Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort.

Loss-of-function (LoF) variants in the filaggrin (FLG) gene are the strongest known genetic risk factor for atopic dermatitis (AD), but the impact of these variants on AD outcomes is poorly understood. We comprehensively identified genetic variants through targeted region sequencing of FLG in children participating in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. Twenty FLG LoF variants were identified, including 1 novel variant and 9 variants not previously associated with AD.

Design and Construction of a Multi-Tiered Minimal Actin Cortex for Structural Support in Lipid Bilayer Applications.

Artificial lipid bilayers have revolutionized biochemical and biophysical research by providing a versatile interface to study aspects of cell membranes and membrane-bound processes in a controlled environment. Artificial bilayers also play a central role in numerous biosensing applications, form the foundational interface for liposomal drug delivery, and provide a vital structure for the development of synthetic cells. But unlike the envelope in many living cells, artificial bilayers can be mechanically fragile.

Gene-environment interactions and their impact on human health.

The molecular processes underlying human health and disease are highly complex. Often, genetic and environmental factors contribute to a given disease or phenotype in a non-additive manner, yielding a gene-environment (G × E) interaction. In this work, we broadly review current knowledge on the impact of gene-environment interactions on human health.

Autism spectrum disorder in the United Arab Emirates: potential environmental links.

Autism spectrum disorder (ASD) has been experiencing an increase in global prevalence in recent decades. While many factors could account for this reality, certain environmental links have been shown to contribute to ASD development and etiology. The Middle East has had relatively little published research on ASD etiology although statistics indicate that ASD affects 1 in 146 births in the United Arab Emirates (UAE).

MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas.

Objectives: Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms, of which OSCC has a worse prognosis. Matrix metalloproteinases (MMPs) are involved in the initiation, invasion, metastasis, and defense of cancer. This study aimed to compare differences in MMP expression in these cancers.

Prospective immunohistochemical analysis of BRAF V600E mutation in melanoma.

The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation is the most common activating genetic alteration of this oncogene and a predictive marker for the therapeutic use of BRAF inhibitors in melanoma. Our aim was to evaluate the performance of BRAF V600E mutation-specific monoclonal antibody (VE1) in a prospective diagnostic setting of melanoma patients (n = 102). All 41 cases (40.

Toll-like receptors -4 and -5 in oral and cutaneous squamous cell carcinomas.

Background: Oral squamous cell carcinoma (OSCC) has a worse prognosis than cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5 are transmembrane proteins that recognize endogenous and microbial agents. Their activation has been connected to cancer invasion.

Osteopontin promotes the invasive growth of melanoma cells by activating integrin αvβ3 and down-regulating tetraspanin CD9.

Overexpression of osteopontin (OPN) is strongly associated with the invasiveness/metastasis of many cancers, including melanomas. However, the molecular mechanisms of OPN in these processes remain poorly understood. We found that forced expression of OPN in early vertical-growth-phase melanoma cells dramatically increased their migration/invasion and growth/survival in a three-dimensional collagen I gel.

[Cutaneous leukocytoclastic vasculitis in a patient with an adenocarcinoma of the colon].

Association of cutaneous leukocytoclastic vasculitis with colon carcinoma has occasionally been reported. We report a case of acute cutaneous leucocytoclastic vasculitis that developed over two weeks after liver resection due to metastatic rectal adenocarcinoma. The primary tumor had earlier been resected and treated with neoadjuvant chemotherapy.

Epithelial and stromal syndecan-1 and -2 are distinctly expressed in oral- and cutaneous squamous cell carcinomas.

Background: Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms of which OSCC has worse survival and higher risk of metastasis than CSCC. The aim of this study was to explore the differences of immunoexpressions between syndecan-1 and -2 in OSCC and head and neck CSCC.

Methods: A total of 35 patients diagnosed with OSCC and 25 with CSCC, presented T1 and T2 tumors and treated at Helsinki University Central Hospital between years 2001 and 2009, were selected into this study.

TGF-β signaling, activated stromal fibroblasts, and cysteine cathepsins B and L drive the invasive growth of human melanoma cells.

Accumulating evidence indicates that interactions between cancer cells and stromal cells are important for the development/progression of many cancers. Herein, we found that the invasive growth of melanoma cells in three-dimensional-Matrigel/collagen-I matrices is dramatically increased on their co-culture with embryonic or adult skin fibroblasts. Studies with fluorescent-labeled cells revealed that the melanoma cells first activate the fibroblasts, which then take the lead in invasion.

Outcome following local recurrence or in-transit metastases in cutaneous melanoma.

Defining clinical factors influencing outcome after local recurrence or in-transit metastasis may help us to improve treatment and develop follow-up guidelines. A retrospective review of melanoma patients with local recurrence in the primary tumor scar or with in-transit metastasis was carried out. Outcome and survival were analyzed for 99 patients.

Transcriptional regulatory mechanisms underlying the GABAergic neuron fate in different diencephalic prosomeres.

Diverse mechanisms regulate development of GABAergic neurons in different regions of the central nervous system. We have addressed the roles of a proneural gene, Ascl1, and a postmitotic selector gene, Gata2, in the differentiation of GABAergic neuron subpopulations in three diencephalic prosomeres: prethalamus (P3), thalamus (P2) and pretectum (P1). Although the different proliferative progenitor populations of GABAergic neurons commonly express Ascl1, they have distinct requirements for it in promotion of cell-cycle exit and GABAergic neuron identity.

[Punch biopsy in the diagnosis of skin tumors].

Punch biopsy is a feasible method in the early diagnosis of nonmelanotic skin cancer in primary health care, but should not be applied to lesions that appear clinically as melanomas. Small skin lesions suspected to be malignant can often be completely excised in primary health care. If the skin tumor is large, a biopsy from the tumor area is worth taking so that the edge of the tumor remains intact.

The dermis graft: another autologous option for acute burn wound coverage.

Background: Split-thickness skin autografts are the gold-standard in providing permanent acute wound closure in major burns. Split-thickness dermal grafts harvested from the same donor site may provide an additional autologous option for permanent acute coverage and increase the number of potential autologous donor sites.

Materials And Methods: We performed 16 dermis grafts (DG) harvested from the skin of the back in 9 consecutive burn patients.

Sentinel lymph node biopsy and survival in elderly patients with cutaneous melanoma.

Background: Sentinel lymph node biopsy (SNB) is a widely adopted staging procedure in patients with cutaneous melanoma. The benefits of SNB have not been evaluated thoroughly in older age groups.

Methods: This was a two-centre retrospective observational study of patients with melanoma aged at least 70 years undergoing SNB.

Tumor burden of sentinel lymph node metastasis in Merkel cell carcinoma.

Background: The applicability of sentinel lymph node biopsy (SLNB) for staging has been recognized in association with Merkel cell carcinoma (MCC). However, the concept of tumor burden with respect to MCC involving sentinel lymph nodes has not been analyzed. Our aim was to assess tumor burden in the sentinel lymph nodes of MCC patients.

Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis.

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind.

Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth.

Although the outgrowth of micrometastases into macrometastases is the rate-limiting step in metastatic progression and the main determinant of cancer fatality, the molecular mechanisms involved have been little studied. Here, we compared the gene expression profiles of melanoma lymph node micro- and macrometastases and unexpectedly found no common up-regulation of any single growth factor/cytokine, except for the cytokine-like SPP1. Importantly, metastatic outgrowth was found to be consistently associated with activation of the transforming growth factor-beta signaling pathway (confirmed by phospho-SMAD2 staining) and concerted up-regulation of POSTN, FN1, COL-I, and VCAN genes-all inducible by transforming growth factor-beta.

Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.

Background: Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2), an activator of polyamine biosynthesis, previously reported to be exclusively expressed in the brain and testis.