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<p><b>OBJECTIVE</b>To evaluate the mechanism and influence of thalidomide on interleukin-6 (IL-6), IL-6 receptor (IL-6R) and its transmitting chain in multiple myeloma patients.</p><p><b>METHODS</b>Serum level of IL-6, expression of IL-6R on myeloma cells and IL-6R beta mRNA in multiple myeloma patients were measured by enzyme linked immunosorbent assay (Elisa), flow cytometry and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Serum level of IL-6 in multiple myeloma patients was 564.8 +/- 319.4 ng/L, with a positive rate on the myeloma cells of 33.6% before oral 200 mg/d thalidomide. They were 560.3 +/- 414.8 ng/L and 31.8% on D14 after oral 200 mg/d thalidomide, which were not significantly different as compared with those before (P > 0.05). On D14, 28, 42, 56 and 84 after oral 400 mg/d thalidomide, the serum level of IL-6 in multiple myeloma patients were 516.7 +/- 131.9 ng/L, 426.7 +/- 180.4 ng/L, 387.9 +/- 187.4 ng/L, 350.1 +/- 85.5 ng/L and 212.3 +/- 92.5 mg/L, with positive rates on the myeloma cells of 28.5%, 24.3%, 21.3%, 12.6% and 10.1%, which were all lower than those before oral 200 mg/d thalidomide (P < 0.05 or P < 0.01). Ratios before and on D14 after oral 200 mg/d thalidomide were 7.8 and 6.9, with no statistical significance (P > 0.05). Ratios on D14, 28 after oral 400 mg/d thalidomide were 5.3 and 2.7, which were lower than those before oral 200 mg/d thalidomide (P < 0.01).</p><p><b>CONCLUSION</b>Reduction of serum level of IL-6 in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA occur on D14 after oral 400 mg/d thalidomide. These changes become more obvious with time. The antitumor mechanism of thalidomide may be related to reduction of IL-6 serum level in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors , Pharmacokinetics , Pharmacology , Interleukin-6 , Blood , Genetics , Multiple Myeloma , Blood , Metabolism , RNA, Messenger , Metabolism , Receptors, Interleukin-6 , Metabolism , Thalidomide , Pharmacokinetics , PharmacologyABSTRACT
AIM and METHODS: To investigate the expression of adhesion molecule ? 2 integrins (CD11a、CD11b) and L-selectin(CD62L )on Acute Lymophocyte Leukemia(ALL) cells and its Clinical Implications. Adhesion molecules CD11a、CD11b、 CD62L of 45 ALL patients and 25 health people were measured by flow-cytometric analysis. RESULTS:①CD11a and CD11b expression were lower on ALL cells than the normal hematopoietic cells. The rate of low expression was 100% for CD11b, 50% for CD11a,respectively. CD62L expression were higher on ALL cells than the normal hematopoietic cells.②The CD11a was lower expressed on B-ALL than T-ALL. CD62L was higher on T-ALL than B-ALL. ③ The expression of CD11a in the invasion group was much higher than that in the non-invasive group(P
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Objective:To investigate the expression of adhesion molecule including CD11a、CD11b、CD62L on malignant lymophoproliferative disorders and its clinical implications.Methods:Adhesion molecule CD11a、CD11b、CD62L of 35 Acute Lymophocytic Leukemia(ALL)、30 multiple myeloma(MM)、4 Chronic Lymophocytic Leukemia(CLL)、14 lymphosarocoma cell leukemia patients and 25 health people were measured by flow cytometric analysis.Results:①CD11a and CD11b expression were lower on ALL、MM、CLL cells than the normal hematopoietic cells.CD62L expression were lower on CLL、MM、lymphosarocoma cell leukemic cells than the normal hematopoietic cells.②The CD11a was lower expressed on ALL than lymphosarocoma cell leukemic cells,CD62L was higher on ALL than lymphosarocoma cells leukemia.③The expression of CD11a in the ALL invasion group was much higher than that in the noninvasive group(P
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AIM: To observe the cytotoxicity on myeloma cells mediated by anti-CD20 monoclonal antibody-mabthera, after heightening level of CD20 expression on myeloma cells membrane by ?-interferon. METHODS: 10 untreated(UT) and 10 relapsed or refractory(RR) MM patients'myeloma cells were cultured with human recombinant ?-interferon (hr?-IFN) at concentrations of (0-800)?10~3 U/L to heighten level of CD20 expression, then complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) on myeloma cells mediated by mabthera were studied through MTT methods. RESULTS: When CD20 expression of UT MM and RR MM patients' myeloma cells increased after treated by hr?-IFN, 12 mg/L and 16 mg/L mabthera mediated ADCC and CDC (against) myeloma cells in group UT patients and group RR patients, respectively. CONCLUSION: After heightened level of CD20 expression on myeloma cells membrane by hr?-IFN, mabthera mediated ADCC and CDC against myeloma cells in vitro.
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AIM and METHODS: To investigate the expression of adhesion molecule β2 integrins (CD11a、 CD11b) and L-selectin(CD62L )on Acute Lymophocyte Leukemia(ALL) cells and its Clinical Implications. Adhesion molecules CD11a、CD11b、 CD62L of 45 ALL patients and 25 health people were measured by flow - cytometric analysis. RESULTS :①CD11a and CD11b expression were lower on ALL cells than the normal hematopoietic cells. The rate of low expression was 100% for CD11b, 50% for CD11a,respectively. CD62L expression were higher on ALL cells than the normal hematopoietic cells.②The CD11a was lower expressed on B - ALL than T- ALL. CD62L was higher on T- ALL than B- ALL. ③The expression of CD11a in the invasion group was much higher than that in the non - invasive group( P < 0.05).④The levels of CD11a,CD11b were returned to normal levels at remission. CONCLUSION: These results suggest that there are abnormalities in the expression of cell adhesion molecules in ALL which may help identify ALL subtypes and the treatment effect.
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Objective To explore the mechanism of hematolo gic abnormality in patients with systemic lupus erythematosus(SLE).Methods Suppression of granulocytic and ery throid colony formation of bone marrow cells fromhealthy individuals was examined in vitro by using methylcell ulose culture with sera or IgGdelete d sera from patients with SLE.Results①Both colony-forming units of erythr ocytes(CFU-E)(in 66.7%of samples tested)and granulocytes(CFU-GM)(in 70%of samples tested)of normal bone marrowcells were sign ificantly inhibited by sera frompatients with SLE(P
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AIM: To investigate the possibility of simultaneously ex vivo generating cytomegalovirus (CMV) pp65 and Epstein - Barr virus (EBV) - specific cytotoxic T lymphocytes (CTL) from human umbilical cord blood (CB). METHODS: Mononuclear cell derived from CB (CBMC) was used to construct EBV - transformed B-lym- phoblastoid cell lines (BLCL). Then BLCL were transduced with a recombinant retrovirus encoding pp65, the immunodominant CMV polypeptide. CBMC from the same CB donor were stimulated with pp65 - expressing BLCL (BLCLpp65) weekly for 5 - 6 weeks. Chromium release assays (CRA) were performed to detect the specific cytotoxicity of the CTL against EBV and CMV. RESULTS: Western blot analysis and immunocytochemistry confirmed that BLCLpp65 could simultaneously express CMVpp65 and EBV antigen. CRA results showed that the generated CTL possessed specific cytotoxic against EBV and CMV, and the cytotoxicity was mediated by CD8+ CTL. CONCLUSION: BLCLpp65 can be used as antigen - presenting cells to stimulate expansion of EBV and CMV specific CTL simultaneously from the predominantly native T cell population in CB.
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Objective:To study the influence and mechanism of thalidomide on bone marrow hematopoietic progenitor cells in multiple myeloma patients and in normal controls.Methods:Bone marrow GM CFU, E CFU and MK CFU from multiple myeloma patients and from normal controls were cultured in methylcellulose semisolid medium in vitro after being treated by different concentration of thalidomide. IFN ? and TNF ? concentration in cell suspension of bone marrow hematopoietic progenitor cells from multiple myeloma patients and from normal controls were measured by ELISA.Results:Thalidomide inhibited GM CFU in multiple myeloma patients and in normal controls at concentration higher than 200 and 100 ?g/ml, respectively, and inhibited MK CFU in multiple myeloma patients and in normal controls at concentration higher than 300 ?g/ml and 150 ?g/ml, respectively. However, there was no significantly influence of thalidomide on E CFU in multiple myeloma patients and in normal controls at concentration between 10 and 400 ?g/ml. Thalidomide increased IFN ? concentration in cell suspension of bone marrow hematopoietic progenitor cells from multiple myeloma patients and from normal controls at concentration greater than 100 and 200 ?g/ml, respectively. The level of thalidomide of higher than 300 ?g/ml reduced TNF ? concentration in cell suspension of bone marrow hematopoietic progenitor cells from multiple myeloma patients.Conclusion:Different concentrations of thalidomide have different influences on the hematopoietic function of bone marrow hematopoietic progenitor cells in multiple myeloma patients and in normal controls, probably mediated through increased IFN ? by thalidomide.
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Objective:To study whether the mobilization process is associated with change in expression of adhesion molecules on CD34 +cells Methods:Two colour fluorescence analysis was used to study the expression of adhesion molecule CD62L,CD49d,CD11a,CD11b on CD34 + cells of peripheral blood stem cells(PBSC) before and after mobilizing with G CSF and cytotoxic chemotherapy in 15 cancer patients undergoing PBCST Results:① The expression of adhesion molecules on CD34 +cells revealed a significant reduction of CD11a, CD49d and CD62L at days 7 compared to the baseline level (P