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Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway.

Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, and megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. T

Expression of stabilin-1 in M2 macrophages in human granulomatous disease and melanocytic lesions.

Stabilin-1 is an endocytotic scavenger receptor, specifically expressed by non-continuous sinusoidal endothelial cells in the liver, spleen and lymph nodes and by M2 or alternatively activated macrophages in human malignancies. We analysed paraffin-embedded tissue of melanocytic lesions and granulomatous diseases for stabilin-1 expression, using the human/murine RS1 antibody. The specificity of the RS1 staining was confirmed in a knockout model, as only M2-like tumor-associated macrophages and vessels of a B16F10 melanoma in wild type mice stained positive; while staining of tumor-associated m

Role of Tip60 in human melanoma cell migration, metastasis, and patient survival.

The tumor suppressor Tip60 regulates gene transcription, DNA damage response, apoptosis, and cancer development, but its role in melanoma is unknown. In this study, we investigated the expression pattern of Tip60 in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 448 cases of melanomas (201 for the training set and 247 for the validation set) and 105 cases of nevi, we found that Tip60 expression was significantly reduced in metastatic melanoma compared to common nevi (P=0.045), dysplastic nevi (P=0.047), and primary melanoma (P=0.001). Kaplan-Meier survival c

Identification of a novel mutation in the PTCH gene in a patient with Gorlin-Goltz syndrome with unusual ocular disorders.

PURPOSE: To document the clinical, functional, and in vivo microanatomic characteristics of a patient with Gorlin-Goltz syndrome with a novel nonsense mutation in PTCH (patched). METHODS: Optical coherence tomography (OCT), fluorescein angiography, electrophysiologic testing, visual field, magnetic resonance imaging, and mutation screening of PTCH gene. RESULTS: Visual acuity was 20/20 in the right eye and 20/25 in the left. Fundus examination revealed myelinated nerve fibers in the left eye and bilateral epiretinal membranes with lamellar macular hole also documented with macular OCT. A red

Pigmented lesions clinic for early detection of melanoma: preliminary results.

BACKGROUND: Early detection of malignant melanoma of the skin is the most important factor in patient survival. Naked-eye diagnostic sensitivity and specificity are low. Patients with multiple nevi are at high risk to develop melanomas and the clinical follow-up of such patients is difficult, resulting in missed melanomas on the one hand and unnecessary biopsies on the other. OBJECTIVES: To describe the set-up of a special clinic aimed at early detection of melanoma and follow-up of high risk patients and preliminary results from 20 months of operation. METHODS: We established a pigmented le

Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma.

PURPOSE: It has been proposed that melanoma cells shift from E-cadherin to N-cadherin expression during tumor development, and recent gene profiling has shown increased expression of Wnt5a/Frizzled in aggressive melanomas possibly by interactions with beta-catenin. We therefore wanted to investigate the role of cadherin subtypes, beta-catenin, and Wnt5a/Frizzled in melanocytic tumors, with focus on prognosis in nodular melanomas. EXPERIMENTAL DESIGN: The immunohistochemical expression of E-cadherin, N-cadherin, P-cadherin, beta-catenin, and Wnt5a/Frizzled was examined using tissue microarrays

Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the correspo

A two-tier polymerase chain reaction direct sequencing method for detecting and typing human papillomaviruses in pathological specimens.

An in-house polymerase chain reaction direct sequencing (PCR-DS) approach for HPV detection and typing was developed, taking advantage of two widely used pairs of human papillomavirus (HPV)-specific PCR primers, MY09/MY11 and GP5/GP6, and 33P-labeled dideoxynucleotides. In this study, 105 pathological specimens were examined: 89% were diagnosed as cervical intraepithelial neoplasia (CIN) grade I-III, 76.2% were HPV-positive by PCR-DS. The PCR using GP5/GP6 (first tier) and MY09/MY11 primers (second tier for the GP5/GP6-negative samples) detected additional 15%-25% HPV-positive samples compared

Self screening for risk of melanoma: validity of self mole counting by patients in a single general practice.

OBJECTIVE: To validate self screening by patients of high mole counts, assess the within family association of sun protection behaviour and mole counts, and estimate prevalence of risk factors for melanoma. SETTING AND SUBJECTS: Systematic sample of families from a single affluent general practice population in Wessex. DESIGN: Subjects completed a questionnaire about risk factors for melanoma and counted their moles. Subsequently a mole count was done by a general practitioner trained at dermatology clinics. MAIN OUTCOME MEASURES: Validation of self counts by observer's count. Within family

Epidemiology of malignant melanoma in central Europe: risk factors and prognostic predictors. Results of the Central Malignant Melanoma Registry of the German Dermatological Society.

The Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society was established in 1983, and 7789 cutaneous malignant melanomas (CMM) were registered by 35 dermatological departments in Germany, Austria and Switzerland until the end of 1989. Population-based incidence rates, risk factors for developing CMM and prognostic parameters for predicting the final outcome were investigated in separate multicenter studies performed by the CMMR. Among the 7789 CMM registered, there was a preponderance of females (57.7%) versus males (42.3%). The age distribution peaked in the 5th and

Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.

The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc

Совпадение в полном тексте источника
… Shh Signaling in Cancer The role of dysregulated Shh signaling in cancer was first characterized by studies of basal cell nevus syndrome. … These mice showed the critical features of basal cell nevus syndrome, such as development of basal cell carcinomas, medulloblastomas, and rhabdomyosarcomas [ 48 , 49 , 52 ]. Abnormal Shh signaling is a hallmark of many cancers. …

Handheld In Vivo Reflectance Confocal Microscopy for the Diagnosis of Eyelid Margin and Conjunctival Tumors.

IMPORTANCE: The clinical diagnosis of conjunctival and eyelid margin tumors is challenging, and new noninvasive imaging techniques could be valuable in this field. OBJECTIVE: To assess the diagnostic accuracy of handheld in vivo reflectance confocal microscopy (IVCM) for the diagnosis of eyelid margin and conjunctival tumors. DESIGN: A prospective observational study was conducted at University Hospital of Saint-Etienne from January 2, 2011, to December 31, 2016 (inclusion of patients until December 31, 2015, and follow-up until December 31, 2016). A total of 278 consecutive patients with ey

Gorlin syndrome-derived induced pluripotent stem cells are hypersensitive to hedgehog-mediated osteogenic induction.

Gorlin syndrome is an autosomal dominant inherited syndrome that predisposes a patient to the formation of basal cell carcinomas, odontogenic keratocysts, and skeletal anomalies. Causative mutations in several genes associated with the sonic hedgehog (SHH) signaling pathway, including PTCH1, have been identified in Gorlin syndrome patients. However, no definitive genotype-phenotype correlations are evident in these patients, and their clinical presentation varies greatly, often leading to delayed diagnosis and treatment. We generated iPSCs from four unrelated Gorlin syndrome patients with loss

Malignant Melanoma Arising in Patients with a Large Congenital Melanocytic Naevus: Retrospective Study of 10 Cases with Cytogenetic Analysis.

Large congenital melanocytic naevi (LCMN) represent the main risk factor for development of melanoma in childhood. This retrospective study of 10 cases of melanoma in patients with LCMN used fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) (6 cases) to elucidate the clinical, histological, and cytogenetic characteristics of this rare disorder. Six melanomas were found within the LCMN, the others in lymph nodes, subcutis and brain. The LCMN was located on the trunk in 8 cases, with satellite naevi in 6 cases. Two distinct groups emerged: 5 melanomas that dev

Pathobiological properties of the ubiquitin ligase Nedd4L in melanoma.

A recent global gene expression profiling study unexpectedly showed that activated oncogenic NRAS may recruit neural precursor cell expressed, developmentally downregulated 4L (Nedd4L; a human homologue of Nedd4-2) in cultured melanoma cells. However, whether Nedd4L was expressed in melanoma tissues or participated in melanoma carcinogenesis remains to be clarified. Here, we investigated the expression status of Nedd4L in human melanocytes, benign nevi and melanoma tissue specimens and subsequently attempted to determine the role of Nedd4L in melanoma cell growth. Immunohistochemical staining

[A silent-growing and fast-killing melanoma in a teenager].

Malignant melanoma is a relatively rare but potentially aggressive tumor in children and adolescents. We report the case of a metastatic malignant melanoma in a 17-year-old girl, first diagnosed on cytological features of a fine-needle lymph node aspiration and then histologically confirmed by both examination of the metastatic adenopathy and a clinically harmless skin lesion of the scalp, which harbored focal microscopic pattern of melanoma. A fluorescent in situ hybridization study revealed that both metastatic and primary cutaneous tumours contained the same and pejorative chromosomal aberr