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2.
Am J Dermatopathol ; 41(11): 810-818, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30839347

RESUMO

INTRODUCTION: Benign cutaneous tumors with follicular differentiation are alleged to differentiate toward parts of the hair follicle. Connexin 43 (Cx43) is a gap junction protein, the tumoral role of which has been investigated in several types of tumors. OBJECTIVE: To study the pattern of expression of Cx43 in benign cutaneous tumors with follicular differentiation and to compare it with that shown by their alleged anatomical counterparts of the hair follicle. MATERIALS AND METHODS: Five cases each of trichofolliculoma, trichilemmoma, fibrofolliculoma/trichodiscoma, trichoblastoma, trichoepithelioma, pilomatrixoma, and proliferating trichilemmal tumor, 3 cases of pilar sheath acanthoma, and 1 case of tumor of the follicular infundibulum were examined. Anti-Cx43 antibody was used. RESULTS: Cx43 was expressed by all follicular tumors studied. Comparisons between trichoblastoma and trichoepithelioma and their respective normal counterparts could not be made. In 3 tumors (trichofolliculoma, pilomatrixoma, and the spectrum fibrofolliculoma/trichodiscoma), there was a parallelism between their Cx43 expression pattern and that of their alleged anatomical counterparts. In pilar sheath acanthoma, trichilemmoma, and the tumor of the follicular infundibulum, we only found partial similarities in Cx43 expression. Only the proliferating trichilemmal tumor showed a discordant pattern of expression. CONCLUSIONS: Cx43 expression is preserved in benign cutaneous tumors with follicular differentiation and the patterns of Cx43 expression in benign cutaneous tumors with follicular differentiation parallel those of their alleged anatomical counterparts in 5 types (either totally or partially). This preservation might be related to the good behavior of the entities studied.


Assuntos
Conexina 43/biossíntese , Doenças do Cabelo/metabolismo , Folículo Piloso/patologia , Neoplasias Cutâneas/metabolismo , Conexina 43/análise , Doenças do Cabelo/patologia , Folículo Piloso/metabolismo , Humanos , Neoplasias Cutâneas/patologia
3.
J Cutan Pathol ; 46(6): 442-446, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30785652

RESUMO

Matrical carcinoma with melanocytic hyperplasia (MCMH), previously referred to as malignant melanocytic matricoma, is a rare variant of the uncommon pilomatrical carcinoma, occurring most often on the head/neck and upper backs of middle-aged men. Nodular lesions may resemble pigmented basal cell carcinoma or melanoma clinically. We present a case of MCMH in a Hispanic patient with history of melanoma. Histopathological clues to appropriate diagnosis include basaloid cells, numerous atypical mitotic figures, matrical differentiation, shadow cells, strong diffuse nuclear and cytoplasmic expression of ß-catenin, and interspersed pigmented dendritic melanocytes.


Assuntos
Carcinoma Basocelular , Carcinoma de Apêndice Cutâneo , Doenças do Cabelo , Melanócitos , Melanoma , Neoplasias Cutâneas , Idoso de 80 Anos ou mais , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Apêndice Cutâneo/diagnóstico , Carcinoma de Apêndice Cutâneo/metabolismo , Carcinoma de Apêndice Cutâneo/patologia , Diagnóstico Diferencial , Doenças do Cabelo/diagnóstico por imagem , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Humanos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patologia , México , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
4.
J Cutan Pathol ; 46(4): 256-260, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30632192

RESUMO

BACKGROUND: The role of the mammalian target of rapamycin (mTOR) in hair follicle tumorigenesis is unclear. mTOR controls cell growth and can be activated through ribosomal S6 kinase. Herein, we sought to evaluate the expression of phospho-S6 in six different benign and malignant follicular tumor types. METHODS: 76 cases were selected (17 fibrofolliculomas, 20 trichoepitheliomas, 10 tricholemmomas, 19 pilomatricomas, 1 malignant proliferating tricholemmal tumor, 8 tricholemmal carcinomas, and 1 trichoblastic carcinoma) and collected over 16 years. Immunohistochemistry with monoclonal antibody for phospho-S6 was performed and analyzed semi-quantitatively; statistical analysis using the χ2 test was performed, with P < 0.05 considered significant. RESULTS: All malignant neoplasms in our series (8/8 [100%] cases of tricholemmal carcinoma, 1/1 [100%] trichoblastic carcinoma, and 1/1 [100%] malignant proliferating tricholemmal tumor) showed a strong and diffuse pattern of staining for phospho-S6 involving 70% to 90% of tumor cells. By contrast, a minority of benign tumors were positive for phospho-S6 and most stained in a patchy pattern including 12/17 (71%) fibrofolliculomas, 9/20 (45%) trichoepitheliomas and 1/10 (10%) tricholemmomas, involving 30% to 50%, 5% to 20%, and 40% to 50% of tumor cells, respectively. Most pilomatricomas (17/19 [89%]) exhibited a stronger, but distinctive staining pattern, staining mostly the basaloid cells with a multifocal distribution, involving 70% to 90% of tumor cells. CONCLUSIONS: Phospho-S6 is differentially expressed among benign and malignant hair follicle tumors (P = 0.0044). While malignant tumors show diffuse expression, only a small subset of benign neoplasms were positive, primarily in a patchy distribution.


Assuntos
Biomarcadores Tumorais/análise , Doenças do Cabelo/diagnóstico , Folículo Piloso/patologia , Proteínas Quinases S6 Ribossômicas/análise , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Folículo Piloso/metabolismo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR/metabolismo , Adulto Jovem
5.
Diagn Pathol ; 13(1): 65, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30153836

RESUMO

BACKGROUND: Pilomatricoma is a relatively common benign cutaneous adnexal neoplasm with differentiation towards the hair matrix, inner sheath of hair follicle and hair cortex. Proliferating pilomatricoma is a rare variant of pilomatricoma that can rapidly increase and may be misidentified as a malignant tumor. We herein report the cytopathological findings of proliferating pilomatricoma misdiagnosed as a malignant parotid tumor. CASE PRESENTATION: A 64-year-old man noticed an acne-like nodule in the left parotid region. It was painless, but it increased to a maximum diameter of 4.5 cm over 2 years. Clinically, left parotid gland carcinoma was suspected, and fine-needle aspiration cytology was performed. Clusters of epithelial cells were observed in a necrotic background, and malignant epithelial cells derived from salivary glands were suspected. Histologically, the resected tumor was diagnosed as proliferating pilomatricoma composed of basophilic cells and shadow cells apart from the parotid gland. However, on a re-evaluation of the cytological specimens, the irregular-shaped epithelial cells were considered to be from basophilic cells. Shadow cells with nuclear disappearance were also confirmed. Tumor recurrence and metastasis have not been observed in the four years since surgery. CONCLUSION: The present case was first interpreted as a malignant parotid gland tumor, but it was actually a benign skin appendage tumor. Pilomatricoma sometimes rapidly increases and may be mistaken for a malignant tumor. Although it is critical to recognize not only basophilic cells but also shadow cells, it cannot be diagnosed by cytological findings. The final diagnosis should be made on excision specimen only.


Assuntos
Proliferação de Células , Erros de Diagnóstico , Doenças do Cabelo/patologia , Neoplasias Parotídeas/patologia , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologia , Biópsia por Agulha Fina , Doenças do Cabelo/metabolismo , Doenças do Cabelo/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Parotídeas/química , Pilomatrixoma/química , Pilomatrixoma/cirurgia , Valor Preditivo dos Testes , Neoplasias Cutâneas/química , Neoplasias Cutâneas/cirurgia
6.
Arch Dermatol Res ; 310(5): 453-462, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29704126

RESUMO

In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF-DWAT interactions under conditions of wounding/stress.


Assuntos
Tecido Adiposo Branco/patologia , Derme/patologia , Doenças do Cabelo/metabolismo , Folículo Piloso/patologia , Cabelo/fisiologia , Tecido Adiposo Branco/metabolismo , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Feminino , Doenças do Cabelo/patologia , Remoção de Cabelo , Humanos , Hiperplasia , Hipertrofia , Camundongos , Camundongos Endogâmicos C57BL , Periodicidade
7.
Exp Cell Res ; 367(1): 104-111, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29604248

RESUMO

In a previous study, we showed that microRNA-675 (miR-675) was significantly down-regulated in patients with tricho-dento-osseous (TDO) syndrome. One of the main features of TDO syndrome is dentin hypoplasia. Thus, we hypothesize that miR-675 plays a role in dentin development. In this study, we determined the role of miR-675 in the odontogenic differentiation of human dental pulp cells (hDPCs). Stable overexpression and knockdown of miR-675 in hDPCs were performed using recombinant lentiviruses containing U6 promoter-driven miR-675 and short hairpin-miR675 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining revealed the promotive effects of miR-675 on the odontogenic differentiation of hDPCs. Further, we found that miR-675 facilitates the odontogenic differentiation process of hDPCs by epigenetic regulation of distal-less homeobox (DLX3). Thus, for the first time, we determined that miR-675 regulates the odontogenic differentiation of hDPCs by inhibiting the DNA methyltransferase 3 beta (DNMT3B)-mediated methylation of DLX3. Our findings uncover an unanticipated regulatory role for miR-675 in the odontogenic differentiation of hDPCs by epigenetic changes in DLX3 and provide novel insight into dentin hypoplasia feature in TDO patients.


Assuntos
Diferenciação Celular/genética , Anormalidades Craniofaciais/genética , Hipoplasia do Esmalte Dentário/genética , Polpa Dentária/citologia , Epigênese Genética/genética , Doenças do Cabelo/genética , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Anormalidades Craniofaciais/metabolismo , Anormalidades Craniofaciais/patologia , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Hipoplasia do Esmalte Dentário/metabolismo , Hipoplasia do Esmalte Dentário/patologia , Polpa Dentária/metabolismo , Dentina/metabolismo , Dentina/patologia , Técnicas de Silenciamento de Genes , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Proteínas de Homeodomínio/genética , Humanos , MicroRNAs/genética , Cultura Primária de Células , Fatores de Transcrição/genética
8.
J Cutan Pathol ; 45(7): 508-514, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29624700

RESUMO

Pilomatrix (pilomatrical) carcinoma is a rare cutaneous adnexal tumor with matrical differentiation and recurrent and metastatic potential. Sarcomatoid pilomatrix carcinoma is a rare variant which shows a sarcomatoid component intermingling with the epithelial one. There are only 4 cases previously published. We present an additional case on the hand of a 78 year-old man which appeared as a 6 mm hyperkeratotic, focally ulcerated plaque. A shave biopsy demonstrated a dermal infiltrative neoplasm, composed of markedly atypical-appearing basaloid cells with focal necrotic/ghost cells, as well as an intimately associated population of atypical oval to spindle-shaped cells. Both the epithelial and the sarcomatoid components expressed cytokeratins (CKs) AE1/AE3, CK 5/6 and CAM 5.2, as well as beta-catenin and LEF-1. The tumor failed to express CK7, CK20, S100, thyroid transcription factor 1 (TTF1), CDX2, prostate-specific antigen (PSA) and CD34. The tumor was completely excised with Mohs surgery, and there has been no recurrence in the 8 months of follow-up to date.


Assuntos
Doenças do Cabelo , Proteínas de Neoplasias/metabolismo , Pilomatrixoma , Neoplasias Cutâneas , Idoso , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Doenças do Cabelo/cirurgia , Humanos , Masculino , Pilomatrixoma/metabolismo , Pilomatrixoma/patologia , Pilomatrixoma/cirurgia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
9.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28792655

RESUMO

Because children diagnosed with WNT-activated medulloblastoma have a 10-year overall survival rate of 95%, active long-term follow-up is critically important in reducing mortality from other causes. Here, we describe an 11-year-old adopted female who developed multiple pilomatrixomas 3 years after diagnosis of WNT-activated medulloblastoma, an unusual finding that prompted deeper clinical investigation. A heterozygous germline APC gene mutation was discovered, consistent with familial adenomatous polyposis. Screening endoscopy revealed numerous precancerous polyps that were excised. This case highlights the importance of long-term follow-up of pediatric cancer survivors, including attention to unexpected symptoms, which might unveil an underlying cancer predisposition syndrome.


Assuntos
Proteína da Polipose Adenomatosa do Colo , Polipose Adenomatosa do Colo , Sobreviventes de Câncer , Neoplasias Cerebelares , Mutação em Linhagem Germinativa , Doenças do Cabelo , Meduloblastoma , Segunda Neoplasia Primária , Pilomatrixoma , Neoplasias Cutâneas , Proteínas Wnt , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Criança , Feminino , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/genética , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Pilomatrixoma/diagnóstico , Pilomatrixoma/genética , Pilomatrixoma/metabolismo , Pilomatrixoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
10.
Acta Derm Venereol ; 98(3): 318-323, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29136266

RESUMO

Prostanoids, including prostaglandins (PGs) and thromboxane A2 (TXA2), are a family of lipid-derived autacoids that modulate many physiological systems and pathological contexts. Prostanoids are generated by sequential metabolism of arachidonic acid, catalysed by cyclo-oxygenase, to PGH2, which is then converted to PGD2, PGE2, PGF2α, PGI2 and TXA2, catalysed by their specific synthases. Recent evidence suggests that prostanoids play a role in regulating hair growth. The PGF2α analogue is Food and Drug Administration-approved in the US and routinely used to enhance the growth of human eyelashes. PGE2 is reported to protect from radiation-induced hair loss in mice. Conversely, PGD2 inhibits hair growth. This paper reviews the metabolism of prostanoids and the expression pattern of prostanoid receptors in hair follicles, focussing on their different and opposing effects on hair growth and the underlying mechanisms. This has potential clinical relevance in the treatment and prevention of hair disorders.


Assuntos
Doenças do Cabelo/metabolismo , Folículo Piloso/metabolismo , Prostaglandinas/metabolismo , Regeneração , Animais , Doenças do Cabelo/tratamento farmacológico , Doenças do Cabelo/fisiopatologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Humanos , Receptores de Prostaglandina/metabolismo , Regeneração/efeitos dos fármacos , Transdução de Sinais
11.
Bioessays ; 39(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28685843

RESUMO

Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition. Multiple parameters can increase the levels of reactive oxygen species in the HF, for example melanogenesis, depilation-induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging-associated mitochondrial dysfunction. In this review, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox-associated HF disorders are therefore discussed.


Assuntos
Doenças do Cabelo/metabolismo , Folículo Piloso/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Doenças do Cabelo/genética , Humanos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
12.
Am J Surg Pathol ; 41(6): 738-749, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28368926

RESUMO

Basal cell carcinoma (BCC) with matrical differentiation is a fairly rare neoplasm, with about 30 cases documented mainly as isolated case reports. We studied a series of this neoplasm, including cases with an atypical matrical component, a hitherto unreported feature. Lesions coded as BCC with matrical differentiation were reviewed; 22 cases were included. Immunohistochemical studies were performed using antibodies against BerEp4, ß-catenin, and epithelial membrane antigen (EMA). Molecular genetic studies using Ion AmpliSeq Cancer Hotspot Panel v2 by massively parallel sequencing on Ion Torrent PGM were performed in 2 cases with an atypical matrical component (1 was previously subjected to microdissection to sample the matrical and BCC areas separately). There were 13 male and 9 female patients, ranging in age from 41 to 89 years. Microscopically, all lesions manifested at least 2 components, a BCC area (follicular germinative differentiation) and areas with matrical differentiation. A BCC component dominated in 14 cases, whereas a matrical component dominated in 4 cases. Matrical differentiation was recognized as matrical/supramatrical cells (n=21), shadow cells (n=21), bright red trichohyaline granules (n=18), and blue-gray corneocytes (n=18). In 2 cases, matrical areas manifested cytologic atypia, and a third case exhibited an infiltrative growth pattern, with the tumor metastasizing to a lymph node. BerEP4 labeled the follicular germinative cells, whereas it was markedly reduced or negative in matrical areas. The reverse pattern was seen with ß-catenin. EMA was negative in BCC areas but stained a proportion of matrical/supramatrical cells. Genetic studies revealed mutations of the following genes: CTNNB1, KIT, CDKN2A, TP53, SMAD4, ERBB4, and PTCH1, with some differences between the matrical and BCC components. It is concluded that matrical differentiation in BCC in most cases occurs as multiple foci. Rare neoplasms manifest atypia in the matrical areas. Immunohistochemical analysis for BerEP4, EMA, and ß-catenin can be helpful in limited biopsy specimens. From a molecular biological prospective, BCC and matrical components appear to share some of the gene mutations but have differences in others, but this observation must be validated in a large series.


Assuntos
Carcinoma Basocelular/patologia , Doenças do Cabelo/patologia , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/mortalidade , Diferenciação Celular , Feminino , Seguimentos , Doenças do Cabelo/genética , Doenças do Cabelo/metabolismo , Doenças do Cabelo/mortalidade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Pilomatrixoma/genética , Pilomatrixoma/metabolismo , Pilomatrixoma/mortalidade , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade
13.
J Pediatr Gastroenterol Nutr ; 64(1): 37-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28027214

RESUMO

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) (inflammatory bowel disease [IBD] before 6 years of age) may manifest as a monogenic disease affecting the gastrointestinal tract. Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE), a rare disorder caused by alteration of a complex involved in RNA degradation, has been reported to present with some degree of colitis and in some cases an IBD-like presentation. METHODS: We reviewed clinical and biological data of 4 previously published cases and added detailed data of 2 new cases of SD/THE with an IBD-like presentation. RESULTS: All the 6 patients presented with typical intractable diarrhea and hair abnormalities. The colon was affected in all of the patients: 1 had ileitis, 2 had panenteritis, and 2 presented with perianal disease. Fecal calprotectin level and erythrosedimentation rate were elevated in 2 cases each. All the therapeutic classes of IBD treatment (mesalazine, steroids, immunomodulators, and biological therapy) were used in the 6 cases. In 2 patients, treatment had no effect. Three showed a partial effect, and 1 patient sustained only a transient effect. CONCLUSIONS: SD/THE can have a similar presentation as VEOIBD, often as pancolitis. IBD treatments appear to have little efficacy for SD/THE, suggesting a different pathogenesis for the IBD-like features in SD/THE compared with classical IBD.


Assuntos
Colo/patologia , Diarreia Infantil/patologia , Retardo do Crescimento Fetal/patologia , Gastroenterite/etiologia , Doenças do Cabelo/patologia , Doenças Inflamatórias Intestinais/patologia , Intestino Delgado/patologia , Complexo Antígeno L1 Leucocitário/metabolismo , Anti-Inflamatórios/uso terapêutico , Terapia Biológica , Colite/etiologia , Diarreia/etiologia , Diarreia Infantil/tratamento farmacológico , Diarreia Infantil/metabolismo , Diarreia Infantil/terapia , Facies , Fezes/química , Feminino , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/terapia , Cabelo , Doenças do Cabelo/tratamento farmacológico , Doenças do Cabelo/metabolismo , Doenças do Cabelo/terapia , Humanos , Ileíte/etiologia , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Mesalamina/uso terapêutico , Síndrome
15.
Sci Rep ; 6: 38680, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27924851

RESUMO

The homeodomain transcription factor distal-less homeobox 3 gene (DLX3) is required for hair, tooth and skeletal development. DLX3 mutations have been found to be responsible for Tricho-Dento-Osseous (TDO) syndrome, characterized by kinky hair, thin-pitted enamel and increased bone density. Here we show that the DLX3 mutation (c.533 A>G; Q178R) attenuates osteogenic potential and senescence of bone mesenchymal stem cells (BMSCs) isolated from a TDO patient, providing a molecular explanation for abnormal increased bone density. Both DLX3 mutations (c.533 A>G and c.571_574delGGGG) delayed cellular senescence when they were introduced into pre-osteoblastic cells MC3T3-E1. Furthermore, the attenuated skeletal aging and bone loss in DLX3 (Q178R) transgenic mice not only reconfirmed that DLX3 mutation (Q178R) delayed cellular senescence, but also prevented aging-mediated bone loss. Taken together, these results indicate that DLX3 mutations act as a loss of function in senescence. The delayed senescence of BMSCs leads to increased bone formation by compensating decreased osteogenic potentials with more generations and extended functional lifespan. Our findings in the rare human genetic disease unravel a novel mechanism of DLX3 involving the senescence regulation of bone formation.


Assuntos
Anormalidades Craniofaciais/genética , Hipoplasia do Esmalte Dentário/genética , Doenças do Cabelo/genética , Proteínas de Homeodomínio/genética , Mutação , Osteogênese/genética , Fatores de Transcrição/genética , Adulto , Perda do Osso Alveolar/genética , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Animais , Biomarcadores , Linhagem Celular , Senescência Celular/genética , Anormalidades Craniofaciais/metabolismo , Anormalidades Craniofaciais/patologia , Hipoplasia do Esmalte Dentário/metabolismo , Hipoplasia do Esmalte Dentário/patologia , Feminino , Expressão Gênica , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , Ligação Proteica , Fatores de Transcrição/metabolismo
16.
J Invest Dermatol ; 136(11): 2131-2132, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27772548

RESUMO

Legrand et al show that JAK/STAT5 signaling in the dermal papilla is required for anagen onset in the murine hair cycle. Interestingly, others have shown that JAK-inhibition is able to induce telogen-to-anagen transition in wild-type mice. This apparent contradiction highlights the complexity of interactions within the hair follicle, and encourages further discussion on the role of JAK-STAT signaling in the various stem cell niches of the hair follicle.


Assuntos
Regulação da Expressão Gênica , Doenças do Cabelo/genética , Folículo Piloso/patologia , Janus Quinases/genética , Fator de Transcrição STAT5/genética , Animais , Ciclo Celular , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Folículo Piloso/metabolismo , Humanos , Janus Quinases/biossíntese , Fator de Transcrição STAT5/biossíntese , Transdução de Sinais
17.
J Dermatol Sci ; 84(3): 232-238, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27523806

RESUMO

Recent advances in molecular genetics have led to the identification of many genes expressed in hair follicle (HF), while the precise roles of these genes in the HF have not completely been disclosed. Using the methods of forward genetics, we and others have recently identified a series of genes responsible for hereditary hair disorders in humans, including monilethrix, woolly hair, and various ectodermal dysplasia syndromes. Furthermore, expression and functional analyzes have gradually revealed that these genes are directly or indirectly related with each other. As such, the journey toward unraveling the molecular basis of hereditary hair disorders will contribute to better understanding of the complex mechanisms for HF morphogenesis and development in humans.


Assuntos
Doenças do Cabelo/genética , Folículo Piloso/crescimento & desenvolvimento , Motivos de Aminoácidos , Displasia Ectodérmica/genética , Cabelo/crescimento & desenvolvimento , Doenças do Cabelo/metabolismo , Humanos , Hipotricose/genética , Japão , Lisofosfolipídeos/metabolismo , Degeneração Macular/genética , Monilétrix/genética , Mutação de Sentido Incorreto , Transdução de Sinais
19.
Br J Dermatol ; 175(3): 520-30, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26914519

RESUMO

BACKGROUND: Epidermal stem cells are multipotent cells that maintain the skin epidermis. Potential markers for stem cells have been identified in mammalian skin from mouse experiments; however, it is unclear if stem cells also contribute to tumour formation in human skin. OBJECTIVES: To investigate the expression of potential stem cell markers, such as leucine-rich repeat-containing G protein-coupled receptor (Lgr) 5, Lgr6, leucine-rich repeats and immunoglobulin-like domain protein 1 (Lrig1) and cytokeratin 15 (CK15) in basal cell carcinomas and tumours of the skin appendages. METHODS: We tested 45 human basal cell carcinomas (BCCs), including superficial, nodular, adenoid, infiltrating and sclerosing types, and 38 human tumours of skin appendages, including 13 sebaceous adenomas and carcinomas, 20 eccrine sweat gland tumours and five pilomatricomas, for the expression of hair follicle stem cell markers such as Lgr5, Lrig1, CK15, ß-catenin and SRY (sex determining region Y)-box 9 (SOX9), and compared these findings with those of healthy age-matched human epidermis. RESULTS: We detected the expression of stem cell markers in all tumours tested. Regarding Lgr5, Lrig1, CK15 and SOX9, expression seemed to be lower in more aggressive tumour types, such as in the most advanced parts of infiltrating BCC, in sebaceous carcinoma and late-stage porocarcinoma, compared with less aggressive superficial or nodular BCC or early-stage porocarcinoma and sebaceous gland tumours. In aggressive, sclerosing BCC, Lrig1 and Lgr5 were downregulated but CK15, SOX9 and nuclear ß-catenin were upregulated. CONCLUSIONS: Expression of potential stem cell markers of the epidermis and hair follicles was observed in skin tumours of appendages and BCCs. However, during tumour progression, many of these markers seemed to be downregulated.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/metabolismo , Neoplasias Cutâneas/metabolismo , Células-Tronco/metabolismo , Regulação para Baixo/fisiologia , Epiderme/metabolismo , Doenças do Cabelo/metabolismo , Folículo Piloso/metabolismo , Humanos , Queratina-15/metabolismo , Glicoproteínas de Membrana/metabolismo , Pilomatrixoma/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Fatores de Transcrição SOX9/metabolismo , Neoplasias das Glândulas Sebáceas/metabolismo , Neoplasias das Glândulas Sudoríparas/metabolismo , Regulação para Cima/fisiologia , beta Catenina/metabolismo
20.
Am J Dermatopathol ; 38(1): 33-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26730694

RESUMO

BACKGROUND: To describe 2 cases of melanocytic matricoma with malignant histological features and systematically review previously reported cases of malignant melanocytic matricoma. METHODS: Two cases of malignant melanocytic matricoma were identified from the practice of the authors. Additional 3 cases were identified in the literature. The clinical and pathological features of these 5 cases are described. RESULTS: Malignant melanocytic matricoma occurs predominantly in sun-damaged skin of elderly individuals. The tumor is composed of atypical epithelial cells with brisk mitotic activity showing evidence of matrical keratinization and widespread positivity with beta-catenin. There is an admixed cytologically bland dendritic melanocytic component. To date, local recurrence has occurred in one case, but no cases of disseminated disease or death have been reported. CONCLUSIONS: Recognition of this rare tumor and separation from a range of diagnostic mimics is important to ensure adequate treatment by local excision and to allow further cases to be identified to better define the biological potential of this lesion.


Assuntos
Doenças do Cabelo/patologia , Melanócitos/patologia , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Doenças do Cabelo/metabolismo , Humanos , Masculino , Necrose/patologia , Pilomatrixoma/química , Neoplasias Cutâneas/química , beta Catenina/análise
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