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The Experimental and Clinical Study on the Effect of Curcumin on Cell Cycle Proteins and Regulating Proteins of Apoptosis in Acute Myelogenous Leukemia

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第4期22卷 295-298页

作者：陈燕吴裕丹何静陈文娟 instituteofhematology

To investigate whether the Bcl- 2 gene family is involved in m odulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL - 6 0 cell line and primary acute m yelogenous leukem ic cells,the Bcl- 2 family member Mcl- 1,Bax and Bak and cell cycle proteins including P2 7kipl,P2 1wafl,cyclin D3and p Rbp- were selected and their ex- pression detected by SABC imm uno- histochem ical stain m *** attitude of sub- G1 peak in DNA histogram was determined by *** TU NEL positive cell percentage was identified by term inal deoxynucleotidyl transferase (Td T ) - m ediated Biotin d U NP end labeling *** was found that when HL - 6 0 cells were treated with 2 5μm ol/ L curcumin for 2 4 h,the expression level of Mcl- 1was down- regulated,but that of Bax and Bak up- regulated time- *** was significant difference in the expression level of Mcl- 1,Bax and Bak between the curcumin- treated groups and control group(P<0 .0 5 - 0 .0 1) .At the sam e time,curcumin had no effect on progress of cell cycle in prim aty acute m yelogenous leukemia at newly diagnosis,but could in- crease the peak of Sub- G1 (P<0 .0 5 ) ,and down- regulate the expression of Mcl- 1and up- regulate the expression of Bax and Bak with the difference being statistically *** expression of P2 7kipl,P2 1wafl and p Rbp- were elevated and thatof cyclin D3decreased in the presence of curcum in. These findings suggested thatthe Bcl- 2 gene fam ily indeed participated in the regulatory process of apoptosis induced by curcumin in HL - 6 0 cells and AML *** can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL - 6 0 *** m echanism appeared to be m ediated by perturbing G0 / G1 phases checkpoints which associated with up- regulation of P2 7kipl,P2 1wafl and p Rbp- expression,and down- regulation of cyclin D3.

关键词： curcum in Bcl- 2 gene family cell cycle protein HL - 6 0 cell prim ary leukemic cell

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Effects of adenovirus mediated vascular endothelial growth factor gene transfer on reconstitution of hematopoiesis in post-bone marrow transplantation mice

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Chinese Medical Journal 2005年第4期118卷 289-295页

作者： ZHONGZhao-dong ZOUPing HUXian-shi YOUYong CHENZhi-chao HUANGShi-ang instituteofhematology UnionHospitalTongjiMedicalCollegeHuazhongUniversityofScienceandTechnologyWuhan430022China

Background Bone marrow transplantation ( BMT) conditioning procedure isconsidered as the cause of damage to bone marrow microvasculature and the delay of hematopoiesisrecovery. However, hematopoiesis regulation post BMT by vascular endothelial growth factor ( VEGF)has not yet been studied. In this study, adenovirus were used to investigate the effects of VEGFgene transfer on preventing damages to bone marrow microenvironment and its promotion ofhematopoiesis in post-BMT mice. Methods Recombinant adenovirus (Ad)-enhanced green fluorescentprotein (EGFP)/hVEGF_(165) was injected via tail vein into BALB/c mice undergoing syngeneic *** the different phases post BMT, the distribution of adenovirus and the plasma levels of hVEGFwere measured as well as the numbers of white blood cells (WBC) , platelet (PLT) and red blood cells(RBC) in peripheral blood. At the same time, the mice were injected with Chinese ink via tail vein,following which the tibias were separated and were used for analysis of bone marrowmicrovasculature surface area and cellularity. Results Significant expression of EGFP and hVEGF wasobserved in multiple organs at different phases post BMT, and the plasma level of hVEGF was up to(866. 67 ± 97. 13 ) pg/ml. The recovery of WBC, PLT and RBC of the group treated with recombinantadenovirus Ad-EGFP/hVEGF_(165) were significantly more rapid than those of other BMT groups (P 0. 05 ]. The restoration of hematopoiesis was retarded more than that of *** cellularity of bone marrow in each group was still lower than that of normal control [ ( 62. 3± 4. 0 ) % , P < 0. 05 ] at the 30th day post BMT, but the percentage in group treated with VEGF atthe 20th and 30th days post BMT [(46.5 ± 5.0)% and (55.1 ± 4.5)%] exceeded those of other BMTgroups (P <

关键词： vascular endothelial growth factor gene transfer bone marrowtranspbntation reconstitution of hematopoiesis

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Successful transplantation of double unit umbilical-cord blood from unrelated donors in high risk leukemia with a long follow-up

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Chinese Medical Journal 2005年第9期118卷 772-776页

作者： WANGFeng-rong HUANGXiao-jun ZHANGYao-chen CHENYu-hong LUDao-pei PekingUniversityPeople＇sHospital InstituteofHematologyBeijing100044China PekingUniversityPeople＇sHospital InstituteofHematologyBeijing100044China

Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.

关键词： cord blood stem cell transplantation unrelated donor double leukemia

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The signal transduction pathways and molecules for ES cells self-renewal

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Chinese Science Bulletin 2005年第8期50卷 721-726页

作者： LIUNa LUMin instituteofhematology ChineseAcademyofMedicalSciences&PekingUnionMedicalCollegeTianjin300020China

Embryonic stem cells (ES cells) are derived from the inner cell mass (ICM) of blastocysts. ES cells can divide and produce identical copies of them over and over again (self-renewal) in vitro for a long time, and retain the capability of differentiating into all cell types when induced by appropriate signals. Their capability of multilineage dif- ferentiation might be exploited for cell-based therapies. Therefore, ES cells have a broad prospect in many clinical applications. To achieve success in the clinical applications, we have to understand how ES cells propagate and differen- tiate into specific cell types. The cytokine LIF can sustain the self-renewal of certain mouse ES cells (mES cells) through activation of the signal transduction pathway LIF/gp130/ STAT3. In this pathway the transcription factor STAT3 is a crucial factor. Furthermore, Oct-3/4 plays a very important role in maintaining the ES cell pluripotency. Oct-3/4 regu- lates embryo development through its co-factor Sox2 and Rox-1. Recently nanog, a new homeodomain gene, was found and it has been shown to be crucial for the renewal and pluripotency of ES cells. Three other signals BMP, Wnt and ERK also can influence differentiation and propagation of ES cells. This review article summarizes recent progress in this area, mainly focusing on the LIF signaling pathway and the transcription factors Oct-3/4 and Nanog. Although it is still unclear how these components cooperate, a model is presented here to provide a design for solving this problem.

关键词：胚胎干细胞自补充功能信号转换路径生物工程

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APPLICATION OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR (FILGRASTIM) FOLLOWING ALLOGENEIC BONE MARROW TRANSPLANTATION

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Chinese Medical Journal 1994年第10期 19-20页

作者： DPLu NLGuo XJHuang JZhang YMFan QShi BJiang instituteofhematology BeijingMedicalUniversityBeijing100044InstituteofHematologyBeijingMedicalUniversityBeijing100044InstituteofHematologyBeijingMedicalUniversityBeijing100044InstituteofHematologyBeijingMedicalUniversityBeijing100044InstituteofHema

The effect of rhG-CSF (Filgrastim by Amgen *** Neupogen and Kirin *** Gran) was evaluated in 20 patients with leukemia after allogeneic

关键词： BMT APPLICATION OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR FILGRASTIM

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Simulating High Reynolds Number Flow by Lattice Boltzmann Method

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Chinese Physics Letters 2005年第6期22卷 1456-1459页

作者：康秀英刘大禾周静金永娟 AppliedOpticsBeijingAreaMajorLaboratory DepartmentofPhysicsBeijingNormalUniversityBeijing100875 instituteofhematology ChineseAcademyofMedicalSciencesTianjin300020

A two-dimensional channel flow with different Reynolds numbers is tested by using the lattice Boltzmann method under different pressure and velocity boundary conditions. The results show that the simulation error increases, and the pressure and the flow rate become unstable under a high Reynolds number. To improve the simulation precision under a high Reynolds number, the number of fluid nodes should be enlarged. For a higher Reynolds-number flow, the velocity boundary with an approximately parabolic velocity profile is found to be more adaptive. Blood flow in an artery with cosine shape symmetrical narrowing is then simulated under a velocity boundary condition. Its velocity, pressure and wall shear stress distributions are consistent with previous studies.

关键词： BGK LBM Zou

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Effects of All－trans Retinoic Acid on hTERT Gene Expression and Telomerase Activity of HL－60 Cells

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The Chinese-German Journal of Clinical Oncology 2003年第3期2卷 169-171,192页

作者： HEDongmei ZHANGYuan instituteofhematology MedicalCollegeofJinanUniversityCuangzhou510632China

Objective: To investigate the effects of all-trans retinoic acid (ATRA) on human telomerase reverse transcriptase (hTERT) protein expression and telomerase activity in HL-60 cells. Methods: The expression of hTERT protein was assayed by immunofluorescence using fluoresce isothiocyanate label and telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay with HL-60 cells untreated or treated with ATRA. Cell cycle was analyzed by flow cytometry. Results: After treatment with 1μmol/L ATRA for 24, 48, 72 h, mean fluorescence intensity of hTERT protein in HL-60 cells was 61.87±4.36, 37.47±2.85， 33.45±2.37，respectively. There was a significant decrease in hTERT protein expression compared to the cells untreated, and the effect had statistically significant difference (P<0.05).Telomerase activity was decreased significantly in HL-60 cells treated with 1μmol/L ATRA for 48, 72h as compared to the cells untreated (P<0.05). Conclusion: ATRA could inhibit telomerase activity and hTERT gene expression in HL-60 cells.

关键词： hTERT基因端粒转移酶 HL-60细胞白血病全反式维甲酸

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Gene Analysis of Arsenic Trioxide—induced Apoptosis of Lymphoma Cells

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The Chinese-German Journal of Clinical Oncology 2002年第3期1卷 149-151页

作者： ZHANGZidong LIWeiyu 等 instituteofhematology MedicalCollegeofJinanUniversityGuangzhou510632China

Objective The effect of arsenic trioxide on apoptosis gene expression of Raji cell was explored when Raji cells were incubated with 0.5μmol/L of arsenic trioxide for 6h。Methods Cell culture,extraction and isolation of mRNA,preparation of probes labeled with fluorescence,hybridization technique of DNA chip(each chip containing 200 apoptosis genes,Chinese Shanghai Biostar,In.)were *** Arsenic trioxide induced significant changes in 10%(20/200 genes)of the apoptosis genes:18 genes were downregulated,only two *** particular,inhibitors of apoptosis protein,such as X-linked inhibitor of apoptosis protein,were significantly downregulated.P53 and the other apoptosis genes were also *** the upregulated genes,high expression of heat-shock protein could promote apoptosis of Raji *** The inhibitors of apoptosis protein play an important role in the process of arsenic trioxide-induced apoptosis of Raji cells.

关键词：淋巴瘤三氧化二砷诱导肿瘤细胞凋亡基因分析

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Inhibition of Leukemic Cell Telomerase Activity by Antisense Phosphorothioate Oligodeoxynucleotides

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The Chinese-German Journal of Clinical Oncology 2002年第2期1卷 104-106页

作者： HEDongmei ZHANGYuan instituteofhematology MedicalCollegeofJinanUniversityGuangzhou510632

Objective To evaluate the effect of human telomerase reverse transcriptase(hTERT) gene antisense oligodeoxynucleotide (ASON) on telomerase activity in K562 *** Telomerase activity was detemined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA) in K562 cells treated with ASODN and hTERTmRNA expression was detected by reverse transcriptase polymerase chain reaction (RT-PCR). Results The hTERTmRNA level was decreased,and telomerase activity was significantly inhibited when the K562 cells were treated with ASODN for 48 h. Conclusion It is suggested that hTETR ASODN might specifically inhibit telomrase activity of K562 cells at translation level,and it is further proved that hTERT gene has significant correlation with telopmerase activity.

关键词：白血病细胞端粒酶活性 hTRT基因反义核酸抑制作用

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Reversal of P—glycoprotein—mediated multidrug resistance by pyronaridine

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中国药理学与毒理学杂志 2002年第6期16卷 423-424页

作者： QiJ WangSB StateKeyLaboratoryofExperimentalHematology InstituteofHematologyChineseAcademyofMedicalSciencesandPekingUnionMedicalCollegeTianjing300020China StateKeyLaboratoryofExperimental

An association between P-glycoprotein(Pgp) level and poor clinical outcome has been *** have been made to search for the modulators of tumor multidrug resistance (MDR) from the components of Chinese herbs and the molecules developed in *** (PND)was found to be able to reverse MDR to doxorubicine(DOX) in K562/A02 and MCF7/ADR,expressing Pgp with more efficacy than *** increased the accumulation of DOX and reduced efflux of Rh123 in the two cell *** reversibility prersisted for at least 24h after removel of the drug from the culture *** administered orally or parenterally,PND significantly enhanced the in vivo antitumor activity of DOX in K562/A02 xenografts,but did not significantly increase the toxicity or alter the plasma pharmacokinetics of *** view of PND has been safely used in clinic for the treatment of malaria for more than 20 years at high dose,the modulator might be the promision in the reversal of MDR in the clinic.

关键词：咯萘啶 P-糖蛋白多药抗药性中草药

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