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Biologic Gray Zone of Melanocytic Tumors in Reality: Defining 'Non-Conventional' Melanocytic Tumors.Dermatology Practical & Conceptual Apr 2024
PubMed: 38810070
DOI: 10.5826/dpc.1402a149 -
Dermatology Practical & Conceptual Apr 2024
PubMed: 38810069
DOI: 10.5826/dpc.1402a153 -
Dermatology Practical & Conceptual Apr 2024Scientific evidence supports dermoscopy as an essential tool in dermatological diagnosis.
INTRODUCTION
Scientific evidence supports dermoscopy as an essential tool in dermatological diagnosis.
OBJECTIVES
The objective is to know the factors that influence its use in Chilean dermatologists.
METHODS
Analytical cross-sectional study. An adapted version of the survey was submitted from the pan-European study by Forsea et al to members of the Chilean Society of Dermatology, between September and December 2020. Analysis using descriptive statistics and multivariate analysis with ordinal logistic regression looking for factors associated with greater use of.
RESULTS
One hundred and ninety-eight responses, mean age 46.3 years and 14.6 years on average practicing as dermatologists. 61.6% trained in dermoscopy during their residency. 98% use a dermatoscope. More than 80% consider dermoscopy useful for the diagnosis of melanomas, follow-up of melanocytic lesions, and diagnosis of pigmented and non-pigmented tumors. Between 50% and 70% consider it useful for monitoring non-melanocytic lesions, nail and hair pathologies. Greater confidence when evaluating pigmented and non-pigmented tumors and capillary pathology. Adjusting for age, sex, confidence, and education, participation in teaching was associated with greater use of dermoscopy in non-pigmented and pigmented tumors, and capillary pathology.
CONCLUSIONS
Percentage of participation in the survey and training in dermoscopy higher than in the reference study, recognizing the usefulness of dermoscopy for the diagnosis and follow-up of tumor pathologies. Participating in teaching is a strong independent factor that is associated with a greater use of dermoscopy in Chile. Dermoscopy is positioned as a tool widely used by Chilean dermatologists in their daily practice.
PubMed: 38810061
DOI: 10.5826/dpc.1402a71 -
Dermatology Practical & Conceptual Apr 2024
PubMed: 38810050
DOI: 10.5826/dpc.1402a126 -
Dermatology Practical & Conceptual Apr 2024
PubMed: 38810033
DOI: 10.5826/dpc.1402a154 -
Nature Communications May 2024Topologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements...
Topologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements of the TADs boundaries do not always lead to significant changes in the activity pattern. Here, we investigated the consequences of the TAD boundaries deletion on the expression of developmentally important genes encoding tyrosine kinase receptors: Kit, Kdr, Pdgfra. We used genome editing in mice to delete the TADs boundaries at the Kit locus and characterized chromatin folding and gene expression in pure cultures of fibroblasts, mast cells, and melanocytes. We found that although Kit is highly active in both mast cells and melanocytes, deletion of the TAD boundary between the Kit and Kdr genes results in ectopic activation only in melanocytes. Thus, the epigenetic landscape, namely the mutual arrangement of enhancers and actively transcribing genes, is important for predicting the consequences of the TAD boundaries removal. We also found that mice without a TAD border between the Kit and Kdr genes have a phenotypic manifestation of the mutation - a lighter coloration. Thus, the data obtained shed light on the principles of interaction between the 3D chromatin organization and epigenetic marks in the regulation of gene activity.
Topics: Animals; Proto-Oncogene Proteins c-kit; Mice; Mast Cells; Melanocytes; Fibroblasts; Chromatin; Vascular Endothelial Growth Factor Receptor-2; Promoter Regions, Genetic; Enhancer Elements, Genetic; Receptor, Platelet-Derived Growth Factor alpha; Epigenesis, Genetic; Genetic Loci; Mice, Inbred C57BL; Organ Specificity; Gene Editing; Ectopic Gene Expression; Male
PubMed: 38806452
DOI: 10.1038/s41467-024-48523-7 -
PloS One 2024Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM...
Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM continue to rise globally. GPR168, also known as MrgprF, is a MAS related GPR family member. The low expression of GPR168 has also been reported in many malignant tumors including MM. In the study, the statistical analysis from The Cancer Genome Atlas (TCGA) revealed a significant down regulation of GPR168 in melanoma compared to normal melanocytes, underscoring its importance in MM. The aim of the present study is to investigate the affect of GPR168 overexpression and elucidate its molecular mechanisms in MM cells. In addition, we used mouse melanoma B16-F10 cell line and xenograph tumor model to explore the function of GPR168 in melanoma. Our findings demonstrate that GPR168 overexpression could inhibit B16-F10 cell proliferation, migration, and xenografts tumor growth. Further, mechanistic studies revealed that GPR168 affected B16-F10 progress through Akt signal pathway with the decreased expression of p-Akt, p-GSK-3β, β-catenin, Myc, CyclinD1 and CDK4. In order to validate these findings, a rescue experiment was formulated employing GPR168 polyclonal antibody (Anti-GPR168 pAbs) to block GPR168 functionality. The addition of Anti-GPR168 pAbs into the culture medium restored both cell proliferation and migration. In conclusion, the overexpression of GPR168 in mouse melanoma B16-F10 cells suppressed proliferation and migration through the Akt signaling pathway. These findings collectively propose GPR168 as a promising novel tumor suppressor in MM, suggesting its potential as a therapeutic target in future interventions.
Topics: Animals; Proto-Oncogene Proteins c-akt; Signal Transduction; Mice; Melanoma, Experimental; Cell Proliferation; Cell Line, Tumor; Receptors, G-Protein-Coupled; Cell Movement; Humans; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL
PubMed: 38805406
DOI: 10.1371/journal.pone.0302061 -
Vision (Basel, Switzerland) May 2024Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical... (Review)
Review
Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. Mutations in neurofibromin, the protein encoded by the tumor suppressor gene, result in dysregulation of the RAS/MAPK pathway leading to uncontrolled cell growth and migration. Neurofibromin is highly expressed in several cell lineages including melanocytes, glial cells, neurons, and Schwann cells. Individuals with NF1 possess a genetic predisposition to central nervous system neoplasms, particularly gliomas affecting the visual pathway, known as optic pathway gliomas (OPGs). While OPGs are typically asymptomatic and benign, they can induce visual impairment in some patients. This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. We focus on recent advancements in preclinical animal models to elucidate the underlying mechanisms of NF1 pathology and therapies targeting NF1-OPGs. Overall, our review highlights the involvement of retinal ganglion cell dysfunction and degeneration in NF1 disease, and the need for further research to transform scientific laboratory discoveries to improved patient outcomes.
PubMed: 38804352
DOI: 10.3390/vision8020031 -
Autopsy & Case Reports 2024Esophageal melanocytosis is a rare entity defined by the proliferation of a melanocytic basal layer of the esophageal squamous lining and deposition of melanin in the...
Esophageal melanocytosis is a rare entity defined by the proliferation of a melanocytic basal layer of the esophageal squamous lining and deposition of melanin in the esophageal mucosa. Esophageal melanocytosis is considered a benign entity of unknown etiology; however, it has been reported as a melanoma precursor. We report a case of esophageal melanocytosis in a diabetic and hypertensive 67-year-old male with recurrent dizziness and syncope for the past 6 months. Given his complaint of dyspepsia, he underwent an upper gastrointestinal endoscopy, in which an esophageal biopsy revealed the diagnosis of esophageal melanocytosis. The definitive diagnosis of esophageal melanocytosis can only be made by histological analysis. The histologic differential diagnoses include melanocytic nevi and malignant melanoma. Therefore, they need to be ruled out.
PubMed: 38803486
DOI: 10.4322/acr.2024.487 -
ENeurologicalSci Jun 2024Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and...
Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.
PubMed: 38803399
DOI: 10.1016/j.ensci.2024.100504