Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly […]
The P2X7 receptor is an intermediate in the retinoic acid-signaling pathway that induces neuronal remodeling in retinitis pigmentosa
Photoreceptor degeneration drives electrophysiological remodeling in downstream retinal neurons, including hyperactive firing of retinal ganglion cells (RGCs) that degrades residual vision. Although Retinoic Acid (RA) and its receptor (RAR) are known to upregulate ion channel genes associated with RGC hyperactivity, these genes lack canonical RAR binding sites required for direct transcriptional regulation. Here, we identify […]
Intratumoral B7H3:CD3 Bispecific T-cell Engager Drives Localized T-cell Accumulation in Canine Sarcoma Patients
Background: Bispecific T-cell Engagers (TCEs) targeting B7H3 (CD276) show promise for solid tumors but are limited by systemic toxicities and poor tumor penetration. Intratumoral (IT) delivery is proposed as a solution, but the safety and spatial pharmacodynamics (PD) remain poorly defined in these malignancies. Spontaneous canine tumors serve as a highly translatable model for human […]
Matched pancreatic cancer liver metastatic model system reveals cancer cell-dependent organotropism and site-specific tumor microenvironment reflective of human disease
Pancreatic ductal adenocarcinoma (PDAC) is a deadly, highly metastatic disease, driven by an interplay between cancer cells and the metastatic site-specific microenvironment. However, pre-clinical models that robustly capture these interactions within the context of matched primary and metastatic tumors are limited. Here, we present a novel transplant model system for matched pancreas and liver tumors […]
Auranofin potentiates cisplatin response through context-dependent NOTCH-associated signaling states in endometrial cancer
Therapeutic resistance remains a major challenge in advanced and recurrent endometrial cancer (EC). Aberrant NOTCH signaling has been associated with aggressive tumor behavior and therapeutic resistance across multiple malignancies, yet its therapeutic significance in EC remains incompletely defined. We investigated whether auranofin (AuR), a noncanonical modulator of NOTCH signaling through the transcriptional effector RBPJ, alters […]
SuFEx and macrocyclic chelation define orthogonal reactivity domains enabling isotopically versatile radiopharmaceuticals from a single peptide precursor
The design of radiotheranostic agents has been constrained by a fundamental chemical incompatibility: existing strategies for fluorine-18 incorporation — nucleophilic substitution, silicon-fluoride exchange, aluminum fluoride chelation, and prosthetic conjugation — either require conditions incompatible with macrocyclic metal coordination, consume the chelator site needed for radiometal labeling, or introduce non-native structural appendages that alter pharmacokinetic behavior. […]