RESUMEN
Synovial sarcoma (SS) is a pediatric muscle cancer that primarily affects adolescents and young adults and has few treatment options. Complicating the treatment of synovial sarcoma is the low mutational burden of SS. Inflammatory pathways have been identified as being upregulated in some SS, leading to the discovery of upregulated oncostatin M receptor (OSMR). It was found that OSMR is upregulated in SS by RNAseq analysis and quantitative PCR, highlighting its potential in the treatment of SS. Also, OSMR is upregulated in mouse models for synovial sarcoma as demonstrated by western blot and immunohistochemistry, and the protein is present in both primary and metastatic sites of disease. Using a radioimmune therapy drug model, targeted therapy was synthesized for use in OSMR expressing SS and it was demonstrated that this drug is stable, while capable of efficient OSMR binding and isotope capture. Finally, this antibody conjugate exhibited ideal pharmacokinetics and targeted sites of disease in our mouse model and was taken up in both primary and metastatic diseased tissue. This suggests OSMR as an ideal target for therapy and this radioimmune therapy provides a novel treatment option for a disease with few therapy choices.
RESUMEN
Optimizing peak bone mass is critical to healthy aging. Beyond the established roles of dietary minerals and protein on bone integrity, fatty acids and polyphenols modify bone structure. This study investigated the effect of a diet containing hempseeds (HS), which are rich in polyunsaturated fatty acids and polyphenols, on bone mineral density, bone cell populations and body composition. Groups (n = 8 each) of female C57BL/6 mice were fed one of three diets (15% HS by weight; 5% HS; 0% HS (control)) from age 5 to 30 weeks. In vivo whole-body composition and bone mineral density and content were measured every 4 weeks using dual-energy X-ray absorptiometry. Ex vivo humeri cell populations in the epiphyseal plate region were determined by sectioning the bone longitudinally, mounting the sections on slides and staining with tartrate-resistant acid phosphatase and alkaline phosphatase stain to identify osteoclasts and osteoblasts, respectively. Mixed models with repeated measures across experimental weeks showed that neither body weight nor body weight gain across weeks differed among groups yet mice fed the 15% HS diet consumed significantly more food and more kilocalories per g body weight gained than those fed the 5% HS and control diets (p < 0.0001). Across weeks, fat mass was significantly higher in the 5% HS versus the control group (p = 0.02). At the end point, whole-body bone mineral content was significantly higher in the control compared to the 5% HS group (p = 0.02). Humeri from both HS groups displayed significantly lower osteoblast densities compared to the control group (p < 0.0001). No relationship was seen between osteoblast density and body composition measurements. These data invite closer examination of bone cell activity and microarchitecture to determine the effect of habitual HS consumption on bone integrity.