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Objective To explore the signaling pathway of apoptosis induced by Paclitaxel (PTX) in leukemia cells and the chemosensitizing effect of adding short hairpin RNA(shRNA) on PTX,which targets the silencer of death domains(SODD).Methods After being treated with PTX,the expressions of SODD,B-cell lymphoma/leukemia-2 (Bcl-2),nuclear factor kappa B (NF-κB) and Caspase-3 proteins in Jurkat cells were determined by Western blot ;the shRNA-SODD vectors were constructed and transfected into Jurkat cells by electroporation,and then G418 was used to select the stable tranfected cell line expressing the shRNA-SODD recombinant plasmids.The incidence of cell apoptosis induced by PTX was determined by flow cytometry labeled with propidium iodide.Results During the process of inducing apoptosis of Jurkat cells,PTX could significantly down-regulate the expressions of SODD and Bcl-2 proteins,degrade Caspase-3 and activate NF-κB.The apoptotic sensibility of Jurkat cells transfected with shRNA-SODD to PTX was significantly increased compared with the control group,and the difference was statistically significant (F =10.35,P ＜ 0.05).Conclusions PTX can effectively induce apoptosis of Jurkat cells.Perhaps,SODD/Bcl-2 represents a specific apoptotic signaling pathway of PTX in leukemia cells and this apoptotic signaling pathway is Caspase-3-dependent,in which the function of NF-κB is to modulate the correlative apoptotic factors.Inhibiting the expression of SODD through transfecting shRNA-SODD vectors can significantly increase the apoptotic sensibility of leukemia cells to PTX.
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Objective To observe the efficacy of autologous hematopoietic stem cell transplantation (auto-AHSCT) in treatment of malignant hemopathy. Methods A retrospective study was accomplished on the auto-AHSCT in the treatment of 28 patients with malignant hemopathy from Oct 1994 to May 2009. The median age of the patients was 30 (16-45) years. Among the 28 patients,19 cases were acute myelocytic leukemia (AML),4 cases were acute lymphoblastic leukemia (ALL) and 5 cases were malignant lymphoma (ML). Mobilization of peripheral blood stem cell was recieved by giving granulocyte colony-stimulating factor (G-CSF) 5-10 μg/kg. The patients were pretreated with melphalan (140-160 mg/m2),cyclophosphamide (120 mg/kg) and arabinosylcytosin (2 g/m2). Results Transplant-related side effects was less and the hematologic recovery of most patients(26 cases) was quite rapid. The days to stable neutrophil count of 0.5×109/L and platelet count of 20×109/L were 12(8-38) d and 14(9-128) d,respectively. The median followup duration was 36(7-68) months. 19 cases (68 %) achieved disease-free survival(DFS) and 9 cases (32 %)died in three years. Of the 9 death patients,7 cases (25 %) died of recurrence and 2 cases (7 %) died of posttransplant complications. Conclusion AHSCT is a safe and effective therapy method for malignant hemopathy.
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Objective To evaluate the efficacy and toxicity for the protocol of low-dose harringtonine and cytarabine(HA regimen)in combination with granulocyte colony-stimulating factor(G-CSF)in elderly patients with acute myelogenous leukemia(AML).Methods Thirty-five AML patients were treated with HAG including low-dose chieved PR.The overall response rate was 83%.5 of 35(14%)was non-remiasion.Two patients died in the duration of treatment.The main complication of chemotherapy is myelosuppresion.Conclusion Low-dose HA regimen in combination with G-CSF is effective and safe in elderly patients with AML.
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Objective To inwst the antagonistic effect of thrombopoietin on adriamycin induced myocardium injury in rats and explore the mechanism.Methods 32 Wistar rats were randomized into four groups(n=8):Control group,ADM group,ADM+TPOL group and ADM+TPOH group.All agents were given by intraperitoneal injection.The control group was given saline.While the other three groups were given adriamycin at the dosage of20mg/kg.TPO group were injected TPO at the dosages of 10μg/kg or 30μg/kg three times on alternale days.ELISA was used to detect the concentration of CK-MB and cTnI in the serum of rats.The change of cardiocyte ultrastructure was observed by the electron microscope,and pathological change Was observed by immunohistochemistry staining.The expression level of 8- hydroxy-2'-deoxyguanosin(8-OHdG)produced by DNA oxidative damage in myocard tissue were detected.IPP6.0 software was used to detect IOD and calculate the 8-OHdG index.Results The energy of CK-MB and cTNI of TPO group was obviously lower than that in ADM group(P<0.01).The ultragtrueture of cardiocyte in the ADM group Wag damaged more severely than that in TPO group.Pathological Score,IOD and 8-OHdG index of TPO groups were lower than ADM group(P<0.05).These indexes had no significant statistics difference between ADM+TPOL group and ADM+TPOH group.Conclusions TPO can provide heart protection by antagonizing oxidative damage of myocardial cell induced by edriamycin.
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Objective To observe the protection effect of thrombopoietin on adriamycin-inducod acute myocardium injury in rats model.Methods 32 Wistar rats were randomized into four groups (n=8):Control group,ADM group,ADM +TPOL group and ADM +TPOH group.All agents were given by intraperitoneal injection.The control group was given normal saline,while the other three groups were given adriamycin at the dosage of 20 mg/kg once.TPO groups were injected TPO at different dosages of 10 μg/kg or 30 μg/kg three times on alternate days.ELISA was used to detect CK-MB and cTnI content of serum in the rats.By HE staining,pathological change was found and grade of tissue morphology was scored.The ultrastructure change of cadiocyte was observed by the electron microscope.Results The energy of CK-MB (14.65±1.91,14.21±1.70) and cTNI (9.66±1.31,10.07±1.20) in TPO groups were obviously lower than that of the ADM group(19.58±3.49,12.50±1.62) (P<0.05),respectively.Pathological score of ADM group was higher than TPO groups (P<0.01).The ultrastructure of myecard tissue in the ADM group was damaged more severely than TPO groups.Above-mentioned indexes were with no significant difference between ADM+TPOL group and ADM+TPOH group.Conclusion TPO can protect the heart which was injured by the ADM.
ABSTRACT
Adriamycin is an effective and broad-spectrum anthracycline antineoplastic agent.However,long-term therapy with adriamycin is associated with a high incidence of cumulative and irreversible cardiomyopathy. Mechanisms about adriamycin-induced cardiotoxieity are complicated, including oxidative stress,mitochondrionopathy,cardiac apoptosis,and so on.For the past few years,a series of measures aye used,which attenuate the cardiotoxicity and uninfluence the antitumor effects.The review focuses on the mechanism and prevention of adriamycin-induced cardiotoxicity in order to improve the long term survival rate of neoplastic patient.