Mass Forming Eosinophilic Cystitis in Pediatric Patients.

Eosinophilic cystitis (EC) is an uncommon inflammatory disorder of uncertain etiology that has been described in adult and pediatric populations. We describe 3 recent cases of EC that presented as a mass lesion in pediatric patients from the New England region of the United States. All patients were initially suspected to have a malignancy, and biopsy was performed, which ultimately led to the diagnosis of EC. We propose the use of eosinophil density of >25 eosinophils per high-power field and myocyte degeneration as supportive histopathologic features to make this diagnosis. It is of utmost importance to consider EC in the differential diagnosis when approaching a pediatric patient with a bladder mass.

Robot-assisted laparoscopic lower pole partial nephrectomy in the pediatric patient.

INTRODUCTION: In pediatric urology, partial nephrectomy is used primarily to remove a non-functioning renal moiety in a duplicated system. There are few data on infants undergoing this procedure. As such, we present a robot-assisted laparoscopic lower pole partial nephrectomy in an infant. METHODS: Our patient was an 11-month-old (10.7 kg) male with a history of prenatal hydronephrosis, who was diagnosed postnatally with a duplicated right collecting system and severe hydroureteronephrosis of the right lower collecting system. A DMSA scan demonstrated no radiotracer uptake in the right lower pole. A robot-assisted laparoscopic lower pole partial nephrectomy was performed. RESULTS: A lower pole partial nephrectomy was accomplished. At 1 month postoperatively, an ultrasound demonstrated no hydronephrosis or perinephric fluid collection. CONCLUSIONS: Robotic partial nephrectomy is safe and feasible in pediatrics including both older children and infants. It is successful for both upper and lower pole partial nephrectomies.

Histone Deacetylase Inhibitors Enhance the Therapeutic Potential of Reovirus in Multiple Myeloma.

Multiple myeloma remains incurable and the majority of patients die within 5 years of diagnosis. Reolysin, the infusible form of human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis and a virus-mediated antitumor immune response. Results from our phase I clinical trial investigating single agent Reolysin in patients with relapsed multiple myeloma confirmed tolerability, but no objective responses were evident, likely because the virus selectively entered the multiple myeloma cells but did not actively replicate. To date, the precise mechanisms underlying the RV infectious life cycle and its ability to induce oncolysis in patients with multiple myeloma remain unknown. Here, we report that junctional adhesion molecule 1 (JAM-1), the cellular receptor for RV, is epigenetically regulated in multiple myeloma cells. Treatment of multiple myeloma cells with clinically relevant histone deacetylase inhibitors (HDACi) results in increased JAM-1 expression as well as increased histone acetylation and RNA polymerase II recruitment to its promoter. Furthermore, our data indicate that the combination of Reolysin with HDACi, potentiates RV killing activity of multiple myeloma cells in vitro and in vivo This study provides the molecular basis to use these agents as therapeutic tools to increase the efficacy of RV therapy in multiple myeloma. Mol Cancer Ther; 15(5); 830-41. ©2016 AACR.

Reps2: a cellular signaling and molecular trafficking nexus.

Since its discovery in the late 1990s as a signaling molecule in the Ras/Ral pathway, Reps2 has emerged as an important player in receptor-mediated endocytosis. Reps2 contains Eps15 homology (EH) domains, proline-rich regions, and a coiled-coil domain that engage in several protein-protein interactions to coordinate the internalization of various receptors with molecular signaling. Reps2 has clinical importance as it suppresses the ability of its binding partner RalBP1 to transport chemotherapeutic drugs, such as doxorubicin, out of a cell. Reps2 is also dysregulated during the progression of prostate cancer and is a potential biomarker for breast and prostate cancer.