We aimed to characterise the response of locally advanced basal cell carcinoma (BCC) to systemic treatment with Vismodegib, a Hedgehog pathway inhibitor, by changes in the expression levels of Hedgehog pathway genes. Data were collected prospectively on 12 patients treated systemically for locally advanced BCC. Biopsy samples taken on admission and after treatment cessation were analysed pathologically and with the NanoString nCounter system to quantify the expression of 40 Hedgehog signaling pathway genes. Findings were compared before and after treatment, between complete and partial responders, and with localised BCC samples from 22 patients. Sixteen Hedgehog pathway genes changed significantly from before to after treatment. GAS1 was the only gene with a significantly different expression at baseline between complete responders (6 patients) and partial responders (4 patients) to Vismodegib (P = 0.014). GAS, GLIS2 and PRKACG1 showed different expression before treatment between the locally advanced and localised BCCs. The baseline expression level of GAS1 appears to be predictive of the response of locally advanced BCC to systemic Vismodegib treatment. A change in expression of many Hedgehog pathway genes, albeit expected by the known activity of Vismodegib, may nevertheless serve as an indicator of the response potential of the tumour.

This study evaluated the potential neuroprotective effect of azithromycin (AZ) intraperitoneal injections in male C57Bl/6 (wild type, WT) and female NOD scid gamma (NSG) mice subjected to optic nerve crush (ONC) as a model for optic neuropathy. Histologically, reduced apoptosis and improved retinal ganglion cell (RGC) preservation were noted in the AZ-treated mice as shown by TUNEL staining—in the WT mice more than in the NSG mice. The increased microglial activation following ONC was reduced with the AZ treatment. In the molecular analysis of WT and NSG mice, similar trends were detected regarding apoptosis, as well as stress-related and inflammatory markers examining BCL2-associated X (Bax), heme oxygenase 1 (Ho-1), interleukin 1 beta (Il1β), superoxide dismutase 1 (Sod1), and nuclear factor-kappa B (Nfkb) levels. In the optic nerve, AZ increased the levels of expression of Sod1 and Nfkb only in the WT mice and decreased them in the NSG mice. In the retinas of the WT and NSG mice, the Bax and Ho-1 levels of expression decreased following the AZ treatment, while the Sod1 and Nfkb expression decreased only in the WT mice, and remained stable near the baseline in the NSG mice. Il1β remained at the baseline in WT mice while it decreased towards the baseline in AZ-treated NSG mice. The neuroprotective effects demonstrated by the reduced RGC apoptosis in AZ-treated WT mice retinae, and in the optic nerves as stress-related and inflammatory gene expression increase. This did not occur in the immunodeficient NSG mice. AZ modulated the inflammatory reaction and microglial activation. The lack of an effect in NSG mice supports the assumption that AZ acts by immunomodulation, which is known to play a role in ONC damage. These findings have implications for the development and repurposing of drugs to preserve RGCs after acute optic neuropathies.

Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg/0.1 mL), intravitreal sildenafil 3 µL, or intraperitoneal sildenafil 0.1 mL (0.24 μg/3 µL). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX/BCL2 ratio, TGFβ, and TNFα levels in the ON and CD45 expression in WT retina. Sildenafil activated TNFα-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage.

Diffusion reflectance spectroscopy measurements targeted with gold nanoparticles (GNPs) can identify residual cutaneous squamous cell carcinoma (SCC) in excision borders. Human SCC specimens were stained with hematoxylin and eosin to identify tumor borders, and reflected onto an unstained deparaffinized section. Diffusion reflection of three sites (normal and SCC) were measured before and after GNPs targeting. Hyperspectral imaging showed a mean of 2.5 sites with tumor per specimen and 1.2 tumor-free (p < 0.05, t-test). GNPs were detected in 25/30 tumor sites (sensitivity 83.3%, false-negative rate 16.6%) and 12/30 non-tumor sites (specificity 60%, false-positive rate 40%). This study verifies the use of nanotechnology in identifying SCC tumor margins. Diffusion reflection scanning has high sensitivity for detecting the residual tumor.

Background: Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes characterized by retinal neovascularization. Predicting which diabetic patients will develop PDR remains challenging. Measuring mRNA expression levels may help elucidate the molecular pathways involved in PDR pathogenesis. This study investigated the expression of genes related to inflammatory and proliferative pathways in the peripheral blood of patients with PDR, compared to patients with non-proliferative diabetic retinopathy (NPDR) and healthy controls, using NanoString technology. The findings may aid in identifying potential biomarkers and therapeutic targets for early intervention. Methods: This prospective study was approved by the institutional ethics review board, and written informed consent was obtained from all participants. The study included patients with PDR (n = 9), NPDR (n = 8), and non-diabetic controls (n = 6). Total RNA was extracted from whole blood samples using the MagNA Pure Compact RNA Isolation Kit (Roche Ltd., Basel, Switzerland) and analyzed with the NanoString platform (Agentek Ltd., Yakum, Israel). Results: Expression levels of 578 genes across 15 signaling pathways, including inflammation (e.g., IL-17, TNF, and NF-κB) and cancer-related PI3K-Akt pathways, were evaluated. Sixty-six genes (11.5%) were differentially expressed (p < 0.05) between the PDR group and the NPDR and control groups. The most prominently overexpressed genes in PDR included TGFβ1, TGFβ1R, IL23R, BAX, and CFB, which were primarily involved in inflammatory and proliferative signaling. Conclusions: Gene expression profiling using NanoString technology revealed significant upregulation of genes related to inflammation and proliferation in patients with PDR. These findings suggest that beyond angiogenesis, inflammatory and proliferative pathways may play a central role in PDR development and could serve as targets for novel therapeutic strategies.