ABSTRACT
Objective To observe the efficacy of arsenic trioxide(ATO) combined all trans retinoic acid (ATRA) versus cytara‐bine (Ara‐C) combined ATRA in the treatment of acute promyelocytic leukemia(APL) .Methods We enrolled 65 patients in our department during the period between January 2002 and August 2008 ,and they were randomly assigned to receive ATRA combined ATO (treatment group ,n= 27) or ATRA combined DA ,HA ,NA which were major of Ara‐C (control group ,n= 38) .Then observe the differences of between the two groups ,such as complete remission(CR) ,the time to complete remission ,overall survival(OS) ,e‐vent free survival(EFS) ,the 5 years disease free survival (DFS) and adverse reactions .Results The CR rate of treatment group (ATRA + ATO) and control group (chemotherapy + ATRA) was 81 .48% and 68 .42% ,respectively ,and the time to complete re‐mission was (28 .50 ± 3 .97)d and (30 .56 ± 2 .39)d ,respectively ,showed that there was no statistical difference between the two groups ( P > 0 .05 ) .The 5 years DFS of the CR patients in the two groups was 51 .9% (ATRA + ATO ) and 50 .0%(Chemotherapy + ATRA) ,respectively ,showed that there was no statistical difference between the two groups(P > 0 .05) .The 5 years EFS of the CR patients in the two groups was 48 .1% and 39 .5% ,respectively ,showed that there was no statistical difference between the two groups(P> 0 .05) .The 5 years DFS of the patients in the two groups was 55 .6% and 67 .6% ,respectively ,showed that there was no statistical difference between the two groups(P > 0 .05) .Bone marrow suppression in the treatment group was significantly lower than in the control group(P< 0 .05) .Conclusion ATRA + ATO can prolong the CR rate ,OS ,EFS and 5 years EFS of newly diagnosed APL patients .ATRA combined with chemotherapy has similar efficacy ,ATRA + ATO has lower bone marrow suppression than the ATRA combined with chemotherapy ,thus may reduce the risk of early death .
ABSTRACT
Objective To evaluate the clinical effect of itraconazole in prevention of invasive fungal infections in allogeneic hema-topoietic stem cell transplantion .Methods In this retrospective study ,110 patients receiving allogeneic hematopoietic stem cell transplants were administed itraconazole or fluconazole for prevention of fungal infection .The occurrence and prognosis of invasive fungal infection ,and the side effect of both pyrroles were observed .Results Proven and probable invasive fungal infections occurred in 5 of 69 itraconazole recipients(7 .2% ) and in 8 of 41 fluconazole recipients(19 .5% ) during the first 180 days after transplanta-tion ,the difference had statistical significance(P<0 .05) .The fatality rate related to fungal infection had no statistical difference be-tween the two groups(2 .9% vs .7 .3% ) .The occurrence of itraconazole adverse reactions were more than fluconazole (26 .9% vs . 7 .0% ) ,and both itraconazole and fluconazole were well tolerated .Conclusion Itraconazole significantly reduces the incidence of inva-sive fungal infection in the patients receiving allogeneic hematopoietic stem cell transplants ,and it is a effective and safe prophylaxis .
ABSTRACT
Objective To investigate the effects and the gene expression of mitochondria on arsenic trioxide-induced apoptosis of acute promyelocytic leukemia (APL) NB4 cells. Methods NB4 cells were treated with As2O3. Fluorescent microscopy and flow cytometry were used and mitochondria membrane potential detection and RT-PCR were performed to observe the NB4 cell apoptosis, growth inhibitory effect and mitochondrial transmembrane potentials. Mitochondria genome primers were designed, and the expression of mitochondria genome at gene and protein levels was studied. Results Induced by As2O3, the NB4 cells showed typical morphological changes of apoptosis with a significant growth inhibitory effect. The ratios of NB4 cells apoptosis were 5.02%, 6.40%, 28.40% and 33.34%, respectively, when treated with As2O3 in concentrations of 0.5?mol/L, 1?mol/L, 2?mol/L and 3?mol/L. When treated with As2O3 in 0.5?mol/L, 1?mol/L, 2?mol/L, 4?mol/L and 8?mol/L at 48h, the mitochondria potential of NB4 cells was decreased by 12.8%, 21.6%, 66.9%, 83.7% and 83.8%, respectively. After the NB4 cell apoptosis was induced by As2O3, RT-PCR assay was used to detect the expression of 13 genes of mitochondria genome. The expression of COX2 gene was down-regulated in this process, while no change was found in the expression of other 12 genes. Conclusions As2O3 has shown to exert a significant effect on promoting apoptosis and growth inhibition on APL cells. The apoptotic effect induced by As2O3 on NB4 cells is closely related to a decrease of mitochondrial membrane potential. The expression change in the mitochondria gene COX2 is involved in the As2O3-induced apoptosis of NB4 cells.
ABSTRACT
Objective Gene microarray technology was used to investigate the differential gene expression of apoptosis related genes in NB4 cells induced by arsenic trioxide. Methods The databases of Evntrez and Human IPI were searched with "apoptosis or apoptotic" as the key words, and 1384 apoptosis related genes were found after the redundant genes were eliminated by chromosomal localization. The probes of these genes were designed using OligoArray 2.0, and then analyzed by BLAST. All the probes were immobilized on the glass slide, which were used as oligonucleotide microarray. After NB4 cells were treated with 2umol/L As2O3 for 48h, the total RNA were extracted. cDNAs of control group and test group were fluorescently labeled with Cy3 and Cy5, respectively, by RT-PCR. The fluorescent samples were hybridized with an oligonucleotide microarray containing 1384 apoptosis related genes to search for the differentially expressed genes in the cells with or without As2O3 treatment. The hybridization signals were scanned by oligonucleotide microarray, and then the fluorescent intensity of Cy3 and Cy5 and the ratio of two fluoresceins were analyzed using certain software. Then the differential expressed genes were analyzed after As2O3 treatment, in which the most distinctly differential expressed genes were chosen as targets, and through PCR amplification and gel electrophoresis the above genes were verified. Results There are 4 genes up-regulated and 12 genes down-regulated in expression in NB4 cells after 48h treatment with 2umol/L As2O3, which were in accordance with the results of RT-PCR and oligonucleotide microarray. Conclusion Differential gene expression in NB4 cells was induced by As2O3 treatment. These differentially expressed genes, with relation to signal transduction, transcription regulation, cell cycles, oxidation response, protein translation and cell differentiation, may play an important role in NB4 cell apoptosis.