No abstract

The state of polymerization of actin and the organization of actin filaments is widely believed to be related to cellular transformation. Since the intracellular monomer (G) and filamentous (F) actin content reflects the state of microfilament polymerization, we measured the G/total actin ratio in primary cultures of normal and malignant human keratinocytes. In normal keratinocytes the mean value of this ratio was 0.30 +/- 0.03 (mean +/- SE, n = 15), while in basal cell carcinoma (BCC) keratinocytes it was 0.49 +/- 0.03 (n = 8) and in squamous cell carcinoma keratinocytes (SCC) 0.5 +/- 0.07 (n = 4), indicating a 1.7-fold increase of the G/total actin ratio in malignant cells. These results imply that the proportion of polymerized actin is decreased markedly in malignant keratinocytes, suggesting alterations of microfilament structures which probably occur during the transformation process. This was supported by the morphological changes of microfilament structures as assessed by fluorescence microscopy. A different distribution of actin filaments in normal and malignant cells became evident; stress-fibres were converging in patches at several points in SCC cells, when compared to normal keratinocytes. Furthermore, incubation of normal and malignant keratinocytes with cytochalasin B indicated differences in the resistance of their microfilament networks. After 1 h exposure to 10(-6) and 10(-5) M cytochalasin B, microfilaments in normal cells appeared to be less affected than their counterparts in neoplastic cells. Even in a high excess of cytochalasin B (10(-4) M), normal keratinocytes preserved their shape, while both basal cell and SCC were totally disrupted.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite brodalumad demonstrated efficacy in clinical trials, real‐world data reflecting clinical benefits in unselected patient populations treated in routine clinical practice are limited. Thus, we performed a longitudinal, retrospective, real‐world analysis assessing the long‐term clinical benefits of patients with moderate‐to‐severe psoriasis treated with brodalumab in Greece in the long term (up to 24 months). Main efficacy assessments included changes from baseline in the psoriasis area and severity index (PASI) and proportions of patients achieving at least 50%, 75%, 90% and 100% reduction from baseline in PASI scores (PASI50, PASI75, PASI90 and PASI100) at different timepoints up to 24 months. Other endpoints included changes in the dermatology life quality index (DLQI) and body surface area (BSA) involvement. Data from medical records of 180 patients with moderate‐to‐severe psoriasis treated with brodalumab for up to 24 months were assessed. Following treatment, mean [standard deviation (SD)] PASI scores were decreased across all visits compared to baseline (p < 0.001). The proportion of patients achieving PASI50, PASI75, PASI90 or PASI100 were high as early as at month 1 and consistently tended to increase over time, mainly during the first 6 months. Improvements on disease severity were further reflected by reductions from baseline on BSA scores across all visits (p < 0.001). Concurrent improvements on DLQI scores were observed across all visits (p < 0.001). This retrospective analysis provides real‐world evidence supporting the long‐term efficacy profile of brodalumab in Greek patients with moderate‐to‐severe psoriasis treated in standard clinical practice, which is characterized by a rapid onset of action generally sustained over time.

Hidradenitis suppurativa and psoriasis are considered chronic inflammatory diseases suggesting the existence of common pathogenetic pathways. We present two cases of comorbid psoriasis and hidradenitis suppurativa, treated with certolizumab pegol and brodalumab due to failure of response to other conventional therapies. Monoclonal antibody therapies have revolutionized the treatment of chronic inflammatory disorders such as psoriasis and hidradenitis suppurativa. Given the good clinical response to anti-IL-17 and anti-tumor necrosis factor agents in patients undergoing psoriasis and hidradenitis treatment, investigations on this direction could represent the starting point in new therapeutic approach for revolutionary treatment in these difficult-to-treat diseases.

On the graphic interfaces the flap movement, the closure of the defect, and the whole deformation were found to match with the skin stripe postincisional alterations. This work permits the prediction and offers planning guides for different skin reconstructions.