Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we identified B7-H3 as the major immunoregulatory molecule expressed by RMS tumors. By using a large cohort of tissue specimens, we demonstrated that B7-H3 is expressed in a majority of RMS tumors while not detected in normal human tissues. Through a deconvolution analysis of the RMS tumor RNA-seq data, we showed that B7-H3-rich tumors are enriched in macrophages M1, NK cells, and depleted in CD8+-T cells. Furthermore, in vitro functional assays showed that B7-H3 knockout in RMS tumor cells increases T-cell mediated cytotoxicity. Altogether, our study uncovers new potential targets for the treatment of RMS and provides the first biological insights into the role of B7-H3 in RMS biology, paving the way for the development of next-generation immunotherapies.
1 December 2007 in The International Journal of Medical Robotics and Computer Assisted Surgery
We describe our experience with robot assisted complex lower urinary tract reconstruction (CUTR) in patients with previous open abdominal surgery (PAS). Patients with any PAS undergoing robot assisted CUTR were included. CUTR was defined as bladder neck reconstruction (BNR) or continent catheterizable conduits (CCC) or both, redo surgery at the bladder neck for persistent incontinence, or any of the above with an antegrade enema channel creation (MACE). Ureteral and renal surgeries were excluded. Patient demographics, surgery performed, operative techniques, operative times and outcomes were assessed. 36 patients met inclusion. 21 patients had multiple laparotomies for ventriculoperitoneal (VP) shunt revisions. 15 had laparotomy with other adjunct procedures in 14 and laparotomy with colostomy in 1. There were no access injuries and 5 conversions. Mean operative time was 8.2 hrs (4-12 hrs). Mean length of stay (LOS) was 74.9 hrs (23-216 hrs). The first 18 cases took longer than the last 18 cases (mean 9.1 hr vs mean 7.5 hr p= 0.002). Patients with multiple VP shunt revisions had higher conversion rates and higher mean operative times when compared to other patients (p=0.01 and p=0.002 respectively). Patients with multiple VP shunt revisions had longer LOS when compared to other patients (p= 0.02). Robot assisted CUTR in patients with PAS is safe and feasible. Longer operative times should be expected early in a surgeon’s experience. Multiple VP shunt revisions have higher conversion rates and longer operative times when compared to other indications for previous surgery.