Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Effect of miR-33a-3p on Chemoresistance of Colorectal Cancer by Regulating EphA2 / 华中科技大学学报(医学版)

@#Objective Toinvestigatetheregulatoryeffect of microRNA-33a-3p(miR-33a-3p)on chemoresistances of colorectal cancer(CRC). Methods Theexpression of miR-33a-3pin CRC parentalcells(HCT8)and drug-resistantcelllines(HCT8/5-Fu and HCT8/DDP) was detected by quantitative real-time PCR. The miR-33a-3p mimics and negative control mimics were constructed andtransfectedinto CRCdrug-resistantcells. Cell proliferation,apoptosis,cellcycledistributionandchemosensitivity weretested. Thetarget genes of miR-33a-3p were predicted via bioinformatics methods,andtheeffect of overexpressed miR- 33a-3p onthe downstreamtarget gene EphA2 was detected by quantitative real-time PCR and Western blot. Results The expression of miR-33a-3pin HCT8/5-Fu and HCT8/DDP cells was significantlylowerthanthat ofthe parentalcells(P <0.01) .Compared with the negative control group,overexpression of miR-33a-3p could suppress HCT8/5-Fu and HCT8/DDP cells proliferation and promotecell apoptosis,and block cells cyclein G2/M phase as well as enhancecell chemosensitivity(P <0.05) .Bioinformatics predictionresults showedthat EphA2 might bea downstreamtarget gene of miR-33a-3p,andits expression was significantlyreducedin HCT8/5-Fu and HCT8/DDP cells transfected with miR-33a-3p mimics. Conclusion The miR-33a-3p mayreversethechemoresistance of CRC byregulatingthe expressionlevel of downstreamtarget gene EphA2.

Progress of erythropoietin-producing hepatocellular A2 receptor in glioma / 肿瘤研究与临床

Erythropoietin-producing hepatocellular A2 receptor (EphA2) is the most common subtype in the largest subfamily of the receptor tyrosine kinase superfamily, and is considered as a key factor in the regulation of malignant tumor progression. EphA2 is highly expressed in glioma, which plays an important role in the development and progression of glioma. This article reviews the structure, function, expression of EphA2 in glioma, and its role in glioma cell migration, maintenance of glioma stem cells, angiogenesis and targeted therapy.

Role of EphA2 in pathogenesis of nasopharyngeal carcinoma and its potential as a therapeutic target / 中国肿瘤临床

The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.

Effects of FTY720-P on EphA2-EphrinA2 bidirectional signaling in osteoclasts / 中国修复重建外科杂志

Objective: To investigate the effects of FTY720-P on EphA2-EphrinA2 bidirectional signaling in osteoclasts. Methods: Murine RAW264.7 macrophages were induced into osteoclasts by dexamethasone and 1α, 25-dihydroxyvitamin D 3, and identified by tartrate resistant acid phosphatase (TRAP) staining. Then, the osteoclasts were divided into 2 groups. The osteoclasts were treated with 400 ng/mL FTY720-P in experimental group and without FTY720-P in control group, respectively. After 48 hours of culture, the cells in 2 groups were detected by real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining. The expressions of EphA2, EphrinA2, RhoA, and the bone reconstruction associated proteins［bone morphogenetic protein 2 (BMP-2) and transform growth factor β 1 (TGF-β 1)］were analyzed and compared. Results: RAW264.7 cells were successfully induced into osteoclasts identified by TRAP staining. Compared with control group, the relative expressions of EphA2 and EphrinA2 mRNAs and proteins in experimental group significantly decreased after 48 hours ( P<0.05), and the relative expression of RhoA protein also significantly decreased ( P<0.05). The relative expressions of BMP-2 and TGF-β 1 mRNAs were significantly increased ( P<0.05), and those protein expressions were enhanced. Conclusion: FTY720-P can down-regulate the expression of RhoA and promote the expressions of TGF- β 1 and BMP-2 by affecting the transduction of EphA2-EphrinA2 bidirectional signaling in osteoclasts.

Progress on glioblastoma multiforme treatment with chimeric antigen receptor T-cells / 中国肿瘤临床

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and its treatment through traditional surgery combined with chemotherapy and radiotherapy has limited efficacy. Chimericantigen receptor T-cells (CAR-T) are recombinant receptors for antigen, which, in a single molecule, redirect and mediateantigen recognition, T-cell activation, and, in the case of second-generation chimeric antigen receptors (CARs) costimulation (CD28 or 4-BB), augment T-cell functionality and persistence. CARs are the focus of attention in emerging treatment options for GBM. This article mainly introduces the development process of CAR-T therapy and the recent success of adoptive transfer of CAR-T cells. Effective targets of the treatment of GBM with CAR-T according to this research are discussed as well. Some of the most extensively studied targets on GBM, especially interleukin-13 receptor α chain variant 2, epidermal growth factor receptor-Ⅷ(EGFRⅧ), human epidermal growth factor receptor 2 (ErbB2), and ephrinA2 receptor (ErbA2), and the different characteristics of each kind of alloantigen-specific CAR-T cells, are the basis for CAR-T therapy and indicate their different characteristics or utilities and the prospect of further clinical research. The discovery of selective expression of interleukin-13 receptor alpha 2 in glioma cells more than 20 years ago prompted the clinical trial of CAR-T therapy in stage I GBM tumors, and the therapy was proven safe and effective. EGFRⅧ is a neoantigen presenting only in cancer cells and glioblastoma stem cells. Its presence is correlated with poor prognosis, and a phase Ⅰ/Ⅱ trial is ongoing at different institutes. ErbB2-specific CARs were also expressed in human Tcells.Adoptive transfer of EphA2 (or ErbB2)-specific T cells resulted in the regression of glioma xenografts. Thus, target-specific CAR-T immunotherapy may be a promising approach for the treatment of different target-positive GBM. Finally, we summarize the application value and challenge of CAR-T cell therapy in the treatment of GBM.

Research on 3-dimentional culture of human choroidal melanoma cell line (OCM-1) in vitro and the mechanism of vasculogenic mimicry / 眼科新进展

Objective To observe vasculogenic mimicry (VM) of human choroidal melanoma cell line OCM-1 cultured in vitro and the expression of PI3K and EphA2 protein,as well as to explore the possible mechanisms.Methods OCM-1 cells were cultured in vitro and stained with periodic acid Schiff (PAS) on days 7,which aimed to observe the formation of PAS-positive cyclic structures,that is,VM formation.Then immunohistochemical staining was performed to detect PI3K and EphA2 on day 1,4,7 and the results were observed.Ressults On day 4 of 3-demintional culture,most of OCM-1 cells were polygonal and the cytoplasm was abundant;the nuclei were round and the nucleoli were visible.A small part of the tumor cells were long spindle.It was found that several long spindle cells were connected to each other to form hemicyclic structure.After 7 days,a large number of tumor cells became long spindle,growing along the collagen scaffold,and long protrusions appeared,forming a ring structure.PAS staining showed that the tumor cells were mostly arranged in a row,and tumor cells imitated the formation of body blood vessels,resulting in cell band and pipeline-like cell layers,with one layer of extracellular matrix (PAS-positive substance) making up the ring structure.Moreover,the expression levels of PI3K and EphA2 on day 4 and 7 were significantly higher than those on day 1 (all P ＜ 0.05),and their expression levels on day 7 were higher than those on day 4 (all P ＜ 0.05).Conclusion EphA2 and PI3K may play an important role in the VM formation in 3-dimentional culture of human choroidal melanoma cell line OCM-1.

A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family.

Background: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five‑generation Chinese autosomal dominant congenital cataract family. Methods: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co‑segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. Results: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in‑house databases and showed co‑segregation in the family. This variant resulted in an altered splice that led to protein truncation. Conclusions: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.

EPHA2 promotes SGC-7901 cell proliferation through enhancing Akt/mTOR signaling pathway / 中国癌症杂志

Background and purpose:EPHA2 has been reported to enhance the proliferation of gastric cancer cells through promoting CyclinD1 expression and cell cycle progression. However, the underlying mechanism that EPHA2 promotes CyclinD1 expression and cell cycle progression is still poorly understood. Akt/mTOR signaling pathway has been reported to enhance the proliferation of gastric cancer cells by promoting CyclinD1 expression and cell cycle progression, and some studies have shown that EPHA2 can activate Akt/mTOR signaling pathway. Based on this, this study investigated whether EPHA2 promoted gastric cancer SGC-7901 cell proliferation through enhancing Akt/mTOR signaling pathway.Methods:Western blot was used to determine the effect of EPHA2 overexpression or knockdown on the phosphorylation of Akt and mTOR in SGC-7901 cells. SGC-7901-NC infected with control lentivi-rus and SGC-7901-EPHA2 cells with EPHA2 overexpression were treated with DMSO, MK2206 (an Akt inhibitor) and RAD001 (a mTOR inhibitor) for different time periods, respectively. Cell proliferation was detected using the CCK8 assay. Cell cycle was detected using lfow cytometry, and the expression of CyclinD1 was determined by Western blot. Results:Overexpression of EPHA2 enhanced Akt/mTOR signaling pathway in SGC-7901 cells, and silencing EPHA2 in SGC-7901 cells inhibited Akt/mTOR signaling pathway. MK2206 and RAD001 antagonized the promoting effect of EPHA2 on the proliferation, S-phase and CyclinD1 expression of SGC-7901 cells, respectively.Conclusion:EPHA2 promotes SGC-7901 cell proliferation through enhancing Akt/mTOR signaling pathway. Akt inhibitor or mTOR inhibi-tor could be an effective treatment strategy for gastric cancer patients overexpressing EPHA2.

Expressions of EphA2 in esophageal squamous cell carcinoma tissues and serums of 2 different ;nations in Xinjiang and its clinicopathological significance / 中国癌症杂志

Background and purpose:The incidence of esophageal cancer of Kazakh race is higher than that of Han people. EphA2, as a member of Eph protein family, is related to a variety of malignant tumors. This study used immunohistochemical method and enzyme-linked immunoassay to detect EphA2 in tissues and serums of Kazakh and Han patients. Therefore to analyze the expression differences of EphA2 in esophageal squamous cell carcinoma (ESCC) tissues and serum of Kazakh and Han patients in Xinjiang, and the relationship with pathological features. Methods:The expression of EphA2 protein was detected by immunohistochemistry method in 100 cases of ESCC tissues and adjacent normal esophageal tissues;Then was tested by ELISA in those cases’ serum and 60 healthy persons. Results:The positive expression rate of EphA2 protein in ESCC and corresponding adjacent tissues were 72.0%, 28.0% in Kazakh, and 62.0%, 26.0% in Han people, respectively, and the differences were statistically significant (P=0.000) in the 2 nations. EphA2 protein levels in serum of ESCC and healthy persons, and Kazakh were (58.36±12.60) and (29.39±7.34) pg/mL, Han Chinese were (58.79±13.29) and (29.39±7.34) pg/mL respectively, there were statistical signiifcance (P=0.000). In ESCC of Kazakh and Han people, EphA2 protein expression had relationship with lymph node metastasis, TNM stage and tumor depth of invasion (P0.05). Conclusion:The high expression of EphA2 protein may contribute to the occurrence, invasion and metastasis of Kazakh and Han ESCC patients. EphA2 protein expression in tissues and serum of patients with ESCC may be related to the primary tumor invasion, lymph node metastasis and TNM stage. The expression of EphA2 protein in peripheral blood of patients with esophageal cancer in Kazakh may be related to depth the of invasion.

Growth Factor-mediated Tumor Progression and Metastasis in Cholangiocarcinoma / 대한췌담도학회지

Different ligands can lead to the activation of epidermal growth factor receptor, and the subsequent signal transduction leads to an increase in cellular motility, proliferation, invasion, and blocking of apoptosis, and all of this contributes to the development and progression of cancer. Our studies clarified; 1) The EGFR expression level is reduced during tumor progression or during ligand-induced EGFR activation. 2) ANXA8 and its regulatory pathway may well be alternative, strategic targets for inhibiting tumor metastasis. 3) The molecular pathway of EphA2 signaling and provide insight into the mechanisms that control cancer progression and metastatic spread in cholangiocarcinoma (CC). Therefore, therapeutic strategies that target EphA2 and its downstream effectors may be useful to control CC.

EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury / 결핵및호흡기질환

BACKGROUND: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. METHODS: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). RESULTS: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group (4.30+/-2.93 vs. 11.45+/-1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33x10(4)+/-8.84x10(4) vs. IgG+LPS: 208.0x10(4)+/-122.6x10(4); p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52+/-0.41 mg/mL vs. IgG+LPS: 1.38+/-1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110gamma, phospho-Akt, nuclear factor kappaB, and proinflammatory cytokines. CONCLUSION: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

miR-141 suppresses cell proliferation by target down-regulating EphA2 in human oral squamous cell carcinoma / 基础医学与临床

Objective To assess the effect of miR-141 on proliferation of human oral squamous cell carcinoma and target relationship between miR-141 and EphA2 .Methods pcDNATM6.2-GW-pre-miR-141 was constructed and identified by qRT-PCR.EphA2-WT and EphA2-MT sequences were respectively cloned into pmirGLO plasmid . The potential proliferation function of miR-141 on CAL27 cells was analyzed by MTT .The target relationship be-tween miR-141 and EphA2 was identified by Dual-Luciferase Assay System , qRT-PCR and Western blot .Results We constructed successfully the recombinant plasmids , including pcDNATM6.2-GW-pre-miR-141, pmirGLO-E-phA2-WT and pmirGLO-EphA2-MT, and the transfection efficiency of pre-miR-141 was increased in CAL27 cells compared to control group(P<0.001).miR-141 could suppress the proliferation of CAL27 cells(P<0.05). Furthermore, a significant reduction of luciferase activities of CAL27 cells co-transfected with pre-miR-141 and EphA2-WT(P<0.001).The mRNA(P<0.001) and protein expression levels of EphA2 were decreased in CAL27 cells transfected with pre-miR-141 .Conclusions Overexpression of miR-141 may suppress cell prolifera-tion by targeting at EphA2 in CAL27 cells.

EphA2/ephrinA1 expression in human malignant gliomas and its relationship with angiogenesis / 中国肿瘤临床

Objective:To investigate the expressions and significance of tyrosine kinase receptor EphA2 and its ligand ephrinA1 in human malignant gliomas and their correlation with tumor angiogenesis. Methods:The expressions of EphA2, ephrinA1, and CD105-stained microvessel density (MVD) were detected via immunohistochemical assay in 62 glioma tissues and 8 normal brain tissues. The correlation between EphA2 and ephrinA1 expression and microvessel counts in the glioma tissues were assessed. Results:Immunohistochemical staining results revealed that variable levels of EphA2 and MVD expression were significantly higher than that of the normal brain samples. Statistical difference was observed in EphA2 and MVD expressions between human gliomas and normal brain samples (P<0.01). The positive rate of EphA2 and MVD expressions was significantly higher in high-grade gliomas (WHO III-IV) than that in low-grade gliomas (WHO I-II) (P<0.01). EphrinA1 was expressed at low levels in most malignant gliomas, and the increased ephrinA1 expression was associated with lower-grade histology. MVD was significantly positively correlated with EphA2 expression (r=0.713, P<0.01) and significantly negatively correlated with ephrinA1 expression (r=-0. 772, P<0.01). EphA2 was significantly negatively correlated with ephrinA1 expression (r=-0.912, P<0.01). Conclusion:Specifically over-expressed EphA2 and its low-expressed ligand ephrinA1 in malignant gliomas may be closely correlated with the invasion and malignant degree of gliomas. Cooperation is involved in the angiogenesis and has an important function in the initiation and progression of gliomas.

Effect of EphrinA1-Fc on phosphorylation of EphA2 and ERK in 786-O renal carcinoma cells / 中国肿瘤临床

Objective:To detect the effect of EphrinA1-Fc on the phosphorylation of EphA2 and extracellular signal-regulated ki-nase (ERK) in 786-O renal carcinoma cells (RCCs). Methods:The soluble ligand EphrinA1-Fc was used to inhibit the 786-O RCCs in vitro. Western blot analysis was used to examine the phosphorylation of EphA2 and ERK1/2 in the 786-O RCCs at different time points. Results:After the intervention with EphrinA1-Fc for 5, 10, 30, and 60 min, the expression of p-EphA2 increased (F=9.392, P=0.025) as well as that of p-ERK (F=4.428, P=0.041). No p-EphA2 and p-ERK expression was observed in the pre-intervention group. Conclusion:One of the possible mechanisms of the inhibitory effect of EphrinA1-Fc on tumor metastasis and recurrence involves the phosphorylation of EphA2 by EphrinA1-Fc, leading to the degradation of EphA2.

Relationship between EphA2 and Laryngeal Carcinoma Angiogenesis / 中国基层医药

ObjectiveTo study the relationship between EphA2 and laryngeal carcinoma angionegesis.MethodsImmunohistochemical staining was used to determine the expression of EphA2 and CD34 in 20 normal squamous epithelium tissues and 50 laryngeal carcinoma.The relationship between EphA2 expression and Microvascular density was analyzed bg Spearman correlation and linear regression.ResultsThe MVD in laryngeal carcinoma (54.89 ± 13.67) was significantly higher than that in normal squamous epithelial tissues ( 17.15 ± 5.21 ) ; The EphA2 in laryngeal carcinoma(4.56 ± 1.38) was significantly higher than that in normal squamous epithelial tissues ( 2.49 ± 1.23 ) ( t =16.721,5.847,all P ＜ 0.05 ).There was significant positive linear correlation between EphA2 and MVD in laryngeal squamous cell carcinoma(P ＜ 0.01 ).ConclusionEphA2 may correlate with angionegesis in laryngeal squamous cell carcinoma.

Expression and significant of EphA2、 EphrinAl and E-cadherin in pancreatic carcinoma / 中华肝胆外科杂志

Objective To investigate the relationship between EphA2, EphrinAl and E-cadherin expressions and tumor stage and prognosis in pancreatic cancer. Method EphA2, EphrinAl and Ecadherin expressions were detected by immunohistochemistry in the tumor tissue and normal tissue specimens from 48 patients with primary pancreatic cancer. Results The expressions of EphA2 and EphrinAl were higher in the pancreatic carcinoma tissues than in the normal pancreatic tissues (P<0. 05). The E-cadherin expression was lower in the pancreatic cancer tissues than in the normal pancreatic tissues (P<0. 05). With decreasing histological differentiation, the expressions of EphA2 and EphrinAl in carcinoma tissues increased significantly (P<0. 05), while the E-cadherin expression decreased significantly (P<0. 05). The positive expressions of EphA2 and EphrinAl in the primary tumor significantly increased in stageⅢ and Ⅳ than in stage Ⅰ and Ⅱ (47. 9%vs 6. 25% , P<0. 05;47. 9% vs 8. 3%, P<0. 05), while the negative expression of E-cadherin was reversely correlated with these tumor stages (14. 6% vs 64. 6%, P<0. 05). Cox multivariate analysis showed that the clinical stage, EphA2 positive expression and E-cadherin negative expression were significantly associated with survival. Conclusion Abnormal expressions of EphA2, EphrinAl and E-cadherin were involved in the progression of pancreatic cancer and they were useful in predicting prognosis.

Expressions of EphA2 and EphrinA1 in bladder carcinomas and their clinical significance / 中国医师进修杂志

Objective To investigate the expressions of EphA2 and EphrinA1 in bladder carcinomas and their clinical significance. Method The expressions of EphA2 and EphrinA1 were detected on bladder carcinomas (75 cases ) by immunohistochemistry S-P method. Results ( 1 ) The positive rates of expression of EphA2 and EphrinA1 were 61.3%(46/75) and 46.7%(35/75) respectively. (2) The expression of EphA2 was related to tumor size, lymphatic metastasis and TNM staging(P＜ 0.05),but not to gender,age and pathology type (P ＞ 0.05 ). ( 3 )The expression of EphrinA1 was related to tumor size and lymphatic metastasis (P ＜ 0.05 ), but not to gender, age, pathology type and TNM staging (P ＞ 0.05 ). (4)There was significantly positive correlation between the expression of EphA2 and EphrinA1 (P ＜ 0.05).Conclusions EphA2 and EphrinA1 are related to the occurrence and development of bladder carcinoma.The combined detection of EphA2 and EphrinA1 can help to predict the clinical and pathologic characteristics of bladder carcinoma. It is an important index to assist treatment, they are predictive factors for bladder carcinoma.

Expression of EphA2 and E-cadherin in colorectal carcinoma / 中国医师杂志

Objective To explore the expression and clinical significance of EphA2 and E-eadherin in colorectal carcinoma.Methods The expression of EphA2 and E-eadherin in 67 cases of eoloreetal carcinoma and 28 cases of normal large intestine tissues were determined by immunohistochemieal method(S-P method),and their relationship to elinicopathological characteristics were analyzed.Results The positive expression of EphA2 and negative expression of E-cadherin in colorectul carcinoma tissues were significantly higher than those in normal intestine tissues(P<0.01).F111e positive expression of EphA2 and negative expression of E-eadherin were positively correlated with tumor histological grade,invasive depth and lymph node metastasis(P<0.01 orP<0.05),but not correlated with tumor～ross type(P> O.05).The expression of EphA2 was negatively related with E-cadherin.Conclusions The abnormal expression of EphA2 and E-cadherin may be together involved in the development and progression of eolorectal carcinoma,It may be a good marker for monitoring the malignant degree and the prognosis of colorectal carcinoma by combining E-eadherin and EphA2.

Expressions of EphA 2 and KAI 1 in human bladder transitional cell carcinoma and its significance / 肿瘤

Objective: To investigate the association of EphA 2 and KAI 1 protein expressions with the occurrence, invasion, and metastasis of bladder transitional cell carcinoma tissues (BTCC). Methods: The expressions of EphA 2 and KAI 1 proteins were determined by immunohistochemical SP method in 88 cases of BTCC tissues and 76 cases of pericancerous normal bladder tissues. Results: The expression of EphA 2 protein was significantly higher in BTCC tissues than in adjacent normal tissues (P < 0.01). The expression of EphA 2 protein was gradually increased with the elevation of pathological grades of BTCC. The positive rate of EphA 2 expression was significantly higher in deeply infiltrating BTCC than superficially infiltrating BTCC (P < 0.05). It was significantly higher in the group with lymph node metastasis than those without lymph node metastasis (P < 0.05). The expression of KAI 1 protein was significantly lower in BTCC tissues than in adjacent normal tissues (P < 0.01). The expression of KAI 1 was gradually decreased with the elevation of pathological grades of BTCC. The positive rate of KAI 1 expression was significantly lower in deeply infiltrating BTCC than in superficially infiltrating BTCC (P < 0.05). It was significantly lower in the BTCC with lymph node metastasis than those without lymph node metastasis (P < 0.05). A significantly negative correlation was observed between the expression of EphA 2 and that of KAI 1 in BTCC tissues with lymph node metastasis (P < 0.05). Conclusion: Overexpression of EphA 2 and weak expression of KAI 1 may be involved in the tumorigenesis, infiltration, and migration of BTCC.