No abstract

Although preliminary, these findings demonstrate that 9 months of combined androgen blockade resulted in a beneficial effect on verbal memory but adversely affected a measure of spatial ability. Intermittent androgen suppression for a period of 9 months in otherwise healthy men with prostate cancer may have beneficial and adverse effects on cognition that are selective.

The growing use of next generation-sequencing to identify cancer-associated alterations as well as the increasing number of targeted drugs holds promise for better matching patients with cancer with effective therapies. The FoundationOne (F1; Foundation Medicine) test sequences clinical tumor samples to characterize the exons of 315 cancer-associated genes and introns from 28 genes involved in rearrangements. The Guardant360 (G360; Guardant Health) test uses cell-free circulating DNA from blood to sequence 70 genes. Both the F1 and G360 tests have high specificities (>99%) and somewhat lower sensitivities. 1,2 However, little is known about how different next-generation sequencing tests compare when used in the same patients with cancer. We compared reports from F1 and G360 testing in 9 patients from a community oncology practice to determine the level of concordance between the platforms. Methods | This study was approved by the University of Washington Institutional Review Board. Patients consented to the study, titled "A Tumor Crowd Modeling Platform for Patients with Cancer," via an online patient information statement. Nine patients (mean [SD] age, 61 [19] years; 2 men and 7 women) underwent both F1 and G360 testing from April 14, 2015, to January 30, 2016. Patient reports from results of F1 tumor and G360 circulating tumor DNA testing were examined to generate a list of all genomic alterations detected by either assay and to assess concordance between reports. Reports from results

No abstract

Rituximab, a chimeric human immunoglobulin G1(IgG1) anti-CD20 monoclonal antibody has been shown to mediate cytotoxicity in malignant B cells via several mechanisms in vitro. These include direct antiproliferative and apoptotic effects, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Glucocorticoids (GCs) are often administered in conjunction with rituximab in chemotherapeutic regimens or as premedication to reduce infusion-related symptoms. The effects of GCs on CDC and ADCC, and the direct apoptotic and antiproliferative effects of rituximab are unknown. Therefore, we evaluated these mechanisms in 9 B-cell non-Hodgkin lymphoma (B-NHL) cell lines using rituximab and GCs. Rituximab and dexamethasone induced synergistic growth inhibition in 6 B-NHL cell lines. Dexamethasone and rituximab induced significant G1 arrest in 9 of 9 cell lines. The combination of rituximab and dexamethasone resulted in supra-additive increases in phosphatidylserine exposure and hypodiploid DNA content in 5 and 3 B-NHL cell lines, respectively. CDC and ADCC were neither impaired nor enhanced when dexamethasone and rituximab were administered concurrently. However, preincubation of both effector and tumor cells with dexamethasone reduced specific lysis in ADCC assays in 4 B-NHL cell lines. Preincubation of tumor cell lines with dexamethasone significantly increased cell sensitivity to CDC in 3 B-NHL cell lines. We conclude that the addition of dexamethasone to rituximab results in supra-additive cytotoxicity with respect to its direct antiproliferative and apoptotic effects, induces a cell-dependent increased sensitivity to rituximab-induced CDC, and has minimal negative impact on ADCC when used simultaneously with rituximab.