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1.
Clin. transl. oncol. (Print) ; 18(9): 878-883, sept. 2016. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-155501

RESUMO

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor of the liver with a poor prognosis. Upregulation of special ATrich sequence-binding protein 1 (SATB1) promotes tumor progression. However, little is known about the role of SATB1 in ICC tumorigenesis. Methods: We firstly investigated the expression of SATB1 in 88 cases of ICC by immunohistochemistry (IHC), QRTPCR, and western blot. Meanwhile, we constructed stably knockdown (shRNA) of SATB1 in ICC cell lines to evaluate the effects of SATB1 on the ability of cell proliferation and invasion by MTT and transwell invasion assay. Results: Our result showed that SATB1 was overexpressed in ICC tissues samples. Knockdown of SATB1 could inhibit ICC cell proliferation, and suppress ICC cell invasion of ICC cell lines. In addition, the depletion of SATB1 expression suppressed the MYC levels in vitro. Conclusions: Our results highlight the significance of SATB1 in ICC and suggest that SATB1 could be a promising therapy target and a potential biomarker for prognosis in ICC patients (AU)


No disponible


Assuntos
Humanos , Colangiocarcinoma/genética , Proteínas de Ligação a DNA/genética , Genes myc/genética , Marcadores Genéticos , Proliferação de Células/genética , Terapia de Alvo Molecular/métodos
2.
Clin. transl. oncol. (Print) ; 16(8): 702-707, ago. 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126557

RESUMO

BACKGROUND: Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is involved in malignancies. However, the role of CHD1L in gastric cancer (GC) has not been elucidated. The aim of this study is to explore the clinical role of CHD1L in GC. METHODS: The gene and protein expression levels of CHD1L were detected by quantitative real-time PCR and Western blot analysis in fresh samples of GC and paired adjacent noncancerous tissue (n = 34). We evaluated the CHD1L expression by immunohistochemistry in a large number of GC patients (n = 616) and paired adjacent noncancerous tissues from December 1, 2004 to December 1, 2008. The correlations of CHD1L expression with clinicopathological features and clinical outcome were analyzed. RESULTS: The gene and protein expression levels of CHD1L were higher in fresh samples of GC than in paired adjacent noncancerous tissues as determined by quantitative real-time PCR and Western blot analysis. Immunohistochemical analysis showed that positive expression rates of CHD1L in GC and paired adjacent noncancerous tissues were 58.7 % (361/616) and 7.3 % (45/616), respectively. CHD1L positivity was significantly associated with clinical stage and distant metastasis. GC patients with positive CHD1L expression had shorter overall survival than those with negative CHD1L expression. Multivariate analysis showed that CHD1L was an independent prognostic marker for overall survival [Hazard Ratio (HR) = 5.952, 95 % confidence interval (CI) = 3.194-11.187, P = 0.0043]. CONCLUSION: These results indicated that CHD1L could serve as a prognostic marker for GC (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Neoplasias Gastrointestinais/diagnóstico , Prognóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/isolamento & purificação , Biomarcadores Tumorais/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Gastrointestinais/secundário , Neoplasias Gastrointestinais/terapia , Expressão Gênica , Análise Multivariada , Oncogenes
3.
Clin. transl. oncol. (Print) ; 16(2): 158-165, feb. 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-127719

RESUMO

INTRODUCTION: Anthracyclines have various mechanisms of action that in the end lead to DNA double-strand breaks. Single-nucleotide polymorphisms (SNPs) in DNA repair genes may alter the protein function, affecting DNA repair proficiency and, therefore, the efficiency of DNA damaging chemotherapy. We have analysed whether SNPs in DNA repair genes (XRCC1, XRCC3 and XPD) could be useful to predict the response to anthracyclines in patients with early-stage breast cancer (EBC). METHODS: Peripheral blood samples from 150 patients with EBC were used for genotyping XRCC3Thr241Met, XRCC1Arg399Gln and XPDLys751Gln. Genotypes were correlated with survival outcomes. RESULTS: Eighty-four patients received treatment with chemotherapy regimens containing anthracyclines. In this group, patients with XRCC1Arg399Arg had a significant improvement in 5-year Disease Free Survival (DFS) compared with those with the Arg/Gln and Gln/Gln variants (84 vs 46 %, p = 0.026). In the multivariate analysis, XRCC1Arg399Arg was reported as an independent prognostic factor for DFS (HR 0.4, CI-95 % 0.2-0.9, p = 0.035). Patients with the XRCC3 Met241Met genotype presented better 5-year OS than those carrying the Thr/Thr and Met/Thr variants (100 vs 70 %, p = 0.030). A multivariate analysis for OS confirmed the independent prognostic value of XRCC3 Met241Met (HR 0.15, CI-95 % 0.02-0.90, p = 0.048). These differences were not significant when patients receiving other chemotherapy treatments, different from anthracyclines, were also considered (n = 150). XPDLys751Lys was associated with older age at diagnosis than the Lys/Gln and Gln/Gln genotypes (65 vs 58 years, p < 0.0001). CONCLUSIONS: XRCC3Thr241Met and XRCC1Arg399Gln may be predictive of survival outcome in EBC patients treated with anthracycline-based chemotherapy regimens (AU)


No disponible


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Polimorfismo de Nucleotídeo Único , Proteína de Xeroderma Pigmentoso Grupo A/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Predisposição Genética para Doença , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
4.
Clin. transl. oncol. (Print) ; 14(3): 163-168, mar. 2012. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126171

RESUMO

Anthracyclines are frequently used in the adjuvant setting for breast cancer treatment since it is considered that anthracycline-based chemotherapy treatment benefits breast cancer patients. Nonetheless, these drugs are associated with severe side effects and predictive factors, for sensitivity to anthracyclines, are warranted in clinical practice. Topoisomerase 2 alpha (TOP2A) is considered to be the molecular target of these drugs. The potential predictive value of TOP2A amplification and overexpression has been extensively studied in breast cancer patients treated with anthracyclines. However, results are not conclusive. In this paper, we review some of the published studies addressing the predictive value of TOP2A as well as the cellular functions of this enzyme and its status in breast cancer tissue (AU)


Assuntos
Animais , Feminino , Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Antígenos de Neoplasias/fisiologia , DNA Topoisomerases Tipo II/fisiologia , Modelos Biológicos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Carcinoma/diagnóstico , Carcinoma/tratamento farmacológico , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/genética
5.
Reumatol. clín. (Barc.) ; 7(supl.3): s18-s21, dic. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-147312

RESUMO

Una de las características principales de las vasculitis asociadas a ANCA (VAA) es la ausencia de depósito de complejos inmunes en las biopsias de los tejidos afectados y de consumo de complemento. Sin embargo, en etapas tempranas de enfermedades similares producidas en modelos animales, se ha observado que el sistema del complemento puede participar en la génesis de estas patologías. Varios modelos se han desarrollado en el intento de disecar los mecanismos patogénicos de enfermedades como granulomatosis con poliangitis (Wegener) (GPA) o poliangitis microscópica siendo más exitosos en esta última, sin que hasta el momento se disponga de un modelo satisfactorio para explicar los cambios que llevan a enfermedad granulomatosa vasculítica, máxime si se asocia a anticuerpos contra proteinasa-3 (PR-3), como es el caso en la GPA. Este manuscrito revisa en forma sucinta las evidencias recientes de la presencia de complemento en biopsias de pacientes con VAA, así como modelos animales que ponen de manifiesto la participación del sistema de complemento en su patogenia (AU)


One of the main characteristics of the vasculitis associated with antineutrophil cytoplasm autoantibodies (AASV) is the absence of immune complex deposition in biopsies of affected tissues as well as a lack of complement depletion. However, in early stages of disease induced in animal models, it has been observed that the complement system may be involved in the generation of these diseases. There are various animal models which have been developed with the aim of knowing which are the pathogenic mechanisms in granulomatosis with polyangiitis (Wegener) (GPA) and microscopic polyangiitis (MPA), the latter being explained using these approaches in a more satisfactory manner, as there is lack of a model which reproduces the changes leading to a granulomatous vasculitis associated with antibodies against proteinase-3, as in GPA. This short review presents recent evidence of the presence of complement in biopsies of patients with AASV and the most recent animal models, which show the participation of complement in their etiology (AU)


Assuntos
Humanos , Animais , Camundongos , Proteínas do Sistema Complemento/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/análise , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Anticorpos Monoclonais/uso terapêutico , Autoantígenos/imunologia , Camundongos Endogâmicos C57BL , Peroxidase/imunologia , Mieloblastina/imunologia , Poliangiite Microscópica/imunologia , Rim/imunologia , Rim/patologia , Biópsia , Ativação do Complemento , Complemento C5/antagonistas & inibidores , Complemento C5a/antagonistas & inibidores , Proteínas de Ligação a DNA/deficiência , Granulomatose com Poliangiite/imunologia
6.
Clin. transl. oncol. (Print) ; 13(11): 826-830, nov. 2011. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-125945

RESUMO

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/patologia , Endonucleases/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Ligação a DNA/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Intervalo Livre de Doença , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Imuno-Histoquímica/métodos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Prognóstico
7.
Int. microbiol ; 13(1): 9-13, mar. 2010. ilus
Artigo em Inglês | IBECS | ID: ibc-87667

RESUMO

Major differences regarding the pathology and host immune response of the Beijing and Canettii genotypes of Mycobacterium tuberculosis have been reported; however, studies on the genetic expression of these genotypes during in vitro dormancy are scarce. This study examined the expression of five cell-cycle-related genes and two dormancy-related genes in M. canettii, M. tuberculosis H37Rv, and M. tuberculosis Beijing during the Wayne model of dormancy. The results showed that under hypoxic conditions the three tuberculosis genotypes were able to transcribe genes involved in DNA replication and cellular division. In addition, dosR was found to be up-regulated in M. tuberculosis Beijing during the exponential growth phase but down-regulated under hypoxic conditions. In this genotype, the replication-related gene dnaA was also strongly down-regulated. These latter two findings suggest that, compared to M. tuberculosis H37Rv and M. canettii, the Beijing genotype has a lower capacity to synthesize dosR, hspX, and dnaA mRNAs during in vitro dormancy (AU)


No disponible


Assuntos
Humanos , Proteínas Quinases/biossíntese , Oxigênio/metabolismo , Mycobacterium tuberculosis/fisiologia , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/biossíntese , Proteínas de Ligação a DNA/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Proteínas Quinases/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Hipóxia , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/genética
8.
Int. microbiol ; 13(1): 33-39, mar. 2010. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-87670

RESUMO

Anaerobic metabolism is controlled by several transcriptional regulators, including ArcA, Fnr, NarP, and NarL, with the Fnr and ArcA proteins sensitive to the cell's redox status. Specifically, the two-component ArcAB system is activated in response to the oxidation state of membrane-bound quinones, which are the central electron carriers of respiration. Fnr, by contrast, directly senses cellular oxidation status through the [4Fe-4S] cluster present in its own structure. In this study, a third additional redox-associated pathway that controls the nitrate respiration regulators NarL and NarP was identified. The results showed that, in Salmonella enterica, the expression of these two transcriptional regulators is under the control of Fur, a metalloregulator that senses the presence of Fe2+ and regulates the homeostasis of this cation inside the cell. Thus, the Fur- Fe2+ complex increases the expression of narL and represses that of narP. Furthermore, studies of S. enteric mutants defective in the Fur-regulated sRNA RfrA and RfrB showed that those sRNA control both narP and narL expression. These results confirm Fur as a global regulator based on its involvement not only in iron uptake and detoxification but also in the control of nitrate/nitrite respiration by sensing cellular redox status (AU)


No disponible


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/biossíntese , Regulação Bacteriana da Expressão Gênica , Nitratos/metabolismo , Proteínas Repressoras/metabolismo , Salmonella enterica/fisiologia , Fatores de Transcrição/biossíntese , Proteínas de Bactérias/biossíntese , Ferro/metabolismo , Oxirredução , Salmonella enterica/metabolismo
9.
Clin. transl. oncol. (Print) ; 11(8): 548-551, ago. 2009. ilus
Artigo em Inglês | IBECS | ID: ibc-123674

RESUMO

INTRODUCTION: The expression of E-cadherin, beta-catenin and topoisomerase II has been associated with clinical outcome of several cancers including sarcomas. We aimed to evaluate the expression of these markers in leiomyosarcomas (LMS). MATERIALS AND METHODS: Paraffin blocks of 19 primary, nonmetastatic LMS were analysed immunohistochemically for the expression of the above-mentioned markers with a cutoff level for positivity of 20% of cell staining. RESULTS: Expression of E-cadherin was negative in all LMS. Nuclear expression of beta-catenin was also negative in all cases, while positive cytoplasmic beta-catenin expression was observed in approximately half of the patients. The majority of LMS had expression of topoisomerase IIalpha, although only in 10 patients was this expression in more than 20% of tumour cells. From the analysed factors, tumour size was statistically significantly correlated with relapse-free survival. CONCLUSIONS: Further evidence with larger series is required in order to determine the implication of these markers in LMS (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Caderinas/metabolismo , Antígenos de Neoplasias/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Leiomiossarcoma/metabolismo , beta Catenina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Imuno-Histoquímica/métodos , Imuno-Histoquímica , Leiomiossarcoma/patologia
10.
Rev. esp. patol ; 42(1): 31-37, ene.-mar. 2009. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-61021

RESUMO

Objetivos: La alteraciones de los genes reparadores deADN llevan a la inestabilidad de microsatélites y caracterizanal adenocarcinoma familiar de colon no asociado a poliposisy al resto de tumores que se han descrito asociados aeste síndrome. Asimismo, aunque se han visto alterados enun número variable de casos de cáncer esporádico, han sidomuy raramente evaluados en los carcinomas de células renales.Material y métodos: Se han seleccionado 7 oncocitomasrenales y 7 carcinomas renales de células cromófobasmediante criterios histológicos e inmunohistoquímicos convencionales,para el estudio de los genes reparadores deADN mediante la expresión inmunohistoquímica de las proteínasMLH1, MSH2, y MSH6. Resultados: Existe un predominioclaro del sexo masculino, tanto entre los oncocitomas(2F/5M) como entre los carcinomas (3F/4M), con edadesmedias de presentación de 66,8 y 63,4 añosrespectivamente. Entre los oncocitomas renales se ha detectadopositividad para CK20 (4 casos) y CD15 (4 casos),negatividad para CK7 en todos los casos, y pérdida de laexpresión proteica de MLH1 en 1 caso, de MSH2 en 2casos, y de MSH6 en 1 caso. En los carcinomas de célulascromófobas se ha observado positividad para CK7 y negatividadpara CK20 y CD15 en todos los casos, y pérdida de laexpresión de MSH2 en 2 casos y de MSH6 en 3. Conclusiones:El patrón de expresión de las proteínas MLH1,MSH2 y MSH6 en oncocitomas y en carcinomas renales decélulas cromófobas es similar, apoyando la teoría vigente deun mismo origen para ambas entidades en la nefrona distal (AU)


Objectives: Mismatch repair gene disorders lead tomicrosatellite instability and characterise the nonpolyposishereditary colonic adenocarcinoma syndrome. Aside fromthat, the syndrome includes other carcinomas in differentlocations. Mismatch repair gene mutations have been alsodescribed in some sporadic carcinomas of diverse topographies,but only very occasionally in renal cortical carcinomas.Material and methods: Seven renal oncocytomas and7 chromophobe cell carcinomas have been selected followingconventional histological and immunohistochemicalmethods for the analysis of MLH1, MSH2 and MSH6 proteins.Results: There is a male predominance, both inoncocytomas and in carcinomas, with average ages of presentationof 66.8 and 63.4 years, respectively. Among theoncocytoma group, a positive immunostaining for CK20and CD15 has been seen in 4 cases each. Loss of MLH1expression has been detected in one case, loss of MSH2 in2, and loss of MSH6 in one. Among the chromophobe cellcarcinomas, CK7 was positive and CK20 and CD15 negativein all cases. Loss of MSH2 expression has been observedin 2 cases and loss of MSH6 in 3. Conclusions: The patternof MLH1, MSH2 and MSH6 expression is analogous inrenal oncocytomas and chromophobe cell carcinomas thussupporting the nowadays accepted theory of a similar originin the distal nephron for both pathological entities (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adenoma Oxífilo/metabolismo , Adenoma Oxífilo/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Adenoma Cromófobo/metabolismo , Adenoma Cromófobo/patologia , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/metabolismo , Imuno-Histoquímica
11.
Rev. esp. med. nucl. (Ed. impr.) ; 27(1): 13-21, ene. 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-058579

RESUMO

La dihidrotetrabenazina (2-hidroxi-3-isobutil-9,10-dimetoxi-1,3,4,6,7-hexahidro-11bH-benzo[a]-quinolizina, DTBZ) se ha convertido en el ligando ideal de los transportadores presinápticos de monoaminas (VMAT2) debido a su elevada afinidad de unión y su lipofilicidad. Objetivo. Desarrollar un procedimiento de síntesis automático para el marcaje con carbono-11 de la DTBZ para utilizarla como marcador en el estudio in vivo mediante tomografía por emisión de positrones de pérdidas neuronales en modelos animales de enfermedad de Parkinson. Material y métodos. Se ha diseñado un nuevo método de síntesis totalmente automatizado para la obtención de 11C-(+)DTBZ. La reacción de metilación del precursor ­(+)desmetildihidrotetrabenazina­ se lleva a cabo a temperatura ambiente, a partir de la obtención de 11CH3I que utilizamos como precursor primario, en presencia de dimetilsulfóxido e hidróxido de potasio. Para los procesos de purificación se han utilizado cartuchos de extracción en fase sólida alúmina y los disolventes residuales del producto final se eliminaron mediante evaporación bajo flujo de helio. Resultados. De las 54 síntesis realizadas se han obtenido, con un tiempo de bombardeo de 5 minutos, y 6 minutos de síntesis tras la obtención de 11CH3I, unas producciones medias de 1,94 ± 0,13 GBq de 11C-(+)DTBZ, estéril, apirógeno y con una pureza radioquímica > 99 %. Conclusiones. Este nuevo procedimiento de síntesis es rápido y simple, ya que para la purificación final se han optimizado técnicas que permitieran la eliminación de los disolventes residuales basándonos en su polaridad y es aplicable a otras síntesis automáticas para la obtención de otros compuestos marcados mediante reacciones de metilación


Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. Objective. To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). Materials and methods. We have developed a new fully automated synthesis procedure to obtain 11C-(+)DTBZ quickly and simply through labelling the precursor ­(+)desmethyldihydrotetrabenazine­ at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11CH3I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. Results. The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free 11C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11CH3I production. 11C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys. Conclusions. This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions


Assuntos
Humanos , Tomografia Computadorizada de Emissão/métodos , Proteínas de Ligação a DNA/análise , Tetrabenazina , Biossíntese Peptídica
12.
Rev. esp. patol ; 40(2): 97-102, abr.-jun. 2007. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-057472

RESUMO

Antecedentes: Los tumores neuroblásticos son de los tumores pediátricos más frecuentes. A pesar de su gran variedad genética, clínica e histopatológica, la amplificación del gen MYCN es siempre un indicador de mal pronóstico. Este oncogen codifica una proteína nuclear que se une al ADN y activa la transcripción de sus genes diana. Un aumento en el número de copias del gen no se corresponde siempre con sobreexpresión de su proteína. El valor pronóstico de la detección de la proteína es controvertido. Métodos: Se han analizado 220 muestras de NB. Mediante la técnica de FISH se ha establecido el estado del gen, mientras que la inmunohistoquímica ha permitido el estudio de la expresión de la proteína en secciones de parafina. Resultados: Los 15 casos con ganancia y 140 de los 141 casos sin amplificación del gen MYCN no expresan la proteína. En el grupo de los 55 casos amplificados, el 76,4% han sido positivos y 23,6% negativos. Conclusiones: Los niveles de expresión génica no siempre corresponden con el número de copias del gen, ya que intervienen muchos mecanismos moleculares. La mayoría de los casos positivos para este anticuerpo presentan amplificación, así que el estudio inmunohistoquímico de su expresión podría utilizarse para aproximar el estado del gen MYCN en aquellos laboratorios de diagnóstico donde las técnicas moleculares no estén disponibles


Introduction: Neuroblastic tumors are one of the most frequent pediatric tumor. Despite their genetic, clinic and histopathologic variety, MYCN gene amplification is always considered as an adverse prognosis factor. MYCN gene encodes a nuclear protein which binds DNA and activates target genes transcription. An increase of gene copies number not always involves a protein overexpression. The prognostic value of the determination of mycN protein is controversial. Materials and methods: 220 NB samples were analyzed. We established the gene status by FISH and we studied the protein expression in paraffin sections by immunohistochemistry. Results: 15 gain samples and 140 from 141 non-amplified samples don’t express MYCN protein. From 55 amplified cases, 76.4% were positive and 23.6% were negative. Conclusions: Gene expression levels do not always match with gene copies number due to different molecular mechanisms. Most of positive cases to mycN protein are amplified samples. This antibody could be used to approach gene status in those laboratories without available molecular techniques


Assuntos
Humanos , Neuroblastoma/patologia , Proteínas Proto-Oncogênicas c-myc/análise , Neuroblastoma/genética , Expressão Gênica , Proteínas de Ligação a DNA/análise , Neoplasias do Sistema Nervoso/patologia
13.
Rev. esp. patol ; 40(2): 97-102, abr.-jun. 2007. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-057503

RESUMO

Antecedentes: Los tumores neuroblásticos son de los tumores pediátricos más frecuentes. A pesar de su gran variedad genética, clínica e histopatológica, la amplificación del gen MYCN es siempre un indicador de mal pronóstico. Este oncogen codifica una proteína nuclear que se une al ADN y activa la transcripción de sus genes diana. Un aumento en el número de copias del gen no se corresponde siempre con sobreexpresión de su proteína. El valor pronóstico de la detección de la proteína es controvertido. Métodos: Se han analizado 220 muestras de NB. Mediante la técnica de FISH se ha establecido el estado del gen, mientras que la inmunohistoquímica ha permitido el estudio de la expresión de la proteína en secciones de parafina. Resultados: Los 15 casos con ganancia y 140 de los 141 casos sin amplificación del gen MYCN no expresan la proteína. En el grupo de los 55 casos amplificados, el 76,4% han sido positivos y 23,6% negativos. Conclusiones: Los niveles de expresión génica no siempre corresponden con el número de copias del gen, ya que intervienen muchos mecanismos moleculares. La mayoría de los casos positivos para este anticuerpo presentan amplificación, así que el estudio inmunohistoquímico de su expresión podría utilizarse para aproximar el estado del gen MYCN en aquellos laboratorios de diagnóstico donde las técnicas moleculares no estén disponibles


Introduction: Neuroblastic tumors are one of the most frequent pediatric tumor. Despite their genetic, clinic and histopathologic variety, MYCN gene amplification is always considered as an adverse prognosis factor. MYCN gene encodes a nuclear protein which binds DNA and activates target genes transcription. An increase of gene copies number not always involves a protein overexpression. The prognostic value of the determination of mycN protein is controversial. Materials and methods: 220 NB samples were analyzed. We established the gene status by FISH and we studied the protein expression in paraffin sections by immunohistochemistry. Results: 15 gain samples and 140 from 141 non-amplified samples don’t express MYCN protein. From 55 amplified cases, 76.4% were positive and 23.6% were negative. Conclusions: Gene expression levels do not always match with gene copies number due to different molecular mechanisms. Most of positive cases to mycN protein are amplified samples. This antibody could be used to approach gene status in those laboratories without available molecular techniques


Assuntos
Humanos , Neuroblastoma/patologia , Proteínas Proto-Oncogênicas c-myc/análise , Neuroblastoma/genética , Expressão Gênica , Proteínas de Ligação a DNA/análise , Neoplasias do Sistema Nervoso/patologia
14.
Int. microbiol ; 9(1): 21-28, mar. 2006. ilus
Artigo em Inglês | IBECS | ID: ibc-044836

RESUMO

Microorganisms can live and proliferate as individual cells swimming freely in the environment, or they can grow as highly organized, multicellular communities encased in a self-produced polymeric matrix in close association with surfaces and interfaces. This microbial lifestyle is referred to as biofilms. The intense search over the last few years for factors involved in biofilm development has revealed that distantly related bacterial species recurrently make use of the same elements to produce biofilms. These common elements include a group of proteins containing GGDEF/EAL domains, surface proteins homologous to Bap of Staphylococcus aureus, and some types of exopolysaccharides, such as cellulose and the poly-b-1,6-N-acetylglucosamine. This review summarizes current knowledge about these three common elements and their role in biofilm development (AU)


Los microorganismos pueden vivir y proliferar como células individuales que nadan libremente en el medio o crecer en comunidades multicelulares muy bien organizadas dentro de una matriz que ellas mismas han sintetizado y asociadas a superficies o interfases. Esta forma de vida microbiana recibe el nombre de biopelículas. La búsqueda intensa de los factores que intervienen en el desarrollo de la biopelícula llevada a cabo estos últimos años ha revelado que especies bacterianas filogenéticamente alejadas recurren a los mismos elementos para producir la biopelícula. Entre los elementos comunes identificados hay proteínas que contienen los dominios GGDEF/EAL, proteínas de superficie que muestran homología con la proteína Bap de Staphylococcus aureus, y algunos exopolisacaridos, como la celulosa y la poli-b-1,6-N-acetilglucosamina. Esta revisión resume los conocimientos actuales sobre estos tres elementos y su función en la formación de la biopelícula (AU)


Assuntos
Proteínas de Membrana/análise , Polissacarídeos/análise , Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Proteínas de Ligação a DNA/análise , Bactérias/crescimento & desenvolvimento , Crescimento Bacteriano
15.
Int. microbiol ; 7(2): 133-137, jun. 2004. ilus
Artigo em Inglês | IBECS | ID: ibc-98755

RESUMO

The abundant presence of temperate phages in the chromosomes of clinical isolates of Streptococcus pneumoniae has been well documented. The genome of MM1, a temperate phage of pneumococcus, has been isolated as a DNA-protein complex. The protein is covalently bound to the DNA, was iodinated in vitro with Na125I, and has an Mr of 22,000. Electron microscopy and enzymatic analyses revealed that the MM1 genome is a linear, circularly permuted, terminally redundant collection of double-stranded DNA molecules packaged via a heedful mechanism. The location of the pac site appears to be downstream of the terminase, between orf32 and orf34 of the MM1 genome (AU)


La abundante presencia de fagos atenuados en el cromosoma de aislados clínicos de Streptococcus pneumoniae ha sido bien documentada. El genoma de MM1, un fago atemperado de neumococo, se ha aislado como un complejo de DNA-proteína. La proteína unida covalentemente al DNA, fue yodada in vitro con Na125I, y tiene una Mr de 22.000. La microscopia electrónica y los análisis enzimáticos revelaron que el genoma de MM1 es una colección de moléculas lineales de DNA de doble cadena, permutadas circularmente y redundantes en la posición terminal, empaquetadas mediante un mecanismo de ensamblado de unidades genómicas discretas. También proponemos la localización del sitio pac en dirección 3´ de la terminas a, entreorf32 y orf34 del genoma de MM1 (AU)


Assuntos
Streptococcus pneumoniae/genética , DNA Bacteriano/análise , Proteínas de Ligação a DNA/análise , Fagos de Streptococcus/genética , Microscopia Eletrônica/métodos , /métodos , Genoma Bacteriano
17.
Arch. Soc. Esp. Oftalmol ; 77(11): 635-638, nov. 2002.
Artigo em Espanhol | IBECS | ID: ibc-18316

RESUMO

Caso Clínico: Describimos el caso de una mujer con foseta papilar y una hipolasia renal bilateral, como síndrome papilorrenal. El análisis del DNA para las mutaciones del PAX2 determinó una mutación heterocigota (nucleótido 619 del exon 9). Un tío y un primo carnal eran portadores de la misma mutación en el PAX2.Discusión: La asociación de colobomas del nervio óptico y anomalías renales forman parte de un síndrome autosómico dominante por mutaciones en el gen PAX2. La expresión de la enfermedad oftalmológica y renal es muy variable; los oftalmólogos deben chequear la función renal cuando un coloboma sea detectado (AU)


Case report: We describe a woman with optic disc pit and bilateral renal hypoplasia as a papillorenal syndrome. DNA analysis for PAX2 mutations revealed a heterozygous mutation (nucleotide 619 in exon 9). A first uncle and a cousin had the same PAX2 mutation. Discussion: The association of optic nerve colobomas and renal anomalies comprises a autosomal dominant syndrome for mutations in the PAX2 gene. Ophthalmic and renal diseases are highly variable; the ophthalmologist must check for a renal problem when a coloboma is detected (Arch Soc Esp Oftalmol 2002; 77: 635-638) (AU)


Assuntos
Pessoa de Meia-Idade , Feminino , Humanos , Mutação , Síndrome , Fatores de Transcrição , Coloboma , Análise Mutacional de DNA , Anormalidades Múltiplas , Rim , Genes Dominantes , Disco Óptico , Proteínas de Ligação a DNA
18.
Arch. Soc. Esp. Oftalmol ; 77(9): 481-484, sept. 2002.
Artigo em Espanhol | IBECS | ID: ibc-18282

RESUMO

Objetivo: Análisis mutacional en un colectivo de pacientes afectos de retinosis pigmentaria autosómica dominante (RPAD).Métodos: Exploración oftalmológica completa que incluye pruebas de electrofisiología, campimetría computerizada y en ocasiones angiografía fluoresceínica y estudio genético del ADN para detección de mutaciones en los genes candidatos (rodopsina, periferina, ROM-1, CRX, RP1 y NRL).Resultados: 148 familias diferentes afectas de RPAD fueron evaluadas en nuestro centro desde junio de 1991 hasta septiembre de 2001 y se hallaron las siguientes mutaciones: 29 familias diferentes (19,5 por ciento) presentaron una mutación en el gen de la rodopsina (RHO) de las que Pro-347-Leu fue la más frecuente; 5 mutaciones en el gen RP1 (3,3 por ciento); 2 mutaciones en el gen periferina/RDS y una mutación en el gen NRL que es la segunda descrita en la literatura mundial. Conclusiones: El gen RHO seguido del RP1 son los que con mayor frecuencia se asocian a RPAD al igual que el resto de estadísticas mundiales y el gen RDS causa principalmente distrofias maculares. En un 25 por ciento se obtuvo un diagnóstico molecular, lo cual es de gran importancia para el consejo genético y pronóstico visual del paciente (AU)


Assuntos
Humanos , Mutação , Rodopsina , Transativadores , Mutação Puntual , Proteínas de Homeodomínio , Proteínas de Membrana , Proteínas do Tecido Nervoso , Retinite Pigmentosa , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Análise Mutacional de DNA , Proteínas de Filamentos Intermediários , Proteínas do Olho , Genes Dominantes , Proteínas de Ligação a DNA
20.
Rev. neurol. (Ed. impr.) ; 34(supl.1): 54-58, 28 feb., 2002.
Artigo em Espanhol | IBECS | ID: ibc-27816

RESUMO

Introducción. El síndrome de Rett (SR), una enfermedad neurológica del desarrollo que constituye la segunda causa de retraso mental profundo en el sexo femenino, es provocada en la mayoría de los casos por mutaciones de novo en un gen situado en el cromosoma X, gen que codifica la proteína de unión a las metil-CpG (MECP2); se han descubierto mutaciones en este gen en aproximadamente un 80 por ciento de los casos comprobados que presentan la forma clásica del SR. También se encontraron mutaciones en el gen MECP2 en aproximadamente un tercio de los casos de SR no clásicos e incluso en otras enfermedades: mujeres con retraso mental leve o profundo, niños con autismo e incluso niños con encefalopatía neonatal o con un cuadro clínico similar al del SR. Desarrollo. Los estudios de correlación genotipo-fenotipo en el SR clásico sugieren que el patrón de inactivación del cromosoma X tiene un efecto más importante en la determinación de la gravedad de la enfermedad que el tipo o la localización de la mutación. Sin embargo, cuando se considera la totalidad de los fenotipos asociados a las mutaciones MECP2, se comprueba que el tipo de mutación tiene alguna correlación con la presentación clínica o la gravedad de la enfermedad. Conclusión. Los recientes avances en la genética del SR presentan, por lo tanto, aplicaciones concretas en el panorama clínico, y proporcionan marcadores auxiliares de diagnóstico y posibles indicadores de pronóstico, así como para el consejo genético a las familias de pacientes con SR (AU)


Assuntos
Feminino , Criança , Humanos , Proteínas Repressoras , Fenótipo , Cromossomos Humanos X , Proteínas Cromossômicas não Histona , Marcadores Genéticos , Mutação , Genótipo , Síndrome de Rett , Proteínas de Ligação a DNA
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