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望病赵
9 years ago
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1 SLXM

3 SLXM-2 SLXM-2, a derivative of cyclophosphamide: study of anti-tumor mechanism and effects on immune system

4 SLXM SLXM

5 AAE A -naphtyl Acetate Esterase α- BSA Bovine serum albumin CAK CDK activating kinase CDK Cyclin-dependent kinase ConA Concanavallin A A CPA Cyclophosphamide CPQA Cyclophosphamide piperazine quaternary ammonium Cyclin DEPC Diethyl Pyrocarbonate ECL Enhanced chemiluminescence kit GPR Granulocyte percentage GRA Granulocyte count H 22 Hepatocarcinoma 22 HCT Hematocrit HGB Hemoglobin i.p. Intraperitoneal LPCR Large platelet cell ratio LPS Lipopolysaccharide LRP Lymphocyte percentage LYMF Lymphocyte count MALT Mucosal-associated lymphoid tissue MCH Mean corpuscular haemoglobin MCHC Mean corpuscular haemoglobin concentration MCV Mean corpuscular volume MCV Melanoma cell vaccine MID Mid-sized cell count MPR Mid-sized cell percentage MPF Mitosis promoting factor - 1 -

6 MPV Mean platelet volume MTT Thiazolyl blue C itrocellulose S ormal saline PBS Phosphate-buffered saline PCA Proliferating cellnuclearantigen PCT Plateletcrit PDW Platelet distribution width PHA Phytohemagglutinin-M -M PLT Platelet count PRA Panelreactive antibody PWM Pokeweed mitogen RBC Red blood cell count RDWA Red cell distribution width absolute RDWR Red blood cell distribution width RT-PCR Reverse transcription-polymerase chain reaction SDS Sodium dodecyl sulfate SLE Systemic lupus erythematosus SPF Specific pathogen-free TEMED Tetramethylethylenediamine Tris Tris(hydroxymethyl)aminomethane Ub Ubiquitin WBC White blood cell count - 2 -

7 Cyclophosphamide CPA SLXM-2 H 22 Western Blotting SLXM-2 H 22 RT-PCR mra ICR T B H mg/kg SLXM-2 30 mg/kg CPA Western Blotting SLXM-2 Cyclin B1 Cdc2 Phospho-cdc2 Tyr15 Phospho-cdc2 Thr161 SLXM-2 CDK7 Cdc25c PT-PCR mra SLXM-2 Cyclin B1 Cdc2 ICR mg/kg SLXM-2 30 mg/kg CPA T B SLXM-2 SLXM-2 SLXM-2-3 -

8 ABSTRACT ABSTRACT BACKGRUD & BJECTIVE Cyclophosphamide (CPA) is a widely used antineoplastic drug with a variety of side effects. This study explored the anti-tumor mechanism of a derivative of cyclophosphamide, SLXM-2, on Hepatocarcinoma 22 (H 22 ) cells and its effects on immune system of ICR mice. METHDS Western Blotting assay was used to investigate the expression of cell cycle related proteins using ICR mice transplanted with the ascitic fluid-type H 22. The mra expressions of cell cycle related proteins were detected by PT-PCR experiment. The routine blood examination was evaluated by the whole blood analyzer using ICR mice on the 0 th, 3 rd, 6 th, 9 th days. n the 10 th day, we investigated the spleen index, the rate of lymphocyte transformation and the phagocytosis of enterocoelia macrophage. RESULTS When the mice transplanted with the ascitic fluid-type H 22 were treated with 0, 30 and 60 mg/kg SLXM-2 by intraperitoneal (i.p.) injection for 10 days, Western Blotting and RT-PCR experiments indicated Cyclin B1 increased, whereas cell division cycle protein 2 (Cdc2) remained constant. However, the results showed an accumulation of tyrosine 15 phosphorylated Cdc2 and a reduction of threonine 161 phosphorylated Cdc2. In addition, SLXM-2 led to a decrease in cyclin-dependent kinase 7 and Cdc25c kinase, which participated in inhibiting the G 2 /M transition. After the treatment of 0, 30, 60 mg/kg SLXM-2 and 30 mg/kg CPA by i.p. injection for 9 days, SLXM-2 had little effect on the spleen index, the rate of lymphocyte transformation and the phagocytosis of enterocoelia macrophage of ICR mice. Meanwhile, CPA significantly inhibited these indexes. CCLUSIS The observed G 2 arrest of SLXM-2 is associated with the changes of cell cycle related proteins. Its decreased potential for immunosuppression - 4 -

9 ABSTRACT indicates that it is less toxic than CPA. These results demonstrated the anti-tumor mechanism of SLXM-2 and its potential use as an antineoplastic drug. KEYWRDS Cyclophosphamide; Derivative; Cell cycle related proteins; Immunosuppression - 5 -

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11 1Cyclophosphamide CPA, - (2- ) -2H-1,3, , -Bis (2-chloroethyl) tetrahydro-2h-1,3,2-oxazaphosphorin-2-amine-2-oxide monohydrate Cl H P Cl P hydroxycyclophosphamide 3 Aldophosphamide 4 5 β 6 Acrolein 7Phosphoramide mustard 1 [1,2,3] - 7 -

12 ph H H 2 P P + H 2 C CH CH H H P H P H 2 CH 2 3 H H 2 P P CH Figure 1 Metabolism pathway of cyclophosphamide in vivo DA -- DA = DA 7 DA 2-8 -

13 + P H 2 C H 3 CH 2 Cl Cl + H H H DA H 2 DA H 2 DA DA 2 Figure 2 Alkylation effect of cyclophosphamide 2.2 AT CG S G 2 [4] 2.3 [5] Kaledin Lymphosarcoma / LS cell line γ [6] HA-1 Li Fas/FasL p53 [7] Chow caspase-3 p21 WAF-1 [8] Bcl-2 p21 WAF-1 p53 DA G 1 DA p53 G 1 /S DA p53 p53-9 -

14 p21 p21 G 1 Cyclin/CDK Proliferating cellnuclearantigen PCA - C- p21 WAF-1 p21 WAF-1 caspase PCA PCA p21 WAF-1 DA caspase-3 p21 WAF DA DA B T T K T 3. CHP [1,2] [3,4] [5]

15 [9] mg/kg/ 12 h P450 ADPH [10] [11]

16 4.4 DA [12,13] Shih 5-8 [14] Eibl 5-9 [15] 10 Borch 6 [16]

成都市人民检察院物业管理采购项目竞争性谈判需求文件

成都市人民检察院物业管理采购项目竞争性谈判需求文件成都市人才流动服务中心教育分中心特级教师体检服务采购项目预公告各潜在供应商 : 成都市公共资源交易服务中心受成都市人才流动服务中心教育分中心的委托, 拟对成都市人才流动服务中心教育分中心特级教师体检服务采购项