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Expression Of Matrix Metalloproteinases (MMPs) And Their Inhibitors (TIMPs) And Angiogenesis Role Of MMP-9 In Human Pituitary Adenomas

Posted on:2004-09-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:J WangFull Text:PDF
GTID:1104360092987026Subject:Surgery
Abstract/Summary:PDF Full Text Request
Pituitary adenomas are common incidental findings in approximately 10% of intracranial neoplasms. Despite the fact that the majority of tumor are benign, a proportion will become locally invasive, leading to bony destruction and infiltration within the cavernous sinus or elsewhere around the pituitary fossa. The surgical treatment of these invasive tumors is often incomplete, and the high recurrence rate is the main reason influencing the curative effect. The reasons for the invasive behavior are poorly understood, and there are, at present, no reliable mechanisms for predicting tumor behavior. To seek the correlative factors as a prognostic for recurrence is a guidance for neurosurgeons to decide the postoperative therapy method.The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that are able to degrade the extracellular matrix. MM P-2 and MMP-9 are both type IV collagenases, which have been shown to be important in tumor invasion in vitro because they are able to break down basement membrane. The activity, of the MMPs is balanced by the tissue inhibitors of metalloproteinases. Relationship between MMPs, TIMPs and pituitary adenomas inasiveness has been researched recently, but the resultsare varied. In this study, expression of MMP-2, MMP-9 and TIMP-2 havebeen detected by methods of immunohistochemistry and RT-PCR respectively in 30 pituitary adenoma cases. And the relationship between MMP-2, MMP-9, TIMP-2 and pituitary adenomas inasiveness has been analyzed.Angiogenesis and tumor invasion both require controlled degradation of the extracellular matrix components to allow cell migration and new tissue formation. There are more than 20 kinds of angiogenesis factors relate to human tumor growth, VEGF is the most important one. To investigate the expression of VEGF can not only find out its relationship with the invasiveness of pituitary adenomas, but also establish its correlation with MMP-9, thus help us to understand the mechanism of MMP-9 act in pituitary tumor.Chapter 1.The Relationship Between Protein Expression of MMPs, TIMPs and Invasiveness of Pituitary AdenomasObjective: To detect protein expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors. And explore the relationship between MMP-2, MMP-9 , TIMP-2 and invasiveness of pituitary adenomas and investigate its clinical value. Methods: Six kinds of hormone secreted by pituitary gland were detected by immunohistochemical postoperatively in 30 pituitary adenomas. MMP-2, MMP-9 and TIMP-2 were detected in 30 pituitaryadenomas and 4 normal pituitary tissue by using immunohistochemical staining. The correlation between expression of hormone, MMP-2, MMP-9, TIMP-2 and tumor invasiveness were studied. Result: Luteinizing hormone (LH) significantly increased in invasive pituitary adenoms. Expression of MMP-9 increased in invasive pituitary adenomas (p<0.01). Expression of TIMP-2 decreased in invasive pituitary adenomas (p<0.01). Significant correlation was not found between MMP-2 and TIMP-2. Conclusion: Higher MMP-9 protein expression and lower TIMP-2 protein expression may play important roles in the invasiveness of pituitary adenoms and may be useful markers to predict the invasiveness. There have subtle relationshi p between MMP-2 and TIMP-2.Chapter 2.The Relationship Between mRNA Expression of MMPs, TIMPs and Invasiveness of Pituitary AdenomasObjective: To detect messenger RNA (mRNA) expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors. And explore the relationship between MMP-2, MM-9, TIMP-2 mRNA and invasiveness of pituitary adenomas, and investigate its clinical value. Methods: MMP-2, MMP-9 and TIMP-2 mRNA expression was determined in 20 invasive pituitary adenomas and 10 non-invasive pituitary adenomas by using comparativereverse transcription-polymerase chain reaction (RT-PCR). The correlation between mRNA expression of MMP-2, MM -9, TIMP-2 and tumor invasiveness were studied. Result: Both mRNA expression of MMP-2 and MMP-9 increased in invasive pituitary a...
Keywords/Search Tags:pituitary adenomas, invasiveness, MMPs, TIMPs, VEGF
PDF Full Text Request
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