Publications by authors named "J C Linehan"

Purpose: UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.

View Article and Find Full Text PDF
Article Synopsis
  • HPK1 is a negative regulator of T-cell receptor signaling, and its inhibition can enhance immune responses and work well with immune checkpoint inhibitors in cancer models.
  • Researchers have discovered a new series of isoquinoline compounds that effectively inhibit HPK1 and promote T-cell activity through fragment-based screening.
  • The best candidate from these efforts showed strong inhibition of HPK1, excellent selectivity for other kinases, a good safety profile, and favorable pharmacokinetic properties for potential cancer immunotherapy use.
View Article and Find Full Text PDF

The non-muscle actomyosin cytoskeleton generates contractile force through the dynamic rearrangement of its constituent parts. Actomyosin rings are a specialization of the non-muscle actomyosin cytoskeleton that drive cell shape changes during division, wound healing, and other events. Contractile rings throughout phylogeny and in a range of cellular contexts are built from conserved components including non-muscle myosin II (NMMII), actin filaments (F-actin), and crosslinking proteins.

View Article and Find Full Text PDF

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [Rh(PNP)]. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere.

View Article and Find Full Text PDF

As cutting-edge technologies applied for the study of body fluid molecular biomarkers are continuously evolving, clinical applications of these biomarkers improve. Diverse forms of circulating molecular biomarkers have been described, including cell-free DNA (cfDNA), circulating tumor cells (CTCs), and cell-free microRNAs (cfmiRs), although unresolved issues remain in their applicability, specificity, sensitivity, and reproducibility. Translational studies demonstrating the clinical utility and importance of cfmiRs in multiple cancers have significantly increased.

View Article and Find Full Text PDF