The discovery of the key negative regulator MDM2 and the detailed mechanism of MDM2-P53 protein-protein interaction provide a great opportunity to activate P53 by inhibiting MDM2-P53 interaction with MDM2 inhibitor.In this article,the author will review the accomplishment in the area of MDM2 inhibitor treatment on tumors of urological system.The detailed mechanism and the signal pathways involved are summarized simultaneously.

Objective To compare the Panel reactive antibody (PRA) producing incidence in living and cadaveric transplant for forecasting long term survival. Methods Retrospectively analyze post-transplant PRA of 48 living transplant patients ( December 2003-Sepdtember 2007 ), and 258 cadaveric transplant patients( Feburary 2003-June 2007 ), which in both groups were all PRA negative in pre-transplant. PRA was detected using LAT-1240 (OneLambda) and QUICKSCREE&BSCREEN (GTI). Serum creatine/urea nitrogen level was provided by clinical laboratory. Results Four recipients in 48 living transplant patients showed PRA positive(8.33% ), while 62 receipients in 258 cadaveric transplant patients showed PRA positive(24.03% ) ( P ＜0.05 ). Three recipients in 35 male living donor transplant patients showed PRA positive(8.57% ) ,while 23.03% PRA positive in male cadaveric transplant patients (P ＜0.05). In females, 1out of 13 living donor transplant patients showed HLA-Ⅱ positive, whereas 20 out of 106 in cadaveric transplant patients( 18.87% ) ( P ＜ 0. 05). Conclusion The incidence of HLA antibody production was much higher in cadaveric transplant patients than that in those of living donor transplant.

Objective To use HSV 1 tk (herpes simplex virus type Ⅰthymidine kinase)/GCV (ganciclovir) in androgen independent prostate cancer cells(C4 2,PC3) in vitro in order to provide useful basis for clinical use. Methods HSV 1 tk gene was ligated to a pN 2A retroviral vector. Recombinant DNA molecules being introduced into a packaging cell line PA317,the high titer virus producer cells (VPC) were screened.The integration and expression of HSV 1 tk gene in VPC was observed by PCR and RT PCR. VPC was co cultured with these cancer cells in the light of 1∶1,1∶2,1∶4,1∶8.Cell viability (cytotoxicity) was assessed by SRB (sulforhodamine B protein dye binding)after the first day,the third day,the fifth and the seventh day. Results The highest titer VPC producing HSV 1 tk gene was isolated. Retrovirus mediated HSV 1 tk gene therapy was effective and active against such prostate cancer cells.The best one was co culture of VPC and cancer cells at 1∶1 and the fifth day followed by GCV. Compared with C4 2, PC3 decreased remarkably.The activation of apoptosis and other ways failed to be found. Conclusions Retrovirus mediated HSV 1 tk gene therapy in Vitro directly killed the tumor cells by cytolytic activity.

BACKGROUND: It remains poorly understood regarding the incidence of panel reactive antibody (PRA) production and its influence to renal function and long-term survival in China. OBJECTIVE: To investigate the incidence of PRA after living renal transplant, so as to provide reference for predicting long-term renal survival. METHODS: A total of 54 patients who received living renal transplantation in Beijing Friendship Hospital from March 2005 and October 2007, were selected. PRA, serum creatinine and urea nitrogen level were detected 1-2 years after transplantation. PRA assay was conducted using One Lambda ELISA HLA-Ⅰ +Ⅱ antigen tray. Serum creatinine and urea nitrogen data were offered by clinical laboratory. RESULTS AND CONCLUSION: A total of 12.96% (7/54) patients showed PRA positive after transplantation, with HLA-Ⅱ antibody positive in 6 patients, and HLA-Ⅰ + Ⅱ antibody positive in 1 patient. In these 7 patients, 6 underwent primary transplantation, and PRA negative before transplantation; 1 patient underwent transplantation for the second time, and HLA-Ⅱ antibody positive before transplantation. Creatine and urea nitrogen level were abnormal in 1 patient with HLA-Ⅰ + ⅠⅡ antibody positive and 2 patients with HLA-Ⅱ antibody highly positive. Creatinine and urea nitrogen levels were normal in 4 patients with low level HLA-Ⅱ antibody. Results show that HLA-Ⅰ +Ⅱ antibody positive and high level HLA-Ⅱ antibody affect renal function in living renal recipients, but low level HLA-Ⅱ antibody has no effect on renal function.

Objective To asses the value of fluorescence in situ hybridization (FISH) in diagnosis of transitional cell carcinoma of bladder in the urine using directly labeled DNA probes to the pericentromeric regions of chromosomes 3 , 7 and 17 and to the region of P16 tumor suppressor gene. Methods Chromosomal and gene abnormalities were detected using directly labeled DNA probes to the pericentromeric regions of chromosomes 3 , 7, and 17 and to the region of P16 tumor suppressor gene. The sensitivity of FISH and Cytology in diagnosing transitional cell carcinoma of bladder was also compared. Results The sensitivity of FISH and Cytology in diagnosing the disease was 85.5% and 34.2%, respectively. The sensitivity of FISH was prior to that of Cytology( P ＜0.05 ) and increased with increasing tumor pathologic grade but not clinical staging. Conclusions High sensitivity of FISH in diagnosing transitional cell carcinoma of bladder was obtained and it might be a potent method to diagnose bladder cancer in Chinese people in the future.

Background Poly(adenosine diphosphate-ribose) polymerase 1 (PARP-1) plays an important role in the pathogenesis of diabetic retinopathy (DR),and Notch1 signal pathway is one of the important signal transduction pathways in the organism which may antagonize retinal vascular diseases.However,if Notch1 signaling pathway is involved in pathogenesis of DR has not been confirmed yet.Objective This study was to investigate the expressions of Notch1,Dll4,PARP-1,Akt,nuclear factor-κB (NF-κB) and caspase-3 in the retina of diabetic mouse model and retinal vascular endothelial cells (RVECs) under the high glucose.Methods The expressions of Notch1,Dll4,PARP-1,Akt,NF-κB and caspase-3 in the retina of diabetic mouse models were investigated using immunochemistry and Western blot method after the diabetic mouse models were established.And these proteins were detected in retinal RVECs under the high glucose by Western blot.Results The expressions of Notch1,Dll4 and phosphorylated Akt (p-Akt) in retinas reduced significantly and simultaneously companied with increases of PARP-1 and caspase-3 in diabetic mice compared with normal mice (all at P＜0.05).However,no obvious change was found in the expression of NF-κB (P＞0.05).Expressions of Notch1 and p-Akt in RVECs increased with the increase of glucose concentration,but expressions of cleaved PARP-1 and caspase-3 decreased,especially in the 30 mmol/L group,showing significant differences in comparison with the normal control group (all at P＜0.05).But no altering of NF-κB expression was seen in the mice with diabetes mellitus.Conclusions The expressions of cleaved-PARP-1 and caspase-3 in the retinas is up-regulated,but the expressions of Notch1 and p-Akt are down-regulated in diabetic mice.

Objective To study the influence on allograft function of HLA antibody in patients who received pairs of allograft from the same donor.Methods In Beijing Friendship Hospital.HLA antibodies were tested from October,2008 to April 2009 in patients.Recently (October,2013-February,2014),renal functions(serum creatinine/urea nitrogen)were studied in 226 patients who received transplant from 113 donors.LATM10x5,One Lambdas used for Panel reactive antibody screen-ing.Results 41 pairs of renal for male,21 pairs of renal for female and 51 pairs of renal for both male and female.PRA posi-tive in 26 patients (only 4 pairs of renal for patients were positive),11 recipients (HLA II antibody positive in only 1 pair of renal for patients)and 36 recipients (only 5 patients produced antibody)in 226 patients,HLA antibody positive in 73 pa-tients,in which renal function lost or decreased in 64 patients.HLA antibody negative in 153 recipients,in which renal func-tion lost or decreased in 4 patients.There was significant difference between the two group (χ2=160.70,P<0.001).Con-clusion HLA antibody is a important factor influence renal function and long term survival.

[ ABSTRACT] AIM:To investigate the effect of microwave radiation at different intensities on the rat myocardium and its possible mechanism.METHODS:The rats were radiated by the intensity of 500, 1 000, 1 500 and 2 000 W/m2 with 2 450 MHz microwave for 6 min.The heart tissue was collected 6 h after microwave radiation.ATP and mitochondria complexⅣandⅤwere measured.The changes of the tissue structures were observed under transmission electron micro-scope.The apoptosis of the myocardial cells was detected by a cell analyzer.The protein level of cleaved caspase-3 was de-termined by Western blotting.RESULTS:The concentration of ATP and activity of mitochondria complexⅣandⅤsigni-ficantly decreased compared with control group in the cardiac tissues.The decreased number, morphological abnormalities such as dissolved cavitation, matrix and obvious tumefaction of mitochondria were observed under transmission electron mi-croscope.The microwave radiation induced the apoptosis of myocardial cells in the rats.The cell apoptotic rate and the pro-tein level of cleaved caspase-3 increased with increasing intensity of microwave radiation ( P<0.05 ) .CONCLUSION:Microwave radiation has obvious injury effect on the rat heart, which can cause cardiac energy metabolism dysregulation and cardiac myocyte apoptosis.

Objective To investigate the influences of HLA mismatching on renal function in the kidney transplant patients re-ceiving pairs of allograft from the same donor.Methods 171 pairs of renal transplant patients receiving the kidneys from the same donors were investigated.They were admitted in our hospital before 2008.Their human leukocyte antigens (HLA)were typed with the commercial polymerase chain reaction (PCR)-sequence-specific primers (SSP)HLA typing kit (One Lambda,Inc.,USA;and GTI Diagnostics,USA).The serum creatinine (SCr)and blood urea nitrogen(BUN)were measured in the clinical laboratory of our hospital.Results Among 171 pairs of renal transplant patients,there were 162 recipients with HLA mismatch≤4,in which the re-nal function was remained stable in 107 recipients and lost or decreased in 55 patients.There were 180 recipients with HLA mis-match >4,in which the renal function was stayed normal in 84 recipients and lost or decreased in 96 patients.The difference in in-fluencing the renal function between the HLA mismatch≤4 and HLA mismatch>4 had statistical significance (χ2 =12.22,P <0.05).Conclusion Excellent HLA typing match has important significance for renal long term survival.

Objective To investigate the influence of very late antigen-4 (VLA-4) antibody and VLA-4 antibody combined with VP_(16) in vitro on childhood leukemic cells' apoptosis and explore the protection of bone marrow stromal cells (BMSC) upon leukemic cells and its related mechanisms. Methods Leukemic bone marrow stromal cells were isolated by human lymphocyte separation medium and in vitro culture of BMSC (adherent) and leukemia cells (suspended) BMSC+leukemic cells group were as control. Then VLA-4 antibody and/or VP_(16) were added respectively to VLA-4 antibody group, VP_(16) group and VLA-4 antibody combined with VP_(16) group to detect the apoptosis of leukemic cells in different groups through Annexin V-FITC double-labeled flow cytometry and the expression of Survivin, bcl-2 genes in each group of leukemic cells detected by RT-PCR. Results The results showed by flow cytometry that compared with the control groups, for 12 h or 24 h, the early and total apoptosis rates of leukemic cells of the three experimental groups were significantly increased(P <0.05); the early and total apoptosis rates of leukemic cells treated with VLA-4 antibody combined with VP_(16) group was markedly increased, compared with the control group (P <0.05); the comparison of the early and total apoptosis rates for the three experimental groups between 12 h and 24 h was significantly different (P<0.01). Moreover, RT-PCR results showed that the expression of Survivin and bcl-2 genes of leukemic cells in three experimental groups was reduced in varying degrees and the reduction of VLA-4 antibody combined with VP_(16) group was the most obvious. Conclusion BMSC plays a protective role on leukemic cells, and VLA-4 antibody can block the adhesion between BMSC and leukemic cells promoting leukemic cells apoptosis and enhance the sensibility of apoptosis of leukemic cells induced by chemotherapeutics.