Laser-assisted topical delivery of vismodegib reduces hedgehog gene expression in human basal cell carcinomas in vivo.

Background: Systemically delivered hedgehog inhibitors including vismodegib and sonidegib are widely used to treat basal cell carcinomas (BCCs). Ablative fractional laser (AFL)-assisted topical delivery of vismodegib has been demonstrated in preclinical studies. The aim of this explorative clinical study was to evaluate intratumoral vismodegib concentrations and effect on hedgehog pathway gene expression following AFL-assisted topical vismodegib delivery to BCCs.

Ablative fractional laser treatment reduces hedgehog pathway gene expression in murine basal cell carcinomas.

This study aimed to investigate the impact of ablative fractional laser (AFL) on hedgehog pathway gene expression in murine microscopic basal cell carcinomas (BCCs) and compare these results to the effect of topical treatment with vismodegib, an FDA-approved hedgehog inhibitor. In 25 mice, 1 cm skin test sites (n = 44) containing microscopic BCCs were exposed to one of three interventions: a single CO AFL treatment (1 pulse, 40 mJ/microbeam, wavelength 10.6 μm, 5% density, pulse rate 250 Hz, n = 12), eight topical vismodegib treatments (3.

Topical Delivery of Hedgehog Inhibitors: Current Status and Perspectives.

Systemic treatment with hedgehog inhibitors (HHis) is available to treat basal cell carcinomas but their utility is limited by adverse effects. Topical delivery methods may reduce adverse effects, but successful topical treatment depends on sufficient skin uptake, biological response, and time in tumor tissue. The aim of this review was to evaluate the current status of topical HHi delivery for BCCs and discuss barriers for translating systemic HHis into topical treatments.

GPR183 Is Dispensable for B1 Cell Accumulation and Function, but Affects B2 Cell Abundance, in the Omentum and Peritoneal Cavity.

B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense against bacteria. The G protein-coupled receptor 183 (GPR183), also known as Epstein-Barr virus-induced gene 2 (EBI2), is an oxysterol-activated chemotactic receptor that regulates migration of B cells.

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice.

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated.