Using an alpha v beta 6-positive 5-Fluoracil order (DX3-beta 6) xenograft model, we observed a similar to 2-fold enhancement in tumor uptake over Ad5-EGFPWT following systemic delivery. Furthermore, similar to 5-fold-fewer Ad5-EGFP(A20) genomes were detected in the liver (P = 0.0002),correlating with reduced serum transaminase levels and E1A expression. Warfarin pretreatment, to deplete coagulation factors, did not improve
tumor uptake significantly with either virus but did significantly reduce liver sequestration and hepatic toxicity. The ability of Ad5-EGFP(A20) to improve delivery to alpha v beta 6, combined with its reduced hepatic tropism and toxicity, highlights its potential as a prototype virus for future clinical investigation.”
“Background
Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter).
Methods
Children with standard-risk hepatoblastoma who were younger
than 16 years of age were eligible for inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered CA3 manufacturer in three preoperative cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection).
Results
Between June 1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone
group and 93% in the cisplatin-doxorubicin group in the intention-to-treat unless analysis (difference, 1.4%; 95% confidence interval [CI],-4.1 to 7.0); these rates were 99% and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to 98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent with combination therapy (74.4% vs. 20.6%).
Conclusions
As compared with cisplatin plus doxorubicin, cisplatin monotherapy achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number, NCT00003912.)”
“In pro- and eukaryotic cells, RuvB-like protein 2 (RBL2) resolves Holliday junction recombination intermediates.