The possible and intriguing relationship between bullous pemphigoid and melanoma: speculations on significance and clinical relevance.

Bullous pemphigoid (BP) is the most common autoimmune bullous disease: it most commonly affects individuals over 70 years old and impacts severely on their quality of life. BP represents a paradigm for an organ-specific autoimmune disease and is characterized by circulating IgG autoantibodies to hemidesmosomal components: BP180 and BP230. While the crucial role of these autoantibodies in triggering BP inflammatory cascade is fully acknowledged, many ancillary etiological mechanisms need to be elucidated yet.

Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes.

Background: Cutaneous melanoma arises from skin melanocytes and has a high risk of metastatic spread. Despite better prevention, earlier detection, and the development of innovative therapies, melanoma incidence and mortality increase annually. Major clinical risk factors for melanoma include fair skin, an increased number of nevi, the presence of dysplastic nevi, and a family history of melanoma.

The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment.

Melanoma progression is a multistep evolution from a common melanocytic nevus through a radial superficial growth phase, the invasive vertical growth phase finally leading to metastatic dissemination into distant organs. Melanoma aggressiveness largely depends on the propensity to metastasize, which means the capacity to escape from the physiological microenvironment since tissue damage due to primary melanoma lesions is generally modest. Physiologically, epidermal melanocytes are attached to the basement membrane, and their adhesion/migration is under the control of surrounding keratinocytes.

The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors.

Therapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanomas.

Hybrid cooperative complexes to decrease VAS score and enhance sexual function in women with vulvar lichen sclerosus.

Objective: Lichen sclerosus is a chronic, inflammatory, progressive skin disease predominantly affecting anogenital areas. Vulvar lichen sclerosus (VLS) is one of the most common conditions treated in vulvar clinics; most patients report distressing symptoms of itching, burning, stinging, and pain (particularly during or after sexual intercourse). A preliminary, prospective, single-center study was performed to investigate the efficacy of hyaluronan hybrid cooperative complex (HCC) comprising high and low molecular weight hyaluronic acid to treat menopausal women with VLS.

Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging.

Aging of human skin is a complex process leading to a decline in homeostasis and regenerative potential of this tissue. Mitochondria are important cell organelles that have a crucial role in several cellular mechanisms such as energy production and free radical maintenance. However, mitochondrial metabolism as well as processes of mitochondrial dynamics, biogenesis, and degradation varies considerably among the different types of cells that populate the skin.

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis.

The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells.

Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture.

Nonvisualized sentinel node on preoperative lymphoscintigraphy in primary cutaneous melanoma: an 11-year retrospective survey.

Background: Sentinel lymph node (SLN) biopsy in cutaneous melanoma patients evaluates the regional draining basin for occult micrometastatic disease. Occasionally, nonidentification of SLN impairs the acquisition of this important prognostic factor.

Objectives: To investigate the outcomes of melanoma patients with negative lymphoscintigraphic findings and patients who underwent SLN biopsy from 2004 to 2015 ( n  = 1200) were retrospectively reviewed for tumor characteristics and clinical outcomes.

A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist.

Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects.

Regenerative Medicine-Based Treatment for Vitiligo: An Overview.

Vitiligo is a complex disorder with an important effect on the self-esteem and social life of patients. It is the commonest acquired depigmentation disorder characterized by the development of white macules resulting from the selective loss of epidermal melanocytes. The pathophysiology is complex and involves genetic predisposition, environmental factors, oxidative stress, intrinsic metabolic dysfunctions, and abnormal inflammatory/immune responses.

Gliptin-associated bullous pemphigoid shows peculiar features of anti-BP180 and -BP230 humoral response: Results of a multicenter study.

Background: Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. However, data on the clinical and immunologic features of gliptin-associated bullous pemphigoid (GABP) are controversial.

Objective: This study aimed to clinically and immunologically characterize a large cohort of GABP patients to get an insight into the pathophysiology of this emerging drug-induced variant of BP.

Research update of adipose tissue-based therapies in regenerative dermatology.

Mesenchymal stromal/stem cells (MSCs) have a spontaneous propensity to support tissue homeostasis and regeneration. Among the several sources of MSCs, adipose-derived tissue stem cells (ADSCs) have received major interest due to the higher mesenchymal stem cells concentration, ease, and safety of access. However, since a significant part of the natural capacity of ADSCs to repair damaged tissue is ascribable to their secretory activity that combines mitogenic factors, cytokines, chemokines, lipids, and extracellular matrix components, several studies focused on cell-free strategies.

Therapeutic potential of adipose tissue-derivatives in modern dermatology.

Stem cell-mediated therapies in combination with biomaterial and growth factor-based approaches in regenerative medicine are rapidly evolving with increasing application beyond the dermatologic field. Adipose-derived stem cells (ADSCs) are the more frequently used adult stem cells due to their abundance and easy access. In the case of volumetric defects, adipose tissue can take the shape of defects, restoring the volume and enhancing the regeneration of receiving tissue.

Evaluation of Hedgehog Pathway Inhibition on Nevoid Basal Cell Carcinoma Syndrome Fibroblasts and Basal Cell Carcinoma-Associated Fibroblasts: Are Vismodegib and Sonidegib Useful to Target Cancer-Prone Fibroblasts?

Activating mutations in the Hh pathway underlies the development of sporadic and familial skin BCC. For these oncogenic proliferations displaying ligand-independent activation of the intracellular pathway, two molecules have been approved for therapeutic purposes: vismodegib and sonidegib. Improper Hh signalling occurs in many human tumours also via a paracrine mechanism (ligand-dependent) in which the secretion of Hh ligands by stromal cells support tumour growth.

Profiling Cancer-Associated Fibroblasts in Melanoma.

Solid tumors are complex systems characterized by dynamic interactions between neoplastic cells, non-tumoral cells, and extracellular components. Among all the stromal cells that populate tumor microenvironment, fibroblasts are the most abundant elements and are critically involved in disease progression. Cancer-associated fibroblasts (CAFs) have pleiotropic functions in tumor growth and extracellular matrix remodeling implicated in local invasion and distant metastasis.

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: In Vitro Evaluation in Non-Melanoma Skin Cancer.

Background: Cancer-associated fibroblasts (CAFs) facilitate many aspects of cancer development by providing a structural framework rich in bioactive compounds. There are emerging studies proposing a combination of conventional anti-cancer therapies directed against neoplastic cells to molecules targeting tumor microenvironments.

Methods: The study evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) regarding non-melanoma skin cancer (NMSC) and the surrounding fibroblasts.

Alterations of the pigmentation system in the aging process.

Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure.

Platelet-rich plasma for genital lichen sclerosus: analysis and results of 94 patients. Are there gender-related differences in symptoms and therapeutic response to PRP?

Background: Lichen sclerosus is a chronic relapsing inflammatory dermatosis with a predilection for anogenital skin in 85%-98% of cases and is more prevalent in women (3%) than in men (> 0.07%).

Objectives: The purpose of this study was to investigate gender differences in clinical presentation and therapeutic response to treatment with platelet-rich plasma (PRP), an emerging innovative strategy for LS.

A Framework of Major Tumor-Promoting Signal Transduction Pathways Implicated in Melanoma-Fibroblast Dialogue.

The development of a modified stromal microenvironment in response to neoplastic onset is a common feature of many tumors including cutaneous melanoma. At all stages, melanoma cells are embedded in a complex tissue composed by extracellular matrix components and several different cell populations. Thus, melanomagenesis is not only driven by malignant melanocytes, but also by the altered communication between melanocytes and non-malignant cell populations, including fibroblasts, endothelial and immune cells.

Adipose tissue stromal vascular fraction and adipose tissue stromal vascular fraction plus platelet-rich plasma grafting: New regenerative perspectives in genital lichen sclerosus.

Lichen sclerosus (LS) is a chronic relapsing, inflammatory skin disorder usually involving the anogenital region of both sexes lacking a resolutive therapy. This study compared adipose tissue derived-stromal vascular fraction (AD-SVF) and AD-SVF-enriched platelet-rich plasma (PRP) therapy in the management of genital LS patients. Additionally, in vitro evaluation of cells and growth factors contained in the injected SVF has been evaluated as possible predictive factors for treatment outcome.