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Objective To observe the clinical features and therapeutic effect of 11p15/NUP98 rearrange-ments in acute leukemia. Methods A total of 598 newly diagnosed acute leukemia patients were detected by con-ventional cytogenetics analysis and fluorescence in situ hybridization(FISH)with the NUP98 double color probe, and the clinical data were analyzed retrospectively in the patients with 11p15/NUP98 abnormality. Results Six cases with 11p15/NUP98 rearrangement were found with a median age of 39 years old,one patient is male,the oth-ers are females. Three patients had acute monocytic leukemia(M5),one patient had acute monocytic leukemia (M2),one patient had acute monocytic leukemia(M4),and one patient had acute lymphoblastic leukemia. 11p15/NUP98 abnormality was detectable in all the patients. The median survival in all the patients was 9 months. Con-clusions Acute leukaemia with 11p15 abnormality frequently involves NUP98 gene and mainly occurrs in women. Patients with lower median age mainly developed in acute monocytic leukemia. The major clinical manifestations are anemia,low platelets and hyperleukocytosis. Acute leukemia with 11p15/NUP98 rearrangement is poorly re-sponsive to routine chemotherapies and to allogeneic hematopoietic stem cell transplantation,and thus has poor prognosis.
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AIM: To demonstrate the effects of telmisartan on the proliferation and apoptosis of U937 cells.METHODS: The proliferation ability of the U937 cells was assessed by CCK-8 assay and colony formation test with methylcellulose.The CD11b expression rate of the U937 cells was identified by flow cytometry.The apoptotic rate was analyzed by flow cytometry with Annexin V-PI double staining and Hoechst 33342 staining.The protein levels of cleaved PARP and cleaved caspase-3 were determined by Western blot.RESULTS: The results of CCK-8 assay confirmed that the viability of U937 cells was inhibited by telmisartan.The colony formation capacity of U937 cells was also significantly inhibited by telmisartan.The differentiation of U937 cells was induced by telmisartan with the expression of CD11b.The results of flow cytometry analysis with Annexin V-PI double staining and Hoechst 33342 staining identified that the apoptosis of U937 cells was induced by telmisartan in dose-dependent and time-dependent manners with the up-regulation of cleaved PARP and cleaved caspase-3 proteins.CONCLUSION: Telmisartan inhibits the proliferation and induces the differentiation of U937 cells.Telmisartan also induces the apoptosis of U937 cells through the caspase pathway.
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[Objective] To investigate the clinical characteristics and blood transfusion status of patients of liver cirrhosis and analyze its rationality.[Methods] We designed questionnaires to collect the data of patients admitted with liver cirrhosis including clinical features,blood transfusion,smoking,drinking and other living habits.We follow up the patients and analyze the blood transfusion rationality.[Results] Data on 198 patients was collected.34.8％ (69/198) of all patients were transfused at least one blood component.Total blood transfusion was 371 times,of which 52.2％ of the blood transfusion cases (36/69) were transfused with two or more blood during hospitalization.Among the 69 cases of blood transfusion,11 cases were treated with the first blood transfusion for the purpose of treatment and 58 cases for prevention.18 of those cases were infused with red blood cells of 90.5 units.54.55 ％ (60/110) and 60.91％ (67/110) of patients who had a pre-transfusion INR＞1.3 did not receive plasma.2.27％ (2/88) of patients who had a pre-transfusion INR≤1.3 received plasma.29.41％ (5/17)who had a pre-transfusion fib≤1.0 received cryoprecipitate.3.87％(7/181) who had a pre-transfusion fib＞1.0 received cryoprecipitate.[Conclusions] Blood transfusion is common in patients with liver cirrhosis.Empirical and preventive blood transfusion is common also.We should take a more scientific restrictive blood transfusion strategy.
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[ ABSTRACT] AIM:To study the antiproliferation and proapoptotic effects of zoledronic acid ( ZOL) on human a-cute myeloid leukemia cell line U937.METHODS:The viability of U937 cells was detected by CCK-8 assay.The cell cy-cle of the U937 cells was analyzed by flow cytometry with PI staining.Apoptotic rate was assessed by flow cytometry with Annexin V-PI and Hoechst 33342 staining.Mitochondrial membrane potential was detected by JC-1 assay.Methylcellulose was used to assess colony formation.The protein levels of p21, Bcl-2 and Bax were determined by Western blot.RE-SULTS:ZOL inhibited the viability of U937 cells.ZOL induced S-phase cell cycle arrest in the U937 cells.The results of flow cytometry analysis with Annexin V-PI and Hoechst 33342 staining showed that ZOL also induced apoptosis in a dose-and time-dependent manner.Mitochondrial membrane potential assay was also used to verify the apoptosis.The apoptotic rate was consistent with the reduction of mitochondrial membrane potential.Colony formation assay showed that ZOL signifi-cantly inhibited the colony formation capacity of the U937 cells.This was achieved by the induction of S-phase cell cycle arrest, and up-regulation of Bax and p21, and down-regulation of Bcl-2.CONCLUSION:ZOL inhibits cell proliferation by regulating the expression of cell cycle-related protein, and induces apoptosis via the mitochondrial apoptotic pathway.
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Objective To evaluate the clinical efficacy and safety of umbilical cord-derived mesenchymal stem cell (MSC ) treatment of refractory chronic graft-versus-host disease (cGVHD ) after allogene hematopoietic stem cell transplantation. Methods Seven patients developed with cGVHD following allogene hematopoietic stem cell transplantation. Conventional immunosuppressive agent treatment yielded no efficacy. Based upon immunosuppressive agent therapy,umbilical cord-derived MSC treatment was supplemented with a cell density of 1 ×1 06/kg,once a week for consecutive 4 times. Clinical efficacy,safety and survival of the patients were observed. Results Among 7 patients receiving MSC injection,2 obtained complete response (CR)and 3 had partial response (PR)with an overall response rate of 5/7,and the remaining 2 cases achieved no response (NR). No adverse reactions were induced by MSC injection. No patient had primary disease recurrence. One patient developed secondary cytomegalovirus pneumonia after PR and died from severe pneumonia. The remaining patients survived. Conclusions Umbilical cord-derived MSC injection is an efficacious and safe therapy of cGVHD.
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AIM:To investigate the expression of aplasia rashomolog member I ( ARHI) gene in acute myeloid leukemia cells (AML) and to study the effects of ARHI on the growth of AML cell line U937.METHODS:The mRNA ex-pression of ARHI in AML cells, 293FT cells, AML primary cells and healthy volunteer blood cells were detected by RT-PCR.After transfection with the MSCV-IRES-GFP-ARHI plasmid to the U937 cells, the growth curve was analyzed by MTT assay.U937 cells were re-suspended by fresh medium and cultured for 24 h, then the cell cycle distribution and ap-optotic rate were determined.RESULTS:The mRNA of ARHI was positively detectable in 293FT cells and healthy volun-teer blood cells instead of AML cell line and AML primary cells.The growth curve showed that cell viability in U937 cells with high expression of ARHI (U937-ARHI) was lower than that in the control cells (U937-GFP) on 6th~8th day.The ratio of G2/M phase and apoptotic rate in the U937-ARHI cells were increased compare with control group ( P<0.05 ) . CONCLUSION:The mRNA level of ARHI is low in AML cells.High expression of ARHI gene in U937 cells inhibits cell growth, arrests the cells at G2/M phase and induces apoptosis.
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Objective To investigate the effect of unrelated cord blood transplantation (UCBT)on the treatment of high-risk childhood and adult acute leukemia.Methods Ten patients with high-risk acute leukemia underwent UCBT.Among the 1 0 patients,3 were children and 7 were adults with the median age of 29 years old (1 1 -41 years old).Six patients underwent one-unit cord blood transplantation and four patients underwent two-unit cord blood transplantation.The myeloablative conditioning regimen without antithymocyte globulin (ATG)was adopted.Cytarabine (Ara-C),fludarabine (Flu)or total body irradiation (TBI)was added on the basis of busulfan (Bu)and cyclophosphamide (Cy).Ciclosporin and mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).Results The transplantation was successful in 8 (80%) patients.The median implant-time of leukocytes was 1 9 d(1 4-25 d)and that of platelets was 40 d(33-60 d).Three patients developed acute GVHD and no patient developed chronic GVHD.The median follow-up time was 24 months (1 -29 months).Seven patients remained in disease-free survival.Both the 2-year overall survival and disease-free survival rates were 66.7%.Conclusions UCBT is feasible in the treatment of high-risk acute leukemia.UCBT is the preferred option for the high-risk patients without HLA-identical sibling donors,which is characterized by low incidence of GVHD and low recurrence rate.It may make patients with acute leukemia remain long-term survival.
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BACKGROUND:Because of their immunological properties, bone marrow mesenchymal stem cells transfusion is developed as a new treatment for refractory graft-versus-host disease. OBJECTIVE:To analyze the safety and curative effect of bone marrow mesenchymal stem cells transfusion on treating different organ damages in graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation. METHODS:Eight patients with malignant hematologic disease were included in this study. The patients developed severe steroid-resistant graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation and received transfusion of mesenchymal stme cell(1×106 of immunosuppressive agent. RESULTS AND CONCLUSION:For the total y eight patients, six got response (two cases of complete remission, and four cases of partial remission) and two showed no remission. Four of five cutaneous damages were ameliorated and one showed no effect. For three cases of oral graft-versus-host disease, two acquired complete remission and one showed partial remission. Two cases of liver graft-versus-host disease and two cases of astro-intestinal graft-versus-host disease obtained complete remission. No response was displayed to three cases of ocular graft-versus-host disease, one case of bronchiolitis obliterans, and one case of urinary graft-versus-host disease. In the median fol ow-up of 28 months (7-62 months), three patients developed posttransplant lymphoproliferative disorders within 3 months after mesenchymal stem cells transfusion. Administration of mesenchymal stem cells is safe for treatment of severe graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation. Mesenchymal stem cells transfusion may be a promising/kg) together with the primary therapy therapy for refractory cutaneous , astro-intestinal, liver and oral graft-versus-host disease but not for pulmonary, ocular and urinary graft-versus-host disease. Whether mesenchymal stem cells transfusion is associated with posttransplant lymphoproliferative disorders needs more case data.
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AIM: To investigate the effect of c-Myc inhibitor 10058-F4 on human chronic myeloid leukemia ( CML) K562 cells and imatinib-resistant K562/G cells.METHODS: The protein expression of c-Myc was detected by Western blotting .Cell proliferation was evaluated by MTT assay and colony formation assay .PI staining was used to deter-mine the cell cycle distribution .Annexin V-PI staining was applied for apoptosis detection .RESULTS:Imatinib-resistant K562/G cells displayed lower sensitivity to imatinib than K 562 cells with high expression of c-Myc.Treatment with specific c-Myc inhibitor 10058-F4 inhibited the cell proliferation in a dose-and time-dependent manner , and K562/G displayed more sensitivity to 10058-F4 than K562 cells.10058-F4 also induced cell cycle arrest in G 0/G1 phase and induced apoptot-ic cell death in the 2 cells.Importantly, 10058-F4 suppressed the colony formation ability in K 562 and K562/G cells. CONCLUSION:c-Myc is a novel target to overcome imatinib-induced drug resistance , and c-Myc inhibitor provides a new approach in CML therapy .
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BACKGROUND: Al ogeneic hematopoietic stem cel transplantation is the main method to cure leukemia, but the patients receiving al ogeneic hematopoietic stem cel transplantation stil have to face the risk of recurrence. Myeloid sarcoma is a rare extramedul ary relapse mode with worse clinical outcomes, so it is necessary to understand the characteristics of myeloid sarcoma and relative treatment methods. OBJECTIVE: To analyze the clinical characteristics and treatment methods of myeliod sarcomas in cardio-phrenic angle after al ogeneic peripheral blood stem cel transplantation. METHODS: One case was diagnosed as single myeloid sacoma in the cardio-phrenic angle after al ogeneic peripheral blood stem cel transplantation. The patient underwent surgical resection of the mass, chemotherapy and radiotherapy. The clinical effect, complications and survival situation were observed. RESULTS AND CONCLUSION: The patient suffered from bacteremia, fungal pneumonia and even life-threatening sepsis shock during two courses chemotherapies. Then, the patient received radiotherapy for mediastinum and the myeloid sacoma never relapsed. However, the patient suffered central nervous system leukemia after free of the disease for 25 months. Myeliod sarcoma after al ogeneic hematopoietic stem cel transplantation is rare and its manifestation is changeful. The diagnosis mainly depends on histopathology and immunohistochemistry. Surgery, chemotherapy, radiotherapy, second transplantation and molecular targeted drugs are the choices of treatment strategy. However, the optimal treatment strategy for individual patients remains to be determined.
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<p><b>OBJECTIVE</b>To investigate the apoptosis inducing effects of ponicidin (PON) on leukemic K562 cells and its mechanisms of action.</p><p><b>METHOD</b>K562 cells in culture medium in vitro were given different concentrations of PON (10-50 micromol x L(-1)) for 24, 48 and 72 h. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rates were detected by flow cytometry (FCM) using Annexin V staining after K562 cells were treated with different concentrations of PON for 72 hours, and cell morphology was observed by Wright-Giemsa staining. Western blot was used to detect caspase-3 and poly(ADP-ribose) polymerase (PARP) expression, and the protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) as well as p-AKT and p-P85 in PI3K/AKT signaling pathways were also detected.</p><p><b>RESULT</b>PON (over 30 micromol x L(-1)) could inhibit the growth of K562 cells in both time- and dose-dependent manner. FCM analysis revealed that apoptotic cells were gradually increased in a dose-dependent manner after treatment for 72 hours, and that marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Wright-Giemsa staining after treatment by 50 micromol x L(-1) PON. Western blot showed cleavage of the caspase-3 zymogen protein (32 kD), with the appearance of its 17 kD subunit, and a cleaved 89 kD fragment of 116 kD PARP was also found. Furthermore, Western blotting also showed that expression of p-AKT and p-P85 in PI3K/AKT signaling pathways was downregulated dramatically whereas the expression of p-P38 as well as p-ERK and p-JNK remained unchanged after the cells were treated by PON for 48 h.</p><p><b>CONCLUSION</b>The results demonstrate that PON exhibits in vitro anti-leukemia effect by induction of apoptosis in K562 cells, and that PON induced apoptosis in K562 cells mainly related to activation of caspase-3 as well as inactivation of PI3K/AKT signaling pathway via down regulation of the expression of p-AKT and p-P85 protein levels. These results provide strong laboratory evidence for further anti-leukemia trials of PON.</p>
Тема - темы
Humans , Apoptosis , Blotting, Western , Caspase 3 , Metabolism , Cell Line, Tumor , Diterpenes , Pharmacology , Poly(ADP-ribose) Polymerases , Metabolism , Signal TransductionРеферат
AIM: To detect the protein expression of TIMP3 and RUNX3 in bone marrow mononuclear cells (BMMCs) from acute leukemia (AL) patients and to investigate the relationship between the methylation status of genes and their expressional levels. METHODS: Protein expression of TIMP3 and RUNX3 in 50 samples of BMMCs and 10 samples of peripheral blood mononuclear cells (PBMCs) from healthy volunteers was detected by Western blotting. The prognostic factors related to AL and data from methylation specific polymerase chain reaction were also analyzed. RESULTS: The expression level of RUNX3 with methylation was less than that without methylation in BMMCs from AL patients. The complete remission (CR) rate was related to RUNX3 expression and blasts in bone marrow (BM). BMMCs from patients with silencing of RUNX3 and higher blasts in BM had a lower CR rate. CONCLUSION: Absence of RUNX3 protein expression resulting from methylation of RUNX3 promoter probably plays a role in the pathogenesis of AL and is of value in prognosis. No relationship between methylation of TIMP3 promoter and the pathogenesis of AL is observed.
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Objective To investigate the apoptosis inducing effects of oridonin on leukemic THP-1 cells and its mechanisms of action. Methods THP-1 cells in culture medium in vitro were given different concentrations of oridonin (16～56 μmol/L) for 24, 48 and 72 h. The inhibitory rate of the cells were measured by MTT assay, apoptotic morphology was observed by Hoechst 33258 staining, and Annexin V/PI staining was used to detect cell apoptosis by flow cytometry (FCM). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression were detected by Western blotting. Results Oridonin (over 32 μmol/L) could inhibit the growth of THP-1 cells and cause apoptosis remarkably, the suppression was both in time-and dose-dependentmanner. Marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Hoechst 33258 staining, and Annexin V/PI staining showed that apoptotic cells gradually increased after the cells treated with oridinon. Western blotting showed cleavage of the caspase-3 zymogen protein (32×103), with the appearance of its 20×103 subunit, and a cleaved 89×103 fragment of 116×103 PARP was also found. Conclusion Oridonin can inhibit cell growth and induce apoptosis in THP-1 cells via activation of caspase-3. The results indicated that oridonin might be an important potential anti-leukemia reagent.
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Objective To investigate the apoptosis inducing effect of peroxisome proliferator-activated receptor r(PPARr)agomst on leukemic K562 cells and its mechanisms of action.Methods K562 cells in culture medium in vitro were given different concentrations of PPARragonist rosiglitazone(RGZ)(20-80 umol/L)for O,24,48 and 72h The inhibitory rate of the cells were measured by MTT assay,cell apoptosis was detected by Annexin V/PI staining,and the expression of P53 protein as well as the activity of caspase-3 were also detected.Results RGZ(over 40umoL/L)could inhibit the growth of K562 cells and cause apopto-sis remarkably,the suppression Was both in time-and dose-dependent manner.The expression of P53 pmtein was upregulated and the activity of caspase-3 Was increased concomitantly after the cells werle treated by RGZ.Conclusion PPARr agonist RGZ(over 40 umol/L)can induce apoptosis on K562 cells signifieantly,upregu-lation the expression of P53 protein as well as increasing caspase-3 activity may be one of its most important mechamisms.
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Objective To investigate the anti-proliferation effect of peroxisome proliferator-activated receptor γ(PPARγ)agonist troglitazone(TGZ)on leukemic Raji cells and its mechanisms.Methods Raji cells in culture medium in vitro were given different concentrations of TGZ(0～60 μmol/L)for 24,48 and 72 h.The inhibitory rates of the cells were measured by MTT assay,cell apoptotic rate was detected by flow cytometry(FCM),agarose gel electrophoresis was used to observe the DNA ladder,and western blotting was used to analyzed the variation of apoptosis related proteins bcl-2,Bax and Survivin.Results TGZ(over 20 μmol/L)could inhibit the growth of Raji cells and cause apoptosis remarkably,the suppression was both in time-and dose-dependent manner.DNA ladder was observed after the cells treated by TGZ for 72 h,and western blotting analysis revealed that anti-apoptotie proteins Survivin and bcl-2 were decreased remarkably while pro-apoptotic protein Bax increased significantly after the cells were treated by TGZ for 48 h.Conclusion PPARγ agonist TGZ can inhibit the growth and induce apoptosis on Raji cells significantly,downregnlating the expression of Survivin and bcl-2 as well as upregulating of Bax expression of Raji cells may be one of its most important mechanisms.
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Objective To investigate the mechanisms of oridonin inducing apoptosis on acute leukeamia NB4 cells and its mechanism. Methods NB4 cells in culture medium in vitro were given with different concentrations (8, 16, 24, and 32 μmol/L) of oridonin. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rate was detected by flow cytometry (FCM), morphology of apoptosis was observed by Hoechst 33258 fluorescence staining, DNA fragmentation was assayed by agarose gel electrophoresis, caspase-3 expression was detected by Western blotting, and caspase-3 activity was assayed with colorimetric assay kit before and after apoptosis occurred. Results Oridonin (over 16 μmol/L) could inhibit the growth of NB4 cells and cause apoptosis significantly, the suppression was both in a timeand dose-dependent manner. Marked changes of apoptosis including condensation of chromatin and nuclear fragmentation were observed very clearly by Hoechst 33258 fluorescence staining and a characteristic "ladder" of DNA fragments was elicited by agarose gel electrophoresis; Western blot analysis revealed that caspase-3 was activated by the loss of caspase-3 proenzyme (32 kDa) and the appearance of its 20 kDa subunit, and that along with the apoptotic process caspase-3 activity was increased concurrently. Conclusion Oridonin can induce apoptosis in NB4 cells via activation of caspase-3. These results will provide laboratory evidence for the clinical treatment of acute leukemia with oridonin.
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AIM: To investigate the effect of granulocyte colony stimulating factor (G-CSF) on arabinosyl cytosine (Ara-C)-induced apoptosis in HL-60 leukemia cells. METHODS: The proliferation of HL-60 leukemia cell was observed by hemopoietic cell culture. Apoptosis was measured by the morphology of apoptosis cell , the quantitation of DNA fragmentation with the diphenylamine reaction. The change in drug sensitivity was measured by “MTT”. RESULTS: G-CSF could stimulate the proliferation of HL-60 leukemia cell and colonies of cell increased to 76.5?18.0, compared to the control group (46.5?13.5. P
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AIM: To investigate the changes of the expression of Bcl-2 and Fas protein and the apoptosis in HL-60 cells induced by cyclosporine A. METHODS: The expression of Bcl-2 and Fas protein and apoptosis in (HL-60) cells were measured by immunohistochemistry analysis and flow cytometric analysis. RESULTS: There was strong expression of Bcl-2 in HL-60 cells, treatment with cyclosporine A (CsA) for 8-10 h down-regulated the expression of Bcl-2. Fas protein expression in HL-60 cells was very low, CsA induced apoptosis of HL-60 cells, but didn't induce Fas protein expression. CONCLUSION: CsA induces apoptosis in HL-60 cells by down-regulating Bcl-2 expression. [
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AIM:To investigate the anti-tumor effects of special cytotoxic T lymphocytes(CTLs)activated by dendritic cells(DCs)loaded with antigens and CD40L in vitro.METHODS:Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation from normal human heparinized blood.The adherent cells were cultured with granulocyte-macrophage colony stimulating factor(GM-CSF),interleukin-4(IL-4),alpha tumor necrosis factor(TNF-?),DCs were co-cultured with frozen-thawed antigen of K562 cells and CD40L,then triggered T cells into specific CTLs.RESULTS:Most suspended cells exhibited distinctive morphological features of DCs which expressed CD40 96%,CD86 97%,CD80 77%,CD1a 69%,and gained the powerful capacity to stimulate proliferation of allogenic lymphocytes.Under the effector∶target ratio of 20∶1,CTLs derived from cultures with DCs and frozen-thawed antigen of K562 cells were showed 71.3% cytotoxicities against K562 cells.CTLs derived from cultures with DCs loaded with frozen-thawed antigen and CD40L were showed 86.9% cytotoxicities against K562 cells.Cytotoxicities by CTLs derived from cultures with unloaded DCs against K562 cells were 37.6% and cytotoxicities by monocytes were 21.1%.Cytotoxicities by CTLs derived from experiment groups were stronger than control groups(P
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AIM: To study the effects of WT1 peptide-loaded dendritic cells (DC) stimulating the cytotoxic T lymphocytes (CTL) on K562 cells in vitro. METHODS: DC were generated from normal human peripheral blood mononuclear cells (PBMC) in the presence of granulocyte-macrophage colony stimulating factor(GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-?) , DC were cultured with WT1 peptides , and then triggered T cells into specific CTL. RESULTS: Most suspended cells exhibited distinctive morphological features of DCs and they stimulated proliferation of allogenic lymphocytes. Under the effector : target ratio of ~20∶1 , CTLs derived from cultures with DC and WT1 peptides were showed 86.1%?26.8% cytotoxicity against K562 cells, cytotoxicity by CTLs derived from cultures with unloaded DC against K562 cells were 47.1%?20.8% and cytotoxicity by lymphocytes were 27.7%?15.3%. Cytotoxicity by CTLs derived from culture with WT1 peptides-loaded DC were the strongest among three groups (P