Shaokai Luo

Sun Yat-Sen University, Guangzhou, Guangdong Sheng, China

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Publications (6)8.68 Total impact

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    ABSTRACT: Dendritic cells (DCs) play a major role in regulating lymphocytes. The emergence of antiplatelet autoantibodies remains the central pathogenetic mechanism in idiopathic thrombocytopenic purpura (ITP); defective DC functions have been implicated in ITP. The purpose of this study was to assess the contribution of DCs to B-cell hyperactivity in ITP patients. Ten ITP patients were studied before treatment (group untreated) and after treatment (group treated ) with improvement. We compared the effects of monocyte-derived DC from ITP and healthy control (group control) on naive B cells in the presence of lipopolysaccharide, or anti-CD40. We measured the proliferation, antibody production, and expression of activation markers for B cells, as well as DC-secreted B-cell activating factor (BAFF) production. We also measured the serum BAFF level in ITP patients and control. The role of DC-produced BAFF was evaluated with anti-BAFF. Lipopolysaccharide, or anti-CD40, stimulated DCs from group untreated increased B-cell proliferation and antibody production as compared with DCs from group treated and group control. Cell-to-cell contact was not necessary for the augmented effect of the ITP DCs. Anti-CD40 treatment induced a higher production of BAFF in group untreated DCs. Serum BAFF levels, supernatant BAFF from anti-CD40-activated DCs, and BAFF mRNA expression of anti-CD40-activated DCs in group untreated were significantly higher than that in group treated and group control. In ITP patients, there was positive correlation among serum BAFF, supernatant BAFF, and BAFF mRNA levels, and there was negative correlation between serum BAFF, supernatant BAFF, BAFF mRNA levels, and blood platelet count. Blocking BAFF abrogated the effects of ITP DCs on naive B partially. Activated monocyte-derived DCs from ITP patients directly increase B-cell effector functions; this effect depends on soluble factors released by activated DCs and cell-to-cell contact. This might play an important role in the antibody production in ITP. DC-secreted BAFF is involved and might contribute to disease development.
    Journal of Clinical Immunology 11/2010; 30(6):814-22. · 3.38 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) is an incurable B-cell malignancy, characterized by the proliferation of malignant plasma cells. B-cell-activating factor (BAFF, also known as BlyS or B-lymphocyte stimulator) and a proliferation-inducing ligand (APRIL), the two members of the tumor necrosis factor ligand superfamily, enhance the production of antibodies and regulate and promote proliferation and survival. Both BAFF and APRIL have an important role in B cell lymphoma and chronic lymphocytic leukemia cell survival. This study evaluates the expression of BAFF, APRIL, and their three receptors in two human MM cell lines (KM3 and PRMI 8226) and ten primary MM cell lines, and their effects on the growth of MM cells in vivo. MM cells were found to express BAFF, APRIL, and their three receptor genes both at the gene and protein levels. ELISA found high concentrations of BAFF and APRIL in the supernatants of these cultured cells. Treatment with PS-341 decreased the concentration of BAFF and APRIL. The WST-1 analysis of growth found that BAFF and APRIL stimulated the proliferation of MM cells. PS-341 inhibited this enhanced proliferation and induced apoptosis. Making use of the rhTACI-Fc to block the BAFF- and APRIL-induced activation of NF-kappaB2, we demonstrated that the NF-kappaB2-p52/RelB signal contributes to MM cell survival. In summary, PS-341 was shown to block this pathway. PS-341 inhibits the autocrine secretion of BAFF and APRIL and thereby MM cell proliferation by the alterative NF-kappaB2 pathway. BAFF and APRIL appear to be the targets of PS-341.
    Medical Oncology 06/2009; 27(2):439-45. · 2.14 Impact Factor
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    ABSTRACT: VEGF (vascular endothelial growth factor), a potent angiogenic molecule specific for vascular endothelial cells, is overexpressed in most tumours including MM (multiple myeloma) and closely associated with tumour growth and prognosis. It has been shown that a soluble fragment of the VEGF receptor Flt-1 (Fms-like tyrosine kinase-1) [sFlt-1 (soluble Flt-1)] has antiangiogenic properties by way of its antagonist activity against VEGF. VEGF and its receptors have been shown to be targets for treating tumours. In the present study, sFlt-1 gene was expressed in Pichia pastoris and the product was applied for studying the effect on KM3 MM cells. sFlt-1 gene was inserted into the pPICZalphaA vector and the expressed product was analysed by SDS/PAGE, immunoblot and ELISA. The sFlt-1 protein was expressed by 0.5% (v/v) methanol induction and it accumulated up to 23% of total proteins in the supernatant. The product was further purified with metal-chelating resin [Ni-NTA (Ni(2+)-nitrilotriacetate)]. The functional analysis of the sFlt-1 protein was performed with HUVEC (human umbilical-vein endothelial cells) proliferation assay. We next showed that the sFlt-1 protein acted directly on MM cells and inhibited the VEGF-induced proliferation of MM cells with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] and (3)H uptake assay. The sFlt-1 protein blocked VEGF-induced ERK (extracellular-signal-regulated kinase) phosphorylation and inhibited the MAPK (mitogen-activated protein kinase) signalling cascades. The present study demonstrated that anti-MM activity of the sFlt-1 protein, coupled with its antiangiogenic effects, provides the basis for clinical trials of this agent to improve the outcome in MM.
    Biotechnology and Applied Biochemistry 03/2008; 49(Pt 2):97-104. · 1.35 Impact Factor
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    ABSTRACT: Angiogenesis is an essential factor in the growth and progression of hematological malignancies including multiple myeloma (MM). Vascular endothelial growth factor and its receptors have been shown to be targets for treating tumors. This study explores the effect of adenovirus-mediated delivery of soluble vascular endothelial growth factor receptor Fms-like tyrosine kinase-1 (sFLT-1) on the growth of MM cell line KM3 in nude mice. sFLT-1 cDNA was amplified by reverse transcription-polymerase chain reaction from human umbilical vein endothelial cells and was used as a transgene to construct an adenoviral vector carrying sFLT-1 (ADV-sFLT). Cell proliferation and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays were carried out to evaluate the effect of ADV-sFLT on human umbilical vein endothelial cells and KM3 cells in vitro. Eighteen female BALB/c nude mice were inoculated subcutaneously with KM3 cells, and they were randomly divided into three groups and injected intravenously with ADV-sFLT, ADV-LacZ, or phosphate-buffered saline (PBS). The volume of KM3 xenografts was measured twice a week. Three weeks after the initial treatment, the volume of MM xenografts in the mice treated with ADV-sFLT, ADV-LacZ, or PBS was 770.32+/-28.73 mm3, 1983.36+/-43.72 mm3, and 2042.05+/-82.31 mm3, respectively (P<0.01, ADV-sFLT versus ADV-LacZ or PBS). The value of microvessel density was 29.17+/-6.85, 79.17+/-7.35, and 78.83+/-8.54 in the tumors treated with ADV-sFLT, ADV-LacZ, and PBS, respectively (P<0.01, ADV-sFLT versus ADV-LacZ or PBS). This study suggested that the adenovirus-mediated sFLT-1 gene greatly inhibits MM-derived tumor growth and angiogenesis in mouse xenograft, and might serve as a new therapy for MM.
    Acta Biochimica et Biophysica Sinica 07/2007; 39(7):499-506. · 1.81 Impact Factor
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    ABSTRACT: 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. 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). 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). 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.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 05/2002; 24(3):254-6.
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    ABSTRACT: ObjectiveTo enhance the understanding of Castleman’s disease (CD), and to improve its diagnosis and management. MethodsClinical features and related information on diagnosis and treatment of 14 cases of CD were retrospectively analyzed and the literature reviewed. ResultsBased on the clinical classification, localized CD was found in 8 of the 14 cases. Both the results of lymph node biopsy and histopathology indicated they were a hyaline-vascular type. The multicentric type CD was detected in 6 cases, among which 4 were plasma cell type and 2 mixed type based on histopathologic examination. There were a variety of clinical situations in the 14 cases, with a lack of specificity. They were previously misdiagnosed as other diseases, and final diagnosis depended on a histopathologic examination. The 8 patients with localized CD underwent excision, without recurrence up to now. The 6 patients with multicentric-type CD were treated with glucocorticoids or combined chemotherapy, and all achieved remission. ConclusionsCD has complicated clinical manifestations and is difficult to diagnose. Lymph node biopsy is important for early diagnosis. An optimal curative effect can be achieved with a suitable therapeutic option, based on histopathology and clinical classification.
    Chinese Journal of Clinical Oncology 4(3):195-200.