uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease.     

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

ABSTRACT

Purpose

New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.     

Effectiveness of a brief psychotherapeutic intervention compared with treatment as usual for adolescent nonsuicidal self-injury: a single-centre,randomised controlled trial

Although nonsuicidal self-injury (NSSI) is a clinically significant behavior, evidence-based, specific, time-, and cost-effective treatment approaches are lacking. The aim of this study was to compare the efficacies of a brief cognitive-behavioral psychotherapy manual, the Cutting Down Programme (CDP), and treatment as usual (TAU) in the treatment of adolescent NSSI. We conducted a single-centre randomised controlled trial (RCT). Eligible participants were aged 12–17 years engaging in repetitive NSSI (at least 5 times within the past 6 months). We randomly allocated 74 participants to CDP (n?=?37) or TAU (n?=?37; in a 1:1 ratio). Outcome measures were administered before treatment (T0), directly after CDP or 4 months after baseline evaluation in the TAU group (T1), and another 6 months later (T2; primary endpoint). Primary outcome was a 50% reduction in NSSI frequency within the past 6 months at 10-month follow-up (T2). Regarding the primary outcome, there were no significant differences between the CDP (n?=?26; 70.3%) and TAU group [n?=?27; 73.0%; χ²(1)?=?0.07; p?=?0.797]; NSSI frequency within the past 6 months was significantly reduced at T2 [χ²(1)?=?12.45; p?<?0.001] with no between-group difference [χ²(1)?=?0.14; p?=?0.704]. However, we found a significant group x point of measurement interaction [χ²(2)?=?7.78; p?=?0.021] regarding NSSI within the last month indicating at T1. CDP was equally effective and achieved faster recovery compared to a significantly more intensive TAU in treating adolescent NSSI. The CDP could provide a brief and pragmatic first treatment within a stepped-care model for NSSI in routine clinical care.

Clinical Trial Registration The trial was prospectively registered in the German Registry of Clinical Trials (https://www.drks.de; DRKS00003605) and is now complete.

     

Infliximab for the treatment of recalcitrant bullous Sweet syndrome in a 10-year-old girl

We report the case of a 10-year-old girl with bullous Sweet syndrome, recalcitrant to high-dose systemic corticosteroids. Subsequent treatment with infliximab resulted in a rapid improvement in cutaneous lesions and systemic symptoms. Cutis laxa was noted in the healed skin. We propose early second-line treatment with infliximab in children with steroid-refractory Sweet syndrome.