Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti-tumor effects.CONCLUSION: Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.

Enrichment of Organic-Inorganic Se and Vitamin E in Quail Products and Its Effect on the Performances and Source of Antioxidant in Quails＇ Eggs

This study aimed to get an optimum level of combined organic selenium, inorganic selenium and vitamin E in obtaining the best production and reproduction of quails as well as the highest antioxidant level in quail eggs. Seven hundred twenty quails （360 females and 360 males） at the age of six weeks old were used in this research. Nine treatment diets were： To （commercial diet/control）, Tl （diet containing 0.46 ppm inorganic Se ＋ 43.50 ppm vitamin E）, T2 （diet containing 0.46 ppm inorganic Se ＋ 87.00 ppm vitamin E）, T3 （diet containing 0.92 ppm inorganic Se ＋ 43.50 ppm vitamin E）, T4 （diet containing 0.92 ppm inorganic Se ＋87.00 ppm vitamin E）, Ts （diet containing 0.46 ppm organic Se ＋ 43.50 ppm vitamin E）, T6 （diet containing 0.46 ppm organic Se ＋ 87.00 ppm vitamin E）, T7 （diet containing 0.92 ppm organic Se ＋ 43.50 vitamin E） and Ts （diet containing 0.92 ppm organic Se 0.92 ＋ 87.00 ppm vitamin E）. The design of the experiment was a factorial nested design. Any significant differences among the treatments were analyzed by using Duncan＇s test. The results of this study indicated that 0.92 ppm organic selenium ＋ 43.50 ppm vitamin E （T7） in general gave the highest content of selenium in meat, in egg albumin, and in egg yolk as well as hatchability. The antioxidants as represented by vitamin E and glutathione peroxidase enzyme in the quail eggs were significantly higher as compared to that of quails fed other treatment diets.

Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation:long-term follow-up of a multicenter,randomized controlled trial

Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.