsenic trioxide (ATX) on suppressing the resistance of pancreatic cancer cells to ETB. The effect of GLI inhibitors was evaluated by measuring mRNA expression levels of EMT factors using quantitative RT-PCR. Immunocytochemistry and flow cytometry were used to assess E-cadherin (E-Cad) and GLI1 protein levels. MTT and apoptosis assays were used to evaluate the synergistic effects for the combination treatment of each GLI inhibitor with ETB. Pancreatic cancer cells PANC-1 treated by GNT showed the highest significant reduction in mRNA levels of GLI1 and other EMT pathway genes. Moreover, GNT was able to upregulate E-Cad and downregulate GLI1 proteins, more than FSK, while ATX had no effect. Apoptosis levels of PANC-1 cells following treatment with LD30 concentrations of FSK, GNT, or ATX, showed 57%, 62% and 67%, respectively, in comparison to ETB (～48%). Importantly, combination treatments of ETB with either FSK, GNT, or ATX demonstrated a significant increase in apoptotic cells reaching 61% (ETB?+?FSK), 80% (ETB?+?GNT) or 88% (ETB?+?ATX). FSK did not have much effect on the drug resistance of PANC-1 cells to ETB. However, GNT, but more effectively ATX, were able to reduce the drug resistance of this cell line to ETB.     

Cyr61/CCN1 Overexpression Induces Epithelial-Mesenchymal Transition Leading to Laryngeal Tumor Invasion and Metastasis and Poor Prognosis

Background: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamouscellcarcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT),invasion, metastasis, and prognosis. Materials and Methods: Immunohistochemistry was used to detect theexpressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases oftumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively,to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical andhistopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61,Vim and E-cad and LSCC invasion, metastasis and prognosis. Results: In LSCC tissues, Vim expression ratewas significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantlylower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stagesT3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, theVim expression rate was significantly higher and the E-cad expression rate was significantly lower in the groupwith lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in thetumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than instages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymphnode metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group thanin the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive andE-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positivegroups, respectively. Conclusions: Cyr61 expression is closely associated with LSCC invasion and lymph nodemetastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasisand poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasisand a new target for LSCC treatment.     

Association between the Epidermal Growth Factor 61*A/G Polymorphism and Hepatocellular Carcinoma Risk: a Meta-Analysis

The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC).However, the conclusions of published reports on the relationship between the EGF 61*A/G polymorphism andHCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge andthe Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate theassociation. Meta-analysis results showed a significant association between the EGF 61*A/G polymorphismand HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32,95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; ho-mozygous model: OR=1.59, 95%CI=1.33-1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiologyand genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF 61*A/G polymorphismis associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from thesource of controls or etiological diversity. Further studies with larger population sizes are needed to confirmthese results.     

Clinical Implication of EGF A61G Polymorphism in the Risk of Non Small Cell Lung Adenocarcinoma Patients: A Case Control Study

Background: The epidermal growth factor (EGF) plays important roles in non-small cell lung cancer (NSCLC) susceptibility and functional polymorphism in the EGF (+61A/G) gene has been linked to increased risk of NSCLC. This study aimed to evaluate the role of the EGF +61A/G polymorphism in risk of NSCLC adenocarcinoma (ADC) occurrence and survival in an Indian population. Materials and Methods: This casecontrol study included 100 histopathologically confirmed NSCLC (ADC) patients and 100 healthy controls. EGF (A61G) was genotyped by AS–PCR to elucidate putative associations with clinical outcomes. The association of the polymorphism with the survival of NSCLC patients was estimated by Kaplan–Meier curves. Results: It was found that EGF 61AG heterozygous and GG homozygous genotype is significantly associated with increased risk of NSCLC (ADC) occurrence compared to AA genotype, [OR 2.61 (1.31-5.18) and 3.25 (1.31-8.06), RR 1.51(1.15-2.0) and 1.72 (1.08-2.73) and RD 23.2 (6.90-39.5) and 28.53(7.0-50.1) for heterozygous AG (p=0.005) and homozygous GG (p=0.009)]. Patients homozygous for the G allele exhibited a significantly poor overall survival. The median survival time for patients with EGF 61 AA, AG, and GG genotypes was 10.5, 7.4, and 7.1 months (p=0.02), respectively. NSCLC (ADC) patients with GG + AG exhibited 7.3 months median survival compared to the AA genotype (p=0.009). Conclusions: The present study revealed that the EGF A61G genotype may be a novel independent prognostic marker to identify patients at higher risk of occurrence and an unfavourable clinical outcome.