Anti-CENPB monoclonal antibody Made to order

The oncogenic transcription factor forkhead box Ml (FoxMl) is overexpressed in a number of different carcinomas, whereas its expression is turned off in terminally differentiated cells. For this reason, FoxMl is an attractive target for therapeutic intervention in cancer treatment. As a first step toward realizing this goal, in this study, using a high-throughput, cell-based assay system, we screened for and isolated the antibiotic thiazole compound Siomycin A as an inhibitor of FoxMl. Interestingly, we observed that Siomycin A was able to down-regulate the transcriptional activity as well as the protein and mRNA abundance of FoxMl. Consequently, we found that the downstream target genes of FoxMl, such as Cdc25B, Sarvivin, and CENPB, were repressed. Also, we observed that consistent with earlier reports of FoxMl inhibition, Siomycin A was able to reduce anchorage-independent growth of cells in soft agar. Furthermore, we found that Siomycin A was able to induce apoptosis selectively in transformed but not normal cells of the same origin. Taken together, our data suggest that FoxMl inhibitor Siomycin A could represent a useful starting point for the development of anticancer therapeutics.

Background: Autoantibodies (autoAbs) help in diagnosis and predicting clinical phenotypes in systemic sclerosis (SSc).Aim of the study: To determine the clinical utility of 13 SSc-related autoAbs in SSc patients.Material and methods: A total of 131 consecutive patients with SSc (111 female, mean age 58.114 years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc [lcSSc]) were analysed by a multiplex line immunoassay (Euroimmun) for autoantibodies (autoAbs) against 13 SSc-related antigens. A total of 22 patients with primary Raynaud phenomenon (RP), and 22 healthy controls were also analysed.Results: ANA by indirect immunofluorescence was present in 128 (97.7%) patients with SSc. Excluding anti-Ro52, 113 (89.3%) SSc patients were positive for at least one autoAb: anti-Topoisomerase I (anti-Topo) I abs in 54 (41.2%), anti-centromere proteins (anti-CENP) in 37 (28.2%, all reactive with centromere protein-A (CENPA) and centromere protein B (CENPB)), anti-RNA polymerase III(RP11) in 19 (14.5%), anti-RNA polymerase III(RP155) in 13 (9.9%), anti-fibrillarin in 4 (3.1%), anti-Ku in 6 (4.6%), anti-nucleolus-organizing region (anti-NOR90) in 8 (6.1%), anti-PM-Scl100 in 2 (1.5%), and anti-PM-Scl75 in 4 (3.1%). There was no immunoreactivity for Th/To or platelet-derived growth factor receptor (PDGFR). Overall, 102 (77.9%) SSc patients had autoAbs against Topo I, CENPA or CENPB, RP11 or RP155. Anti-Topo I abs were strongly associated with dcSSc, interstitial lung disease (ILD) (p<.001), pulmonary hypertension (PH) (p=.019) and ILD-PH (p=.003). Anti-CENPB abs were associated with lcSSc, and negatively associated with ILD. Anti-RP11 and anti-NOR90 abs were associated with male gender, and anti-NOR90 associated with ILD.Conclusions: Anti-Topo I, anti-CENP, and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and anti-NOR90 abs are associated with ILD and/or PAH.