Journal Of Investigative Dermatology

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Essential Role for Integrin-Linked Kinase in Melanoblast Colonization of the Skin

Fri, 2019-07-19 00:00
Melanocytes are pigment-producing cells found in the skin and other tissues. Alterations in the melanocyte lineage give rise to a plethora of human diseases, from neurocristopathies and pigmentation disorders, to melanoma. During embryogenesis, neural crest cell subsets give rise to two waves of melanoblasts, which migrate dorsolaterally, homing to the skin and differentiating into melanocytes. However, the mechanisms that govern colonization of the skin by the first wave of melanoblasts are poorly understood.

Understanding curly hair mechanics: Fibre strength

Fri, 2019-07-19 00:00
The relationship between the geometric and mechanical profiles of hair fibres has been studied, with special focus on curly samples. Incidental observations pointed to a significantly different viscoelastic character with varying curliness. Further investigations confirmed initial observations, showing an initial distinct toe-region behaviour for curly-fibres on the stress-strain plot, which is absent for straight fibres. This behaviour suggested a difference in viscoelastic nature of the curly fibre that is linked to mechanical energy stored in the fibre.

Response to Clarifying the Current Understanding of Syndromic Basal Cell Carcinomas.

Fri, 2019-07-19 00:00
A majority of individuals with BCNS have germline mutations affecting PTCH1, and BCCs that develop in these individuals are highly responsive to Smoothened inhibitors. However, BCCs which develop in minority of BCNS patients with underlying SUFU mutations may be less responsive to Smoothened inhibitors because inactivation of SUFU is downstream of SMO. Development of next-generation HH antagonists that target components downstream of SMO are under development for efficacy in Smoothened inhibitor resistant BCCs and may have efficacy in BCCs with SUFU mutations.

Human mesenchymal stromal cells engineered to express collagen VII can restore anchoring fibrils in recessive dystrophic epidermolysis bullosa skin graft chimeras

Fri, 2019-07-19 00:00
Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ).With no curative treatments presently available, retrovirally-transduced autologous epidermal grafts and intradermal lentivirally-engineered fibroblast injections are being investigated. Alternative approaches aim to infuse allogeneic mesenchymal stromal cells (MSCs) to provide a more generalised treatment for RDEB.

Clarifying the current understanding of syndromic basal cell carcinomas

Fri, 2019-07-19 00:00
Chiang et al. presented important data on the lower mutational load and increased genomic stability of basal cell nevus syndrome (BCNS) – basal cell carcinomas (BCCs) in contrast to sporadic BCCs in an original article titled “Genomic Stability in Syndromic Basal Cell Carcinoma” (Chiang et al., 2018).

A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U trial)

Thu, 2019-07-18 00:00
Psoriasis is a Th17 autoimmune disease associated with an increased risk cardiovascular events and mortality. Ustekinumab, an antibody to p40, blocks cytokines IL12 and IL23, and is a highly effective and safe treatment for psoriasis.

Variation in cutaneous patterns of melanomagenesis according to germline CDKN2A/CDK4 status in melanoma-prone families

Thu, 2019-07-18 00:00
CDKN2A and CDK4 are well-established melanoma susceptibility genes, but their effect on tumor location/distribution is unknown. We used a case-case study design to assess for differences in tumor location between mutation carriers (CDKN2A = 141 patients, 348 melanomas; CDK4 = 15 patients, 54 melanomas) and non-carriers (104 patients, 157 melanomas) in U.S. melanoma-prone families. Associations between groups were assessed with chi-square tests. Odds ratios (ORs) for tumor location were adjusted for diagnosis age, gender, and superficial spreading subtype.

Mechanical forces in the skin: roles in tissue architecture, stability, and function

Thu, 2019-07-18 00:00
Tissue shape emerges from the collective mechanical properties and behavior of individual cells and the ways by which they integrate into the surrounding tissue. Tissue architecture and its dynamic changes subsequently feed back to guide cell behavior. The skin is a dynamic, self-renewing barrier that is subjected to large-scale extrinsic mechanical forces throughout its lifetime. The ability to withstand this constant mechanical stress without compromising its integrity as a barrier requires compartment-specific structural specialization, and capability to sense and adapt to mechanical cues.

Second primary cancers in patients with invasive and in situ squamous cell skin carcinoma, Kaposi sarcoma and Merkel cell carcinoma: role for immune mechanisms?

Sat, 2019-07-06 00:00
Second primary cancers (SPCs) are becoming a common cancer entity, which may interfere with survival in relatively benign first primary cancers. We wanted to examine the hypothesis that immune dysfunction may contribute to SPCs by assessing SPCs associated with known immune responsive skin cancers, invasive and in situ squamous cell carcinoma (SCC), Kaposi sarcoma (KS) and Merkel cell carcinoma (MCC). Cancers were identified from the Swedish Cancer Registry from the years 1958 through to 2015. Standardized relative risks (RRs) were calculated bi-directionally for any SPC after skin cancer and for skin cancer as SPC.

MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma

Fri, 2019-07-05 00:00
Despite the fact that the transcription factor atonal homolog 1 (ATOH1) is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependency oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, i.e. one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression.

Oxygen-mediated control of the keratinocyte proliferation-differentiation axis

Fri, 2019-07-05 00:00
The epidermis differentiates and functions in direct contact with the atmosphere (21% oxygen), leading to the common practice of maintaining keratinocytes in vitro at this oxygen level. However, studies have reported that the in vivo oxygen level in skin is much lower (<10%) (Evans et al. 2006).