[Impact of PEG-packed islets upon anti-rejection therapy in homogeneous murine islet transplantation].

OBJECTIVE: To investigate the impact of polyethylene glycols (PEG) upon islet survival in homogeneous murine islet transplantation and understand the impact of PEGylation in combination with rapamycin upon anti-rejection therapy in homogeneous mice islet transplantation. METHODS: The subcutaneously pre-vascularized STZ-induced diabetic mice treated with transplanted islets of BALB/c mice were randomly divided into 6 groups: Group A with normal mice islets; Group B with PEG-packed islets; Group C with normal mice islets and 1.5 mg x kg(-1) x d(-1) rapamycin; Group D with PEG-packed islets and 1.5 mg x kg(-1) x d(-1) rapamycin; Group E with normal mice islets and 3 mg x kg(-1) x d(-1) rapamycin; Group F with PEG-packed islets and 3 mg x kg(-1) x d(-1) rapamycin. The post-transplantation blood glucose was monitored. Transplanted islets were analyzed by H&E and insulin immunostain. RESULTS: The survival time in group B was significantly prolonged as compared with group A (P < 0.01). The survival time in group C were (35.0 +/- 3.1) d and groups D, E, F had survival of up to 6 weeks. Transplantation sites of group A were observed with a more abundant infiltration of immune cells than group B. And the unmodified islets in group A were completely destroyed after transplantation. Insulin-positive islet cells were not detected at the entire transplantation site in group A while the presence was found at the transplantation site in group B. CONCLUSION: PEG-packed islets can significantly improve the survival time of transplanted islets. When combined with rapamycin, it can reduce the dose of rapamycin.

A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer.

This study compared the short-term efficacies of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) through pair-wise and network meta-analyses (NMA). Randomized controlled trials (RCTs) identified in a comprehensive online literature search met our inclusion criteria. Direct and indirect evidence was combined to compare odds ratios (OR) and surfaces under the cumulative ranking curves (SUCRA) across the different treatment regimens. Twelve eligible RCTs were finally included, involving eight regimens (Paclitaxel + Carboplatin [PC], Gemcitabine + Carboplatin [GC], Carboplatin, Pegylated Liposomal Doxorubicin + Carboplatin [PLD + Carboplatin], Paclitaxel, Paclitaxel + Carboplatin + Topotecan [PC + Topotecan], Paclitaxel + Carboplatin + Epirubicin [PC + Epirubicin] and Docetaxel + Carboplatin [DC]). The NMA results revealed that in terms of overall response rate (ORR) and disease control rate (DCR), PC (ORR: OR=2.59, 95%CI=1.20-6.22; DCR: OR=2.58, 95%CI=1.05-6.82) and GC (ORR: OR=2.08, 95%CI=1.08-4.37; DCR: OR=2.43, 95%CI=1.07-5.80) were more effective against AOC than Carboplatin alone. Similarly, PC (OR=0.21, 95%CI=0.05-0.69), GC (OR=0.31, 95%CI=0.09-0.90) and PLD + Carboplatin (OR=0.22, 95%CI=0.04-0.92) slowed disease progression better than Carboplatin alone. We also found that PC was more efficacious against AOC than Carboplatin or Paclitaxel single-agent chemotherapy. Combination chemotherapy is thus recommended for AOC, and should guide subsequent drug development and treatment strategies.

[Effect of heme oxugenase-1 on delayed xenograft rejection: experiment of guinea pig-to-rat liver xenotransplantation].

OBJECTIVE: To investigate the effects and mechanism of heme oxygenase-1 (HO-1) in liver xenotransplantation and mechanism thereof. METHODS: Thirty male guinea-pigs used as donors were injected intravenously with cobra venom factor (CVF) and then randomly divided into 3 groups 24 hours after: Group A injected intraperineally with NaCl, Group B injected intraperineally with cobalt-protoporphyrin (CoPP), heme oxygenase-1 inducer, and Group C injected intraperineally with CoPP and zinc protoporphyrin (ZnPP), HO-1 inhibitor zinc before their livers were harvested. Thirty male SD rats used as recipients underwent the above-mentioned treatment 24 hours before receiving the xenografts. Five pairs of guinea pigs and rats in each group underwent collection of blood and liver tissues 3 hours after the recovery of blood perfusion in the transplanted livers for detection of serum enzymes by biochemical methods and expression of HO-1 mRNA and protein in the transplanted livers by RT-PCR and Western blotting respectively. The other 5 pairs in each group were used to observe the survival time. RESULTS: The survival time of Group B was 15.5 h +/- 3.8 h, significantly longer than those of Group A (7.3 h +/- 2.1 h) and Group C (6.7 h +/- 2.9 h, both P < 0.01). The values of ALT and LDH of Group B were significantly lower than those of Group A and C (all P < 0.05). HOI-1 mRNA expression was not detected or only expressed in trace amount in the livers of normal guinea pigs, expressed in a small amount in the transplanted livers of Group A. The expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group B were significantly higher than those of Group A (both P < 0.01), and the expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group C were not significantly different from those of Group A (both P > 0.05). Remarkable NF-kB band was detected in Groups A and C, and only weak NF-kB band was seen in Group B. The E-selectin expression was significantly lower in the transplanted livers of Group B than in those of Group A and C (both P < 0.05). CONCLUSION: HO-1 delays the occurrence of delayed xenograft rejection in liver xenotransplantation. This effect depends, at least in part, on HO-1-mediated inhibition of endothelium activation in xenografts.