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Background: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. Methods: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). Results: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. Conclusion: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. Trial registration number: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, there has been an increasing scientific interest in the interaction between anaesthesia and cancer development. Retrospective studies show that the choice of anaesthetics perioperatively may influence cancer outcome and cancer recurrence; however, these studies show contradictory results. Reviewing the recent and relevant literature for the biological effects of anaesthetics on cancer cells in comparison to the clinical effects, it was found that sevoflurane, propofol, opioids and lidocaine are likely to display direct biological effects on cancer cells. However, significant effects are only found in studies with exposure to high concentrations of anaesthetics for longer than practical durations, therefore incomparable to their clinical use. In recent years, there has been an increasing scientific interest in the interaction between anaesthesia and cancer development. Retrospective studies show that the choice of anaesthetics may influence cancer outcome and cancer recurrence; however, these studies show contradictory results. Recently, some large randomized clinical trials have been completed, yet they show no significant effect of anaesthetics on cancer outcomes. In this scoping review, we compiled a body of in vivo and in vitro studies with the goal of evaluating the biological effects of anaesthetics on cancer cells in comparison to clinical effects as described in recent studies. It was found that sevoflurane, propofol, opioids and lidocaine are likely to display direct biological effects on cancer cells; however, significant effects are only found in studies with exposure to high concentrations of anaesthetics and/or during longer exposure times. When compared to clinical data, these differences in exposure and dose–effect relation, as well as tissue selectivity, population selection and unclear anaesthetic dosing protocols might explain the lack of outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules Results In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE) and the non-invasive P-cadherin over-expression variant (BLM P-cad). Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules. Conclusions Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cells

Background: Despite the popularity of hyaluronic acid (HA) filler treatments, few publications focus on their effects on adipose tissue.Objectives: The authors assessed the deposition pattern in the subcutis of injected HA, the tissue response at short and intermediate term, and the effects of remodeling the filler by strong finger pressure immediately after the treatment.Methods: Two brands, specifically developed by the industry for deep injection, were compared. The gels were injected subcutaneously in 5 candidates for abdominoplasty or breast reduction, in the area of excision, 6 to 98 days before surgery. Ultrasound measurements and films were compared with postoperative histological findings. Tissue response was scored semi-quantitatively.Results: Real-time ultrasound showed a slightly different deposition pattern of the 2 brands. Histologically, both were present in large pools of the same magnitude and looked the same. Linear retrograde injection sometimes resulted in a globular deposit due to elastic recoil of septae. After remodeling and over time, HA deposits became difficult to detect by ultrasound. Firm remodeling of the tissue immediately after injection or time had no significant effect on filler spread or tissue response. Except for 1 zone of granuloma formation, tolerance for both fillers was good.Conclusions: HA deposition in adipose tissue occurs in much larger pools than in the dermis. Ultrasound examination is useful during and immediately after the injection but less reliable after filler remodeling or over time. Filler deposition can be less precise, and reshaping by finger pressure can have less effect than expected.Level Of Evidence:4: [ABSTRACT FROM AUTHOR]