ABSTRACT
This study was purposed to investigate the relationship of expressions of gluthatione-S-transferase-pi (GST-pi), multidrug resistance protein-1 (MRP-1), lung resistance protein (LRP) with multidrug resistance of acute leukemia (AL), the correlation between 3 kinds protein expressions and the correlation of their protein expression with clinical features of AL patients. The S-P immunohistochemical staining method was used to determine the expressions of GST-pi, MRP1 and LRP proteins in 80 AL patients and 30 normal subjects. The results showed that there was the correlation between GST-pi, MRP1, LRP protein expression and chemotherapy resistance, meanwhile CR rates of patients with positive expression of those proteins were lower than that of patients with negative expression (P<0.05), so those protein expressions may be accounted for poor prognosis. There was the positive relationship between expression of GST-pi and MRP1 in refractory group (r=0.851, P<0.01). It is concluded that co-examination of GST-pi and MRP1 has greater significance than examination of one kind of protein in evaluating poor prognosis of leukemia patients. LRP protein expression increase obviously when WBC counts >or= 10 x 10(9)/L (63.6%, P<0.05), therefore LRP protein has great judging value for evaluating drug resistance and prognosis of acute leukemia patients whose peripheral blood WBC counts were high.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Drug Resistance, Multiple , Genetics , Drug Resistance, Neoplasm , Genetics , Glutathione S-Transferase pi , Genetics , Leukemia, Myeloid, Acute , Drug Therapy , Metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Metabolism , Vault Ribonucleoprotein Particles , GeneticsABSTRACT
To evaluate the expression of cyclin G2 mRNA in patients with acute leukaemia (AL) and its clinical value, the expression of cyclin G2, G1 and P53 mRNA in the bone marrow from 74 AL patients and 10 normal individuals as control were detected with reverse transcription polymerase chain reaction (RT-PCR). The positive segment of cyclin G2 was analyzed by DNA sequencing. The results showed that (1) the positive rate and the expressing level of cyclin G2 in AL patients (52.7%, 0.552 +/- 0.498) were significantly lower than those in normal control (100%, 1.953 +/- 0.675) (P < 0.01); (2) among new diagnosed AL patients, the complete remission (CR) rate (69.2%) in the positive cyclin G2 patients was higher than that (40%) in negative cyclin G2 patients (P < 0.05); (3) the positive rate of cyclin G2 (43.6%) in resistance group was significantly higher than that (68.6%) in sensitive group (P < 0.01); (4) following-up for 14.3 month (11 - 18.5 month) in 28 AL patients with CR, there were 10 relapsed in 11 AL patients with low expression level of cyclin G2 (90.9%); and 7 relapsed in 17 AL patients with high expression (41.2%), and there was significant difference (P < 0.05). In conclusion, the expression of cyclin G2 in AL patients was higher than that in normal control, the abnormal expression of cyclin G2 might be a prognostic marker of CR in AL patients.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Acute Disease , Biomarkers, Tumor , Genetics , Cyclin G2 , Cyclins , Genetics , Gene Expression Regulation, Leukemic , Leukemia , Genetics , Pathology , Prognosis , RNA, Messenger , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
To investigate the effect of cyclin G1 antisense oligodeoxynucleotide (ASON) with liposomal transfection on mediating proliferation of HL-60 cell, the cyclin G1 ASON with liposomal transfection was used in vitro in co-culture with HL-60 cell, the protein and mRNA expression levels of cyclin G1 were measured by immunocytochemistry assay and RT-PCR. The cell apoptosis was detected by electron microscopy, in situ cell apoptosis detection kit (POD), DNA gel electrophoresis and flow cytometry (FCM). The results showed that in the cyclin G1 ASON group the protein and mRNA expression of cyclin G1 were significantly inhibited as compared with sense oligodeoxynucleotide (SON) group and blank group. When the ASON concentration increased, the proliferation ratio of HL-60 cell and CFU of HL-60 were also significantly inhibited. There was apoptosis of HL-60 cell. In conclusion, cyclin G1 ASON can specifically inhibit its protein and mRNA expression levels as well as the HL-60 cell proliferations and can accelerate the apoptosis of leukemia cells with concentration-dependent effect of ASON.
Subject(s)
Humans , Apoptosis , Cell Division , Cyclin G , Cyclin G1 , Cyclins , Genetics , Flow Cytometry , HL-60 Cells , Cell Biology , Liposomes , Microscopy, Electron , Oligonucleotides, Antisense , Pharmacology , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To study the inhibition effect of cyclin G(1) antisense oligodeoxynucleotides (ASON) on the growth of HL-60 cells in nude mice.</p><p><b>METHODS</b>(1) Nude mice were divided into control group, sense oligodeoxynucleotides (SON) group and ASON group. After (60)Co radiation, with HL-60 cells SON group and ASON group were subcutaneously innoculated; (2) The weight and volume of tumors were continually measured; (3) The morphology of tumor cells was observed by microscope; (4) The protein and mRNA expression levels of cyclin G(1) were determined by flow cytometry (FCM) and reverse transcription polymerase chain reaction (RT-PCR); (5) The cell apoptosis was detected by electron microscopy and FCM.</p><p><b>RESULTS</b>(1) The inhibition rate of tumor in ASON group was 69.4%. In ASON group, the wight and volume of tumor were significantly lower than those in SON group and control group. (2) The HL-60 cells in ASON group showed morphologically smaller nuclei, less mitosis, less heteromorphosis and apoptosis.</p><p><b>CONCLUSION</b>The cyclin G(1) ASON can inhibit the growth of HL-60 cells in nude mice and induce apoptosis.</p>