Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.

Type 1 diabetes (T1D) negatively influences skeletal muscle health; however, its effect on muscle satellite cells (SCs) remains largely unknown. SCs from samples from rodents (Akita) and human subjects with T1D were examined to discern differences in SC density and functionality compared with samples from their respective control subjects. Examination of the Notch pathway was undertaken to investigate its role in changes to SC functionality. Compared with controls, Akita mice demonstrated increased muscle damage after eccentric exercise along with a decline in SC density and myogenic capacity. Quantification of components of the Notch signaling pathway revealed a persistent activation of Notch signaling in Akita SCs, which could be reversed with the Notch inhibitor DAPT. Similar to Akita samples, skeletal muscle from human subjects with T1D displayed a significant reduction in SC content, and the Notch ligand, DLL1, was significantly increased compared with control subjects, supporting the dysregulated Notch pathway observed in Akita muscles. These data indicate that persistent activation in Notch signaling impairs SC functionality in the T1D muscle, resulting in a decline in SC content. Given the vital role played by the SC in muscle growth and maintenance, these findings suggest that impairments in SC capacities play a primary role in the skeletal muscle myopathy that characterizes T1D.

Introduction: We sought to evaluate the accuracy of prostate volume estimates in patients who received both a preoperative transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) in relation to the referent pathological specimen post-radical prostatectomy. Methods: Patients receiving both TRUS and MRI prior to radical prostatectomy at one academic institution were retrospectively analyzed. TRUS and MRI volumes were estimated using the prolate ellipsoid formula. TRUS volumes were collected from sonography reports. MRI volumes were estimated by two blinded raters and the mean of the two was used for analyses. Pathological volume was calculated using a standard fluid displacement method. Results: Three hundred and eighteen (318) patients were included in the analysis. MRI was slightly more accurate than TRUS based on interclass correlation (0.83 vs. 0.74) and absolute risk bias (higher proportion of estimates within 5, 10, and 20 cc of pathological volume). For TRUS, 87 of 298 (29.2%) prostates without median lobes differed by >10 cc of specimen volume and 22 of 298 (7.4%) differed by >20 cc. For MRI, 68 of 298 (22.8%) prostates without median lobes differed by >10 cc of specimen volume, while only 4 of 298 (1.3%) differed by >20 cc. Conclusions: MRI and TRUS prostate volume estimates are consistent with pathological volumes along the prostate size spectrum. MRI demonstrated better correlation with prostatectomy specimen volume in most patients and may be better suited in cases where TRUS and MRI estimates are disparate. Validation of these findings with prospective, standardized ultrasound techniques would be helpful.

Second malignancies of the abdomen-pelvis are uncommon in men with low-grade testicular cancer. In this study, the risk of second cancer was not associated with the amount of diagnostic radiation exposure.

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