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The Clinical And Experimental Study Of CyclinA For Proliferation And Regulated In Leukemia Cell

Posted on:2003-08-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:J MaFull Text:PDF
GTID:1104360065450260Subject:Internal Medicine
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Cyclin A was a kind of positive regulation of cell cycle, one of the member of a growing superfamily of cyclins. It was originally as the site of hepatitis B virus intergration in a hepatocellulai carcinama,and this intergration and subsequent cyclin A overexpression may contribute to tumorigenesis. Cyclin A appear at Gl phase before synthesis of DNA and was located in nucleur and combine with corresponding CDK2 and CDC2. It participate synthesis and replication of DNA and propel cell in to mitosis phase. Cyclin A was required for S phase entry and passage through G2/M phase. Its normal expression represents normal proliferative activity.Abnormal expression of cyclin A would lead the mistake DNA directly passage through cell cycle. Researched in the field subsequently , showed that the cyclin A gene was overexpression and played an important role in any kind of carcinoma, and up-regulated by c-myc and is link to adhesion-independent cell proliferation, is the index of uncontrol magligant carcinoma cell growing and assiociated with prognosis in cancer. Many research observed that the cyclin A expression was positive correlated with the cumulative percentage of cells in S and G2/M phase in leukemia . Therefore , we investigated the expression of cyclin A in patients with acute leukemia(AL) and chronic myelogenous leukemia(CML), and relationship with leukemia development as well as its clinical value.Antisense nucleotides techonology is a method of inhibition the expression of the target gene by antisense RNA. This method have been used in the researching of tumor and genetic discords. So we wish diagram a specially cyclin A antisense oligodeoxynucleotide (ASON) to inhibit cyclin A gene expression, and also study the effect of cyclin A onproliferation regulated and apoptosis of leukemia cell in vitro and in vivo of the animal.1 Clinical significance of cyclin A expression in adult patients with acute leukemiaObjective To investigate the clinical significance of cyclin A expression in adult patients with acute leukemia .Method 100 cases of acute leukemia (AL) and 10 cases of normal control were examed for cyclin A and P21cipl protein and mRNA expression levels using FACS and RT-PCR.Result (1 )The distribution of cyclinA protein was often no difference in cell cycle in AL patients. It appeared at GO/G1 phase, increased at S phase and achieved the summit at G2/M phase,which was concordance with the distribution of cyclin Ain the normal cell. By survey sequence analysis ,we observed the positive segment of cyclin A which was completely consistent to the objective gene in the genebank. But the positive rates(66.7%, 59% )and average expression levels (18.5%, 0.539 ?0.990 ) of protein and mRNA of cyclin A significantly higher than normal person (P<0.01). (2)The cyclinA protein expression was paralled to that of mRNA expression. (r=+0.597,P=0.000 ). All that explained that cyclinA can be regulation and controled in the levelof transcripition.(3) The protein and mRNA levels of cyclinA were positively correlated with the cumulative percentage of cells in S and G2/M phase.(PO.01). (4) The protein expression of cyclin A was negative correlated (r= - 0.295, P=0.010) with WBC counts in AL patients. There were no correlation between cyclin A expression and age ,sex , the rate of blast cell and FAB classification of AL patients (P>0.05 ). (5) The positive rates and the expression levels of cyclin A were on difference between the de novo and relapse AL patients(P<0.05). But analysed for the patient with difference FAB classification and discovered that the expression levels of cyclin A in the relapsed AL group(15.4%) was obviously lower than those of de novo group (29.5%) (t=14.418,P=0.022 ) , the expression levels of cyclin A wereall obviously higher than the remission and the normal control group(P<0.01 ) .(6) The CR rates (87.9%,85.7%) of AL patients with the high expression levels of cyclinA were obviously higher than those of the lowlevels(38.2%,53.5%). (P<0.01). With the logical regression analy...
Keywords/Search Tags:cyclinA, leukemia, multidrug resistance, antisense nucleotides, lipid plastid transfection, cell apoptosis
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