Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361003

RESUMO

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Benzilisoquinolinas/farmacologia , Dermatite Atópica/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/toxicidade , Células HaCaT/efeitos dos fármacos , Células HaCaT/metabolismo , Humanos , Interferon gama/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-34432128

RESUMO

PURPOSE: Programmed death-ligand 1 (PD-L1) expression may influence the prognosis of patients with localized esophageal cancer. The current study compared the prognostic value of PD-L1 expression between tumor cells and immune cells. METHODS: Archival esophageal tumor tissue samples were collected from patients who received paclitaxel and cisplatin-based neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal squamous cell carcinoma (ESCC) in three prospective phase II trials. PD-L1 expression on tumor and immune cells was examined immunohistochemically by using the SP142 antibody and scored by two independent pathologists. The association of PD-L1 expression with patient's outcomes was analyzed using a log-rank test and Cox regression multivariate analysis. RESULTS: A total of 100 patients were included. PD-L1 expression on tumor cells was positive (≥ 1%, TC-positive) in 55 patients; PD-L1 expression on immune cells was high (≥ 5%, IC-high) in 30 patients. TC-positive status was associated with poor overall survival (OS) (HR: 1.63, P = 0.035), whereas IC-high status was associated with improved OS (HR: 0.44, P = 0.0024). Multivariate analysis revealed that TC-positive, IC-high, and performance status were independent prognostic factors for progression-free survival and that IC-high and performance status were independent factors for OS. Furthermore, the combination of IC-high and TC-negative status was associated with the optimal OS, whereas that of TC-positive and IC-low status was associated with the worst OS. CONCLUSION: PD-L1 expression on tumor and immune cells may have different prognostic value for patients with locally advanced ESCC receiving neoadjuvant CRT. A combination of these two indexes may further improve the prognostic prediction.

3.
Hum Pathol ; 107: 69-79, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33186588

RESUMO

The mechanism of high-grade transformation in gastrointestinal stromal tumors (GISTs) remains to be clarified. We aim to discover the key progression events by studying biphasic GISTs. The study group included 101 GISTs. Nineteen of these had been screened from 263 GISTs to represent the early stage of GIST high-grade transformation, characterized by juxtaposed low-grade and high-grade regions in the same tumor (so-called biphasic GISTs). Mutational analyses, fluorescence in situ hybridization (FISH), NanoString analyses, telomere analysis, and gene expression profiling were carried out, followed by in silico analyses, cell line study, and immunohistochemical validation. Using gene expression analysis, downregulation of SFRP1 was revealed to be the main event in GIST high-grade transformation (p = 0.013), accompanied by upregulation of EZH2. In silico analyses revealed that downregulation of SFRP1 was a common feature in GIST progression across several different series. Immunohistochemically, the expression of SFRP1 was validated to be significantly lower in high-grade GISTs (WHO risk group 3a or higher) than in low-grade GISTs (p < 0.001), and attenuation/loss of SFRP1 was associated with GIST tumor progression (p < 0.001). By NanoString and FISH analyses, chromosomal 9/9p loss was the only recurrent large-scale chromosome aberration in biphasic GISTs, with a correlation with SFRP1 downregulation. Subclones containing chromosome 9/9p loss could be appreciated in the low-grade parts of biphasic GISTs. TP53 mutation, RB1 loss, KIT/PDGFRA mutation, and alternative lengthening of telomeres did not play a significant role in GIST high-grade transformation. In conclusion, high-grade transformation of GISTs features SFRP1 downregulation and chromosome 9/9p loss.

4.
Med Phys ; 47(3): 1021-1033, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31834623

RESUMO

PURPOSE: Prostate cancer (PCa) is a major health concern in aging males, and proper management of the disease depends on accurately interpreting pathology specimens. However, reading prostatectomy histopathology slides, which is basically for staging, is usually time consuming and differs from reading small biopsy specimens, which is mainly used for diagnosis. Generally, each prostatectomy specimen generates tens of large tissue sections and for each section, the malignant region needs to be delineated to assess the amount of tumor and its burden. With the aim of reducing the workload of pathologists, in this study, we focus on developing a computer-aided diagnosis (CAD) system based on a densely connected convolutional neural network (DenseNet) for whole-slide histopathology images to outline the malignant regions. METHODS: We use an efficient color normalization process based on ranklet transformation to automatically correct the intensity of the images. Additionally, we use spatial probability to segment the tissue structure regions for different tissue recognition patterns. Based on the segmentation, we incorporate a multidimensional structure into DenseNet to determine if a particular prostatic region is benign or malignant. RESULTS: As demonstrated by the experimental results with a test set of 2,663 images from 32 whole-slide prostate histopathology images, our proposed system achieved 0.726, 0.6306, and 0.5209 in the average of the Dice coefficient, Jaccard similarity coefficient, and Boundary F1 score measures, respectively. Then, the accuracy, sensitivity, specificity, and the area under the ROC curve (AUC) of the proposed classification method were observed to be 95.0% (2544/2663), 96.7% (1210/1251), 93.9% (1334/1412), and 0.9831, respectively. DISCUSSIONS: We provide a detailed discussion on how our proposed system demonstrates considerable improvement compared with similar methods considered in previous researches as well as how it can be used for delineating malignant regions.


Assuntos
Diagnóstico por Computador , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Humanos , Masculino
6.
Am J Surg Pathol ; 43(7): 928-942, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31094921

RESUMO

Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.


Assuntos
Biomarcadores Tumorais/genética , Diferenciação Celular , Fusão Gênica , Rearranjo Gênico , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Sarcoma/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Neoplasias Uterinas/genética , Idoso , Proteínas de Ligação a DNA/genética , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Pessoa de Meia-Idade , Mitose , Coativador 1 de Receptor Nuclear/genética , Coativador 2 de Receptor Nuclear/genética , Neoplasias Ovarianas/patologia , Fenótipo , Prognóstico , Proteínas Proto-Oncogênicas/genética , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genética , Proteínas Repressoras/genética , Sarcoma/patologia , Análise de Sequência de RNA , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Taiwan , Carga Tumoral , Neoplasias Uterinas/patologia
7.
Asian J Surg ; 42(8): 832-838, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30711441

RESUMO

BACKGROUND: Atypical lipomatous tumor (ALT) is a low-grade malignancy that frequently occurs at a subfascial anatomical location. While marginal excision is adequate for lipomas, excision with a surgical margin is suggested for ALTs. However, ALTs and lipomas are difficult to differentiate preoperatively, even with the help of imaging studies. In this study, we aimed to formulate a scoring system based on selected clinical and imaging characteristics to enhance the accuracy of pre-operative diagnosis of deep-seated ALTs. METHODS: We enrolled 417 cases of deep-seated lipoma and 53 cases of ALTs from soft tissue treated between 2005 and 2016. Tumors arising from the bone, internal cavities, retroperitoneum, or nervous system were excluded. Clinical data were analyzed along with magnetic resonance image (MRI) features. We further developed a scoring formula to distinguish deep-seated ALTs from lipomas. RESULTS: Older age, tumor location at lower limbs, and the presence of MRI features (larger size, thick septa > 2 mm, contrast enhancement>1 cm, fat component <75%) are identified as risk factors of ALT and were utilized to develop a scoring system for distinguishing ALTs from lipomas. The formula exhibited 90% sensitivity and 92.5% specificity, and a score more than 0.214 suggested a diagnosis of ALT. CONCLUSIONS: The scoring system developed in this study can facilitate the pre-operative diagnosis of deep-seated ALTs and lipomas. If ALT is suspected, further tumor biopsy followed by molecular diagnosis can establish a definite diagnosis. Therefore, this scoring system can serve as a cost-effective tool for the clinical management of deep-seated lipomatous tumors.


Assuntos
Lipoma/diagnóstico , Lipossarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/diagnóstico por imagem , Lipossarcoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Projetos de Pesquisa , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/diagnóstico por imagem
8.
Histopathology ; 74(6): 933-943, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30604891

RESUMO

AIMS: Spindle cell/sclerosing rhabdomyosarcomas (SC/SRMS) feature spindled and/or rounded rhabdomyosarcomatous cells within variably hyalinised stroma. Only 30-67% of SC/SRMSs harbour neomorphic MYOD1 p.L122R mutations, indicating heterogeneity in this RMS type. We compared MYOD1-mutant and non-mutant cases to characterise the histological and genetic spectrum of mutated SC/SRMS. METHODS AND RESULTS: Seventeen RMSs with spindled, sclerosing or hybrid histology were sequenced to identify MYOD1 and PIK3CA mutations and reappraised to assess histological features and myogenic immunophenotypes. Twelve SC/SRMSs harboured MYOD1 mutations, including homozygous p.L122R (n = 8), heterozygous p.L122R (n = 3) and heterozygous p.E118K (n = 1). MYOD1-mutant tumours affected nine females and three males aged 8-64 years (median = 22.5), had a median size of 4.2 cm (range = 2-22) and involved the head and neck (n = 7), extremities (n = 4) and mediastinum (n = 1). Fascicular/spindle histology was predominant in four cases, including one with heterologous lipoblasts in focally myxoid stroma. Four sclerosing cases mainly comprised rounded cells, including one with multinucleated tumour cells. Four cases were histologically hybrid. The only PIK3CA (p.H1047R) mutation was detected in a predominantly spindled MYOD1-p.L122R-mutated case, but not in its laser-microdissected lipoblast-containing area. All MYOD1-mutant cases exhibited diffuse MYOD1 expression but patchy myogenin reactivity. At final follow-up (median = 13.5 months), recurrences (n = 4), metastases (n = 2) or both (n = 1) occurred in seven MYOD1-mutant cases; one had died of disease. Five non-mutated cases were reclassified as spindle embryonal (n = 3), dense embryonal (n = 1) and unclassifiable (n = 1) RMSs. CONCLUSION: MYOD1-mutant RMSs are uncommonly mutated with PIK3CA and behave aggressively with an expanded morphological and genetic spectrum, including lipoblastic differentiation, multinucleated cells and the alternative p.E118K mutation.


Assuntos
Proteína MyoD/genética , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Adolescente , Adulto , Criança , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/patologia , Adulto Jovem
9.
Int J Cancer ; 142(9): 1878-1889, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29266245

RESUMO

Sorafenib, a multikinase inhibitor with antiangiogenic activity, is an approved therapy for hepatocellular carcinoma (HCC). It is unclear whether the proinflammatory and immunosuppressive mechanisms may limit the therapeutic efficacy of sorafenib in HCC. We used a syngeneic mouse liver cancer cell line to establish orthotopic liver or subcutaneous tumors to study how proinflammatory and immunosuppressive mechanisms impact on the efficacy of sorafenib. We found sorafenib exhibited a potent therapeutic effect in subcutaneous tumors, but a less potent effect in orthotopic liver tumors. The protein levels of interleukin-6 (IL-6) and vascular endothelial growth factor A (VEGF-A) were persistently elevated in orthotopic liver tumors, but not in subcutaneous tumors, treated with sorafenib. Likewise, the tumor-infiltrating Ly6G+ myeloid-derived suppressor cells (MDSCs) and immune suppressors were increased in orthotopic liver tumors, not in subcutaneous tumors, treated with sorafenib. The tumor-infiltrating Ly6G+ MDSCs of sorafenib-treated orthotopic liver tumors significantly induced IL-10 and TGF-ß expressing CD4+ T cells, and downregulated the cytotoxic activity of CD8+ T cells. IL-6, but not VEGF-A, protected Ly6G+ MDSCs from sorafenib-induced cell death in vitro. The combination of anti-Ly6G antibody or anti-IL-6 antibody with sorafenib significantly reduced the cell proportion of Ly6G+ MDSCs in orthotopic liver tumors, enhanced the T cells proliferation and improved the therapeutic effect of sorafenib synergistically. Modulating tumor microenvironment through targeting tumor-infiltrating Ly6G+ MDSCs represents a potential strategy to improve the anti-HCC efficacy of sorafenib.


Assuntos
Antígenos Ly/imunologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/imunologia , Células Mieloides/imunologia , Sorafenibe/farmacologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Antineoplásicos/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Interleucina-6/imunologia , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Células Mieloides/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
PLoS One ; 12(5): e0177126, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28472158

RESUMO

Studies surveying melanomas associated with melanocytic nevi in Asia are rare. In this study, we examined whether nevus-associated melanomas differ from de novo melanomas in terms of their associations with clinical factors, histologic characteristics, and patient survival in Taiwan. Using data on cancer cases obtained from the Department of Pathology archives and the Cancer Registry of National Taiwan University Hospital, we conducted a retrospective analysis of 103 consecutive melanoma patients who were diagnosed between 2010 and 2015 and received follow-up through November 2016. Approximately 17.5% of the melanomas in question were associated with a nevus. In patients under 65 years of age, non-acral lentiginous melanomas were significantly associated with a higher percentage of nevus-associated melanomas. The superficial spreading subtype, younger patient age, thinner tumor, intermittent solar exposure, and early stage were significant predictors of a melanoma being histologically associated with a nevus. The appearance of a nevus associated with a melanoma predicted better recurrence-free survival compared with de novo melanomas. Although acral lentiginous melanomas (70.9%) constituted the most common histologic subtype, only 9.6% of the acral lentiginous melanomas were associated with a nevus. Furthermore, there was no statistically significant difference between the nevus-associated and de novo acral lentiginous melanomas with regard to clinicopathological factors and survival. In conclusion, nevus-associated melanomas were uncommon among acral lentiginous melanomas. Relatedly, because over half of all melanomas in Asians are acral lentiginous melanomas, Asians are less likely than Caucasians to have nevus-associated melanomas.


Assuntos
Melanoma/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Nevo/epidemiologia , Neoplasias Cutâneas/epidemiologia , Análise de Sobrevida , Taiwan/epidemiologia
11.
Nat Commun ; 8: 14674, 2017 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-28270683

RESUMO

KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs. MAX genomic inactivation is associated with p16 silencing in the absence of p16 coding sequence deletion and MAX induction restores p16 expression and inhibits GIST proliferation. Hence, MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proliferação de Células/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Ciclo Celular/genética , Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Análise Mutacional de DNA , Progressão da Doença , Feminino , Inativação Gênica , Humanos , Mutação com Perda de Função , Masculino , Neurofibromina 1/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Succinato Desidrogenase/genética
12.
Mod Pathol ; 30(5): 728-733, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28084336

RESUMO

Giant cell tumors of bone are locally aggressive bone neoplasms with a predilection for young adults. Histologically, they are composed of histiocytoid to spindled mononuclear cells, admixed with numerous large osteoclastic giant cells. Giant cell tumors of soft tissue are rare tumors that bear striking histological resemblance to giant cell tumors of bone and might be regarded as a soft tissue analog thereof. Point mutations of the H3F3A gene (coding for a histone H3.3 protein) at the Gly34 codon, mostly G34W resulting from a GGG>TGG nucleotide change, have recently been identified in a vast majority of giant cell tumors of bone. To delineate the possible pathogenic linkage between both tumor types, we analyzed the H3F3A genotypes in a series of 15 giant cell tumors of soft tissue by Sanger sequencing and found no mutation in any case. We then sequenced cognate histone H3 genes with an identical nucleotide sequence ('GGG') at the codon Gly34, including the H3F3B, H3F3C, HIST2H3A, HIST2H3C, and HIST2H3D genes, and no somatic mutation was detected. These results reveal that giant cell tumors of soft tissue are probably genetically distinct from their bone counterparts and suggest that they might be pathogenically unrelated. Given the prominence of non-neoplastic cells in these tumors and the limitations of the current study, however, analyses using more sensitive techniques might be required to solve the issue.


Assuntos
Tumores de Células Gigantes/genética , Histonas/genética , Neoplasias de Tecidos Moles/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/genética , Criança , Pré-Escolar , Feminino , Genótipo , Tumor de Células Gigantes do Osso/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Dermatology ; 233(6): 446-455, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29554651

RESUMO

BACKGROUND: Longitudinal melanonychia (LM) may occur as a result of nail apparatus melanoma. Knowledge of etiology plays an important role in the management of LM. OBJECTIVES: The study is aimed to compare the diagnosis of LM in different age groups. METHODS: We collected 63 cases (45 adults and 18 children) with LM who underwent nail matrix biopsy or excision in a 21-year cohort and assessed their clinicopathological features. RESULTS: Melanomas in adults and children were 40% and none, while nevi accounted for 15.6% in adults and 94.4% in children. There was a statistically significant difference between the average age at diagnosis for melanoma (54.5 ± 13.3 years) and nevus (15.2 ± 18.5 years). Logistic regression related the occurrence of melanoma to older ages with a relative risk of 1.2 compared to nevus, but no cutoffs between age groups could be defined between LM-associated nevus and melanoma. CONCLUSION: The adult group has a significantly higher risk of melanoma, while children with LM show mostly nonmelanoma etiologies. Tissue proof is more warranted in adult cases, and it is needed in selected cases of children with LM.


Assuntos
Hiperpigmentação/etiologia , Melanoma/diagnóstico , Melanoma/patologia , Doenças da Unha/etiologia , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idade de Início , Idoso , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Hiperpigmentação/patologia , Lactente , Recém-Nascido , Masculino , Melanoma/complicações , Pessoa de Meia-Idade , Doenças da Unha/patologia , Unhas/patologia , Nevo Pigmentado/complicações , Neoplasias Cutâneas/complicações , Adulto Jovem
14.
PLoS One ; 11(6): e0158018, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27336363

RESUMO

Developing a robust, novel method for performing multiple reactions in a single tube is not only time- and cost-saving but also critical for future high-throughput whole-slide in situ techniques on diseased tissues. In this study, we introduce the use of perfluorocarbons and compound-coated magnetic particles to create pseudochambers in a single tube, allowing different reactions to be performed in different phases. Perfluorocarbons also serve as cell lysis buffer and polymerase chain reaction (PCR) buffer owing to their highly penetrating, repellent and emulsifiable properties. Using this method, nucleic acids can be isolated and purified from various sample types and sizes, followed by PCR, real-time PCR, or multiplex PCR in the same tube. No incubation or enzyme digesting time is needed and the risk of cross-contamination is reduced. Tests can be performed in microemulsions (water-in-oil droplets) containing sequence-specific captures and probes for further high-throughput detection. We present a simple, quick, and robust procedure as a prerequisite step to future high-throughput in situ techniques.


Assuntos
Fluorcarbonetos , Reação em Cadeia da Polimerase/métodos , Animais , Humanos , Camundongos , Reação em Cadeia da Polimerase Multiplex , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real
15.
Mod Pathol ; 29(9): 1070-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27255164

RESUMO

Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin tissue. In conclusion, we identified frequent chromosome 12q amplifications, including loci containing potential pharmacological targets. Global chromosomal instability and chromothripsis were more frequent in cases with sarcomatous overgrowth. To our knowledge, this is the first time that evidence of chromothripsis has been demonstrated in paraffin-embedded clinical tissues and in adenosarcomas.


Assuntos
Adenossarcoma/genética , Biomarcadores Tumorais/genética , Cromotripsia , Variações do Número de Cópias de DNA , Dosagem de Genes , Ductos Paramesonéfricos/patologia , Neoplasias Uterinas/genética , Adenossarcoma/química , Adenossarcoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Coloração Cromossômica , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Ductos Paramesonéfricos/química , Inclusão em Parafina , Fenótipo , Neoplasias Uterinas/química , Neoplasias Uterinas/patologia , Adulto Jovem
16.
J Dermatol ; 43(9): 1062-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27099208

RESUMO

Neutrophilic dermatosis on the site of lymphedema is a rare condition and considered as a localized and less severe variant of Sweet syndrome. Only 13 cases of this variant have been reported after mastectomy for breast cancer in the English-language published work. However, this condition has never been described on the lower limbs or from other causes of lymphedema. Herein, we report two cases of localized Sweet syndrome on the lymphedematous lower limbs: one occurred after radical hysterectomy, bilateral pelvic lymph node dissection and radiotherapy for cervical cancer; the other developed after radiotherapy for malignant melanoma on the right groin. Based on clinical and histological features, we suggest the name "lymphedema-associated neutrophilic dermatosis" for this underrecognized disease entity.


Assuntos
Histerectomia/efeitos adversos , Linfedema/etiologia , Melanoma/radioterapia , Radioterapia/efeitos adversos , Síndrome de Sweet/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Administração Oral , Idoso , Antibacterianos/uso terapêutico , Biópsia , Proteína C-Reativa/análise , Cefalosporinas/uso terapêutico , Feminino , Febre/etiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/uso terapêutico , Histerectomia/métodos , Infusões Parenterais , Leucocitose/sangue , Extremidade Inferior , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/patologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Pele/patologia , Síndrome de Sweet/sangue , Síndrome de Sweet/tratamento farmacológico , Síndrome de Sweet/etiologia , Trombocitopenia/sangue , Neoplasias do Colo do Útero/patologia
17.
Appl Immunohistochem Mol Morphol ; 24(1): 57-63, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25710581

RESUMO

PAX8 is a transcription factor crucial for the development of the kidneys, thyroid glands, and Mullerian system. It is commonly expressed by epithelial tumors from these organs. Recently, the diagnostic utility of PAX8 has been expanded to pancreatic neuroendocrine tumors (NETs). However, PAX8 is not expressed by pancreatic islets during organogenesis. The potential cross-reactivity of polyclonal PAX8 antibody to other PAX family members makes it essential that related findings need to be validated. In this study, we used 4 antibodies (1 polyclonal and 3 monoclonal) on 115 NETs from various organs (pancreas, n=20; thymus, n=16; cervix, n=27; parathyroid, n=7; and thyroid, lung, ileum, stomach, duodenum, appendix, rectum, ovary, and skin, each n=5) to test the utility of PAX8 as a differential diagnosis marker of NETs. Our results showed that NETs from a large variety of organs except for lung and ileum could be immunoreactive to the 2 less specific antibodies that have been observed to cross-react with other PAX proteins (Proteintech polyclonal and Cell Marque MRQ50). However, all NETs were immunonegative for the other 2 monoclonal antibodies specific for the less conserved C-terminal portion of PAX8 (Abcam PAX8R1 and Biocare BC12). We concluded that PAX8 may provide help in the differential diagnosis of NETs in certain specific contexts but the antibody used and the clinical information must be considered.


Assuntos
Anticorpos Monoclonais/química , Biomarcadores Tumorais/genética , Imuno-Histoquímica/normas , Tumores Neuroendócrinos/diagnóstico , Fatores de Transcrição Box Pareados/genética , Neoplasias de Tecidos Moles/diagnóstico , Afinidade de Anticorpos , Especificidade de Anticorpos , Reações Cruzadas , Diagnóstico Diferencial , Reações Falso-Positivas , Expressão Gênica , Humanos , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Fator de Transcrição PAX8 , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia
18.
Hum Pathol ; 46(9): 1360-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26190196

RESUMO

Alternative lengthening of telomeres (ALT) is a mechanism using homologous recombination to maintain telomere length and sustain limitless replicability of cancer cells. Recently, ALT has been found to be associated with inactivation of either α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated (DAXX) protein. In this study, 119 tumors (88 angiosarcomas, 11 epithelioid hemangioendotheliomas, and 20 Kaposi sarcomas) were analyzed to determine the ALT status, its relationship to loss of ATRX/DAXX expression, and the clinicopathological features. In addition, the mutation status in the telomerase reverse transcriptase gene (TERT) promoter was also studied. Loss of ATRX expression was observed in 21% (16/77) of the primary angiosarcomas and 9% (1/11) of epithelioid hemangioendotheliomas. DAXX expression was intact in all but 2 ATRX-deficient angiosarcomas. Telomere-specific fluorescence in situ hybridization assay showed 28% (17/61) of the primary angiosarcomas were ALT positive. Remarkably, ALT was highly associated with loss of ATRX expression: all but 2 ALT-positive angiosarcomas were ATRX deficient. Notably, hepatic angiosarcomas were frequently ATRX deficient (8/13) and/or ALT positive (8/12). None of the secondary angiosarcomas were ATRX/DAXX deficient or ALT positive. The only ATRX-deficient epithelioid hemangioendothelioma was positive for ALT. Forty-seven angiosarcomas were tested for TERT promoter mutation. Despite the fact that angiosarcoma occurs most commonly in sun-damaged skin, mutation was detected in only 1 radiation-associated angiosarcoma (2%). We conclude that ALT is an important telomere maintenance mechanism in primary angiosarcomas. This feature is highly associated with loss of ATRX expression and is frequently observed in hepatic angiosarcomas.


Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , DNA Helicases/análise , Hemangiossarcoma/enzimologia , Hemangiossarcoma/genética , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Proteínas Nucleares/análise , Homeostase do Telômero , Telômero/genética , Adulto , Idoso , Análise Mutacional de DNA , Regulação para Baixo , Feminino , Hemangioendotelioma Epitelioide/enzimologia , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/patologia , Hemangiossarcoma/mortalidade , Hemangiossarcoma/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Regiões Promotoras Genéticas , Sarcoma de Kaposi/enzimologia , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Telomerase/genética , Proteína Nuclear Ligada ao X
20.
J Pathol ; 235(4): 539-45, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25319834

RESUMO

Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour-induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1-FGFR1 fusion gene in three out of four PMTs by next-generation RNA sequencing. The fusion transcripts and proteins were subsequently confirmed with RT-PCR and western blotting. Fluorescence in situ hybridization analysis showed six cases with FN1-FGFR1 fusion out of an additional 11 PMTs. Overall, nine out of 15 PMTs (60%) harboured this fusion. The FN1 gene possibly provides its constitutively active promoter and the encoded protein's oligomerization domains to overexpress and facilitate the activation of the FGFR1 kinase domain. Interestingly, unlike the prototypical leukaemia-inducing FGFR1 fusion genes, which are ligand-independent, the FN1-FGFR1 chimeric protein was predicted to preserve its ligand-binding domains, suggesting an advantage of the presence of its ligands (such as FGF23 secreted at high levels by the tumour) in the activation of the chimeric receptor tyrosine kinase, thus effecting an autocrine or a paracrine mechanism of tumourigenesis.


Assuntos
Biomarcadores Tumorais/genética , Fibronectinas/genética , Fusão Gênica , Hipofosfatemia Familiar/etiologia , Neoplasias de Tecido Conjuntivo/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Western Blotting , Feminino , Fibronectinas/análise , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/química , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias de Tecido Conjuntivo/patologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...