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The novel deep learning method is a computer based system that differentiates objects by morphological parameters such as colors, shape and other abstract features. The augmented accuracy of deep convolutional neural networks and the accessibility of clinical pictures, have brought about the increasing use of this method for visual recognision of images in medicine. In melanoma, deep convolutional nets may be implicated for early identification of suspicious lesions, therefore may reduce melanoma mortality and improve survival.
Long non-coding RNAs (lncRNAs) have emerged as putative biomarkers and therapeutic targets in cancer. Here, we have examined the role of LINC00346 in keratinocyte-derived cutaneous squamous cell carcinoma (cSCC). LINC00346 expression was upregulated in cSCC cells compared to normal human epidermal keratinocytes. Elevated expression of LINC00346 was also noted in tumor cells in cSCC tissue sections in vivo as compared to cSCC in situ and actinic keratosis by RNA in situ hybridization, whereas LINC00346 expression in benign epidermal papilloma (seborrheic keratosis) and normal skin was very low.
Anti-PD1 immunotherapy facilitates antitumor immune response and is shown to increase survival of melanoma patients. However, response rates are low and not always predictable. Molecular markers that predict response to therapy may direct therapeutic regimens. The unfolded protein response (UPR) protects the cell from apoptosis augmented by misfolded or unfolded proteins. Activation of the UPR has been reported to promote tumorigenesis and to alter immune response in different types of cancer. Glucose regulatory protein 78 (GRP78) is the master regulator of the UPR.
The activation of the RAS-RAF-MEK-ERK signal pathway has been associated with tumor progression. A selective BRAF protein kinase inhibitor, vemurafenib, exhibits anti-tumorigenic activity in patients with metastatic melanoma. However, adverse reactions such as an acne-like rash and dry skin appear in patients treated with vemurafenib. Such cutaneous disorders have been associated with the dysfunction of sebaceous glands and pilosebaceous units, allowing us to speculate that vemurafenib may influence sebum production in sebaceous glands.
Sentinel lymph node (SLN) biopsy is currently a valuable and reliable diagnostic procedure for precise staging of malignant melanoma (MM) patients. We assessed whether the genetic testing in SLNs from MM patients can be an independent prognostic factor. A retrospective study analysis was conducted for 35 patients (ratio of men to women, 17:18) who underwent SLN biopsy and primary cutaneous melanoma excision in our institution from January 2013 to June 2018. The median patient age was 71 years (range, 13-83 years).
microRNAs are considered as a class of epigenetic regulators that results in translational repression or decay of target mRNAs. Each microRNA may have up to several hundred mRNA targets, and several genes may be regulated by one unique microRNA. Therefore microRNAs are involved in numerous pathological conditions regulation including carcinogenesis. MiR-204-5p was revealed as one of the most down-regulated microRNAs in melanoma versus melanocytic nevi according to our microarray studies. Functional analysis of melanoma cells was performed and included gain and loss of function experiments followed by melanoma cells proliferation, apoptosis, migration, invasion, colony formation evaluation.
We examined the relationship between nitrogen mustard (NM)-induced lymphomatoid papulosis (LyP) in patients with mycosis fungoides (MF). Nine patients were included who were initially diagnosed with MF and subsequently developed LyP in the setting of NM induced inflammation. The average time from initiation of NM therapy to development of LyP was 5.2 months. The majority of patients presented to their follow-up visit with new red bumps, most commonly located on the buttocks/lower extremities, with symptoms of pain and pruritus in 6/9 patients.
The pathogenesis of basal cell carcinoma (BCC) is multifactorial and not fully elucidated. Previous studies showed, that behaviour of the tumour may be influenced by immune system and identified CD4+CD25+FoxP3+ regulatory T cells (Tregs) as a dominant immune cells in BCC microenvironment. The function and development of Tregs is regulated by FOXP3 encoding transcription factor, Forkhead box P3 (FoxP3). FoxP3 regulates transcription of many genes, including up-regulation of cytotoxic lymphocyte-associated antigen-4 gene (CTLA-4).
Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect the tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6 - the upstream element of IL-6/JAK/STAT3 pathway. In the present study rs1800795 (-174 G/C) IL-6 gene polymorphism and STAT3 rs2293152 (intron 11, C/G) and rs4796793 (–1697, C/G) polymorphisms were assessed in relation to the BCC risk and clinical course.
The incidence of Merkel cell carcinoma (MCC), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. Clinical biomarkers are urgently needed for MCC prognosis, treatment response monitoring, and early diagnosis of relapse. The clinical interest of circulating tumors cells (CTCs) has been validated in many solid cancers. The aim of this study was to compare CTC detection and characterization in blood samples of patients with MCC using the CellSearch® System and the RosetteSep™ -DEPArray™ workflow, an innovative procedure to enrich, detect and isolate single CTCs.
Cutaneous squamous cell carcinoma (cSCC) results from a combination of UV-induced DNA damage in keratinocytes and immune dysfunction. In this study, we investigated the role of CD39, an ecto-ATPase, in UV-induced epidermal DNA damage and cSCC progression. UVB irradiation increased CD39 expression in wildtype but not IL27RA knockout murine skin. γH2AX expression, a marker of DNA damage, was increased in UVB-irradiated human keratinocytes cultured with media from human skin T cells primed with IL-27.
Ulceration is an adverse prognostic factor in melanoma for which the underlying cause remains undefined. Recently, the combined loss of epidermal AMBRA1 and Loricrin (AMLo) as a prognostic biomarker for AJCC Stage I melanoma has been reported to be mediated by a melanoma secretory mechanism (Ellis et al. 2019). Coupled with bioinformatic data revealing TGFβ responsive elements in the AMBRA1 promotor and the known association of increased isoform specific TGFβ2 with metastatic melanomas, these data led to the current hypothesis that melanoma TGFβ2 secretion results in loss of AMBRA1, epidermal integrity and tumour ulceration.
We tried to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. We retrospectively collected data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018. Our studies were shown that all of the 8 lesions of melanoma was located on the finger pulps and distal to the ‘emotional line’ of the palm, and that melanomas were not present proximal to the emotional line.
Acral lentiginous melanoma (ALM), presenting on the palms of the hands, the soles of the feet, and the subungual area, is the most common type melanoma in Asian. Casein kinase 1α (CK1α, encoded by the CSNK1A1 gene) is involved in multiple cellular processes including gene transcription, cell division, nuclear localization, DNA repair, and carcinogenesis. CK1α has been reported as tumor promoter or tumor suppressor in different tumor types and tumor sites. In this study, we aim to investigate the role of CK1α in ALM.
The cAMP pathway is both important for normal melanocyte biology and implicated in melanoma development. We have shown that transformation of melanocytes by oncogenic BRAF inhibits cAMP signalling. This inhibition is due to overexpression of the phosphodiesterase PDE4D, enzyme that physiologically degrades cAMP. PDE4D expression is increased in patients with advanced melanoma and promotes melanoma invasion. Our recent work shows that PDE4D is overexpressed in BRAF-mutated melanoma cells which are resistant to BRAF inhibitors.
CMM is the deadliest form of skin cancer, responsible for approximately 500 deaths annually in Sweden, with an increasing incidence over last few years. Early CMM detection enables good prognosis, whereas disseminated disease is associated with poor prognosis due to intrinsic and acquired drug resistance. We have identified afatinib and crizotinib as an efficacious and promising alternative targeted combination therapy option independent of BRAF/NRAS mutational background for CMM patients. We hypothesize that other drug targets beyond canonical targets are more important in mediating anti-tumorigenic responses as observed both in vitro and in vivo.
Malassezia yeast plays a role in the pathogenesis of chronic dermatitis, especially in apocrine areas, by polarizing the local immunologic background to a Th2/Th17 state through aryl hydrocarbon receptor (AhR)-dependent pathways. Extra-mammary Paget’s disease (EMPD) is an adenocarcinoma of apocrine origin and, except for cases associated with Malassezia yeast and their metabolites, the lesions typically develop in areas not exposed to environmental material. The purpose of this study was to investigate 1) the immunomodulatory effects of Malassezia metabolites on normal human keratinocytes (NHKCs), focusing on interleukin (IL)-17 and related cytokines/chemokines (IL-23, IL-36g, CCL20), 2) the expression of these factors in lesion-affected skin in EMPD, and 3) the activation of tumor-associated macrophages (TAMs) by the productions of IL-17 induced factors.
RAS is frequently mutated in various tumors and known to be difficult to target. NRASQ61K/R are the second most frequent mutations found in human skin melanoma after BRAFV600E. Besides surgery, various approaches, including targeted therapies, immunotherapies, and combination therapies, is used to treat patients carrying NRAS mutations, but it remains poorly efficient. Here, we established mouse NRASQ61K melanoma cell lines and genetically derived isografts (GDIs) from Tyr::NRASQ61K mouse melanoma that can be used in vitro and in vivo in an immune-competent environment (C57BL/6) to test and discover novel therapies.
Melanoma is a malignant neoplasm originating from pigment producing skin cells known as melanocytes. It is the most fatal among the cutaneous carcinomas. Despite being more commonly encountered in Western countries among Caucasian populations, Southeast Asian countries, including the Philippines, have a subset population affected with the disease. In this retrospective study, a chart and slide review of all the recorded melanoma cases in the Philippine General Hospital from 2010 until 2017 was done.
The development of targeted therapies and immune checkpoint inhibitors has revolutionised melanoma treatment over the past decade. However, there remains an urgent need to identify new pro-metastatic pathways in melanoma. Vaspin was identified in a phage display screen against two in vitro melanoma models. The effect of recombinant human vaspin (rhVaspin) was tested on a range of melanoma lines including. Phenotypic changes were assessed using 2D cell migration assays and monitoring cell invasion through Matrigel-coated Boyden chambers or fluorescently labelled gelatin-coated glass coverslips.