Objective To investigate the effect of rosiglitazone (ROS),a peroxisome poliferator- activated receptor (PPAR)?ligand,combined with all-trans retinoic acid (ATRA) on anti-angiogenesis of transplanted gastric cancer in nude mice,and to explore the mechanism of anti-angiogenesis prelimina- rily.Methods The model of xenograft tumor in nude mice were established by inoculating human gastric cancer cells line MGC803 (lower differentiated) into the back of nude mice subcutaneously.The cancer- bearing nude mice were divided randomly into 5 groups:group 1 (n=6) with no treatment;ROS treat- ment (group 2,n=6),ROS combined ATRA treatment including:low dose treatment (group 3,n= 6),moderate dose treatment (group 4,n=6) and high dose treatment (group 5,n=6).After treated for forty days,the volume change of tumor and tumor inhibition rates were observed.The expression of CD34,vascular endothelial growth factor (VEGF) in grafts were detected by immunohistochemical and calculated the difference of MVD.The mRNA expression levels of VEGF,HIF-l?were detected by RT- PCR assay accordingly.Results①The volume of tumor was significantly decreased in ROS treatment group compared with group 1 (P＜0.01).The tumor inhibition rates of group 2 were similar to group 3 (P＞0.05).With the increasing of the dose of ROS the tumor inhibition rates were increased.They were dose-dependent in specified dose-range.②ROS could inhibit angiogenesis of xenograft tumor and depress expression of mRNA of VEGF and HIF-l?.When ROS combined with ATRA,the increasing of dose of ROS,inhibiting angiogenesis of tumor and depressing expression of mRNA of VEGF and HIF-l?were found (P＜0.05).Conclusion ROS (25 mg?kg?2 d~(-1)) can inhibit the growth of tumor,and ROS combined with ATRA can further inhibit the growth of tumor,which may be through the path of PTEN by inhibiting the angiogenesis of tumor

In recent years, the biopharmaceutical industry has grown rapidly, and the market size of monoclonal antibody drugs has increased significantly. Accurate structural characterization and quality control are the supporting technologies for the development of monoclonal antibody drugs. As a significant post-translational modification of antibody drugs, glycosylation has an important influence on its efficacy, stability, and immunogenicity. The existing literature usually uses liquid chromatography-mass spectrometry to perform major glycosylation modifications of monoclonal antibody drugs. Characterization, there are few studies on low-abundance glycosylation, but the characterization and control of low-abundance glycosylation cannot be ignored. In this study, we have established a qualitative and quantitative analysis technology for N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs. This method has a short sample processing time and high sensitivity. It can not only characterize the main glycoforms of three monoclonal antibody drugs (adalimumab, bevacizumab, and trastuzumab) but also can quantify low-abundance N-glycans. The results of the study showed that the main glycoforms specified in the Pharmacopoeia could be detected in different batches of monoclonal antibody drugs, but the content of N-glycans in different batches of samples is not identical. After that, we analyzed the N-glycans connection sites and glycoforms at the intact glycopeptide level, further enriching the N-glycans structure information of the monoclonal antibody. The qualitative and quantitative analysis technology of N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs can realize the in-depth characterization and control of glycosylation modification of monoclonal antibody drugs.

The research and development of monoclonal antibodies (mAbs) is a rapidly developing field. From the first generation of murine mAbs to the fourth generation of fully human mAbs, the efficacy and safety of mAbs in the treatment of various diseases have been continuously improved. In order to regulate the development and evaluation of mAbs, drug regulatory agencies and pharmacopeias of America and China have tried to issue feasible test procedures and acceptance criteria for quality evaluation of mAbs and biosimilars. Mass spectrometry (MS) technique with high sensitivity, resolution, selectivity, and specificity has become an important tool to evaluate the quality characteristics of monoclonal antibody-related products or specify mAb quality. The research of MS-based monoclonal antibody study involves structure characterization, impurity analysis, pharmacokinetics/pharmacodynamics (PK/PD), etc. This review focuses on the current quality control requirements of mAb related products and the development of MS technique for mAb quality characterization and specification. It is expected to provide information and references for evaluating the quality of monoclonal antibodies under research and development.

Objective:To investigate the influence of fetal liver AFT024 cells on the transfection efficiency of multidrug resistant gene 1(MDR1)and the in vitro expansion of CD34+ cells derived from umbilical cord blood.Methods:CD34+ cells were isolated from human umbilical cord blood by MACS CD34 Progenitor Cell Isolation Kit and co-cultured with AFT024 cells(AFT024 group)or cultured alone(control group)for 7 days.During the subsequent 14 days,retrovirus carrying MDR1 gene was supplemented twice a week to transfect CD34+ cells.On the 7th,14th and 21st day after culture,the number of total nucleated cells(TNC)was counted,the ratio of CD34+ cells was assayed by flow cytometry(FCM)and the number of CD34+ cells was calculated,and colony-forming cells(CFC)were counted by methylcellulose cultures.RT-PCR method was used to detect the level of MDR1 mRNA in the transfected cells.The expression and function of P-glycoprotein(P-gp)were evaluated by FCM assay and Rhodamine-123 efflux assay,respectively.The gene transfection efficiency was calculated by drug-resistant colony-forming cells assay.Results:(1)The MDR1 mRNA level in AFT024 group than that in control group.The gene transfection efficiency in AFT024 group was significantly higher than that in control group(46.0% vs 15.2%,P0.05).On the 14th day,the expansion fold of TNCs in control group was significantly higher than that in AFT024 group(P0.05).The expansion folds of CD34+ cells and CFCs in the AFT024 group were significantly higher than that of the control group(P

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Female ; Gene Amplification ; Genital Neoplasms, Male ; genetics ; metabolism ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Paget Disease, Extramammary ; genetics ; metabolism ; pathology ; surgery ; Paget's Disease, Mammary ; genetics ; metabolism ; pathology ; surgery ; Penile Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Receptor, ErbB-2 ; genetics ; metabolism ; Scrotum ; Vulvar Neoplasms ; genetics ; metabolism ; pathology ; surgery

Objective To investigate the effect of high dose mifepristone and high dose progesterone in the treatment of patients with endometrial carcinoma and to explore the possible mechanisms associating with them Methods Thirty untreated patients diagnosed as endometrial carcinoma through dilation and curettage of the uteri were divided into 3 groups at random Each group was given medroxyprogesterone acetate(MPA),(500 mg/day) or mifepristone(MIF),(100 mg/day)or MIF(100 mg/day)+ MPA(500 mg/day)for 5 days respectively On the sixth day, hysterectomy was performed on these patients The endometrial cancer specimen of post hysterectomy was compared with the one of pre administrating The morphologic changes of the endometrial cancer cells were observed through light microscope Immunohistochemistry assay (SP method) was applied to determine the localization and immunoreactive intensity of proliferating cell nuclear antigen(PCNA), estrogen receptor (ER), progesterone receptor (PR), B cell leukemia lymphoma 2 (bcl 2), bcl 2 associated X protein(bax) and CD 44 v6 Results Better differentiation degree and active excretion were observed in all of the post hysterectomy endometrial specimen In the same time, apoptosis of carcinoma cells was observed The most significant changes were seen in the MIF+MPA group In the MPA group,the pre treatment and post treatment expression of PR(2 9?1 1,1 6?0 8),ER(2 8?0 9,1 4?0 9),PCNA(0 84?0 10,0 60?0 12),bcl 2(0 236?0 089,0 157?0 981) and CD 44 v6 (4 6?1 8,2 5?1 9) were all decreased(all P 0 05) In the MIF+MPA group, the expression of PR(3 2?1 0,0 8?0 8),ER(2 7?0 9,0 7 ?0 9 ),PCNA(0 81?0 09,0 25?0 09),bcl 2(0 225?0 091,0 066?0 009)and CD 44 v6(4 5?1 9,2 7?1 6) were all decreased(all P

Objective To explore the in vitro isolation of ?2m-/Thy-1+ bone marrow-derived liver stem cells(BDLSCs) which bear double features of stem and liver cells from bone marrow stem cells(BMSCs)as so to provide suitable donor cells for the treatment of liver diseases by cellular transplant. Methods ?2m-/Thy-1+ BDLSCs were isolated by magnetic bead cell sorting(MACS) method from cholestatic rats in vitro,and cell purity was detected using flow cytometry.Liver associated phenotype markers were characterized by RT-PCR and immunofluorescence staining. Results BDLSCs isolated by MACS were purified and viable,and possessed hepatocyte-like features at gene and protein levels. Conclusion ?2m-/Thy-1+ BDLSCs are special subsets of BMSCs which may have promising potentials in the stem cell-based treatment of liver diseases.

?AIM: To explore the effects of “one week with one case” teaching method with college - enterprise cooperation in the theoretical classes of contact lens courses, which provide the basis for teaching reform.?METHODS: Fifty-six students in optometry major of Grade 2012 from Xi’an Medical College were divided into 2 groups randomly. The experimental group of 28 students used “one week with one case” teaching method with college-enterprise cooperation; the control group of 28 people used traditional “one week with one case”teaching method. The examination scores and questionnaire were used to evaluate the teaching effects.?RESULTS:The students of experimental group acquired higher test scores in short-answer questions and the case analysis questions compared with students of control group (P<0. 05). The questionnaire survey showed the“one week with one case” teaching method with college-enterprise cooperation acquired higher scores in 6 items which include the intensity of learning interest, information acquisition ability, team cooperation ability, communication skills, oral communication ability and the satisfaction of teaching method (P<0. 05). Four items included participation, preparation, communication ability and team spirit of experimental group students were significantly superior to those of the control group students (P<0. 05).?CONCLUSION:“One week with one case” teaching method with college-enterprise cooperation can improve comprehensive ability of students. It is an effective teaching method with the characteristics of the contact lens courses.

Objective To investigate the value of hepatic T2 value in evaluation of chronic HBV-related acute-on-chronic liver failure (HBV-ACLF).Methods The HBV-ACLF group,chronic hepatitis B group and control group who underwent liver MRI (M-GRASE sequence) were enrolled.The T2 map was produced from the post-processing software,and the mean T2 and R2 value of liver was calculated.The blood biochemical indexes from HBV-ACLF and chronic hepatitis B group were collected in 2 days pre-MR scaning.The differences of T2 and R2 values among 3 groups and the correlation between biochemical indexes and T2 value were analyzed.ROC curve was conducted to evaluate diagnostic efficiency of T2 value for HBV-ACLF.Results There were significant differences of T2value (x2 =19.074,P＜0.001) or R2 value (F=10.411,P＜0.001) among the 3 groups.The AUC of T2 value for diagnosing HBV-ACLF was 0.86 (P＜0.001),with the cut-off value 57.73 ms (R2=0.017).Moderate positive correlation was shown between T2 values and international normalized ratio (INR),prothrombin time (PT),haluronicacid (HA) values (rs =0.65,0.67,0.39,all P＜0.05),and moderate negative correlation was shown between T2 values and prothrombin activity (PTA),albumin (ALB),prealbumin (PA) values (rs =-0.67,-0.48,-0.37,all P＜0.05).Conclusion T2 or R2 value could reflect the liver function,and were correlated with some biochemical indexes,which illustrated a good diagnostic efficiency for diagnostic of HBV-ACLF.