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The Regulation Of Nuclear Factor-Kappa B To Proliferation And Metastasis Of Acute Leukemic Cell

Posted on:2003-04-28Degree:MasterType:Thesis
Country:ChinaCandidate:H Y HuFull Text:PDF
GTID:2144360065456392Subject:Medical clinical hematology
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Acute Leukemia is the most common malignant disease of hematology. The features of leukemia are suppression of normal hematopoiesis by blast cells of a clone arising from malignant transformation of hematopoietic stem cell and organ infiltration. Until now, the concrete cause of mechanism of malignant transformation and metastasis has remained poorly understood. At present, many researches suggest that Nuclear Factor-Kappa B(NF- K B) be closely associated with Acute Leukemia(AL). NF- K B is the prototype of a family of dimeric transcription factor. NF- K B combines with the DNA K B sequence of the promoter and enhancer of multiple genes ,then regulates their activation inducing antiapoptosis, proliferation, malignant transformationand metastasis. It plays a critical role in initiative and progressive mechanism of cancer, so scientists pay more and more attention to it. For domestic field, no report about the relation between NF- K B and metastasis of AL has been published so far. However the pivotal clinic problem of AL is reoccur, furthermore it is organic infiltration that induces reoccur. Matrix Metalloproteinase(MMP) is a family of Zone-containing proteinase enzyme regulated by NF- K B and oncogene-Ras that has been proved closing to induce AL, which can degradate almost all kinds of extracellular matrixes and basement membranes. It has been determined that the level expression of MMPs is related to metastatic phenotype of cancerous cells. Aberrant expressions of NF- K B, MMP-2 and MMP-9 may contribute to the progress of AL, so in this study by using immunocytochemical method staining bone marrow smears of newly diagnosed untreated AL, remission stage of AL and normal control to determine the expression of NF- K B, P21, MMP-2 and MMP-9Method : Subjects were divided to three groups :l.The newly diagnosed untreated AL group (n=45, Male 21, Female 24, Mean Age 33.98Y) including Acute lymphocytic Leukemia(ALL) 14 cases and non-ALL 31 cases. According to the diagnostic standard worked out by FBA in 1986, it was further subdivided into Mj 4 cases, M2 15cases, M3 4 cases, M4 5 cases and M5 3 cases; 2. The remission stage of AL group (n=30, Male 13, Female 17, Mean Age 30.45Y) including ALL 13cases and non-ALL 17 cases. According to the remission standard worked out on Suzhou meeting in 1987. it also was further subdivided into MI 2 cases, M2 9 cases, M3 3cases, M4 3 cases and M5 1 cases; 3 The normal control group n=30, Male 8, Female 22, Mean Age 27.63. Collecting the bone marrow smear of all subjects, test the positive rate of NF- KB, P21, mmp-2 and MMP-9 by using immunocytochemical method.(Count 500 cells and the positive cell to gain the rates and scours) The results were analysised with chi-square test by SPSS10.0,and we establish the standard of statistic significence as a = 0.05.Results: (1) The positive rate of NF- K B in the patients with newly diagnosed untreated AL is significant higher than that of remission stage of AL and normal control group (P<0.05). There is no significant difference between the remission group and the normal group (P>0.05). (2) The positive rate of Ras in the patients with newly diagnosed untreated AL is significant higher than that of remission stage of AL and normal control group (P<0.05). There is no significant difference between the remission group and the normal groups (P>0.05). (3) The positive rate of MMP-2 in the patients with newly diagnosed untreated AL is significant higher than that of remission stage of AL and normal control group (P<0.05). There is no significant difference between the remission group and the normal group (P>0.05). (4) The positive rate of MMP-9 in the patients with newly diagnosed untreated AL is significant higher than that of remission stage of AL and normal control group(P<0.05). There is no significant difference between the remission group and the normal groups.(P>0.05). (5) There are positive relations between NF- K B and P21, MMP-2, MMP-9 in all three groups.(r are 0.767, 0.729 and 0.803 respectively, P<0.05)(6)There are po...
Keywords/Search Tags:NF-кB, MMP-2, MMP-9, Ras, Antiapoptosis, Malignant prolieration, Onganic infiltration
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