ABSTRACT
The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Antineoplastic Agents , Therapeutic Uses , Bone Marrow , Allergy and Immunology , Pathology , Cytokine-Induced Killer Cells , Cell Biology , Allergy and Immunology , Transplantation , Dendritic Cells , Cell Biology , Allergy and Immunology , Transplantation , Immunotherapy, Adoptive , Methods , Injections, Subcutaneous , Interleukin-2 , Therapeutic Uses , Leukemia, Myeloid, Acute , Allergy and Immunology , Pathology , Therapeutics , Neoplasm, Residual , Primary Cell Culture , Recurrence , Remission Induction , Treatment OutcomeABSTRACT
The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.
Subject(s)
Humans , Cytokines , Blood , Diagnosis, Differential , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute , Blood , Microarray Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Blood , Prognosis , RNA, Messenger , BloodABSTRACT
The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.
ABSTRACT
The clinical characteristics of patients with seizures after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were analyzed. A total of 8 cases of seizures after allo-HSCT were investigated. Clinical data of these cases were studied retrospectively. Of 159 cases subjected to allo-HSCT, seizure occurred in 8 cases during 29-760 days after transplantation, median survival time was 46 days, and there were 6 cases of tonic-clonic seizure. The incidence of seizure after matched unrelated HSCT was higher than that after related HSCT (P=0.017). Of 7 cases treated with cyclosporine A (CsA), 4 cases obtained high blood levels of CsA. In addition, hyponatremia was diagnosed in 5 cases. Abnormal electroencephalogram and brain MRI findings were found in some cases. During 20 days after seizure, 2 cases died due to infection and graft-versus-host disease (GVHD), respectively. It was suggested that multiple factors are associated with seizures after allo-HSCT. Rapid identification and correction of the causative factors are very important to prevent permanent central nervous system damage and reduce the mortality.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Anticonvulsants , Therapeutic Uses , Fatal Outcome , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Methods , Phenytoin , Therapeutic Uses , Retrospective Studies , Seizures , Diagnosis , Drug Therapy , Transplantation, Homologous , Treatment Outcome , Valproic Acid , Therapeutic UsesABSTRACT
The clinical characteristics of patients with seizures after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were analyzed. A total of 8 cases of seizures after allo-HSCT were investigated. Clinical data of these cases were studied retrospectively. Of 159 cases subjected to allo-HSCT, seizure occurred in 8 cases during 29-760 days after transplantation, median survival time was 46 days, and there were 6 cases of tonic-clonic seizure. The incidence of seizure after matched unrelated HSCT was higher than that after related HSCT (P=0.017). Of 7 cases treated with cyclosporine A (CsA), 4 cases obtained high blood levels of CsA. In addition, hyponatremia was diagnosed in 5 cases. Abnormal electroencephalogram and brain MRI findings were found in some cases. During 20 days after seizure, 2 cases died due to infection and graft-versus-host disease (GVHD), respectively. It was suggested that multiple factors are associated with seizures after allo-HSCT. Rapid identification and correction of the causative factors are very important to prevent permanent central nervous system damage and reduce the mortality.
ABSTRACT
This study was aimed to explore the expression of survivin in leukemia cells and to investigate the effect of GM-CSF on survivin expression. The survivin expressions in 37 previously untreated leukemia patients and 10 normal persons as well as in three kinds of leukemia cell lines (K562, HL-60, U937) were analyzed by RT-PCR. The HL-60 cells were treated by the proper concentration of GM-CSF, and the changes of survivin mRNA and protein expression levels were detected by using RT-PCR and Western blot respectively. The results indicated that the positive rate of survivin gene in 37 leukemia patients was 67.6% (25/37) and significantly higher than that in normal control (20.0%). The expression level was higher in ALL cells than that in AML cells (73.3% vs 63.6%). Moreover, three kinds of leukemia cell lines all expressed survivin. After treating with the proper concentration of GM-CSF for 2 days, the expression of survivin obviously increased and the expression level of survivin mRNA was up-regulated by 26%, the expression level of survivin protein was up-regulated by 49%. It is concluded that the survivin gene extensively express in leukemia and its cell lines, and its expression can be obviously increased by GM-CSF.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Granulocyte-Macrophage Colony-Stimulating Factor , Pharmacology , HL-60 Cells , Inhibitor of Apoptosis Proteins , K562 Cells , Leukemia, Myeloid, Acute , Metabolism , Microtubule-Associated Proteins , Genetics , Neoplasm Proteins , Genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Metabolism , U937 CellsABSTRACT
Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, expressed in the most human cancers but not in terminally differentiated adult tissues, so survivin may be a target for tumor therapy. In addition, some scholars found that survivin expression is associated with the resistance in chemotherapy. To explore the relationship between survivin and drug-resistance, the alteration of survivin mRNA and protein of HL-60 cells treated with daunomycin (DNR), mitoxantrone (MIT) and arsenic trioxide (As2O3) was investigated, the expressions of survivin mRNA and survivin protein were detected on the first and third day by RT-PCR and Western blot, respectively. The results showed that survivin mRNA levels all decreased after the first day of treatment with drugs. It was decreased by 10% in DNR group, 40% (P < 0.01) in MIT group, and 25% (P < 0.01) in As2O3 group in comparison with control cells. In the third day, the survivin mRNA treated with DNR was up-regulated by 20% (P < 0.05), compared with the first day, and MIT was up-regulated by 65% (P < 0.01), but As2O3 was still down-regulated by 32% (P < 0.01). In Western blot, survivin protein level increased 14% after treated with DNR for three days, compared with the control cells, and 11% in MIT, but decreased by 82% in As2O3. It is concluded that after treatment with chemotherapeutic drugs, the survivin level descended at first day and then ascended obviously. This phenomenon may be associated with the resistance in chemotherapy for leukemia. On the other hand, As2O3 shows a different mechanism that may play a significant role to reverse resistance.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Arsenicals , Pharmacology , Daunorubicin , Pharmacology , Drug Resistance, Neoplasm , HL-60 Cells , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins , Genetics , Mitoxantrone , Pharmacology , Neoplasm Proteins , Genetics , Oxides , Pharmacology , RNA, Messenger , GeneticsABSTRACT
The study was purposed to investigate the effect of phosphorylated-chk1 on cell cycle and apoptosis of human erythroleukemic cell line K562 and K562/A02, and to explore the mechanism of chk1 in regulation of drug-resistance of leukemia cells. After treatment with adrimycin for six hours, the cell cycle distribution was detected by flow cytometry; the Chk1mRNA expression was detected by RT-PCR and the Chk1 phosphorylation level was detected by Western blot. Under the condition of down-regulation of Chk1mRNA expression in cells transfected with Chk1 short hairpin RNA, the cell apoptosis rates were detected by flow-cytometry following adrimycin. The results indicated that the proportion of K562/A02 cell line in G2/M phase was (54.12 +/- 0.57)% at 6 hours after drug treatment, significantly higher than that of K562 cell line (36.99 +/- 1.28)%. No evident difference of the Chk1mRNA expression was observed between K562 and K562/A02 cell lines, while elevated Chk1 phosphorylation following DNA damage induced by adriamycin was observed in the K562/A02 cell line (0.79 +/- 0.56), significantly higher than that in K562 cell line (0.27 +/- 1.47). The cell apoptosis rate of the Chk1 shRNA group in K562/A02 cell line was 3.84-fold of blank vector group, but that in K562 cell line was 1.30-fold of blank vector group. It is concluded that the increased chk1 activity that delay the progress of cell cycle are associated with cellular resistance to adrimycin in the K562/A02 cell line.
Subject(s)
Humans , Apoptosis , Physiology , Checkpoint Kinase 1 , Doxorubicin , Pharmacology , Drug Resistance, Neoplasm , Genetics , G2 Phase , K562 Cells , Mitosis , Phosphorylation , Protein Kinases , Genetics , Metabolism , RNA Interference , RNA, Messenger , Genetics , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To explore factors affecting occupational adaptability in nurses for offering basis to increase their occupational adaptability.</p><p><b>METHODS</b>Five hundred and forty-five nurses were investigated with work ability index questionnaire and occupational stress instruments.</p><p><b>RESULTS</b>There were many risk factors affecting occupational adaptability in nurses. The main variables that influenced occupational adaptability included work-overtime, mental load, social support, physical environment, and job hazards. The social support was the factor increasing the occupational adaptability of the nurses (P < 0.01, OR = 0.912). Five factors including work overtime, mental load, social support, physical environment and job hazards were introduced in the Logistic equation. The established functions were: Logit (P) = -11.357 + 1.011x(1) + 0.335x(2) - 0.076x(3) + 0.260x(4) + 0.129x(5).</p><p><b>CONCLUSION</b>There are many risk factors affecting occupational adaptability in nurses. Relevant measures should be taken to promote the occupational adaptability in nurses to reduce the risk factors.</p>
Subject(s)
Adolescent , Adult , Humans , Middle Aged , Adaptation, Psychological , Logistic Models , Nurses , Psychology , Occupational Health , Risk Factors , Social Support , Stress, Psychological , Epidemiology , Surveys and Questionnaires , Workload , PsychologyABSTRACT
To investigate apoptosis of mouse leukemia cell (WEHI-3) induced by econazole and its mechanism, apoptosis induced by econazole was examined by flow cytometry, while free calcium ([Ca(2+)]i) was determined by Fura-2 fluorescein load technique. The protein was isolated from endoplasmic reticulum of WEHI-3 cells, and then the expression of caspase-12 and caspase-7 was evaluated by Western blot. The results showed that WEHI-3 exhibited typical change of apoptosis when it was treated by econazole, [Ca(2+)]i was significantly higher in comparison with the control. The expression of caspase-12 and caspase-7 enhanced as the econazole concentration increased. In conclusion, econazole can induce WEHI-3 cell apoptosis and the caspase-12 plays a key role in this process.