[Hyperthermia increases the sensitivity of RPMI 8226 cells to adriamycin].

This study was purposed to explore the effect of hyperthermia on sensitivity of multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The working concentration of ADM against RPMI 8226 cells was defined by MTT assay. RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42°C) group, chemotherapy (ADM) group and combination group (42°C + ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI 8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate of cells, intracellular ADM concentration and P-gp expression level were measured by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration in the experiment. The results indicated that the hyperthermia promoted the entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the expression of P-gp protein on cells in hyperthermia and combination groups was down-regulated, the intracellular ADM concentration in combination group obviously increased. It is concluded that the hyperthermia combined with ADM obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through down-regulating the expression of P-gp protein on cells and increasing the intracellular ADM concentration.

[ABVD chemotherapy scheme at day 1 and 8 for treatment of primary Hodgkin's lymphomas].

OBJECTIVE: To explore the effect of adriamycin, bleomycin, vincristine and dacarbazinum (ABVD) chemotherapy scheme executed at day 1 and day 8 for primary Hodgkin's lymphomas (HL). METHODS: 62 patients with primary HL in stages II - IV treated in our department from October 2005 to October 2006 were divided into group A and B at random with 31 patients in each group. The patients in group A received ABVD chemotherapy scheme executed at day 1 and day 8 for 6 - 8 cycles. The patients in group B received ABVD chemotherapy scheme executed at day 1 and day 15 for 6 - 8 cycles. The patients of the groups received radiotherapy by the same doctor after chemotherapy according to the patients condition and the radiotherapy regimens were not affected by the grouping. RESULTS: The complete remission rate (CR) in group A after chemotherapy was 90.3% (28/31); the one-year and two-year disease free survival (DFS) rates were 87.1% (27/31) and 80.0% (20/25) respectively. The CR rate in group B after chemotherapy was 83.9% (26/31); the one-year and two-year DFS rates were 80.6% (25/31) and 72.0% (18/25) respectively. The discrepancy of CR rates and the one-year and two-year DFS rates between the two groups was not significant (P > 0.05). The incidences of therapeutic side effects such as myocardial ischemia grade III - IV liver function impairment, pulmonary fibrosis and serious marrow inhibition between the two groups were not significant too (P > 0.05). Average chemotherapy period for the patients in group A was 159 days; it was 69 days shorter than that in group B. CONCLUSION: The CR rate, 1-year DFS rate and 2-year DFS rate of ABVD chemotherapy scheme executed at day 1 and 8 are similar to those of ABVD chemotherapy scheme executed at day 1 and 15 for primary HL in stages II - IV. The side-effects of chemotherapy between group A and B are similar too. The chemotherapy period in group A is shortened significantly.

[The efficacy of high-dose cytarabine for patients with t(8;21) AML and with normal karyotype AML].

OBJECTIVE: To compare the efficacy of high-dose cytarabine (HD-Ara-C) based chemotherapy for post-remission treatment in patients with t(8;21) (q22;q22) AML-M2 and those with normal karyotype AML-M2. METHODS: AML-M2 patients were grouped into with (21 cases) or without (23 cases) t(8;21) (q22;q22) karyotype groups. After achieved remission by induction therapy, all patients received four cycles of HD-Ara-C (3 mg/m2 per 12 hours by three-hour infusion day 1 to day 3) with either mitoxantrone (7 mg m(-2) d(-1)) or aclarubicin (30 mg m(-2) d(-1)) or etoposide (70 mg m(-2) d(-1)) for 3d as post-remission treatment. RESULTS: Relapse rate in the t(8;21) and the normal karyotype groups was 29% and 57% respectively (P<0.05); 3 year disease-free survival (DFS) rate was 71% and 43% respectively (P < 0.05). and 3 year over-all survival (OS) rate was 76% and 65% respectively (P >0.05). CONCLUSION: Four cycles of high-dose cytarabine based combination chemotherapy as post-remission treatment improves long-term disease-free survival in patients with t(8;21) (q22;q22) AML-M2.

[Application of all-trans retinoic acid combining chemotherapy and As4S4 in the maintenance treatment of patients with acute promyelocytic leukemia].

OBJECTIVE: To compare the efficacy of all-trans retinoic acid (ATRA) combining chemotherapy and As4S4 with ATRA combining chemotherapy for the maintenance treatment of patients with acute promyelocytic leukemia (APL). METHODS: Sixty patients with APL induced to complete remission by ATRA and consolidated by chemotherapy were randomly divided into two groups. Thirty patients as As4S4 group received ATRA + As4S4 + chemotherapy, and another thirty patients as non-As4S4 group were treated only with ATRA + chemotherapy as maintenance therapy. The therapeutic effects, side effects and PML-RARalpha gene expression were analyzed. RESULTS: The three-year continuous complete remission (CCR) rate was 90.0% for As4S4 group and 61.1% for non-As4S4 group, the difference being statistically significant. Significant difference was also found in the positive rate of PML-RARalpha fusion gene between the two groups. The side effects were mild. CONCLUSION: APL patients in maintenance therapy with ATRA + 6-MP + MTX + As4S4 can obtain a higher CCR.

[Detection and screening for human cytomegalovirus infection in allogeneic hematopoietic stem cell transplantation recipients by different methods].

The aim of study was to explore the better detection method for cytomegalovirus (CMV) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients and to compare the efficiency of fluorogenic quantitative PCR (FQ-PCR), flow cytometry (FCM) and ELISA. The plasma DNA loading and serum level of IgM antibody against CMV in 214 clinical specimens from 19 allo-HSCT patients were detected by real-time FQ-PCR and ELISA respectively, the pp65 antigen in 118 peripheral blood leukocyte samples were measured by FCM. The results showed that the positive rates of pp65 antigen, IgM antibody and DNA load were 30.85% (58/188), 13.08% (28/214) and 35.51% (76/214) respectively, the coincidence between their sequential detection positive rates and clinical diagnosis were 7/8, 7/8 and 3/8 respectively. There was no statistical significant difference between the positive rate of pp65 antigen and of DNA amount (P > 0.05), and they have manifested relationships (P < 0.05). The positive rate of IgM antibody detected by ELISA was obvious lower than that of DNA quantitated by FQ-PCR and pp65 antigen detected by FCM, but the difference between them showed statistical significance (P < 0.05), Smaller relativity was found between IgM antibody detection and the other two methods (P > 0.05). It is concluded that FQ-PCR and FCM are sensitive, rapid, suitable and reliable methods for monitoring recipient reactive CMV infection of allo-HSCT recipients and are worthy to extensively use for guiding antiviral therapy.

[MEKK2 regulates the production of interleukin 2].

OBJECTIVE: To study the role of MEKK2 on the production of IL-2 in Jurkat cells stimulated by PHA/anti-CD28 antibody. METHODS: The MEKK2 and JNK kinase activities were measured in both dominant negative MEKK2 Jurkat (dnMEKK2 Jurkat) cells and parental Jurkat cells. The AP(1) and IL-2 promotor activities were measured by luciferase activity assay. The IL-2 mRNA and protein were detected by RT-PCR and Western blot. RESULTS: After stimulation by PHA/anti-CD28, JNK was activated in parental Jurkat cells but not in dnMEKK2 Jurkat cells. The luciferase report gene activities of AP1 and IL-2 promotors were increased by 4- and 5-folds in parental cells whereas only by 1 fold in dnMEKK2 Jurkat cells. The level of IL-2 mRNA and IL-2 protein were increased in parental Jurkat cells but not in dnMEKK2 Jurkat cells. CONCLUSION: MEKK2 plays an important role on the production of IL-2 in Jurkat cell stimulated with PHA/anti-CD28 antibody. It is a potential drug target for the treatment of GVHD and autoimmune disease.

[Multidrug resistance mechanisms in cell line HL-60/VCR].

BACKGROUND & OBJECTIVE: Drug resistance is a major factor in chemotherapeutic failure of leukemia. Multidrug resistant cell lines are the good models for investigating the mechanisms and reversal of acquired drug resistance. This study was designed to explore the multidrug resistance (MDR) mechanisms in cell line HL-60/VCR. METHODS: Flow cytometry and a panel of antibodies were used to analyze the expression of MDR proteins (P-gp, MRP, LRP, BCRP, GST-pi) and apoptosis-modulating proteins (bcl-2, bcl-x, bax, bad) in MDR cell line HL-60/VCR and drug sensitive cell line HL-60. RESULTS: The expression levels of MDR proteins (P-gp, MRP, BCRP, GST-pi) were (18.62, 1.19, 1.50, 1.32-flod) higher in HL-60/VCR than in HL-60, while the expression of LRP level was similar. The levels of apoptosis-modulating proteins(bcl-2, bcl-x, bad) were (2.48, 1.25, 1.08-fold) higher in HL-60/VCR than in HL-60, while the pro-apoptosis protein bax contrarily decreased in HL-60/VCR. CONCLUSION: Various MDR mechanisms were involved in multi-drug resistance HL-60/VCR cell line, which including increasing expression of drug-resistance protein (P-gp, MRP, BCRP, and GST-pi); the apoptosis-modulating proteins (bcl-2, bcl-x, bax, and bad) might take part in the mechanism of drug resistance.