ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy.

Only one in five patients respond to immune checkpoint inhibitors, which primarily target adaptive immunity. Ectonucleotide pyrophosphatase/phophodiesterase 1 (ENPP1), the dominant hydrolase of 2'3'-cyclic-GMP-AMP (cGAMP) that suppresses downstream stimulator of interferon genes (STING) signaling, has emerged as a promising innate immunotherapy target. However, existing ENPP1 inhibitors have been optimized for prolonged systemic residence time rather than effective target inhibition within tumors.

Tuning the structure of thienoisoindigo (TIG) copolymers to afford bright near-infrared emission for bioimaging through aggregation-enhanced emission.

Near-infrared (NIR) emitting materials underpin emerging medical diagnostics and therapeutic bionanotechnologies. Conjugated polymer nanoparticles offer unique advantages due to their remarkable absorption cross-sections, photostability, synthetic tunability, and biocompatibility. Despite the vast library of NIR-absorbing conjugated polymers, relatively few narrow bandgap structures have been explored for NIR imaging.

Defining the antitumor mechanism of action of a clinical-stage compound as a selective degrader of the nuclear pore complex.

Cancer cells are acutely dependent on nuclear transport due to elevated transcriptional activity, suggesting an unrealized opportunity for selective therapeutic inhibition of the nuclear pore complex. Through large-scale phenotypic profiling of cancer cell lines, genome-scale functional genomic modifier screens, and mass spectrometry-based proteomics, we discovered that the clinical drug PRLX-93936 is a molecular glue that binds and reprograms the TRIM21 ubiquitin ligase to degrade the nuclear pore complex. Upon compound-induced TRIM21 recruitment, the nuclear pore is ubiquitylated and degraded, resulting in the loss of short-lived cytoplasmic mRNA transcripts and induction of cancer cell apoptosis.

Building the foundations for an organized population-based cervical cancer screening program with primary HPV self-sampling in Catalonia, Spain: findings from a pilot implementation study.

Introduction: As part of the transition from opportunistic cytology-based screening to an organized, population-based HPV screening program, Catalonia, Spain, launched an implementation pilot in 2021.

Methods: The pilot combined home-based HPV self-sampling with pharmacy-based distribution, coordinated by a screening office using an SMS-based invitation and reminder system, alongside structured follow-up of HPV-positive cases by midwives.

Results: From July 2021 to December 2023, 6,355 women seeking cervical cancer screening were invited to participate in HPV self-sampling via SMS, with high participation (80.

HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages.

Background: Human papillomavirus type 16 (HPV16) positive cancers have a tumor environment that induces antigen-presenting cells to increase IL-23 expression. Unclear is if HPV16 E6/E7 oncoproteins expressed in these cancers play a role in upregulating interleukin (IL)-23 in the tumor microenvironment (TME), and how this cytokine impacts the antitumor cytotoxic T-cell response in HPV16+ cancer.

Methods: CD8 T-cells targeting HPV16+ cancer cells were isolated from C57BL/6 mice bearing HPV16+ C3.