Search

Primers and conditions used in PCR analysis.

MeWo melanoma cell spreading is controlled by VCAM-1 density in a reciprocal fashion.

Summary Background The association of atopic dermatitis (AD) and allergic contact dermatitis has been a matter of considerable uncertainty. Study results range from lack of any association to increased sensitization for multiple allergens, but fail to identify consistent allergen associations. Objective We studied a large patch test cohort of patients stratified by their atopic skin diathesis using the Erlangen Atopy Score (EAS), independent of active skin disease. Methods Retrospective multi‐center data analysis from five departments of dermatology in Germany with 4,509 patients. Patients were grouped as “no atopic skin diathesis” (n = 2,165) and “atopic skin diathesis” (n = 1,743), according to EAS. Results Significantly more individuals with atopic skin diathesis showed at least one positive patch test reaction to the baseline series compared to individuals without atopic skin diathesis (49.1 % vs. 38.3 %). In logistic regression analyses, atopic skin diathesis was associated with a significantly higher risk of sensitization to methylchloroisothiazolinone/methylisothiazolinone (OR 2.383) and methylisothiazolinone (OR 1.891), thiuram mix (OR 1.614), as well as nickel (OR 1.530), cobalt (OR 1.683), and chromium (OR 2.089). Conclusions Atopic skin diathesis proved to be the most important intrinsic risk factor for contact sensitization to few, specific allergens. Past or present AD was a less relevant variable.

The biophysical fine-tuning of cancer cell plasticity is crucial for tumor progression but remains largely enigmatic. Although vascular cell adhesion molecule-1 (VCAM-1/CD106) has been implicated in melanoma progression, here its presentation on endothelial cells was associated with diminished melanoma cell spreading. Using a specific nanoscale modulation of VCAM-1 (tunable from 70 to 670 ligands/μm²) next to integrin ligands (RGD motifs) in a bifunctional system, reciprocal regulation of integrin α4 (ITGA4/VLA-4/CD49d)-dependent adhesion and spreading of melanoma cells was found. As the VCAM-1/VLA-4 receptor pair facilitated adhesion, while at the same time antagonizing RGD-mediated spreading, melanoma cell morphogenesis on these bifunctional matrices was directly regulated by VCAM-1 in a dichotomic and density-dependent fashion. This was accompanied by concordant regulation of F-actin cytoskeleton remodeling, Rac1-expression, and paxillin-related adhesion formation. The novel function of VCAM-1 was corroborated in vivo using two murine models of pulmonary metastasis. The regulation of melanoma cell plasticity by VCAM-1 highlights the complex regulation of tumor–matrix interactions. Implications: Nanotechnology has revealed a novel dichotomic function of the VCAM-1/VLA-4 interaction on melanoma cell plasticity, as nanoscale tuning of this interaction reciprocally determines adhesion and spreading in a ligand density-dependent manner. Mol Cancer Res; 16(3); 528–42. ©2017 AACR.

Background: Palmoplantar pustulosis (PPP) is arecalcitrant chronic inflammatory skin disease. Datarelevant for the medical care of patients with PPP arescarce. Thus, the aim of this work was to investigatethe disease burden, clinical characteristics, andcomorbidity of PPP patients in Germany. Patientsand Methods: PPP patients were examined in a crosssectionalstudy at seven specialized psoriasis centersin Germany. Results: Of the 172 included patients withPPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris,28.2% had documented psoriatic arthritis, and 30.2%had a family history of psoriasis. In 77 patients themean Dermatology Life Quality Index (DLQI) was 12.2± 7.7 (mean ± SD). The mean Psoriasis PalmoplantarPustulosis Area and Severity Index (PPPASI) was 12.6 ±8.6. Mean body mass index was above average at 27.1± 5.5. The PPP patients had previously received anaverage of 2.6 ± 2.1 different anti-psoriatic systemicdrugs or UV-therapies. The systemic drugs that hadbeen used most frequently were corticosteroids in40.1% of patients, followed by acitretin (37.8%), andmethotrexate (27.9%). The PPPASI was 13.4 ± 8.9 inpatients without current systemic therapy and 10.4 ±7.9 in patients with systemic therapy. Conclusion: ManyPPP patients had a concomitant diagnosis of psoriasisvulgaris and/or psoriatic arthritis or had a familyhistory of psoriasis. Despite the fact that many of thepatients were using anti-psoriatic therapies, there wasstill a high burden of disease within this PPP cohort.This insufficient control of symptoms demonstratesthe urgent need for new PPP treatments.