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Study On The Relationship Between MMPs And The Lympho-plasmacytic Malignancies

Posted on:2008-05-13Degree:MasterType:Thesis
Country:ChinaCandidate:S H WeiFull Text:PDF
GTID:2144360212996253Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
[Background] Malignancies are frequently occurring but common dieases,which are harmful for the health of human.Recently,there is significant progression about the research on the etiology,histogensis and early diagnosis of tumor.Especially the medical treatment of tumor is faced with a new perspect:new durgs, such as taget therapy aiming at gene and receptor,vasodepressor and those inducing cell differentiation and apoptosis ,are being used or will be used.At present,there are a lot of researches about the relationship betweem MMPs and Malignancies.The growth,infiltr- ation and metastasis of tumor are multi-step and complicated courses which are influenced by many factors.Among the courses,the rido disequilibrium of MMPs and TIMPs plays an important role by resulting in the degradation of extracellular matrix(ECM). The reason is that the degradation of ECM blocks new vessel formation,which is prerequisite for tumor growth.In a word,there is a close relationship among angiogenesis,tumor and MMPs.MMPs are a family of endopeptidases excreted by a number of cell-types such as tumor cell,stromal,eddothelial and inflammatory cells.MMPs are capable of cleaving several macromolecules of the ECM.Based on their substrate specificity,the human MMPs are roughly divided into five groups.Gelatinases ,that is MMP-2 and MMP-9,aremainly hydrolyze components of basal lamina,gelatin and collagen type IV.Basement membrane is the form of specialized ECM.After all,by hydrolyzing ECM and activating the growth factors,MMPs play a key role on tumor angionenesis,tumor growth,tumor cell infiltration and metastasis.Angiogenesis is a process that requires proteolysis of the ECM, migration as well as proliferation of endothelial cells,and synthesis of new matrix components.Angiogensis plays a role in non-pathological conditions,like the reproductive cycle in women,wound healing as well as placental development.In these condition,angiogenesis is strictly regulated. Dysregulation of angiogenesis may lead to pathological conditions like:reheumatoid arthritis,diabetic retinopathy and psoriasis.Moreover, angiogene -sis is essential for cancer progression.It has been demonstrated that tumors cannot grow beyond several mm3 without new vessel formation.In acute leukemia,increased vessel density is found at diagnosis, disappearing when complete remission is achieved.At present,many researches are about MMPs and the solid tumor.It has shown that the proMMP-2 and proMMP-9 expressions are increased in malignant cancer compared to benign tumor.Moreo- ver,MMP-2 has been show to be a prognostic factor in different malignancies such as ovarian cancer,gastric carcinoma andnon-small cell lung carcinoma.The reports aboard show that The MMP-2 expression is increased in AML,but MMP-9 decreased,while in ALL they are both increased.Hazar pointed out that MMPs can be the factor representing bad prognosis and therapeutic effiancy .The research by Vacca show that MMPs increases in MM,either active stage or non-active stage.There are correlation reports internal showing that MMP-2 and MMP-9 has close relation to hematology tumor.With more and more investigation,MMPs has been a attractive target used to treat tumor.There are many researches about MMPs inhibitors,such as the TIMPs andα2-macroglobulin might be interesting candidates for development of angiogenesis inhibitors.The reports show that methylation can decrease the MMP-9 expression in NHL;arsinic trioxide can inhibit the expression of MMP-2 and MMP-9 in multidruge resistant leukemic cell. It's help for us using MMPs as a target to judge the progression and prognosis of dieases by studying the relationship of MMPs and the lypho-plasmacytic tumor.It also offer a new method to design new drugs anti-cancer reasonably. [Objectives] To investigate the difference of the expression of proMMP-2,MMP-2, proMMP-9, MMP-9 in serum of patients with lympho-plasmacytic tumor separately at diagosis stage, relapse stage,release stage,and health people as contrast group.And to evaluate the function of MMPs in lympho-plasmacytic tumor,toapproach MMPs can or not be a new indicatrix to judge pathogenetic condition progression and tumor load.And to provide theory evidence to use TIMP reasonabally.[Methods]The expression of proMMP-2,MMP-2, proMMP-9, MMP-9 were examined by SDS-PAGE zymograph in 32 patients who were on at diagosis stage, replse stage, relapse stage,comparing with the expression of normal persons.[Result]Compared with the contrast group,the expression of proMMP-2,MMP-2, MMP-9 were higher in at diagosis stage, relapse stage(p<0.05); Compared with the release group,the expression of proMMP-2,MMP-2, MMP-9 were higher in at diagosis stage, relapse stage(p<0.05);[Conclusions]There is a positive correlation between MMPs and lympho-plasmacytic tumor;MMPs can be a new indicatrix to judge pathogenetic condition progression and tumor load. It also offer a new method and theory evidence to design new drugs-TIMP to treat lympho-plasmacytic tumor reasonably.
Keywords/Search Tags:Matrix Metalloproteinases, Lympho-plasmacytic tumor, Extracellular matrix, Angiogenesis
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