1.Recent Research in Role of CD4+CD25+Regulatory T Cell in Pathogenesis of Immune Thrombocytopenia
Tianjin Medical Journal 2014;(4):390-392
Immune thrombocytopenia (ITP), the most common hemorrhagic disease, is an organ-specific autoimmune disease characterized by decreased platelets count due to auto-antibodies mediating platelets destruction and insufficient platelets production. The etiology of ITP is still not completely known. Regulatory T cells, also called Tregs, are character-ized by CD4+CD25+, and positive of transcription factor forkhead box P3. They belong to a subpopulation of T cells special-ized for immune regulation and play an important role in maintaining the immune balance. Decreased production and defect-ed function of CD4+CD25+Treg was found not only in the ITP animal model but also in the ITP patients. It indicates that the Treg was involved in the pathology of ITP. This review focus on the characteristic and function of Tregs and their relationship with pathogenesis of ITP.
2.Immunosuppressive action of Stro-1~+ and Stro-1~- subgroups of human mesenchymal stem cells
Yizhuo ZHANG ; Wanming DA ; Dandan ZHAO
Medical Journal of Chinese People's Liberation Army 2001;0(10):-
Objective To explore the difference of immunosuppresive effect between the expanded Stro-1+ and Stro-1-subgroups of human mesenchymal stem cells in vitro. Methods Mononuclear cells (MNCs) were isolated from bone marrow (BM) samples and seeded in a T-75 cm2 tissue culture flask contained with Dexter medium. When 50% confluence was obtained, adherent cells were collected and incubated with anti-stro-1 antibody, and the Stro-1+ and Stro-1-MSCs were further seeded for expansion. The total culture time (median) was 15 days. Cells were then analyzed by flow cytometry. One-way mix lymphocyte reaction (MLR) (1?105 responding cells and an equal number of stimulating cells/well were co-cultured in 96-well plates) and nonspecific mitogenic stimuli phytohemagglutinin (PHA) plus interleukin-2 (IL-2) induced lymphocytes proliferation (PBL 1?105/well were mixed with PHA 10?g/ml and IL-2 500U/ml in 96-well culture plates) were established in vitro. 1?103-3?104 irradiated Stro-1+ MSCs and Stro-1-MSCs were added into the two systems at the beginning of reaction. Immunosuppressive actions of both Stro-1+ or Stro-1-MSCs were compared. Results Adherent cells contained a median of 9% (range 5%-26%) Stro-1+ cells, which expressed higher immunophenotype of MSCs. In both reaction systems, suppressive actions occurred in a dose-dependent fashion when whatever Stro-1+ MSC or Stro-1-MSC were added. However, that the addition of 1?103 Stro-1-cells enhanced rather than inhibited the lymphocyte proliferation in one-way MLR. In the presence of various concentrations of MSCs, Stro-1+ MSCs always showed a significantly increased inhibitory effects in comparison to Stro-1-MSCs (P
3.Studies on the molecular mechanism involved in different immunosuppressive effects between Stro-1~+ and Stro-1~- MSC
Yizhuo ZHANG ; Wanming DA ; Dandan ZHAO
Medical Journal of Chinese People's Liberation Army 2001;0(11):-
35), while the expression level of TGF-?1 in Stro-1-MSC was significant higher than that detected in Stro-1+MSC (2-??Ct=0.39, P
4.Clinical observation of IEP followed EP chemotherapy in treatment of extensive-stage small cell lung cancer
Runbo ZHONG ; Baohui HAN ; Qian MIAO ; Yizhuo ZHAO
China Oncology 2009;19(10):774-778
Background and purpose: The overall survival time of extensive-stage small cell lung cancer is not satisfactory. No chemotherapy schemes more effective than etoposide combined with cisplatin, and other optimum combinations should be under evaluation. The aim of this study was to investigate the survival advantage of IEP followed by EP chemotherapy in the treatment of extensive-stage small cell lung cancer compared with EP chemotherapy alone. Methods: From Jan 2004 to Sep 2007, 68 extensive-stage small cell lung cancer patients were enrolled in this project and were randomly divided into research group and control group in the ratio of 1:1. In the research group, 34 patients accepted IEP chemotherapy at least two times followed by EP chemotherapy maintenance therapy. 34 patients as control group accepted EP chemotherapy only. Statistical significance was defined as P<0.05. Results: The median overall survival time of the research group was 15.32 months and the control group was 9.30 months. There were no significant differences between the two groups (P=0.0787). The median time to progression of the research group was 7.83 months and 6.92 months for the control group, respectively. There were no significant differences between the two groups (P=0.0164). It is suggested that IEP followed by EP chemotherapy in treatment of extensive-stage small cell lung cancer could get a better progression free survival, but the overall survival time has not been improved. Conclusion: We conclude that those patients with extensive-stage small cell lung cancer could get better progression free survival by accepting IEP chemotherapy.
5.Effects of fluoride on expressions of TGF-? and Smad2/3 in fibroblasts and osteoblasts
Yizhuo ZHAO ; Ling QI ; Hui XU ; Ling JING
Journal of Jilin University(Medicine Edition) 2006;0(06):-
Objective To explore the effects of fluoride with different doses on the expressions of TGF-? and Smad2/3 in fibroblast and osteoblast at different periods.Methods Fibroblasts and osteoblasts were exposed to different concentrations of fluoride(0,0.0001,0.001,0.1,1,10 and 20 mg?L~(-1)).The levels of TGF-? protein and Smad2/3 at 2,4,24,48 and 72 h after treatment were measured by using ELISA method.The expression of TGF-? mRNA was tested with RT-PCR method.Results In fibroblasts,the contents of TGF-? protein were decreased in the groups of 0.001,0.1,1,10 and 20 mg?L~(-1) F~-at the time of 2 h and in the groups of 1.0001,0.001,0.1,10 and 20 mg?L~(-1) at the time of 4 h(P
6.Comparative study on immunomodulatory effects of mesenchymal stem cells derived from different sources
Zhigang ZHAO ; Xiaofang WANG ; Yizhuo ZHANG ; Yong YU ; Hongliang YANG
Chinese Journal of Organ Transplantation 2010;31(9):549-552
Objective To study the difference in immunomodulatory effects among non-Hodgkin lymphoma (NHL)-, Hodgkin lymphoma (HL)- and normal adult bone marrow-derived mesenthymal stem cells (MSCs). Methods MSCs were obtained from HL, NHL and normal adult bone marrow and cultured in expanded medium. Immunophenotype was investigated by FACS. The levels of cytokines were evaluated by enzyme linked immunosorbent assay (ELISA). T-cell suppression ability was evaluated by Transwell. Moreover, the immunoregulatory ability of HL-, NHL- and normal adult bone marrow-derived MSCs was detected by mixed lymphocyte culture assay. Results HL-, NHLand normal adult bone marrow-derived MSCs were similar in morphology and immunophenotype, and they did not express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). All HL-,NHL- and normal adult bone marrow-derived MSCs could significantly suppress T lymphocytes'proliferation in a dose-dependent manner and such an effect could be reversed by anti-TGF-β1 antibody.MSCs differentiated into various mesenchymal lineages did not alter their immunosuppressive effects on T-cell proliferation. Conclusion The similar immunomodulatory effects were found among HL-,NHL- and normal adult bone marrow-derived MSCs, which was not changed by differentiation.
7.Phenotypic genetic regulation and treatment of malignant lymphoma.
Shanqi GUO ; Haifeng ZHAO ; Yizhuo ZHANG
Chinese Journal of Oncology 2014;36(3):161-164
Antineoplastic Agents
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therapeutic use
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Enhancer of Zeste Homolog 2 Protein
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Epigenesis, Genetic
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Histone Deacetylase Inhibitors
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therapeutic use
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Humans
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Hydroxamic Acids
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therapeutic use
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Indoles
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therapeutic use
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Lymphoma
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classification
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drug therapy
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genetics
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metabolism
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MicroRNAs
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metabolism
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Phenotype
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Polycomb Repressive Complex 2
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metabolism
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Polycomb-Group Proteins
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metabolism
8.Management of patients with retinoblastoma treated with vitrectomy due to misdiagnosis
Hongshu ZHAO ; Wenbin WEI ; Jitong SHI ; Xiaolin XU ; Yizhuo WANG
Chinese Journal of Ocular Fundus Diseases 2021;37(5):344-347
Objective:To explore the clinical treatment of retinoblastoma (RB) after being treated with vitrectomy (PPV) due to misdiagnosis.Methods:A retrospective case study. From July 2015 to July 2018, 5 cases and 5 eyes of RB children diagnosed by pathological examination at the Eye Center of Beijing Tongren Hospital were included in the study. Among them, there were 3 males with 3 eyes and 2 females with 2 eyes; all of them had monocular disease. The average age was 4.8±1.7 years old. At the first visit, the diagnosis was endophthalmitis in 2 eyes (40%, 2/5); vitreous hemorrhage in 3 eyes (60%, 3/5). All were treated with PPV. All children underwent slit lamp microscopy, orbital MRI and CT, and eye color Doppler ultrasound blood flow imaging. If there was no clear extraocular spread, the eyeball removal combined with artificial orbital implantation was performed; if there was clear extraocular spread, the modified orbital content enucleation operation was performed with part of the eyelid preserved. The average follow-up time after surgery was 34.6±7.9 months.Results:Among the 5 eyes, 2 eyes (40%, 2/5) underwent eyeball enucleation combined with stage I artificial orbital implantation, and 3 eyes (60%, 3/5) with modified orbital content enucleation. There were 2 eyes of endogenous type (40%, 2/5), 1 eye of diffuse infiltration type (20%, 1/5), and 2 eyes of mixed type (40%, 2/5). The orbit spread in 3 eyes, the tumor invaded the optic nerve in 1 eye, and regional lymph node metastasis in 2 eyes. All children received systemic chemical therapy (chemotherapy). During the follow-up period, there were no new metastatic diseases and no deaths.Conclusions:After RB misdiagnosis and PPV, surgical treatment should be performed as soon as possible. If there is no clear extraocular spread, eyeball removal or combined stage I orbital implantation should be performed. If there is clear extraocular spread, the orbital contents should be enucleated; Chemotherapy should be combined after surgery.
9.Chronic myelomonocytic leukemia complicated with Sweet 's syndrome developed into acute myelomonocytic leukemia: a case report and review of the literature
Jiaju WANG ; Yizhuo ZHANG ; Yong YU ; Xiaofang WANG ; Zhigtmg ZHAO ; Hongliang YANG ; Yafei WANG
Journal of Leukemia & Lymphoma 2011;20(9):554-556
ObjectiveTo improve the understanding of chronic myelomonocytic leukemia associated with Sweet' s syndrome.MethodsRetrospective analysis of a case of chronic myelomonocytic leukemia associated with skin herpes was reported. Skin biopsy was performed. DA and CAG regiment were administrated.ResultsSweet's syndrome was diagnosed by skin biopsy.Corticosteroids therapy alone was not effective. Complete remission was achieved by CAG regiment and skin rash has been effectively controlled.Three months later Sweet' s syndrome relapsed and chronic myelomonocytic leukemia developed into acute myelomonocytic leukemia. ConclusionChronic myelomonocytic leukemia associated with Sweet's syndrome is rare but implies a quick progression to acute myelomonocytic leukemia.
10.Inhibitory effects of the phosphoinostitide-3'-kinase delta inhibitor CAL-101 on Raji and SUDHL-10 lymphoma cells and its relative mechanism
Yafei WANG ; Bing XIA ; Fulian QU ; Xiaowu LI ; Shanqi GUO ; Tian YUAN ; Weipeng ZHAO ; Yizhuo ZHANG
Chinese Journal of Clinical Oncology 2015;(3):135-140
Objective:To detect the inhibitory effects of CAL-101, a selective inhibitor of phosphoinostitide-3'-kinase delta (PI3Kδ), on Burkitt's lymphoma cell line Raji and diffused large B-cell lymphoma cell line SUDHL-10 and elucidate its relative mechanism. Methods:Raji and SUDHL-10 cells were treated with various concentrations of CAL-101. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the inhibitory effect of CAL-101 on lymphoma cells, and cell apoptosis was measured by Annexin V/PI and DAPI staining. Migration assays were performed with transwell to detect the migration of lymphoma cells derived from the stromal cell line HK. Western blot was used to detect the phosphorylation status of the ERK pathway. MTT and CalcuSyn software analyses were preformed to detect whether or not combining CAL-101 with bortezomib induces synergistic cytoxicity. Results:CAL-101 at con-centrations of 5, 10, 15, and 20μmol/L inhibited cell proliferation in a dose-dependent manner. The proliferation rates of the Raji cells treated with 5, 10, 15, and 20μmol/L for 48 h were 29.17%± 1.23%, 38.15%± 1.51%, 46.46%± 1.78%, and 55.8%± 2.01%, respec-tively, which were significantly higher (P<0.05) than that of the control group (1.15% ± 0.02%). Similar results were found in the SUDHL-10 cells after treatment with CAL-101 (P<0.05). CAL-101 also exerted an apoptotic effect on the lymphoma cells. The apop-totic rates of the Raji cells treated with CAL-101 for 21 h were 22.69%± 3.83%and 49.96%± 7.36%, respectively, which were signifi-cantly higher (P<0.05) than that of the control group (5.23%± 2.04%). Similar results were found in the SUDHL-10 cells (P<0.05). Treatment with 5 and 10 μmol/L CAL-101 dose-dependently inhibited the migration activity of lymphoma cells to stromal cells (P<0.05). Western blot analysis showed that the expression level of ERK phosphorylation protein was significantly downregulated in the cells treated with CAL-101. A synergistic effect between CAL-101 and bortezomib was verified. That is, these two drugs can signifi-cantly inhibit the proliferation of lymphoma cells with CI values less than 1. Conclusion:The PI3Kδ-specific inhibitor CAL-101 sup-pressed the proliferation of Raji and SUDHL-10 cells, induced apoptosis, and inhibited stromal cell-derived migration. This inhibitory effect may be induced by blocking the ERK pathway. Overall, our study indicated that CAL-101 is a novel and potential agent in the therapeutic strategy against aggressive B-cell lymphoma.