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Expression And Prognosis Of Survivin And EphA2 Proteins In Meningioma Tissues

Posted on:2020-08-27Degree:MasterType:Thesis
Country:ChinaCandidate:H SuFull Text:PDF
GTID:2404330623957847Subject:Outside of the surgery (God)
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Background Meningioma originates in the dura inside arachnoid membrane of tumor cells,most of meningiomas are the benign tumor,whose courses are slow growth,a small number of meningiomas are invasive,which are not ideal treatment effect,so the factors affecting the prognosis of patients with clear to judge prognosis,it is very important to know the relationship between tumor recurrence and meningioma classification.Generally,the prognostic factors of tumor patients include: general factors of patients,including age,gender,the presence or absence of basic diseases,complications,etc.;Surgical factors,including surgical method,tumor proximity,complete resection of tumor,etc.;In addition,pathological grade of tumor,etc.As a solid tumor rich in blood vessels,the growth and invasion of meningiomas require abundant capillaries to supply them with oxygen and nutrients.The rapid growth of tumors leads to the imbalance of vascular endothelial cytokines,especially the balance between angiogenesis and anti-angiogenesis factors.Therefore,the study on the molecular mechanism of meningioma angiogenesis is helpful to understand the internal mechanism of meningioma angiogenesis and the characteristics of the invasive biological behavior of meningioma,providing theoretical basis for antivascular therapy of meningioma and postoperative adjuvant molecular targeted therapy to reduce the recurrence rate.In the clinical treatment of meningioma,bevacizumab as vascular endothelial growth factor monoclonal antibody(VEGF-A),have been in class II,III grade meningioma and recurrent meningioma has certain antiangiogenesis effect,although its efficacy is limited,but the research and development of angiogenesis drugs represents the development direction of meningioma molecular target therapy.Survivin,a member of the smallest molecular weight inhibitor of apoptotic proteins(IAP)family,is low or not expressed in normal cells,and high in malignant cells,which can reduce apoptosis and regulate cell mitosis.Studies havedemonstrated that Survivin inhibition reduces tumor cell growth and enhances the sensitivity of tumor cells to chemotherapy drugs.Epithelial-mesenchymal transition(EMT)is the basis of the invasion and metastasis of tumor cells originating from epithelial tissues,leading to tumor invasion and metastasis.To study the pathogenesis of meningioma invasion and EMT is helpful to find therapeutic targets.Tumor cells of EMT process involving a variety of signal transduction process,at present,the receptor tyrosine kinase(RTK)family has a larger members-erythropoietin producing hepatocyte receptor(Eph),EphA2 receptor belongs to members of the family of RTK,highly expressed in many tumor tissues,is invasion and metastasis of tumor angiogenesis and new targets for therapy.Therefore,the in-depth study of the molecular mechanism of meningioma angiogenesis and the exploration of new targets will provide a beneficial theoretical basis for the in-depth understanding of the mechanism of meningioma angiogenesis,increase the clinical efficacy of anti-meningioma angiogenesis therapy,and provide a beneficial theoretical basis for the postoperative adjuvant molecular targeted therapy of meningioma.Purpose To review the clinical imaging,62 patients with meningioma and histopathologic data,observe meningioma tissue microvascular generation,explore apoptosis inhibiting protein Survivin and vasculogenic mimicry(VM)protein kinase(EphA2)epithelial cells expressed in meningioma in the organization,and the joint detection of meningioma prognostic significance;Observe both expressed in different histological grading of meningioma,and Survivin protein and EphA2 protein and microvascular density(MVD)in meningioma,to each other and to further explore meningioma in angiogenesis and invasive biological behaviour,for meningioma surgery assisted antiangiogenic provide theoretical basis for molecular target therap.Methods According to classification standard of the World Health Organization(WHO)(2016)in meningiomas of the nervous system,collected 62 cases meningioma with neurosurgery from February 2014 to July 2018,whose symptoms due to the progression of headache in the First Affiliated Hospital of Anhui MedicalUniversity,general condition and imaging examination review preoperative clinical data,patients with postoperative tumor tissue hematoxylin – eosin(HE)staining to observe the histologic change,Immuno-histochemical staining(IHC staining)with streptomycin anti-biotin protein--peroxidase(SP)assay was used to detect Survivin and EphA2 expression in meningioma meninges.Western blot was used to detect EphA2 and Survivin protein expression according to meningioma grade.Immunohistochemical SP method to detect the eighth Factor associated antigen(FVIII-RAg)polyclonal antibody staining showed meningioma tissue microvascular situation,at the same time,in the study of angiogenesis mimicry(VM),the joint line periodic acid Schiff’s(PAS)staining,angiogenesis index using microvessel density(MVD)showing the tumor angiogenesis.In the control group,20 cases of craniocerebral trauma underwent large craniotomy during the same period.Western blot was used to examine the protein expression of EphA2 and Survivin,and the correlation between EphA2 and Survivin proteins and MVD was statistically analyzed.Results All the 62 patients had headache,increased intracranial pressure,nausea and vomiting.Imaging examination showed that all the patients were single lesions,mainly located near the sagittal sinus,and the enhancement of the lesions showed varying degrees on the enhanced image scanning.The histochemical staining with PAS and immunohistochemical staining with FVIII-RAg polyclonal antibody in 62 meningioma tissues showed that 27 cases(43.55%)presented typical non-vascular endothelial cell VM structure and PAS staining was positive.Compared with grade I meningiomas,grade II and III meningiomas had significantly higher MVD values(P<0.05,P<0.01).With the increase of grade I,grade II and grade III of meningioma,the positive expression rate of EphA2 and Survivin proteins in meningioma was gradually increased,and correlated with meningioma recurrence(P<0.01).Compared with grade I meningioma,the expression of EphA2 and Survivin proteins in high-grade meningioma was correlated,and the differences were significant(P<0.05,P<0.01).Western blot confirmed the correlation between the expression of EphA2 and Survivin protein and the pathological grade ofmeningioma.Conclusion Meningioma is a common tumor of nervous system and imaging examination is of great significance in the diagnosis of meningioma.The apoptosis-inhibiting proteins Survivin and VM-forming related proteins EphA2 are involved in the formation of new blood vessels in meningiomas,which affecting the invasion and invasive growth.In the occurrence and progression of meningioma,MVD can reflect the invassibility of meningioma,Survivin and EphA2 proteins can be used as molecular targets for antivascular therapy of meningioma.
Keywords/Search Tags:Meningioma, Angiogenesis mimicry, Apoptosis inhibiting protein, EphA2, Survivin
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