Opposing effects of STAT3 targeting in epidermolysis bullosa.

Opposing effects of STAT3 targeting in epidermolysis bullosa. Br J Dermatol. 2019 Nov 01;: Authors: Mittapalli VR, Kühl T, Kuzet SE, Gretzmeier C, Kiritsi D, Gaggioli C, Bruckner-Tuderman L, Nyström A Abstract Dystrophic epidermolysis bullosa (DEB) is a skin blistering disease caused by mutations in the COL7A1 gene encoding the anchoring fibril-constituent collagen VII.1 Secondary to skin fragility, DEB manifests as chronic wounds and progressive soft tissue fibrosis. As a consequence of a chronically injured and stiffened dermal microenvironment people with severe DEB are prone to develop early-onset metastatic cutaneous squamous cell carcinomas (cSCCs).1,2 Dermal fibrosis in DEB is paradigmatic of injury- and inflammation-driven activation of fibrogenic processes2 (and references therein). PMID: 31675440 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research

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Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early de...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Letter to the Editor Source Type: research
Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin fragility disorder caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the major component of anchoring fibrils (AFs) that ensure dermal-epidermal adherence. From birth, RDEB patients endure lifelong skin and mucosal blistering with both local and systemic complications including aggressive metastatic squamous cell carcinomas (SCC).1 Currently, treatments are only symptomatic although clinical studies of novel therapeutics, including gene2 and cell3 therapies are emerging. One potential safety issue with suc...
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
PMID: 31486079 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB) have a pronounced muco-cutaneous fragility, which triggers the formation of blisters spontaneously or in response to minimal trauma. RDEB is also associated with chronic inflammation; patients have wounds that do not close and aggressive squamous cell carcinomas. The disease is due to mutations in the COL7A1 gene that codifies for collagen VII (C7). One of the most promising therapeutic options is the use of mesenchymal stromal cells (MSCs) from healthy donors that, in addition to producing C7 and having anti-inflammatory properties, are well tolerated by the ...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Clinical Research and Epidemiology Source Type: research
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin fragility disorder characterized by deficient dermo-epidermal adhesion, due to mutations in the gene encoding collagen VII. Patients with RDEB suffer chronic wounds and inflammation that ultimately trigger fibrosis and highly aggressive squamous cell carcinoma development. We previously reported a clinical case of two siblings carrying in homozygosis the same null mutation (c.6527insC) in the COL7A1 gene, but with marked phenotypic differences with respect to the extent of mucocutaneous involvement, skin fragility and fibrosis.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Wound Healing and Tissue Remodelling Source Type: research
Recessive Dystrophic epidermolysis bullosa (RDEB) is a skin genetic disease caused by mutations in COL7A1 (coding type VII collagen). Type VII collagen is essential to maintain the fully functional dermal-epidermal junction, and the loss of type VII collagen results in detachment of epidermis. RDEB patients, without functional type VII collagen, suffer from the repetitive blistering and have high risk of early-onset aggressive squamous cell carcinoma. Currently, no fundamental treatment is available for RDEB.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research
Epidermolysis bullosa (EB) comprises rare genodermatoses associated with widespread blistering due to fragility of the skin. Squamous cell carcinomas (SCC) are major complications of EB. We analysed molecular and mutational signatures of 48 SCC obtained from patients with EB, 10 with recessive dystrophic epidermolysis bullosa (RDEB), seven with Kindler syndrome (KS) and one patient with junctional epidermolysis bullosa (JEB). Although we observed significant tumour heterogeneity, some common characteristics emerged.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetics and Cell Based Therapy Source Type: research
Recessive Dystrophic Epidermolysis Bullosa (RDEB), caused by mutations in COL7A1 leading to a reduction or loss of type VII collagen (Col7), is a severe blistering disease associated with an increased risk of developing aggressive squamous cell carcinoma. Using RNASeq global transcriptomics we identified dysregulation of genes involved in cell cycle control, DNA damage response and chromosomal instability (CIN) with loss of keratinocyte Col7. To investigate the role of Col7 in DNA damage and CIN, keratinocytes with Col7 and Col17 (type XVII collagen) knockdown were treated with UV or mitomycin-C to induce DNA damage.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetics and Cell Based Therapy Source Type: research
The most lethal complication of recessive dystrophic epidermolysis bullosa (RDEB) is the development of aggressive cutaneous squamous cell carcinoma (cSCCs), which lead the high mortality rates in these patients. Elevated levels of phospho-STAT3 have been found in two RDEB-derived cSCC cell lines, demonstrating that constitutive activation and dysregulation of the JAK/STAT pathway may play a role in RDEB-cSCC pathogenesis. Ruxolitininb is an FDA approved JAK1/2 inhibitor that has efficacy in myelofibroblast, human head, and neck squamous cell carcinomas, as well as lung and breast carcinomas.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research
Abstract Some bone lesions are reported to mimic bone metastasis on imaging tests. Herein, we report a case of a 55-year-old Japanese man who presented with a skin tumor on the left lower extremity. He also had a history of recurrent generalized cutaneous blister and erosion formation since childhood. His skin lesions were diagnosed as cutaneous squamous cell carcinoma complicated by recessive dystrophic epidermolysis bullosa. Magnetic resonance imaging of the left lower extremity detected multiple focal bone lesions mimicking bone metastases in the left femur and tibia. However, bone biopsy revealed that the bone...
Source: Acta Dermato-Venereologica - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research
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