Cutaneous Squamous Cell Carcinoma: An Updated Review.

Representing the second most common skin cancer, the incidence and disease burden of cutaneous squamous cell carcinoma (cSCC) continues to increase. Surgical excision of the primary site effectively cures the majority of cSCC cases. However, an aggressive subset of cSCC persists with clinicopathological features that are indicative of higher recurrence, metastasis, and mortality risks. Acceleration of these features is driven by a combination of genetic and environmental factors. The past several years have seen remarkable progress in shaping the treatment landscape for advanced cSCC. Risk stratification and clinical management is a top priority. This review provides an overview of the current perspectives on cSCC with a focus on staging, treatment, and maintenance strategies, along with future research directions.

Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.

Folate receptors can perform folate transport, cell adhesion, and/or transcription factor functions. The beta isoform of the folate receptor (FRß) has attracted considerable attention as a biomarker for immunosuppressive macrophages and myeloid-derived suppressor cells, however, its role in immunosuppression remains uncharacterized. We demonstrate here that FRß cannot bind folate on healthy tissue macrophages, but does bind folate after macrophage incubation in anti-inflammatory cytokines or cancer cell-conditioned media. We further show that FRß becomes functionally active following macrophage infiltration into solid tumors, and we exploit this tumor-induced activation to target a toll-like receptor 7 agonist specifically to immunosuppressive myeloid cells in solid tumors without altering myeloid cells in healthy tissues. We then use single-cell RNA-seq to characterize the changes in gene expression induced by the targeted repolarization of tumor-associated macrophages and finally show that their repolarization not only changes their own phenotype, but also induces a proinflammatory shift in all other immune cells of the same tumor mass, leading to potent suppression of tumor growth. Because this selective reprogramming of tumor myeloid cells is accompanied by no systemic toxicity, we propose that it should constitute a safe method to reprogram the tumor microenvironment.

Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice.

Dendritic cell-derived exosomes have been proven to be efficient adjuvant options for anti-tumor vaccines in cancer immunotherapy. However, their potency in atherosclerosis remains unclear. Here we summarize the association of microRNA-203-3p (miR-203-3p) with dendritic cell-derived exosomes and atherosclerosis. Firstly, dendritic cell-derived exosomes and bone marrow-derived macrophages were isolated, after which expression of miR-203-3p and cathepsin S was determined. After the establishment of atherosclerosis mouse models, gain- and loss-of-function experiments were conducted for the analysis of effects of miR-203-3p and cathepsin S on foam-cell formation, lipid accumulation, collagen deposition and serum total cholesterol. The results found high expression of cathepsin S in atherosclerosis mice and downregulation of miR-203-3p in the serum of atherosclerosis patients and ox-LDL-simulated bone marrow-derived macrophages. Cathepsin S was the target gene of miR-203-3p. miR-203-3p transporting from exosomes to bone marrow-derived macrophages resulted in inhibition of cathepsin S expression and atherosclerosis-related phenotypes in bone marrow-derived macrophages, thus alleviating atherosclerosis in mice, and this process was found to involve the p38/MAPK signaling pathway. These findings provided evidence that the transfer of miR-203-3p by dendritic cell-derived exosomes targeted cathepsin S in bone marrow-derived macrophages to attenuate atherosclerosis progression in mice, serving as a promising clinical target for atherosclerosis.

Meta-analysis of Duration of Continuous Dual Antiplatelet Therapy and Late Stent Thrombosis After Second-Generation Drug Stent Implantation.

INTRODUCTION: The aim of the present study was to perform a systematic comparison of the incidence of late and extremely late stent thrombosis (ST) with short-term and long-term dual antiplatelet therapy (DAPT) after a second-generation drug-eluting stent (DES) implantation. METHODS: Randomized controlled trials using short-term and long-term DAPT and reporting late ST (30 days-1 year) and extremely late ST (longer than 1 year) after a percutaneous coronary intervention (PCI) with DES were searched and compared in the Life Sciences and Biomedical Information Bibliographic Database (MEDLINE), EMBASE, Cochrane Central, and ClinicalTrials.com. ST was used as the primary endpoint of the therapeutic outcome, and the fixed-effects model (I2 < 50%) or random-effects model (I2 ≥ 50%) was adopted for the combined analysis. The odds ratio (OR) and 95% confidence interval (CIs) were used to represent the results. P < 0.05 in the combined result indicated that the difference was statistically significant. RESULTS: A total of five randomized controlled trials consisting of 7142 patients were included, with 3556 cases of short-term DAPT (at most 6 months), and 3586 cases of long-term DAPT (at least 12 months). There was no significant difference between late ST and administration duration of DAPT (OR 0.98, 95% CI 0.30-3.18; P = 0.97, I2 = 0%). There was also no significant difference between the incidence of extremely late ST and the duration of DAPT application (OR 0.30, 95% CI 0.03-2.95; P = 0.31). CONCLUSION: The duration of continuous DAPT application had no effect on the occurrence of late and extremely late ST.

Duration of Dual Antiplatelet Therapy and Late Stent Thrombosis Following Percutaneous Coronary Intervention with Second-Generation Drug-Eluting Stents: A Simple Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The aim of this simple meta-analysis was to systematically compare the occurrence of late and very late stent thrombosis with a short versus a longer duration of dual anti-platelet therapy (DAPT) use following the implantation of second-generation drug-eluting stents (DES). METHODS: Randomized controlled trials that compared short- and long-term DAPT use following percutaneous coronary intervention (PCI) with DES and that reported late (> 30 days but < 1 year) and very late (> 1 year) stent thromboses were searched from the bibliographic database of life sciences and biomedical information, which is also known as MEDLINE, as well as other searched databases including EMBASE, the Cochrane Central and http://www.ClinicalTrials.com . Statistical analysis was carried out using RevMan software [odds ratios (OR) and 95% confidence intervals (CIs) represented the results]. RESULTS: This simple analysis consisted of five randomized controlled trials with a total of 7142 patients. The current results showed no significant difference in late stent thrombosis associated with a shorter or longer duration of DAPT use (OR 0.98, 95% CI 0.30-3.18; P = 0.97, I2 = 0%). The result for very late stent thrombosis was also not significantly different (OR 0.30, 95% CI 0.03-2.95; P = 0.31). CONCLUSIONS: This simple analysis showed no impact of DAPT duration on the occurrence of late and very late stent thrombosis. Similar late and very late stent thrombosis rates were observed with 6-month versus 12-month duration of DAPT use following PCI with second-generation DES.