Font Size: a A A

Exploring Study Of Key Proteins In Glioma Progression

Posted on:2013-03-02Degree:MasterType:Thesis
Country:ChinaCandidate:Z F SunFull Text:PDF
GTID:2234330374498590Subject:Oncology
Abstract/Summary:PDF Full Text Request
ObjectiveGlioma is the most common primary neuroepithelium malignant tumor of central nervous system. Owing to the feature of invasive growth, glioma is hard to be removed completely by surgery, besides, clinical results of chemotherapy and radiotherapy are unsatisfied caused by blood brain barrier, chemoresistance and radioresistance. So the glioma has the characteristics of high morbidity, high recurrence rate, high mortality rate and low cure rate. It is considered that the occurence and development of glioma is a complicated process, and it will benefit the treatment and the prognosis of glioma to clarify its molecular mechanisms.Notch-1can control differentiation and proliferation, which plays an important role in embryogenesis. Deregulation of Notch-1is involved in the development of some cancers. Due to the importance for the development of neural system, Notch-1has attracted increasing attention in glioma. The MMP family plays an important role in the degradation of extracellular matrix in various physiological and pathological conditions. It contributes to cancer cell invasion and metastasis through the ECM degradation. MMP-2and MMP-9are significantly correlated with tumor cell invasiveness in human gliomas. We use immunohistochemistry to observe the expression of Notch-1, MMP-2and MMP-9in glioma and their relationship with the progression and prognosis of malignant glioma. The results are as follows:1. Notch-1was detected in glioma tissues but not in adjacent non-cancerous tissues. The expression of Notch-1protein was positively correlated with pathological grade of glioma (P<0.05). Notch-1was also positive in tumor-derived vascular endothelial cells.2. MMP-2and MMP-9were detected in glioma tissues but not in adjacent non-cancerous tissues, and the difference was significant (P<0.05). But there was no statistical correlation of the expression of MMP-2and MMP-9with pathological grade (P>0.05).3.Patients with intensive expression of Notch-1had a shorter survival time than those with weak expression (P<0.05).4. Significant difference in survival time was observed between patients with negative and positive expression of MMP-9(P<0.05) but not MMP-2(P>0.05).5. Significant positive correlation was observed between the expression of Notch-1and MMP-2(rs=0.434, P<0.01)as well as MMP-9(rs=0.273, P<0.05), but there was no significant correlation between MMP-2and MMP-9(P>0.05). is a downstream target of Notch signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-kappa B activation. It’s a member of the atypical PKC subfamily expressed in lung, kidney, testis, especially in brain, and it’s widely implicated in the regulation of cellular functions including cellular proliferation, cell cycle control, differentiation, polarity, survival and neural development. It’s also involved in the malignant behavior of human cell transformation, glioblastoma cell migration and invasion. The immunohistochemistry and Western blotting were used to observe the expression of PKC ζ in glioma patients. The relationship of PKC ζ expression with malignant glioma progression and prognosis was also evaluated. The results showed that:The expression rate was increased in accordance with the degree of pathological grade of the gliomas; PKC ζ was not detected in adjacent non-cancerous tissues; and a significant difference in survival time was observed between patients with negative and positive expression respectively (P<0.05), indicating that the prognosis of patients with negative PKC ζ expression was more favorable than patients with PKC ζ positive expression.Conclusion1. The expression of Notch-1in glioma was correlated significantly to tumors pathology grade, which displays that Notch-1may play an important role in the development process of glioma.2. MMP-2and MMP-9were detected in glioma tissues but not in adjacent non-cancerous tissues, it may takes part in the malignant transformation of glioma.3. Compared to MMP-2, MMP-9may play a more important role in determining the prognosis of malignant glioma. MMP-9and Notch-1may be the biological markers for prognosis of malignant glioma patients.4. There was postive correlation between the expression of Notch-1and MMP-2as well as MMP-9, so Notch-1may participate in the regulation of MMP-2and MMP-9.5. PKC ζ expression in gliomas is positively associated with the pathological grades of gliomas, the patients with PKC ζ positive expression have poor prognosis, suggesting that PKC C may be involved in the tumorigenesis and progression of gliomas. It may become a new target for tumor therapy.
Keywords/Search Tags:Glioma Notch-1MMP-2MMP-9PKCζ, Prognosis
PDF Full Text Request
Related items