Mouse anti-Human CILP monoclonal antibody, clone 3D6

Purpose This analysis of patients in the Children's Oncology Group A3973 study evaluated the impact of extent of primary tumor resection on local progression and survival and assessed concordance between clinical and central imaging review-based assessments of resection extent. Patients and Methods The analytic cohort (n = 220) included patients who had both central surgery review and resection of the primary tumor site. For this analysis, resection categories of < 90% and >= 90% were used, with data on resection extent derived from operating surgeons' assessments (all patients), as well as blinded central imaging review of computed tomography scans for a subset of 84 patients; assessment results were compared for concordance. Treatment outcomes included event-free survival (EFS), overall survival (OS), and cumulative incidence of local progression (CILP). Results Surgeon-assessed extent of resection was >= 90% in 154 (70%) patients and, 90% in 66 (30%). Five-year EFS, OS, and CILP (+/- SE) were 43.5% +/- 3.7%, 54.9% +/- 3.7%, and 11.9% +/- 2.2%, espectively. EFS was higher with +/- 90% resection (45.9% +/- 4.3%) than with < 90% resection (37.9% +/- 7.2%; P = .04). Lower CILP (P = .01) was associated with >= 90% resection (8.5% +/- 2.3%) compared with < 90% resection (19.8% +/- 5.0%). On multivariable analysis, >= 90% resection was associated with longer EFS after adjustment for MYCN amplification or diploidy but had no significant effect on OS. Concordance between surgeons' assessments of resection extent and central image-guided review was low, with agreement of 63% (< 90% v >= 90%; simple k = -0.0301). Conclusion Despite discordance between clinical assessment of resection extent and assessment via central imaging review, a surgeon-assessed resection extent >= 90% was associated with significantly better EFS and lower CILP. Improving OS, however, remains a challenge in this disease. These findings support continued attempts at >= 90% resection of the primary tumor in high-risk neuroblastoma. (C) 2016 by American Society of Clinical Oncology

Background: Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-beta inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction. Results: Statistically significant interaction of the CILP rs2073711 T and ASPN D15 alleles with hand OA was observed (OR = 2.48, 95% CI 1.27-4.85, p = 0.008) in a Finnish hand. OA cohort of 543 women (aged. 45-63). When stratified by variation in working tasks, low variation of working tasks increased the risk further (OR = 3.00, 95% CI 1.35-6.66, p = 0. 007). Based on the analysis of ASPN and CILP protein-coding regions, functional studies were performed with one observed variant, rs41278695 in the ASPN 'gene. Analyses showed that bone morphogenetic protein 2 (BMP2) mediated expression of aggrecan (Agc1) and type II collagen (Col2a1) was significantly suppressed (p = 0.011 and p = 0.023, respectively) in a murine chondrocytic cell line (ATDC5) with cells stably expressing ASPN rs41278695. Conclusions: The carriage of either ASPN D15 or CILP rs2073711 TT is associated, with increased risk of symmetrical hand. OA, particularly in individuals with low variation in work tasks. ASPN rs41278695 SNP had an effect on Agc1 and. Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition.