Therapeutic Efficacy of VICP+L-ASP/TKI on Adult Patients with B-ALL / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy of VICP+L-ASP/TKI on adult patients with B-ALL and to explore the influence factors.</p><p><b>METHODS</b>Forty-one adult B-ALL patients treated with VICP+L-ASP/TKI from August 2008 to June 2014 were following-up. The complete remission(CR) rate, toxicity, overall survival(OS) and event free survival(EFS) after induction treatment were analyzed, the therapeutic outcome of patients between different risk stratification subgroups was compared, the influence of standardized consolidatory and maintaining treatment as well as allogeneic hematopoietic stem cell transplantation(allo-HSCT) on survival time was analyzed.</p><p><b>RESULTS</b>The early death not occurred in 41 patients with B-ALL including 37 cases with CR; the CR rate of 1 course treatment was 90.2%. The follow-up time lasted to March 17, 2015, the median follow-up time was 25(9-79) months; the 1 year OS rate was 75.3%, the EFS rate was 58.3%. Analysis of risk factors showed that the initial WBC count over 30×10/L, LDH over 250 U/L and minimal residual disease(MRD) over 10after treatment were poor prognostic factors. After remission, the standardized consolidatory treatment or allo-HSCT according to the "2012 China adult ALL diagnosis and treatment expert consensus" could improve long-term survival, 3 years OS rate was 73.8% and 61.5% respectively, 3 years EFS were 63.5% and 65.7% respectively. The main toxic and side effects were hematologic reactions, the hematologic adverse reaction of IV grade was observed in 97.6%(40/41) during induction treatment.</p><p><b>CONCLUSION</b>Induction chemotherapy based on VICP+L-ASP/TKI and standardized consolidatory after remission according to the "2012 China adult acute lymphoblastic leukemia diagnosis and treatment expert consensus" can improve the therapeutic efficacy. The allo-HSCT should be actively performed for B-ALL paients with high risk(elevated initial WBC count and LDH level); at some time, the regularly monitoring MRD and adjusting therapeutic protocol according to monitoring result can promote the prognosis of adult B-ALL patients.</p>

Matrine and CYC116 synergistically inhibit growth and induce apoptosis in multiple myeloma cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.</p><p><b>METHODS</b>The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.</p><p><b>RESULTS</b>Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).</p><p><b>CONCLUSION</b>CYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.</p>

Apoptosis of acute myeloid leukemia HL-60 cells induced by CDK inhibitor SNS-032 and its molecular mechanisms / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of cycle-dependent kinase (CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia (AML) HL-60 cells and its molecular mechanisms.</p><p><b>METHODS</b>Cultured AML HL-60 cells were treated with various concentrations of SNS-032. Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK2/STAT3 pathway were detected by Western blotting.</p><p><b>RESULTS</b>Apoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9±1.7)%, (12.1±3.1)% and (59.4±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032. MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378c were down-regulated by SNS-032,whereas the levels of miR-320a and miR-H7* were up-regulated. Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT3 and protein expression of JAK2,C-MYC and MCL-1.</p><p><b>CONCLUSION</b>CDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family.</p>

Imatinib mesylate for chronic myeloid leukemia: in patients with initial treatment versus those with Recombinant Human IFN-α2b treatment failure / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the efficacy of imatinib mesylate (IM) for patients with newly diagnosed chronic myeloid leukemia (CML) and patients after failure of Recombinant Human interferon-α2b (IFN-α2b) therapy.</p><p><b>METHODS</b>A total of 86 patients with CML in chronic-phase, including 61 newly diagnosed cases and 25 cases of IFN-α2b failure, who received IM at 400 mg daily were retrospectively analyzed. Conventional cytogenetic analysis of R-banding was used to detect chromosome abnormalities and real-time PCR was used to detect BCR-ABL fusion gene.</p><p><b>RESULTS</b>81.9% of newly diagnosed patients and 36.0% of IFN-α2b failure patients achieved partial cytogenetic response (PCyR) by 6 months. In addition, 86.9% of newly diagnosed patients and 68.0% of IFN-α2b failure patients achieved complete cytogenetic response (CCyR) in 24 months. There was significant difference between two groups (P<0.001). The median time achieved CCyR in newly diagnosed group and IFN-α2b failure group were 6 months and 15 months, respectively. Compared with newly diagnosed group, IFN-α2b failure group showed lower rate of complete molecular remission (CMR) (70.4% vs 40.0%, P=0.033). There are 14 patients (22.9%) in newly diagnosed patients with cytogenetic resistance, among whom 4 with primary cytogenetic resistance; while there were 14 patients (56.0%) in IFN-α2b failure group with cytogenetic resistance, all of whom with primary resistance.</p><p><b>CONCLUSION</b>Compared with newly diagnosed patients, CML patients after failure of IFN-α2b therapy have a high rate of primary cytogenetic resistance and low response rate to IM.</p>

Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To clarify the effects and mechanisms of homoharringtonine (HHT) monomer therapy or combination therapy with arsenic trioxide (ATO) on human multiple myeloma (MM) cell line RPMI 8226 in in vitro researches.</p><p><b>METHODS</b>Effects of HHT, ATO, and HHT combined ATO on the growth of MM cell line RPMI 8226 were detected using MTT assay. The morphological changes of cell apoptosis were detected by Hoechst staining. The early apoptosis rate was detected using flow cytometry. Expressions of Caspase-3, Caspase-9, poly-ADP-ribose polymerase (PARP), Bcl-2, Mcl-1, Bcl-xl, and AKT protein were detected by Western blot.</p><p><b>RESULTS</b>HHT and ATO inhibited the proliferation of RPM1 8226 cell line in a time- and dose-dependent manner (P < 0.05). Synergistic effects was shown in the combination group (Cl < 1). HHT and ATO induced the apoptosis of RPMI 8226 in a dose-dependent manner with typical morphological changes of apoptosis and higher early stage apoptosis rate. The enhancement in apoptotic induction was seen when two agents were combined. HHT activated expressions of Caspase-3 and PARP in a dose dependent manner at 24 h. HHT at 40 ng/mL and ATO at 8.5 micromol/L could significantly activate expressions of Caspase-3 and Caspase-9, and down-regulate expressions of anti-apoptotic proteins Bcl-xl and Mcl-1. In addition, the combination therapy of HHT at 40 ng/mL and ATO at 8.5 micromol/L inhibited phosphorylation of AKT in a time-dependent manner.</p><p><b>CONCLUSION</b>HTT, ATO, and combination therapy of HHT and ATO induced the apoptosis of RPMI 8226 cell line possibly through activating Caspase pathways, regulating expressions of Bcl-2 families, and inhibiting phosphorylation of AKT.</p>

Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.</p><p><b>RESULTS</b>The overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.</p><p><b>CONCLUSION</b>The HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.</p>

Synergistic effect of histone deacetylase inhibitor suberoylanilide hydroxamic acid with imatinib on K562 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.</p><p><b>METHODS</b>K562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.</p><p><b>RESULTS</b>SAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.</p><p><b>CONCLUSION</b>Combining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.</p>

Killing effect of aurora kinase inhibitor ENMD-2076 on acute myelogenous leukemia cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of aurora kinase inhibitor ENMD-2076 on human acute myelogenous leukemia (AML) cell lines.</p><p><b>METHODS</b>AML THP-1 and Kasumi-1 cells were treated with ENMD-2076 for 24 h and 48 h,respectively. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit. Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.</p><p><b>RESULTS</b>ENMD-2076 significantly induced growth arrest and apoptosis in THP-1 and Kasumi-1 cells. Enhanced apoptosis was observed in ENMD-2076 group evidenced by strong activation of Caspase-9,Caspase-3 and PARP. Furthermore,the ENMD-2076 treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,up-regulated expression of pro-apoptotic protein Bak,Bad and Bax was detected after ENMD-2076 treatment.</p><p><b>CONCLUSION</b>ENMD-2076 can kill effectively AML cells by inhibiting cell growth and inducing apoptosis,which is associated with activation of Caspase pathway and regulation of pro-apoptotic and anti-apoptotic proteins.</p>

Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.</p><p><b>METHODS</b>The phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS). The effect of HHT on leukemia stem-like cells with immunophenotype of CD34(+)CD38(-)CD96(+) was detected with FACS. Cell growth was measured by MTT assay. Activation of Caspase pathway and expression of apoptosis-related regulator proteins were examined by Western blotting.</p><p><b>RESULTS</b>FACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34(+)CD38(-)CD96(+), while 26.7% on Kasumi-1 cells expressed this marker. In contrast,U937 cells showed CD96 negative. HHT significantly inhibited cell growth of KG-1 cells with an IC(50) of 16.9 ng/ml at 48 h. The ratio of CD34(+)CD38(-)CD96(+) cells decreased from 63.6% to 17.1% after HHT treatment. Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphorylated-Akt.</p><p><b>CONCLUSION</b>HHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphorylated-Akt.</p>

Antitumor activity of histone deacetylase inhibitor suberic bishydroxamate on acute myeloid leukemia cell lines / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of histone deacetylase inhibitor suberic bishydroxamate (SBHA) on human acute myeloid leukemia (AML) cell lines.</p><p><b>METHODS</b>AML U937, KG-1 and Kasumi-1 cells were treated with SBHA. Cell growth was measured by MTT assay. Apoptosis was determined using flow cytometry. Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.</p><p><b>RESULTS</b>SBHA significantly induced growth arrest and apoptosis in U937, KG-1 and Kasumi-1 cells. Enhanced apoptosis was observed in SHBA group evidenced by strong activation of Caspase-9, Caspase-8 and Caspase-3. SHBA treatment resulted in down-regulation of anti-apoptotic protein Bcl-2 and Bcl-xl expression; down-regulated expression of antiapoptotic proteins survivin, XIAP and cIAP was also detected after SBHA treatment.</p><p><b>CONCLUSION</b>SBHA can effectively kill AML cells by inhibiting cell growth and inducing apoptosis, which is associated with the activation of Caspase pathway and regulation of apoptotic related proteins.</p>

Research advances on mechanisms of chemoresistance in acute myeloid leukemia / 浙江大学学报·医学版

Acute myeloid leukemia (AML) is a common type of hematopoietic malignancies seriously threatening human life. Resistance to chemotherapy is one of the main reasons for recurrence and refractoriness of acute myeloid leukemia. The mechanisms of chemoresistance are complex. This article reviews the mechanisms of chemoresistance in acute myeloid leukemia,the current research advances and the possible approach for reverse of drug resistance.

Clinical study of Philadelphia chromosome-positive adult acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).</p><p><b>METHODS</b>The clinical data of 117 newly diagnosed adults with Ph(+)ALL in our hospital between January 1995 and December 2009 were retrospectively analyzed. And their prognoses were followed up.</p><p><b>RESULTS</b>There were 117(16.1%) of 727 aALL patients diagnosed as Ph(+)aALL. Among the 117 cases, 64.1% patients were classified as pre-B immunophenotype and 31.3% as common B immunophenotype, 37.5% patients with co-expression of myeloid antigens (CD13 or CD33), and 98.4% patients with positive CD34. The complete remission (CR) rate after 1 or 2 cycles of induction chemotherapy was 62.2% in Ph(+)aALL group versus 82% in Ph(-)aALL group (P = 0.000). The median disease-free survival time of Ph(+) group was 6 months and the median survival time was 9 months. Sole karyotype abnormality subgroup t(9;22) accounted for 53% of all Ph(+)aALL patients and additional karyotype abnormality subgroup, t(9;22) plus other chromosome variation, accounted for 47%. Patients in sole karyotype abnormality subgroup had slightly lower CR rate (59.6% vs 62.5%, P = 0.768), longer median survival time (7 months vs 4 months, P = 0.158), and higher 3-year overall survival rate (27.3% vs 14.4%, P = 0.271). For the myeloid antigen co-expressed patients and the only lymphocytic antigen expressed ones, CR rate was 56.0% and 61.5% (P = 0.750), the median survival time was 5 months and 4 months (P = 0.182), and the 3-year overall survival rate was 16.0% and 15.0% (P = 0.354), respectively. In the imatinib plus combination chemotherapy treatment group, 81.3% patients achieved CR, compared with that of 58.3% in patients treated with only traditional combination chemotherapy (P = 0.083). The median survival time was 9.5 months and 6 months (P = 0.003) in these two subgroup, and 3-year overall survival rate was 52.2% and 10.3% (P = 0.029), respectively. For the patients receiving allo-HSCT after CR and that receiving traditional consolidation chemotherapy, the median survival time was 15 months and 6 months (P = 0.000), and the 3-year overall survival rate was 62.0% and 10.3% (P = 0.000), respectively. For the patients receiving imatinib as consolidation-maintenance treatment and that receiving allo-HSCT, the median survival time was 12 months and 15 months (P = 0.300), and the 3-year overall survival rate was 64.7% and 62% (P = 0.505), respectively.</p><p><b>CONCLUSION</b>Of all adult ALL patients, the Ph(+) subgroup accounted for about 16.1%, which have unfavorable prognosis such as lower CR rate and shorter survival duration under traditional chemotherapy. Neither additional chromosome abnormalities to t(9;22) nor co-expression of myeloid antigen had negative effect on CR rate and survival duration. Addition of imatinib to the therapy was beneficial to improve the CR rate and survival duration. Either receiving imatinib as consolidation-maintenance treatment or allo-HSCT after complete remission can improve long-term survival rate of Ph(+) adult ALL group significantly.</p>

Effects of fludarabine on apoptosis and gene expression profile in multiple myeloma cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the in vitro effects of fludarabine on apoptosis and gene expression profile in human multiple myeloma (MM) cells.</p><p><b>METHODS</b>Cell growth was measured by a MTT assay. Cells apoptosis was evaluated by flow cytometry. The activation of caspase cascade was determined by Western blot analysis. The expression profile of apoptosis-related genes in human MM cells was detected by cDNA expression array system.</p><p><b>RESULTS</b>The growth of RPMI8226 and KM3 cells was suppressed by fludarabine treatment in a dose and time-dependent manner. After treatment with fludarabine for 24 h, the IC(50) for RPMI8226 cells was 2.13 µg/ml, and 0.36 µg/ml for KM3 cells. Apoptotic cells of RPMI8226 and KM3 increased in a dose- dependent manner after exposure to fludarabine for 24 h. Western blot analysis showed the activation of caspase-3 and PARP in the MM cells treated with fludarabine. The cDNA expression array showed that multiple pathways were involved in the apoptosis induced by fludarabine. Among 97 apoptosis-related genes, 25 genes were differently expressed and 13 expressions were up-regulated in fludarabine treated group, involving in Bcl-2 pro-apoptotic gene, tumor necrosis factor (TNF) and its receptor superfamily gene, and caspase recruitment domain family, 12 genes expression down-regulated, including Bcl-2 antiapoptotic gene, TNF superfamily and its receptor related factor gene and apoptosis inhibitor protein family.</p><p><b>CONCLUSION</b>Fludarabine can significantly inhibit MM cell growth and induce apoptosis in vitro. The multiple pathways may be involved for the apoptosis in MM cells.</p>

Research progress on autophagy in hematopoietic malignancies / 浙江大学学报·医学版

Autophagy is a process of bulk degradation of proteins and organelles in cytoplasm.Autophagy has many normal physiological functions in cellular catabolism; therefore is essential for cell homeostasis. In some circumstances autophagy can induces cell death, namely autophagic cell death. Recent studies have suggested that autophagy plays an important role in both normal tissue development and a variety of diseases, including cancer. Therefore, the strategy targeting autophagy pathway may represent a new way of cancer treatment.

Inhibitive effects of chimeric oncolytic adenovirus SG235 on leukemia cells in vitro / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the inhibitive effects of chimeric oncolytic adenovirus SG235 on leukemia cells in vitro.</p><p><b>METHODS</b>The ability of SG235 to infect leukemia cells and the expression of CD46 on blasts from the patient with leukemia were detected by flow cytometry (FACS). The cytotoxicity of the virus was evaluated by MTT assay. Apoptosis induced by SG235 was detected with Annexin-V/PI staining and TUNEL assay followed by FACS analysis.</p><p><b>RESULT</b>The majority of leukemia cells from the patient with acute leukemia was CD46-positive. GFP-positive cells were 45.1%, 35.7%, 54.2%, 37.0%, 30.1%, %67.1, 17.2% and 33.1% in Mutz-1, Kasumi-1, K562, HL60, Molt- 4, RPMI8226, L428, and Jurkat cell lines treated with SG235-EGFP vector at MOI (multiplicity of infection) of 50 for 48 h.SG235 treatment resulted in marked growth inhibition and apoptosis of Kassumi-1 cells, and also significantly inhibited expression of p-Akt.</p><p><b>CONCLUSION</b>The chimeric oncolytic adenovirus SG235 can infect leukemia cell effectively and results in the growth inhibition and apoptosis of Kasumi-1 cells in vitro.</p>

Mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) ZD55 by interleukin-24 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) by interleukin-24 (IL-24).</p><p><b>METHODS</b>The ability of CRAd ZD55 to infect leukemia cells was detected by flow cytometry. The expressions of vascular endothelial growth factor (VEGF) in leukemia cells treated with PBS, ZD55, ZD55-IL-24, and an adenovirus carrying IL-24 (Ad-IL-24) were determined by Western blot analysis. Animal xenograft tumor model was established by Mutz-1 cell line.Deparaffinized tumor sections were incubated with anti-CD31, and VEGF antibody, followed by immunohistochemistry analysis.</p><p><b>RESULT</b>The GFP-positive cells were 5.1% and 42.3% in Mutz-1 cells treated with ZD55-EGFP vector at MOI of 10 and 100 for 48h, respectively. ZD55-IL-24 treatment resulted in the marked down-regulation of VEGF protein expression and ZD55 inhibited VEGF slightly; however, there was no change observed in the cells treated with Ad-IL-24. Immunohistochemistry analysis showed that Ad-IL-24 inhibited slightly angiogenesis and ZD55 treatment resulted in significant inhibition of angiogenesis. ZD55-IL-24 treatment almost completely inhibited angiogenesis in tumor tissues.</p><p><b>CONCLUSION</b>IL-24 enhances the antileukemia activity of ZD55 by inhibiting VEGF protein expression and angiogenesis in vitro and in vivo.</p>

Clinical study of amphotericin B in the treatment of invasive fungal infection in 111 hematological disorder patients with neutrocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the differences in clinical therapeutic effect and safety between amphotericin B and its liposome form in treating invasive fungal infection (IFI) in hematological disorder with neutrocytopenia.</p><p><b>METHODS</b>Of 111 patients with IFI, 82 were treated with amphotericin B and 29 with amphotericin B liposome. The mean cumulative dose of amphotericin B was 617 (60-1895) mg and the mean course was 18 (7-60) d, and those for amphotericin B liposome was 925 (140-3420) mg and 13 (7-50) d, respectively.</p><p><b>RESULTS</b>The total effective rates of amphotericin B and its liposome groups were 69% and 58%, respectively (P>0.05). The adverse effect rates of chill and fever in amphotericin B and its liposome groups were 21% and 10% (P>0.05), hypopotassemia 34% and 14% (P=0.03), hepatic impairment 22% and 17% (P>0.05), and renal impairment 9% and 3%, respectively (P>0.05).</p><p><b>CONCLUSION</b>The therapeutic effect for IFI of amphotericin B and its liposome was similar. The severe adverse reaction of amphotericin B liposome was slightly lower than that of amphotericin B.</p>

Expression of telomere binding factor 2 (TRF2) on leukemia cell lines and primary leukemia cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To detect the expression levels of telomere binding factor 2 (TRF2) on leukemia cell lines and primary leukemia cells.</p><p><b>METHODS</b>The expression of TRF2 mRNA was detected with quantitative real-time RT-PCR in leukemia cell lines and primary leukemia cells. The Western blot analysis was used for the detection of TRF2 protein expression.</p><p><b>RESULT</b>TRF2 was overexpressed in T-cell leukemia cell lines but not in myelogenous leukemia cell lines. Significant higher expression levels of TRF2 were observed in primary leukemia cells from patients with M0 and M1 subtypes of acute myelogenous leukemia (AML) compared with normal control and other subtypes of AML.</p><p><b>CONCLUSION</b>Increased TRF2 expression levels are found in T-cell leukemia cell lines and AML patients with poor prognosis, which suggests that TRF2 expression might be related to the prognosis of leukemia.</p>

HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of newly diagnosed adult acute myeloid leukemia (AML) patients treated with HAA (homoharringtonine, cytarabine and aclarubicin) regimen and explore the efficacy and safety of this regimen.</p><p><b>METHODS</b>Eighty patients were treated with HAA regimen. The complete remission (CR) rate was observed. Kaplan-Meier method was used to estimate relapse free survival (RFS) rate and the differences were compared with 2-sided log-rank test.</p><p><b>RESULTS</b>Of the 80 patients, 65 (81%) attained CR and the CR rate after the first course of induction was 75%. For the CR patients, the median follow-up was 26 (2 -69) months, and the estimated 3-year overall survival (OS) rate was 51% and the estimated 3-year RFS was 53%. For the AML-M5 and AML-M /M2 patients the CR rate was 74% and 87% and 3 year RFS of CR patients was 75% and 37%, respectively. The CR rate of 100%, 83% and 20% was achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. The 3 year OS for favorable and intermediate group was 76% and 50% respectively. The median survival time of unfavorable group was only 6 months.</p><p><b>CONCLUSION</b>HAA regimen is a safe, efficacious, and well-tolerable induction therapy for newly diagnosed AML.</p>

Mechanisms responsible for antitumor activity of melanoma differentiation-associated gene -7/interleukin-24 / 浙江大学学报·医学版

The melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) is a novel candidate of tumor suppressor, which can experimentally inhibit the proliferation of cancer cells and induce apoptosis of various human malignant cells.