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1.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(7): 636-641, jul.- ago. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-223013

RESUMO

El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)


Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Melanoma/diagnóstico , Melanoma/genética , Nevo Azul/diagnóstico , Nevo Azul/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Prognóstico , Melanoma/patologia , Nevo Azul/patologia , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
2.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(7): t636-t641, jul.- ago. 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-223014

RESUMO

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)


El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Melanoma/diagnóstico , Melanoma/genética , Nevo Azul/diagnóstico , Nevo Azul/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Prognóstico , Melanoma/patologia , Nevo Azul/patologia , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
3.
Clin. transl. oncol. (Print) ; 23(9): 1874-1884, sept. 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-222187

RESUMO

Purpose Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance. Methods In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan–Meier was performed to determine the prognostic significance. Results High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010). Conclusion Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Biomarcadores Tumorais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Melanoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Oxirredutases/metabolismo , Hipóxia Tumoral , Neoplasias Uveais/metabolismo , Corioide , Estimativa de Kaplan-Meier , Melaninas/biossíntese , Melanoma/mortalidade , Melanoma/patologia , Pigmentação , Fatores de Risco , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Neoplasias Uveais/mortalidade
4.
Clin. transl. oncol. (Print) ; 23(3): 450-458, mar. 2021. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-220880

RESUMO

Purpose Increasing evidence suggested that microRNA plays an important role in ovarian cancer. In this study, the role of miR-92 in ovarian cancer was investigated. Methods In this study, miR-92 expression in clinical sample was evaluated, role of miR-92 was investigated in vitro, and underlying mechanism was investigated using Chip, co-IP, and western blot. Results In this study, we show that miR-92 is overexpressed in ovarian cancer tissue compared with normal cancer tissue. Transfection of miR-92 increased proliferation of ovarian cancer cell, and increased migration capacity and colony formation were observed after miR-92 transfection; we found that expression of LATS2 was decreased by miR-92, and this was further confirmed by luciferase assay, which proved that miR-92 is targeting 3′ of the endogenous LATS2 gene. Downregulation of LATS2 resulted in increased translocation of YAP1 and upregulation of PD-L1, which subsequently suppressed NK cell function and promoted T cell apoptosis. Moreover, co-transfection of YAP1-targeted shRNA could relieve miR-92-induced immune suppression effect. Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confirm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. Conclusions Our data revealed a novel mechanism which finally resulted in immune suppression in ovarian cancer (AU)


Assuntos
Humanos , Feminino , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células Matadoras Naturais/imunologia , Neoplasias Ovarianas/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , MicroRNAs/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Elementos Facilitadores Genéticos , Regulação para Baixo , Inativação Gênica , Imunoprecipitação , Neoplasias Ovarianas/metabolismo , Proteínas Supressoras de Tumor/genética , Antígeno B7-1/metabolismo
5.
Clin. transl. oncol. (Print) ; 23(3): 459-467, mar. 2021.
Artigo em Inglês | IBECS | ID: ibc-220881

RESUMO

Purpose This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma. Methods Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall. Results There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049–0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015–0.998, p = 0.050). Conclusions After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Ácido Aminolevulínico , Isocitrato Desidrogenase , Fármacos Fotossensibilizantes , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Glioblastoma/metabolismo , Glioblastoma/cirurgia , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética
6.
Clin. transl. oncol. (Print) ; 23(3): 612-619, mar. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-220896

RESUMO

Background Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. Methods Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. Results Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-β–dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. Conclusion This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells (AU)


Assuntos
Humanos , Temozolomida/farmacologia , Antineoplásicos Alquilantes/farmacologia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Metilases de Modificação do DNA/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais
7.
Arch. esp. urol. (Ed. impr.) ; 72(6): 545-553, jul.-ago. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-187657

RESUMO

Objetivo: En los últimos años, numerosos estudios se han centrado en la genética del sistema renal. Betchel et al. en 2010, demostraron como la metilación, fenómeno epigenético, estaría implicado en la perpetuación de la fibrosis. En nuestro estudio queremos demostrar si la epigenética tiene relación con la estenosis pieloureteral y en caso de ser así, si podría ser utilizada como material pronóstico y diagnóstico. Material y métodos: Se ha realizado un estudio descriptivo observacional o transversal en el que se analizó la metilación en el ADN extraído de las muestras de unión pieloureteral en pacientes pediátricos obtenidas durante la cirugía entre 1999 y 2015, resultando un total de 20 pacientes. Los datos clínicos-radiológicos se analizaron según correlación y agrupación de los mismos mediante un paquete software filogenético/estadístico denominado PHYLIP de acceso libre gratuito. Los genes seleccionados sobre los que se realizó la PCR específica de metilación (MSP) fueron: p16, RASSF1A, MGMT, Ciclina D-2, HIN-1, E-Cadherina y RASAL-1. Resultados: Los datos clínico-radiológicos analizados filogenéticamente mediante el programa PHYLIP establecieron 7 grupos de pacientes. Los resultados con respecto a la metilación mostraron una proporción considerable de metilación aberrante en la región del promotor de los genes p16 (25%), MGMT (15%), E-Cadherina (25%),HIN-1 (25%) y RASAL-1 (35%). Se analizó la asociación de los grupos clínico-radiológicos con los estados de metilación/no metilación de cada gen. Conclusiones: Se demuestra que la metilación sí tiene un papel en la fibrosis desarrollada en la estenosis pieloureteral destacando dos patrones clínicos de mal pronóstico asociados a dos clusters epigenéticos de metilación. RASAL-1, E-Cadherina, HIN-1 y p16 serían los candidatos para desarrollar estudios futuros sobre sus implicaciones pronósticas en la estenosis pieloureteral


Objective: In the last few years, numerous studies have focused on the genetics of the renal system. Betchel et al in 2010 demonstrated that methylation, as a epigenetic phenomenon, would be involved in the perpetuation of fibrosis. In our study, we want to demonstrate whether epigenetics is related to pyeloureteral stenosis and, if that is the case, if it could be used as prognostic and diagnostic biomarker. Methods: This is a descriptive observational and cross-sectional study that analyzed the methylation in DNA extracted from pyeloureteral junction samples obtained from surgery in pediatric patients in the period from 1999 to 2015, resulting in a total of 20 patients. Clinical data were analyzed using correlation tests and they were grouped with a free access software statistical phylogenetic package called PHYLIP. The selected genes for methylation-specific PCR (MSP) were the following: p16, RASSF1A, MGMT, Cyclin D-2, HIN-1, E-Cadherin and RASAL-1. Results: The clinical-radiological data analyzed phylogenetically by the PHYLIP program established 7 groups of patients. The results of methylation showed a considerable proportion of aberrant methylation in the promotor region of the genes p16 (25%), MGMT (15%), E-Cadherin (25%), HIN-1 (25%) and RASAL-1 (35%). The association of the clinical-radiological groups with methylation/non-methylation states of each gene was also analyzed. Conclusions: This study demonstrates that methylation does have a role in fibrosis developed in pyeloureteral stenosis. Two clinical patterns of poor prognosis associated with two epigenetic methylation cluster. RASAL-1, E-Cadherin, HIN-1 and p16 would be candidates for future studies on their prognostic implications in pyeloureteral stenosis


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Metilação de DNA/genética , Epigênese Genética/genética , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética , Obstrução Ureteral/diagnóstico , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Estudos Transversais , Marcadores Genéticos , Filogenia , Prognóstico
8.
Arch. Soc. Esp. Oftalmol ; 93(11): 562-566, nov. 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-175142

RESUMO

OBJETIVO: Reportar el hallazgo de la meibografía infrarroja en un paciente mexicano con el síndrome de EEC (Ectrodactyly-ectodermal dysplasia-cleft syndrome) confirmado por análisis molecular del gen p63. CASO CLÍNICO: Paciente varón de 31 años de edad que acude por presentar una historia de pérdida visual progresiva en ambos ojos asociada a fotofobia de larga duración. El paciente nació con labio y paladar hendido, y ectodactilia de la mano derecha; posteriormente presentó displasia ungueal, anodoncia y alopecia, con lo que se diagnosticó displasia ectodérmica. Las alteraciones oftalmológicas se limitaron a los anexos y la superficie ocular. La meibografía infrarroja in vivo mostró la ausencia total de glándulas de Meibomio en los párpados inferiores y deficiencia severa en los párpados superiores. Además, identificamos que el paciente es un portador heterocigoto de una mutación de sentido equivocado R304W (C -> T) en el exón 8 del gen p63. DISCUSIÓN: La mutación R304W en la región del gen p63 está definitivamente relacionada con características tales como la ausencia de glándulas de Meibomio


OBJECTIVE: To report the finding of infrared meibography in a Mexican patient with EEC syndrome (Ectrodactyly-ectodermal dysplasia-cleft syndrome) confirmed by molecular analysis of the p63 gene. Clinical case: A 31 year-old male patient was seen due to a history of progressive visual loss in both eyes associated with long-term photophobia. The patient was born with cleft lip and palate, ectrodactyly of right hand, and afterwards, displayed nail dysplasia, anodontia and alopecia, with which ectodermal dysplasia was diagnosed. The ophthalmological findings were limited to the adnexa and the ocular surface. In vivo infrared meibography showed total absence of Meibomian glands in the lower eyelids and severe deficiency in the upper eyelids. In addition, it was shown that the patient was a heterozygous carrier of a missense mutation R304W (C -> T) in exon 8 of the p63 gene. DISCUSSION: The R304W mutation in the p63 gene region is definitely related to characteristics such as the absence of Meibomian glands


Assuntos
Humanos , Masculino , Adulto , Mutação/genética , Displasia Ectodérmica/genética , Fissura Palatina/genética , Mutação , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Glândulas Tarsais/diagnóstico por imagem , Fissura Palatina/diagnóstico , Displasia Ectodérmica/diagnóstico , Pálpebras/diagnóstico por imagem , Reação em Cadeia da Polimerase
9.
Clin. transl. oncol. (Print) ; 20(9): 1185-1195, sept. 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-173704

RESUMO

Purpose: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, and its outcome is poor. The purpose of this study was to determine the association between JNK1 and vitamin D receptor (VDR) expression and the prognosis of ESCC. Methods: Immunohistochemical staining was conducted on ESCC tissue microarrays (362 pairs of ESCC and normal esophagus tissues). The epithelial and stromal expression levels of c-jun NH2-terminal kinase 1 (JNK1) and VDR were scored and correlated with the ESCC characteristics. Laser-capture-based quantitative RT-PCR was performed on ESCC tissues. The effects of JNK1 and VDR on ESCC cell proliferation and migration were analyzed in vitro by transient transfection, and protein changes were evaluated by immunoblotting. Results: Both JNK1 and VDR were reduced in ESCC epithelial cells in comparison with the normal esophagus, but the expression of JNK1 and VDR in ESCC stromal tissues, not epithelial cells, was strongly associated with the survival time of ESCC patients. Functional studies showed that increased JNK1 suppressed cancer cell proliferation, mobility, and migration, which were linked to the alterations of VDR and metastasis-associated proteins. Conclusion: JNK1 and VDR act as tumor suppressors, and their stromal expression levels are associated with prognosis in esophageal squamous cell carcinoma


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Células Estromais/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/isolamento & purificação , Receptores de Calcitriol/isolamento & purificação , Prognóstico , Biomarcadores Tumorais/análise , Proteínas Supressoras de Tumor/isolamento & purificação
10.
Clin. transl. oncol. (Print) ; 20(3): 274-285, mar. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-171314

RESUMO

Because of advances in the understanding of histological and molecular characteristics in ovarian cancer, it is now possible to recognize the existence of five subtypes, which in turn has allowed a more refined therapeutic approach and better design of clinical trials. Each of these five subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in the diagnosis and follow-up of these malignancies. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer having prognostic and predictive value. This article will review the histological and molecular characteristics of the five subtypes of ovarian cancer, describing the most important biomarkers and mutations that can guide in diagnosis, screening and tailored treatment strategy (AU)


No disponible


Assuntos
Humanos , Feminino , Neoplasias Ovarianas/patologia , Proteínas Supressoras de Tumor/análise , Biomarcadores Tumorais/análise , Marcadores Genéticos , Mutação/genética , Detecção Precoce de Câncer
12.
Rev. neurol. (Ed. impr.) ; 57(supl.1): s53-s64, 6 sept., 2013. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-149006

RESUMO

Introducción. Las miopatías congénitas son un grupo heterogéneo de enfermedades que comparten clínica de inicio precoz y alteraciones histopatológicas musculares específicas. El estudio genético permite determinar la mutación causal en la mayoría de los casos. Existe heterogeneidad fenotípica y genotípica, lo que se ilustra al observar que un genotipo puede expresarse en más de una forma clinicopatológica y un fenotipo puede estar causado por diferentes mutaciones genéticas. Desarrollo. En esta revisión, se detallan las características de las principales miopatías congénitas que permiten su identificación clínica, patológica y genética. Se describen los hallazgos de la biopsia muscular que constituyen el principal pilar diagnóstico. Se enfatiza y se detalla la importancia del diagnóstico diferencial, descartando otras patologías que se presentan con hipotonía en la lactancia o el período neonatal. Se destacan las formas neonatales graves (nemalínica, miotubular ligada al X) que se deben identificar precozmente para establecer el pronóstico y brindar un consejo genético adecuado. Se subrayan las mutaciones del gen rianodina (RYR1) por su asociación a la hipertermia maligna y las mutaciones de la selenoproteína 1 (SEPN1) y la miopatía nemalínica por su asociación a hipoventilación nocturna. Conclusiones. El conocimiento profundo de las miopatías estructurales congénitas facilita la confirmación diagnóstica de la miopatía congénita, lo que permite la aplicación oportuna de medidas relacionadas con la respiración y la alimentación de los casos más graves y con la optimización de la función motora en todos los pacientes con miopatía congénita (AU)


Introduction. Congenital myopathies are a heterogeneous group of diseases that share clinical early onset and specific hystopathological alterations in muscle. Genetic studies allow to determine the causative mutation in most cases. Genotypic and phenotypic heterogeneity exists, which is illustrated by noting that a genotype can be expressed in more than one clinicopathologic way and a phenotype may be caused by different genetic mutations. Development. In this review we detail the characteristics of major congenital myopathies that allow clinical, pathological and genetic identification. We describe the findings of muscle biopsy that are the mainstay diagnosis. We emphasize and detail the importance of differential diagnosis by ruling out other diseases that present with hypotonia in infancy or neonatal period. We highlight the severe neonatal forms (nemaline, X-linked myotubular) to be identified early to establish prognosis and provide appropriate genetic counseling. We emphasize mutations of ryanodine gene (RYR1) through its association with malignant hyperthermia and mutations of selenoprotein 1 (SEPN1) and nemaline by its association with nocturnal hypoventilation. Conclusions. The deep knowledge of structural congenital myopathies facilitates diagnostic confirmation of congenital myopathy, allowing the timely implementation of measures related to breathing and feeding in more severe cases and the optimization of motor function in all patients with myopathy congenital (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Miopatias Congênitas Estruturais/classificação , Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Miopatias da Nemalina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Genótipo , Genes Recessivos , Genes Dominantes , Proteínas Musculares/genética , Fenótipo , Proteínas Adaptadoras de Transdução de Sinal/genética , Músculo Esquelético/patologia , Miopatia da Parte Central/genética , Selenoproteínas/genética , Tropomiosina/genética , Proteínas Supressoras de Tumor/genética
15.
Clin. transl. oncol. (Print) ; 13(9): 677-685, sept. 2011. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-125873

RESUMO

INTRODUCTION: Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB). MATERIAL AND METHODS: We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients. RESULTS: We found concordance between MGMT methylation status in tissue and serum (Cohen's Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival. CONCLUSION: Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable (AU)


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metilases de Modificação do DNA/sangue , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Glioblastoma/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais , Análise Química do Sangue/métodos , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Enzimas Reparadoras do DNA/análise , Enzimas Reparadoras do DNA/sangue , Glioblastoma/sangue , Glioblastoma/mortalidade , Imuno-Histoquímica , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/sangue
16.
Rev. esp. patol ; 43(2): 79-85, abr.-jun. 2010. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-79825

RESUMO

Antecedentes. El cáncer de mama es un grupo heterogéneo de tumores. Los estudios de microarrays de ADN han llevado a la clasificación del carcinoma invasor de mama en diferentes clases moleculares. El objetivo de este estudio fue determinar la expresión de p63 y citoqueratina 5/6 en carcinomas ductales invasores y su relación con las diferentes clases moleculares, en especial con el subgrupo de tipo basal. Métodos. Se realizó estudio inmunohistoquímico con los anticuerpos p63 y CK5/6 en 200 muestras de carcinoma ductal invasor sin otra especificación. En cada caso se había determinado previamente el estado de los receptores de estrógeno y progesterona (RE, RP), y de HER2. De acuerdo a estos datos, los tumores se clasificaron como luminal A, luminal B, HER2+ y tipo basal (triple negativo). Resultados. Se observó expresión de p63 en 5 casos de HER2+ y 19 casos de tumores del tipo basal (23,2%), se demostró una fuerte relación entre la expresión de CK5/6 y los tumores de tipo basal (59,8%, p<0,0001), pero también se expresó en un caso luminal A, 3 luminal B y 8 HER2+. Conclusiones. No todos los casos triple negativo son de tipo basal. Es necesario estandarizar la clasificación molecular basada en inmunohistoquímica, así como el panel de anticuerpos a utilizar, en especial para la identificación del tipo basal(AU)


Background. Breast cancer is a heterogeneous group of tumors. DNA microarray profiling studies have led to the classification of invasive breast carcinoma called molecular classes. AIMS: To study the expression of p63 and cytokeratin (CK) 5/6 in invasive ductal carcinomas and their relationship to the different molecular classes, especially the basal like subgroup. Methods. Immunohistochemistry with the antibodies p63 and CK5/6 was performed in 200 samples of invasive ductal carcinomas with no other specification. Each case had previous results of estrogen and progesterone receptor (ER, PR), and HER2. According to these data they were classified as luminal A, luminal B, HER2+ and basal like (triple negative). Results. p63 was expressed in 5 cases of HER2+ and 19 cases of basal like tumours (19.5%). There was a strong relationship between CK5/6 expression and basal like tumours (68.9%, p<0.0001), but it was also expressed in one luminal A, three luminal B and eight HER2+ cases. Conclusions. Not every triple negative tumors express basal markers. It is necesary to standarize the molecular classification of breast cancer and the panel of markers to use in its caracterization, especially for the basal like(AU)


Assuntos
Humanos , Feminino , DNA , Queratinas , Neoplasias Ductais, Lobulares e Medulares/diagnóstico , Neoplasias Ductais, Lobulares e Medulares/patologia , Imuno-Histoquímica , Receptor ErbB-2/análise , Análise em Microsséries/métodos , Análise em Microsséries , /análise , Proteínas Supressoras de Tumor/análise , Neoplasias da Mama/química , Carcinoma/química , Análise em Microsséries/classificação , Análise em Microsséries/instrumentação , Análise em Microsséries/tendências
17.
Clin. transl. oncol. (Print) ; 9(5): 278-289, mayo 2007. ilus
Artigo em Inglês | IBECS | ID: ibc-123308

RESUMO

Decreased oxygen availability is a common feature during embryonic development as well of malignant tumours. Hypoxia regulates many transcription factors, and one of the most studied is the hypoxia-inducible factor (HIF). As a consequence of HIF stabilisation, the cell constitutively upregulates the hypoxic programme resulting in the expression of genes responsible for global changes in cell proliferation, angiogenesis, metastasis, invasion, de-differentiation and energy metabolism. Of the three known alpha subunits of HIF transcription factors, HIF-1alpha and HIF-2alpha have been the most studied. Their differential expression and function have been widely discussed, however no clear picture has been drawn on how these two transcription factors differently regulate common and unique target genes. Their role as oncogenes has also been suggested in several studies. In this review we provide an overview of the current knowledge on some of the most important aspects of HIFalpha regulation, its role in tumour angiogenesis and energetic metabolism. We also give an overview of how the modulation of HIF regulating pathways is a potential therapeutic target that may have benefits in the treatment of cancer (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Fatores de Transcrição Winged-Helix/fisiologia , Proteínas Supressoras de Tumor , Fator 1 Induzível por Hipóxia/fisiologia , Neoplasias/etiologia , Neoplasias/tratamento farmacológico , Genes Supressores de Tumor/fisiologia , Neoplasias/genética , Neoplasias/metabolismo , Doença de von Hippel-Lindau/etiologia
18.
Arch. esp. urol. (Ed. impr.) ; 59(2): 125-131, mar. 2006. tab
Artigo em Es | IBECS | ID: ibc-046789

RESUMO

OBJETIVO: Determinar si la expresión de p53 en pacientes con carcinoma vesical infiltrante tiene valor pronóstico en el estadiaje clínico y supervivencia del tumor.MÉTODOS: El análisis inmunohistoquímico de p53 se realizó en 34 pacientes (33 hombres y 1 mujer) tratadoscon cistectomía por carcinoma vesical infiltrante con seguimiento medio de 16 meses.RESULTADOS: Se detectó sobreexpresión de p53 en 18 pacientes (64%). En el grupo con positividad p53 se encontraron 2 pacientes con estadio T1G3, 18 pacientesT2, 1 paciente T3 y 2 pacientes T4. En el grupo con negatividad inmunohistoquímica se encontró una mejor correspondencia entre el estadiaje de la RTU y de la cistectomíaencontrándose empeoramiento del estadio en solo 3 pacientes. Tras el seguimiento los pacientes p53 positivos presentaron peor evolución al tener peor estadio,aunque no significativa estadísticamente (p 0,24). En los pacientes que pasaron a protocolo de conservaciónvesical (n=6), los p53 negativos experimentaron una remisión completa de la enfermedad.CONCLUSIONES: Observamos una diferencia significativade infraestadiaje/evolución local más agresiva en pacientes p53 positivos y no mayor mortalidad en este grupo. La expresión de p53 no contraindica la entrada de un paciente en protocolo de conservación vesical aunque serán necesarios estudios más amplios para confirmar estos resultados


OBJECTIVES: To determine if p53 expression in patients with infiltrative bladder cancer is a prognostic factor on clinical staging and cancer specific survival. METHODS: Immunohistochemical analysis of p53 in 34 patients (33 males and 1 female) undergoing radical cystectomy for infiltrative bladder cancer, with a mean follow-up of 16 months. RESULTS: p53 overexpression was detected in 18 patients (64%). In the p53 positive group two patients were stage T1G3, 18 patients T2, 1 patient T3, and 2 patients T4. In the negative group a better correspondence between TUR and cystectomy stage was found, with stage worsening only in 3 patients. On follow-up, p53 positive patients showed worse outcomes due to their worse stages, although no statistical differences were found (p = 0.24). In the group of patients following a bladder sparing protocol (n = 6), p53 negative patients had complete remission of the disease. CONCLUSIONS: We see significant differences on understaging/more aggressive local outcome in p53 positive patients, with no greater mortality in this group. P53 expression does not contraindicate the inclusion of a patient in a bladder sparing protocol, although larger studies would be necessary to confirm these results


Assuntos
Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Humanos , Proteínas Supressoras de Tumor/análise , Neoplasias da Bexiga Urinária/química , Proteína Supressora de Tumor p53/análise , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
19.
Med. oral patol. oral cir. bucal (Internet) ; 10(5): 454-461, nov.-dic. 2005. ilus, graf
Artigo em Es | IBECS | ID: ibc-042649

RESUMO

Objetivos: Determinar la sobreexpresión de las proteínas cerb-B2, p53, bcl-2, Ki67 y CD44varV6 y establecer su valorpronóstico en el carcinoma epidermoide de labio.Diseño del estudio: Estudio inmunohistoquímico de las proteínasp53, c-erb-B2, bcl-2, ki67 y CD44varV6 en 79 carcinomasepidermoides de labio diagnosticados y tratados a lo largo deun periodo de 20 años. Los datos obtenidos fueron sometidosa análisis estadístico uni y multivariante.Resultados: La inmunotinción fue positiva en el 75% de los casospara la proteína c-erb-B2, en el 70,6% para la proteína p 53, enel 3,8% para la proteína bcl-2 y en el 89,9% para la molécula deadhesión cd44varV6. La expresión proteica de ki67 osciló entreun mínimo de 0% y un máximo de 6,29%. Los factores inmunohistoquímicosanalizados no presentaron valor pronóstico enel carcinoma epidermoide de labio, y solamente los pacientesafectados por este tipo de tumores que expresaban la moléculade adhesión CD44varV6 se asociaron de forma significativa conuna mayor supervivencia mediante el análisis de Kaplan-Meier.Conclusiones: Las técnicas inmunohistoquímicas analizadaspara el estudio anatomopatológico del carcinoma epidermoidede labio no deberían realizarse rutinariamente, dado su mayorcoste y su menor utilidad en la práctica clínica diaria


Objectives: To determine the expression of the c-erb-B2, p53,bcl-2, Ki67 and CD44varV6 proteins, and to establish theirprognostic value in epidermoid carcinoma of the lip.Study design: Immunohistochemical study of the c-erb-B2,p53, bcl-2, Ki67 and CD44varV6 proteins in 79 epidermoidcarcinomas of the lip, diagnosed and treated over a period of 20years. The data obtained were subjected to uni- and multi-variatestatistical analyses.Results: Immunostaining was positive in 75% of cases for c-erb-B2 protein, in 70.6% for p53 protein, in 3.8% for bcl-2 proteinand in 89.9% for adhesion molecule CD44varV6. Ki67 proteinexpression varied between a minimum of 0% and a maximum of6.29%. Most immunohistochemical factors analyzed presentedno prognostic value for epidermoid carcinoma of the lip. Onlythose patients affected by this type of tumor that expressed theadhesion molecule CD44varV6 were significantly associatedwith a greater survival calculated by means of Kaplan-Meieranalysis.Conclusions: The immunohistochemical techniques analyzedfor the anatomicopathological study of epidermoid carcinomaof the lip should not routinely be used due to their high cost andlow utility in daily clinical practice


Assuntos
Humanos , Carcinoma de Células Escamosas/química , Biomarcadores Tumorais/análise , Neoplasias Labiais/química , Proteínas de Neoplasias/análise , Receptores de Hialuronatos/análise , Análise Custo-Benefício , Imuno-Histoquímica , Antígeno Ki-67/análise , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Análise de Sobrevida , Proteínas Supressoras de Tumor/análise , Glicoproteínas/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína Supressora de Tumor p53/análise
20.
Rev. esp. med. nucl. (Ed. impr.) ; 24(3): 185-190, mayo-jun. 2005. tab
Artigo em Es | IBECS | ID: ibc-037403

RESUMO

Objetivo: La proteína pS2 (TFF1/pS2) es una molécula inducida por los estrógenos en los carcinomas mamarios. Nosotros hemos querido estudiar su expresión en carcinomas ductales infiltrantes de mama RE + y RP + , correlacionarla con otros parámetros clínico-biológicos y conocer su impacto en la evolución. Material y metodos: La pS2 citosólica fue determinada utilizando un IRMA (CIS. BioInternational. Francia). Hemos analizado, además, las concentraciones citosólicas de catepsina D y activador del plasminógeno tipo tisular (t-AP), así como las del receptor del factor de crecimiento epidérmico (EGFR), oncoproteína erbB2, CD44v5 y CD44v6 en las membranas celulares. El tamaño tumoral, grado histológico (GH), afectación axilar, metástasis a distancia, ploidía, índice de DNA y fase de síntesis celular (FS) fueron también considerados. Resultados: Los tumores pS2-positivos (> 5ng/mg prot.) mostraron mayores concentraciones de catepsina D (p:0,0043) y t-AP (p:0,0089) y fueron, asimismo, menos frecuentemente GH3 (p:0,0231), FS > 7 % (p:0,0005) y FS > 14 % (p:0,0014). Durante el período de seguimiento (i: 1-147; 50,1+/­31,7; mediana 37 meses) los tumores pS2 positivos mostraron menor número de recidivas (5/101 vs 6/69; p:0,059), pero no de muertes por el tumor (1/101 vs 2/6); ns). Conclusiones: Nuestros resultados apoyan la relación inversa de la pS2 con la proliferación celular en los tumores RE+ y RP+, lo cual puede sugerir una nueva función biológica distinta a la de indicadora de la hormonodependencia. Sin embargo, necesitamos tener mayor tiempo de seguimiento para poder precisar si ello incide directamente en la evolución ulterior del tumor


Objective: The trefoil factor 1 (TFF1/pS2) is an estrogen-induced molecule in breast tumours. We wanted to study its expression in ER+ and PgR+ infiltrating ductal carcinomas of the breast (IDCs), and to correlate it with other clinical-biological parameters and the outcome. Material and methods: Cytosolic pS2 levels were measured using an IRMA (CIS. Biointernational. France) in 170 tumors. Likewise we determined the cytosolic levels of cathepsin D and tissue-type plasminogen activator (t-PA), as well as the concentrations of the epidermal growth factor receptor (EGFR), erbB2 oncoprotein, CD44v5 and CD44v6 on cell surfaces. Also the tumour size, histological grade (HG), axillary lymph node involvement, distant metastasis, ploidy, DNA index and of cellular synthesis phase (SP) was taken in account.Results: The pS2-positive (> 5 ng(/mg prot.) tumours showed higher concentrations of cathepsin D (p: 0.0043) and t-PA (p: 0.0089) than the pS2-negative ones. Likewise, they were less frequently HG3 (p: 0.0231), SP > 7 % (p: 0.0005) and SP > 14 % (p:0.0014). During the follow-up time (r: 1-147; 50,1+/­31,7; median 37 months) the pS2-positive tumors showed a less number of recurrences (5/101 vs 6/69; p: 0.059) but not of deaths by the tumor (1/101 vs 2/69). Conclusions: These results support an inverse relationship between pS2 positivity and cellular proliferation in IDCs and suggest a new role of this protein (different of the hormonodependence) in the biology of these breast carcinomas, while further studies will be required to establish the impact of this finding on their outcome


Assuntos
Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Carcinoma Ductal de Mama/química , Citosol/química , Estrogênios , Progesterona , Proteínas Supressoras de Tumor/análise , Neoplasias da Mama/química , Proteínas de Neoplasias/análise , Neoplasias Hormônio-Dependentes/química , Aneuploidia , Receptores de Hialuronatos/análise , Catepsina D/análise , Neoplasias da Mama/patologia , DNA de Neoplasias/análise
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