Synthesis and Optimization of 1-Substituted Imidazo[4,5-]quinoline TLR7 Agonists.

TLR7 agonists have significant therapeutic potential in a variety of oncology and autoimmune applications. We recently reported a potent TLR7 selective agonist that could be delivered by antibody-drug conjugate (ADC) technology to elicit potent anticancer activity. Herein we report synthetic chemistry and structure-activity relationship studies to develop TLR7 agonists with improved potency for next-generation ADC efforts.

Evaluation of an ester-linked immunosuppressive payload: A case study in understanding the stability and cleavability of ester-containing ADC linkers.

In spite of their value in prodrug applications, the use of esters in antibody-drug-conjugate (ADC) payloads and linkers has generally been avoided due to the ubiquitous and promiscuous nature of human esterases. ADCs generally have a long circulating half life (3-7 days) that makes them susceptible to esterase-mediated metabolism. Moreover, it is largely unclear whether lysosomal and cytosolic esterases cleave ester-containing linkers upon ADC internalization.

Immediate pre-learning stress enhances baseline startle response and fear acquisition in a fear-potentiated startle paradigm.

Extensive work has shown that stress time-dependently influences hippocampus-dependent learning and memory. In particular, stress that is administered immediately before learning enhances long-term memory, while stress that is temporally separated from learning impairs long-term memory. We have extended these findings by examining the impact of immediate, pre-learning stress on an amygdala-dependent fear conditioning task.

Polarization-resolved second harmonic generation imaging of human ovarian cancer.

Remodeling of the extracellular matrix in human ovarian cancer can be manifested in increased collagen concentration, changes in alignment within fibrils/fibers and/or up-regulation of different collagen isoforms. We used pixel-based second harmonic generation (SHG) polarization microscopy analyses to probe these molecular changes in human ovarian tissues [normal stroma, benign tumors, and high-grade serous (HGS) tumors] by: (i) determination of the α-helical pitch angle via the single-axis molecular model, (ii) collagen alignment within fibrils via SHG anisotropy, and (iii) chirality via SHG circular dichroism (SHG-CD). Pixel approaches are required due to the complex structure of the matrix that lacks a high degree of fiber alignment.

Multicenter Trial of the VenaTech Convertible Vena Cava Filter.

Purpose: To demonstrate rates of successful filter conversion and 6-month major device-related adverse events in subjects with converted caval filters.

Materials And Methods: An investigational device exemption multicenter, prospective, single-arm study was performed at 11 sites enrolling 149 patients. The VenaTech Convertible Vena Cava Filter (B.