3.The effects of Erlotinib,an epidermal growth factor receptor inhibitor,on the angiogenesis of pancreatic cancer
Ying-Ying LU ; Da-Dao JING ; Ming XU ; Al ET ;
Chinese Journal of Digestion 2001;0(09):-
Objective To investigate the mechanisms of inhibitory effect of Erlotinib,an epidermal growth factor(VEGF) receptor inhibitor,on angiogenesis of pancreatic carncer.Methods①In a tube formation assay,Erlotinib(100?mol/L) was applied to the culture media and compared to the serum free media.The expression of vascular endothelial growth factor(VEGF) in BxPC-3 cells treated with Erlo- tinib at different concentrations(5,50,100,200?mol/L) was determined by RT-PCR.②The xeno grafts derived from BxPC 3 cancer cells were inoculated into the BALB/C nude mice.The mice were treated with either Erlotinib(100 mg/kg of Erlotinib oral lavage daily) or saline for four weeks.The vol- ume of the xenografts was measured and the tumor growth rate was calculated.The microvessel density (MVD) of tumor tissue was determined by immunohistochemistry with an antibody against factorⅧ. Results There were less endothelium cells and close hollow tubular structures in grlotinib treated group compared to the control group in the tube formation assay.The mean weight of xenografts in Erlotinib treated group[(0.397?0.550)g] was significantly lower than that in the control group[(1.570?1.060)g] with a inhibitary rate of 74.5%.The expression of VEGF mRNA in Ertotinib treated groups (=50?mol/L) were decreased comparing to the control group.The VEGF expression in xeno- grafts tumor tissues was also markedly down-regulated.The MVI) was significantly decreased in Erlotinib treated group( 1.86?0.43)than that in the control group (5.98?1.27,P
4.Cytomegalovirus retinitis after allogeneic bone marrow transplantation: a case report and literature review.
Jin LU ; Xiao-jun HUANG ; Dao-pei LU
Chinese Journal of Hematology 2003;24(6):312-315
OBJECTIVETo report a case with cytomegalovirus retinitis (CMVR) after bone marrow transplantation (BMT). A review of the literature and possible mechanisms were presented.
METHODSCase report and literature review.
RESULTSThe patient received large dose of immunosuppressants after allo-BMT appeared CMV infection. There were bleeding and effusion around the ocular vessels. The patient improved after anti-CMV therapy.
CONCLUSIONPatients who undergone allo-BMT were in immunosuppressed condition, when continuous CMV antigenemia and antigenuremia were detected, associated with characteristic change in retinitis, CMVR could be diagnosed.
Adult ; Bone Marrow Transplantation ; adverse effects ; Cytomegalovirus Retinitis ; drug therapy ; etiology ; Humans ; Male ; Transplantation, Homologous
5.Effects of plumbagin on the human acute promyelocytic leukemia cells in vitro.
Journal of Experimental Hematology 2006;14(2):208-211
According to previous clinical experiences of the authors, plumbago zeylanica was effective against acute promyelocytic leukemia (APL). However, its effectiveness has never been proven experimentally or unequivocally clinically. This study was aimed to investigate the effects of plumbagin on the proliferation, cell cycle and apoptosis of APL cell line NB4 Cells. Cell inhibitory rates were detected by MTT colorimetric assay; morphologic changes were observed under light microscope and transmission electron microscope; apoptosis-inducing effects were determined by DNA gel electrophoresis, annexin V/PI double-stained and PI single-stained flow cytometry. The results demonstrated that 2-15 micromol/L plumbagin inhibited the proliferation of NB4 cells in a dose-dependent manner. The morphologic changes of cell apoptosis, such as chromsome condensation and apoptotic body formation, were observed by light microscope and transmission electron microscope. Cell cycle analysis showed that NB4 cells were blocked in G2/M phase of cell cycle. And plumbagin induced annexin V+/PI- cell increase and DNA fragmentation. There was a correlation between cell apoptosis rates and the concentrations of plumbagin in dose-dependent manner (P < 0.05). It is concluded that for the first time the present study shows that plumbagin can inhibit cell proliferation, block cell cycle and induce apoptosis of APL cell line NB4 cells.
Antineoplastic Agents, Phytogenic
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pharmacology
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Apoptosis
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drug effects
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Cell Cycle
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drug effects
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Cell Line, Tumor
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Cell Proliferation
;
drug effects
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal
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pharmacology
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Humans
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Leukemia, Promyelocytic, Acute
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pathology
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Naphthoquinones
;
pharmacology
7.A murine model of three mixed allogeneic bone marrow transplantation (A + B + C-->A).
Journal of Experimental Hematology 2003;11(2):184-187
In this paper, a model of three allogeneic mixed bone marrow transplantation of mice (BALB/c, H-2(d); C57BL/6, H-2(b); and CBA/N, H-2(k)) was established and whether or not prolongation of the survival time in recipient mice was observed. Lethally irradiated mice were transplanted with a mixture of a syngeneic plus two allogeneic bone marrow (A + B + C-->A, in a ratio of 1:4:4). At same time, mixed lymphocyte culture (MLC) with three allogeneic lymphocytes in vitro and two allogeneic antigens stimulated delayed type hypersensitivity (DTH) in vivo were performed. The results showed that the mice receiving mixed bone marrow transplant survived 56.6 +/- 27 days and the longest 103 days, however, only 15 +/- 5 days in the single allogeneic transplantation group. Whether two reacting cells to one stimulating cells or one reacting cells to two stimulating cells, all showed lower activity of MLC than that in one to one control group. In DTH assay, the mice sensitized with two allogeneic antigens showed lower reactivity than that in one antigen stimulated mice. It was concluded that the survival time of recipient mice was significantly prolonged after transplantation with three mixed allogeneic bone marrow.
Animals
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Bone Marrow Transplantation
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immunology
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mortality
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Graft vs Host Disease
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etiology
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Hypersensitivity, Delayed
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etiology
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Lymphocyte Culture Test, Mixed
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Mice
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Mice, Inbred Strains
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Models, Animal
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Survival Rate
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Transplantation, Homologous
8.Expression of lipoprotein related genes in subchondral bone of early experimental osteoarthritis.
Rong-Kai ZHANG ; Lu-Kun YANG ; Li-Juan HUANG ; Qing ZHAO ; Dao-Zhang CAI
China Journal of Orthopaedics and Traumatology 2014;27(1):54-57
OBJECTIVETo study the expression of lipoprotein related genes in subchondral bone of early experimental os-teoarthritis, which may play an important role in the pathogenesis of osteoarthritis.
METHODSAnimals are equally divided into two groups: experimental group and control group, both of which contain fifteen rats of similar weight. The right knee joints of experimental group underwent surgery,which involved in both medial collateral ligament(MCL) transaction and medial meniscectomy, while the control group was only carried out with a sham operation. Rats were killed at 1, 2 and 4 weeks postsurgery to obtain the right knee joints. Total RNA of the subchondral bone was extracted,and then hybridized to Agilent Whole Rat Genome Microarray. Differentially expressed genes analysis was used to study the chemokine signaling pathway.
RESULTSApoa5 expression was down-regulated at 1, 2 weeks post-surgery, Apoc2 expression was up-regulated at 1 week after surgery, Apol3 expression was up-regulated at 1 and down-regulated at 4 weeks post-surgery, Lrp1 expression was down-regulated at 1, 2 weeks after surgery. Lrp5 was down-regulated at 2 weeks after surgery. Gpihbp1, Lpl, Tfpi and Vldlr were up-regulated at 1 weeks after surgery. Lrpap1 and RGD1309808 were down-regulated at 4 weeks after surgery.
CONCLUSIONDysregulation of lipoprotein related genes plays an important role in pathogenesis of early experimental osteoarthritis.
Animals ; Disease Models, Animal ; Knee Joint ; metabolism ; Lipoproteins ; genetics ; Male ; Oligonucleotide Array Sequence Analysis ; Osteoarthritis ; genetics ; Rats ; Rats, Sprague-Dawley ; Transcriptome
9.Preparation of placental-eluted gamma globulin and its immunosuppressive effect in vitro and in vivo.
Journal of Experimental Hematology 2006;14(3):529-534
The aim of this study was to establish a simple, convenient and efficient method of producing placental-eluted gamma globulin (PEGG) from human placenta, explore its inhibitory effect on the function of T lymphocyte in vitro and graft-versus-host disease (GVHD) in vivo. PEGG was prepared by elution at acid pH from human placental tissues that were extensively washed. Its effects on T lymphocyte proliferation induced by PHA and mixed lymphocyte reaction (MLR) were analysed by BrdU ELISA, its effect on the CD25 and CD69 expression on T cells was observed by flow cytometry, and the interferon gamma (IFN-gamma) and interleukin-4 (IL-4) quantification in MLR supernatant were assayed by ELISA. A murine GVHD model was established, the effect of PEGG on the manifestation and pathologic change of GVHD and 45-day survival rate were observed. The results showed that considerable level of immunoglobulin could be eluted from placenta at acid PH, of which the main components were IgG checked by SDS-PAGE analysis. In vitro study indicated that PEGG significantly inhibited both the proliferative response of T cells to PHA and the MLR, down-regulated the expression of CD25 and CD69 on T cells stimulated by PHA, and decreased the secretion of IFN-gamma but increased the production of IL-4 in MLR supernatant. In vivo, recipient mice treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. It is concluded that PEGG can inhibit the proliferation and activation of T cells, regulate the direction of T helper cells differentiating towards Th2 type, and effectively prevent GVHD in a murine model. In short, PEGG may be a potent therapeutic agent for GVHD.
Animals
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Bone Marrow Transplantation
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adverse effects
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Female
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Graft vs Host Disease
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drug therapy
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Humans
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Immunosuppressive Agents
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isolation & purification
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pharmacology
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therapeutic use
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Placenta
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chemistry
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T-Lymphocytes
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drug effects
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immunology
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gamma-Globulins
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isolation & purification
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pharmacology
;
therapeutic use
10.Donor Hematopoietic Cell Tracking In Vivo at the Homing Phase of Allo-Bone Marrow Transplantation in Mice
Kai SUN ; Yi-Lan WANG ; Dao-Pei LU
Journal of Experimental Hematology 2001;9(3):243-246
It has been well-known that intravenously infused hematopoietic stem and progenitor cells can home to the bone marrow and reconstitute hematopoiesis. However, little is understood about the homing efficiency or percentage of infused stem and progenitor cells. In order to examine distribution pattern of infused hematopoietic cells in the organs and tissues, a direct assay system to trace transplanted cells in vivo by employing PKH-26, a red fluorescent membrane dye, to label hematopoietic cells in inbred strain of mice transplanted cells (stem cell antigen-1 positive subpopulation cell, Sca-1(+) cells) was introduced. The numbers of labeled cells was measured by means of flow cytometry and fluorescence microscopy. The early fate of infused Sca-1(+) donor bone marrow cells after intravenous administration in a allogeneic mouse model was examined. The presence of infused donor cells with the fluorescent dye PKH-26 was evaluated within 60 hours in hematopoietic organ (bone marrow and spleen) and non-hematopoietic organ (lungs and liver) of recipients. The data showed that (1) Following intravenous infusion, Sca-1(+) donor bone marrow cells were detained in lungs shortly. (2) Sca-1(+) donor bone marrow cells localized to both hematopoietic organ (bone marrow and spleen) and non-hematopoietic organ (lungs and liver) for periods of up to 60 hours following infusion, however, the number of donor hematopoietic cells localized to bone marrow was more than that localized to non-hematopoietic organ (P < 0.05). These results indicated that there were also donor early hematopoietic cells in non-hematopoietic organ of recipients at the homing phase in allo-BMT mice.