Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers.

Background: Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.

Methods: We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients.

Silver In Situ Hybridization for the Rapid Assessment of MDM2 Amplification in Soft Tissue and Bone Tumors. Validation Based on an Audit of 192 Consecutive Cases Evaluated by Silver In Situ Hybridization and Fluorescence In Situ Hybridization.

The discovery of almost invariable mouse double minute 2 (MDM2) amplification among atypical lipomatous tumors (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma is incorporated into the contemporary diagnostic workup of fatty lesions. MDM2 amplifications are also found frequently in intimal sarcomas and in low-grade osteogenic sarcoma. At present, fluorescence in situ hybridization (FISH) is the reference test for MDM2 assessment.

Causes of ring-related leg injuries in birds - evidence and recommendations from four field studies.

One of the main techniques for recognizing individuals in avian field research is marking birds with plastic and metal leg rings. However, in some species individuals may react negatively to rings, causing leg injuries and, in extreme cases, the loss of a foot or limb. Here, we report problems that arise from ringing and illustrate solutions based on field data from Brown Thornbills (Acanthiza pusilla) (2 populations), Siberian Jays (Perisoreus infaustus) and Purple-crowned Fairy-wrens (Malurus coronatus).

Potent and selective nonpeptidic inhibitors of procollagen C-proteinase.

6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux.