1.Effects of genomic HLA-DR compatibility on long-term survival in first-cadaver kidney transplants
Chinese Journal of Organ Transplantation 2000;21(2):109-111
Objective To study the effect of genomic HLA-DR compatibility on long-term survival in renal transplantation.Methods A retrospective study was performed on 518 first-cadaver renal transplants by using genotyping technique.Results More than 10%recipients shared HLA-DR matching at DNA level.half of 1 DR mismatches.The recipients with HLA-DR matched transplants showed a significant decrease of acute rejection episodes and a smooth recovery of early renal function as compared with those of DR mismatching kidneys.The 1 to 5 year-person survival rate was increased by 17%to 37.7% (P<0.01)respectively.Multivariate analysis of 10 variables by Cox regression model revealed that DR mismatching was the most important factors influencing the long-term graft survival.Conclusion Genomic HLA-DR compatibility had a significant impact on long-term survival of first-cadaver kidney transplantation.
2.Neoral C2 monitoring in Chinese renal transplantation recipients
Chinese Journal of Urology 2001;0(03):-
Objective To explore the single point target concentration for Neoral at 2 h postdose (C2) in Chinese renal transplantation recipients for the first 3 months following surgical procedures. Methods Neoral trough levels (C0) and C2 monitoring were measured by fluorescence polarization immunoassay (TDX) in 114 cases of cadaver renal transplants treated with Neoral (6~7 mg?kg -1 ?d -1 ), mycopherolate mofetil (MMF,1.0~1.5 g/d) and steroids for the first 3 months after renal transplantation.The effectiveness of the new monitoring method in predicting the acute rejection and side effects was retrospectively analyzed. Results The acute rejection rate of 114 transplants for the first 3 months was 15.8%(18/114).The incidence of side effects was 30.7% (35/114),including hepatoxicity(26.3%) and nephrotoxicity(7.0%).The results of 234 pairs of Neoral C0, C2 monitoring showed that the difference was not statistically significant between C0 levels of rejection and non rejection,while the difference between C2 levels [(921.55 ?431.31) vs (1 185.17?358.86)ng/ml) ] was significant.There was also no statistically significant between C0 levels of the recipients with side effects and those without side effects,but statistically significant difference was found between C2 levels [(1 302.59?450.21) vs (1 105.23? 371.64 )ng/ml].Analysis of the relationships between C2 levels and the incidences of acute rejection and side effects showed that no acute rejection and side effects rate of 4.3% were observed in the Neoral C2 interval from 1 250 ng/ml to 1 500 ng/ml. Conclusions Neoral C2 monitoring is a more sensitive predictor not only for acute rejection but also for side effect rate.The optimal C2 target level of Chinese renal transplantation recipients is 1 250 ~1 500 ng/ml for the first 3 months post transplantation.
3.The prospective randomized study on prevention of cadaveric renal allograft rejection by Tacrolimus (FK506)
Xianghui WANG ; Xiaoda TANG ; Da XU
Chinese Journal of Organ Transplantation 2000;21(2):117-118
Objective To compare the efficacy and safety of Tacrolimus(FK506)and Neoral CsA in conjunction with MMF(2.0g/d)and steroid in preventing renal allograft rejection.Methods 98 cases of renal transplant recipients were randomly divided into two groups:FK506 group(n=40),receiving tacrollimus,MMF and prednison(Pred);CsA group(n=58),receiving CsA,MMFand Pred.Results The mean follow-up time in both two groups Was 12.5 months.Acute transplanted renal rejection occurred in 2 cases in FK506 group and 9 cases in CsA group respectively.The one-year person/kidney survival rate was 100%/100%in FK506 group and 100%/94.8%in CsA group respectively.The dosage of Pred in FK506 group was lower than in CsA group.12 cases in FK506 group had stopped using Pred.Hypergly cermia occurred in 7 cases in FK-506 group.Polytricosis,gingival hyperplasia and liver function disorder dominantly occurred in CsA group.Infection Was found in 9 cases of FK506 group and 11 cases of CsA group respectively.Conclusion FK506 combined with MMF could decrease the occurrence of acute trans planted renal rejection and the dosage of Pred.The good adjustment of the dose of FK506 iS helpful for re ducing the side effects and preventing rejection.
4.Down-regulation of midkine by small interfering RNA increase chemosensitivity in bladder cancer cells
Yu FAN ; Xiao GU ; Xiaoda TANG
Chinese Journal of Urology 2010;31(9):604-607
Objective To study the effects of knock down midkine(MK)by siRNA on chemosinsitivity in bladder cancer cells. Methods Three MK siRNAs were designed and constructed. After transfected with MK siRNA or scrambled siRNA for different time, cultured cells were harvested to carry on the next experiments. Expression of MK was determined by real-time RT-PCR and western blot, and apoptosis were evaluated by caspase-3 activity and TUNEL assay. MTT was performed to examine the inhibition effect of Paclitaxel (PTX) on cells. Results MK siRNA could down-regulate the MK expression in a dose- and time-dependent manner. The MTT results showed that the inhibit rates were (18.21±0.36)%, (18.19±0.29)%, (17.89±0.33)%, (1.86±0.52)%, (32.56±0.53) %, (53. 83±0.38) % and (78. 95±0.55) % in different groups PTX alone(0.2μmol/L), ConA +PTX(0.2 μmol/L), Con-B +PTX(0.2 μmol/L), siRNA alone(12. 50 nmol/L), siRNA(3. 125nmol/L) + PTX (0. 2 μmol/L), siRNA (6. 25 nmol/L) + PTX (0. 2 μmol/L) and siRNA (12. 50nmol/L)+PTX(0.2 μmol/L), respectively. The TUNEL results showed that apoptosis index was (1.81 ±0. 36)%, (1. 89±0. 38)%, (5. 56±0. 58)%, (9. 68±0.55)% and (15. 25±0.56)% in different groups (Con-A, Con-B, siRNA (3. 125 nmol/L), siRNA (6. 25 nmol/L) and siRNA ( 12. 5nmol/L), respectively. The activity of caspase-3 increased significantly in transefected cells with a dose-and time-dependent manner. Conclusion MK siRNA could sensitize human bladder cancer cells to chemotherapy which might be through the apotosis.
5.Role of androgen receptor in the pathogenesis of human prostate cancer
Xiwu FANG ; Shujie XIA ; Xiaoda TANG
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To investigate molecular mechanisms associated with the acquisition of androgen-independent growth of human prostate cancer during progression. METHODS: Upon continuously passaging, the androgen-independent LNCaP cell model was established. The expression of AR and PSA proteins in the course of prostate cancer progression was determined by Western blot. RESULTS: Upon continuous passage, the biological behavior of androgen-dependent parental LNCaP C-33 cells (passage number less than 33) was altered. LNCaP C-81 cells (passage number higher than 80) exhibited more aggressive growth and lower androgen-dependence than C-33 and C-51 cells (passage number between 33 and 80). C-81 cells secreted a higher level of PSA and the degree of DHT stimulation on PSA secretion was lower in C-81 cells than C-33 cells. The three LNCaP subclones expressed a similar level of total AR protein, but C-81 cells showed a characteristic loss of expression of the AR-B and increase in expression of the AR-A. CONCLUSION: Multiple factors, including the different expression of AR isoforms, contribute to the development of androgen-independent growth of prostatic carcinoma cells. [
6.Expression and clinical implication of CC chemokines and receptor in long-term survived renal transplant recipients
Xiao GU ; Xiaoda TANG ; Jiaquan XIAO
Chinese Journal of Urology 2000;0(12):-
Objective To investigate the expression and clinical implication of CC chemokines and receptor in long surviving kidney grafted patients of different immune states. Methods 73 cases of recipients surviving more than 3 years were divided into three groups: control group of normal renal function(C group,n=32), group under low dosage of immunosuppressants(L group,n=20) and group with chronic allograft dysfounction(D group,n=21). The plasma RANTES、MCP 1 and MIP 1?were detected by sandwich ELISA.The expression of CCR5 was determined by flow cytometry(FACS). Results Concentrations of RANTES and MIP 1? as well as expression rate of CCR5 in L group were lower than those of C group ( P 0.05).Plasma level of MCP 1 was significantly higher in group D than that in group C( P 0.05). Conclusions Expression of CC chemokines and receptor closely correlated with the immune state of renal transplant recipients and could be valuable to estimate and monitor the immune state of patients.
7.The efficacy and safety of Prostant~(TM) in the treatment of chronic prostatitis:a multi center, randomized, double blinded, placebo controlled trial
Gang XU ; Jun LU ; Xiaoda TANG
Chinese Journal of Urology 2000;0(05):-
Objective To evaluate the efficacy and safety of Prostant TM in the treatment of chronic prostatitis. Methods A multi center, randomized, double blinded, placebo controlled trial was carried out during March 2001 and May 2001. 72 cases of patients who had been diagnosed as chronic prostatitis were separated into tow groups: 36 cases in the trial group treated with Prostant TM and the other 36 cases in the controlled group using placebo. The efficacy was evaluated by the WBC in EPS and NIH Chronic Prostatitis Symptom Index after a one month follow up. The efficacy of the therapy was divided into four levels:cure,the symptom index score being reduced over 90%, and the number of WBC in the EPS less than 10/HP; effective, the symptom index score being reduced 60%~89% and the number of WBC in the EPS lowered over 50% or less than 15/HP;improved,the symptom index score being reduced 30%~59% and the number of WBC in the EPS lowered over 25%; no effect, the symptom index score being reduced less than 30% or the number of WBC in the EPS lowered no more than 25%. Results All but two cases had completed the follow up.One case (2.8%) was completely cured,remarkable effective in 7 cases (20.0%) of the trial group;and improred in 16 cases (45.7%).Only 2 cases (5.7%)seemed effective and 8 cases (22.8%) improved in the controlled group. The efficacy showed significant difference between these two groups ( P
8.The effect of NF-?B decoy on the chemokine expression of human bladder cancer cell line
Donghua XIE ; Xiaoda TANG ; Shujie XIA
Chinese Journal of Urology 2000;0(05):-
Objective To investigate the effect of nuclear factor ?B(NF-?B)decoy on the chemokine expression in bladder cancer cell line. Methods Human bladder cancer cell line EJ,NF-?B decoy ODN were used as a NF-?B inhibitor(scrambled NF-?B decoy was used as control).NF-?B DNA binding activity was detected by electrophoretic mobility shift assay (EMSA);and p65 subunit of NF-?B was detected by RT-PCR and Western blot.Chemokines including IL-8,MCP-1,RANTES were detected by RT-PCR. Results EMSA showed that NF-?B decoy inhibited NF-?B activation induced by TNF-?.RT-PCR or Western blot test suggested that p65,IL-8,MCP-1 and RANTES were upregulated by TNF-? and downregulated by NF-?B decoy.However,mutated decoy ODN had no effect on them. Conclusions Chemokines can be detected in bladder cancer.They are activated by TNF-? and inhibited by NF-?B decoy.
9.Microenviroment character of immune response under dominant regulation
Yong LIU ; Xiaoda TANG ; Jianming TAN
Chinese Journal of Organ Transplantation 1996;0(04):-
Objective To observe the dynamic change of cytokines and effect of different stimulating combinations on dominant regulation, and describe the microenviroment character of local immune response. Methods PBMCs were separated from peripheral blood of healthy donors with density gradient centrifugation. The expression levels of cytokine genes under different stimulating combinations, including IL-2, IFN-?, IL-12, IL-4, IL-10 and TGF-?1, were detected by ELISA and RT-PCR. Results ELISA results indicated that secretion level of IL-2, IL-4, IL-12 and IFN-? were inhibited by IL-10. There were significant differences in IL-4 and IL-12 between control group and stimulating groups under the stimulation by anti-CD3 monoclonal antibody (McAb) or anti-CD3 McAb + anti-CD28 McAb combination. Significant differences in IL-2 only appeared in anti-CD3 antibody stimulating group. The concentrations of IFN-? were decreased moderately. At the mean time, IL-10 significantly promoted the secretion of TGF-?1 under the anti-CD3 McAb stimulation. There were similar results on the genes level for the studied cytokines. Conclusion The induction and maintenance of dominant regulation were dependent mainly on IL-10, which inhibits the overexpression of IL-4 and IL-12. It is the vital step for dominant regulation to avoid the mono-polarization development at the beginning of immune response.
10.Establishment of androgen-independent human prostate cancer cell strain,LNCaP C-81
Xiwu FANG ; Shujie XIA ; Xiaoda TANG
Chinese Journal of Urology 1994;0(02):-
Objective To establish and validate andro ge n-independent human prostate cancer LNCaP cell model. Methods Androgen-dependent LNCaP parental C-33 cells were maintained in a regul ar cell-culture medium,that is,phenol red-positive RPMI 1640 medium supplement ed with 10% fetal bovine serum,1% glutamine and 0.5% gentamicin.Upon continuousl y passaging,androgen-dependence of these LNCaP cells decreased gradually,thus,t he androgen-independent LNCaP cell model which derived from androgen-dependent cells was established. Results Upon continuous passage, the biological behavior of androgen-dependent parental LNCaP C-33 cells (pass age number less than 33) was altered.LNCaP C-81 cells (passage number higher th an 80) clearly exhibited more aggressive growth and lower androgen-dependence t han C-33 and C-51 cells (passage number between 34 and 81) in vitro and in viv o. Conclusions The LNCaP cell model closely recapitulate s the transition of human prostate cancer from androgen-dependent to hormone-r efractory state under the androgen nondeprived condition. This cell model may pr ovide the opportunity to understand the molecular mechanisms involved in the and rogen-independent growth of cancer cells during prostate cancer progression.