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1.
Leukemia ; 29(5): 1177-85, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25428260

RESUMEN

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.


Asunto(s)
Factores de Transcripción de Tipo Kruppel/genética , Linfoma de Células B de la Zona Marginal/genética , Mutación , Neoplasias del Bazo/genética , Biopsia , Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas de Unión al ADN/metabolismo , Exoma , Mutación del Sistema de Lectura , Reordenamiento Génico de Cadena Pesada de Linfocito B , Variación Genética , Genotipo , Guanilato Ciclasa/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Linfoma/metabolismo , Linfoma de Células B de la Zona Marginal/diagnóstico , Mutación Missense , Proteínas Nucleares/metabolismo , Reacción en Cadena de la Polimerasa , Receptor Notch2/metabolismo , Recurrencia , Análisis de Secuencia de ADN , Transducción de Señal , Neoplasias del Bazo/diagnóstico , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
2.
Actas Urol Esp ; 35(1): 37-41, 2011 Jan.
Artículo en Español | MEDLINE | ID: mdl-21256393

RESUMEN

INTRODUCTION: we present our preliminary experience and results of practising the prostate enucleation technique using a diode laser (DiLEP) and intravesical morcellation, following the same principles of holmium laser enucleation (HoLEP). MATERIALS AND METHOD: we endoscopically treated benign prostate hyperplasia with DiLEP in 17 patients over a period of five months. They were all followed up for three months with flowmetry and IPSS. We have described the prostate enucleation and morcellation technique in detail, as well as the materials required to perform them. We have also commented on the lessons learned having practised on more than 300 cases with HoLEP, with a view to applying this new technology. RESULTS: the mean age was 74.2 and the mean prostate volume was 61.26 (47-110) cc. The mean loss of haemoglobin was 2.1 (1.4-3.1) gr/dl. There were no major consequences or complications. All the patients were discharged from the hospital 24 hours after the operation. The improvement in the IPSS (22.3±4.1 vs. 7.1±1.06) and in the Q max (7.14±2.6 vs. 21.4±3.6) was sustainable. CONCLUSIONS: It is the first description of the DiLEP technique for the surgical treatment of benign prostate hyperplasia. We believe the results obtained are promising and that they could signify some advantages as opposed to HoLEP. However, prospective randomized studies are required to confirm this opinion.


Asunto(s)
Láseres de Semiconductores , Prostatectomía/métodos , Hiperplasia Prostática/cirugía , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad
3.
Actas urol. esp ; 35(1): 37-41, ene. 2011. tab, ilus
Artículo en Español | IBECS | ID: ibc-88143

RESUMEN

Introducción: se presenta la experiencia preliminar y resultados de practicar la técnica de enucleación prostática mediante láser diodo (Dilep) y morcelación intravesical, siguiendo los mismos principios de la enucleación con láser de Holmio (Holep). Material y método: a lo largo de 5 meses se ha llevado a cabo el tratamiento endoscópico de la hiperplasia benigna de próstata mediante Dilep en 17 pacientes. Todos ellos han sido seguidos tres meses con flujometría e IPSS. Se describe con detalle la técnica de enucleación prostática y de morcelación, así como el material necesario para llevarla a cabo. Se comentan también las enseñanzas aprendidas con la práctica de más de 300 casos con Holep, de cara a la aplicación de esta nueva tecnología. Resultados: la edad media fue 74,2 años y el volumen prostático medio 61,26 (47-110) cc. La pérdida media de hemoglobina fue 2,1 (1,4-3,1) g/dl. No sucedieron secuelas ni complicaciones mayores. Todos los pacientes abandonaron el hospital a las 24 horas de la intervención. La mejoría en el IPSS (22,3±4,1 vs. 7,1±1,06) y en el Qmax (7,14±2,6 vs. 21,4±3,6) fue ostensible. Conclusiones: se trata de la primera descripción de la técnica Dilep para el tratamiento quirúrgico de la hiperplasia benigna de próstata. Pensamos que los resultados conseguidos son prometedores y que podría suponer algunas ventajas frente a Holep. No obstante, se necesitan estudios prospectivos aleatorizados que confirmen esta opinión (AU)


Introduction: we present our preliminary experience and results of practising the prostate enucleation technique using a diode laser (DiLEP) and intravesical morcellation, following the same principles of holmium laser enucleation (HoLEP). Materials and method: we endoscopically treated benign prostate hyperplasia with DiLEP in 17 patients over a period of five months. They were all followed up for three months with flowmetry and IPSS. We have described the prostate enucleation and morcellation technique in detail, as well as the materials required to perform them. We have also commented on the lessons learned having practised on more than 300 cases with HoLEP, with a view to applying this new technology. Results: the mean age was 74.2 and the mean prostate volume was 61.26 (47-110) cc. The mean loss of haemoglobin was 2.1 (1.4-3.1) gr/dl. There were no major consequences or complications. All the patients were discharged from the hospital 24hours after the operation. The improvement in the IPSS (22.3±4.1 vs. 7.1±1.06) and in the Q max (7.14±2.6 vs. 21.4±3.6) was sustainable. Conclusions: It is the first description of the DiLEP technique for the surgical treatment of benign prostate hyperplasia. We believe the results obtained are promising and that they could signify some advantages as opposed to HoLEP. However, prospective randomized studies are required to confirm this opinion (AU)


Asunto(s)
Humanos , Masculino , Hiperplasia Prostática/cirugía , Terapia por Láser/métodos , Complicaciones Posoperatorias/epidemiología , Evaluación de Resultados de Intervenciones Terapéuticas , Láseres de Semiconductores/uso terapéutico
4.
Ann Oncol ; 22(1): 139-144, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20603439

RESUMEN

BACKGROUND: neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients. PATIENTS AND METHODS: we assessed BRCA1 messenger RNA expression levels in paraffin-embedded pre-treatment tumor samples obtained by transurethral resection from 57 patients with locally advanced bladder cancer subsequently treated with neoadjuvant cisplatin-based chemotherapy. BRCA1 levels were divided into terciles and correlated with pathological response and survival. RESULTS: a significant pathological response (pT0-1) was attained in 66% (24 of 39) of patients with low/intermediate BRCA1 levels compared with 22% (4 of 18) of patients with high BRCA1 levels (P = 0.01). Median survival was 168 months in patients with low/intermediate levels and 34 months in patients with high BRCA1 levels (P = 0.002). In the multivariate analysis for survival, only BRCA1 expression levels and lymphovascular invasion emerged as independent prognostic factors. CONCLUSIONS: our data suggest that BRCA1 expression may predict the efficacy of cisplatin-based neoadjuvant chemotherapy and may help to customize therapy in bladder cancer patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteína BRCA1/biosíntesis , ARN Mensajero/biosíntesis , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Adhesión en Parafina , ARN Mensajero/genética , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/cirugía , Vinblastina/administración & dosificación
5.
Actas urol. esp ; 34(8): 713-718, sept. 2010. tab
Artículo en Español | IBECS | ID: ibc-83351

RESUMEN

Objetivos: Evaluar la implantación de la enucleación con láser de holmio en nuestro centro incluyendo la curva de aprendizaje de un cirujano mediante el análisis de los pacientes tratados por este método. Material y métodos: Se analizaron 150 procedimientos de manera retrospectiva con un seguimiento medio de 11 meses. Se determinaron preoperatoriamente, así como a los 6 y a los 12 meses, los valores de Q max, IPSS y Qol realizando su análisis estadístico. El PSA fue medido preoperatoriamente, así como a los 3 meses de la cirugía. Se analizaron las complicaciones, así como el tiempo quirúrgico y el tiempo de ingreso hospitalario. Resultados: La edad media de los pacientes fue de 72,4 años. El tamaño prostático medio fue de 71,3g (18–150 g). Las horas medias de ingreso fueron 22. Los datos de Q max preoperatoria a los 6 y a los 12 meses fueron de 7,53, 23,24 y 21,62ml/s, siendo estadísticamente significativa (p<0,01). La tasa de transfusión fue del 1,3% y la de estenosis de la uretra del 4%. La mejoría del IPSS a los 6 y a los 12 meses también obtuvo significación estadística (p<0,01). Conclusiones: La enucleación con láser de holmio es una técnica segura y eficaz con una tasa de complicaciones inferior a la resección transuretral de próstata, incluso durante la curva de aprendizaje (AU)


Objectives: Evaluate the introduction of the enucleation with Holmium laser in our center, including the surgeon's learning curve by the analysis of the patients. Materials and methods: 150 procedures have been analyzed in a retrospective manner with an average follow-up of 11 months. Qmax, IPSS and Qol have been determined before surgery, at 6 months and 12 months, realizing their statistic analysis. PSA was measured before surgery and after 3 months. Complications, surgical time and hospital stay have been analyzed. Results: Average patient age was 72, 4 years. Average prostatic size was of 71,3gr (18–150). Average hospital stay was of 22h. Qmax before surgery, 6 months, 12 months was of 7,53ml/s, 23,24ml/s and 21,62ml/s being statistically significant (p<0,01). Transfusion rate was of 1,3% and urethral stenosis rate of 4%. IPSS improvement at 6 and 12 months was statistically significant as well (p<0, 01). Conclusions: Enucleation with Holmium laser is a safe and effective technique with lower complication rate than TURP, included during the learning curve (AU)


Asunto(s)
Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Láseres de Estado Sólido/uso terapéutico , Terapia por Láser/métodos , Estudios Retrospectivos , Antígeno Prostático Específico/análisis , /estadística & datos numéricos , Transfusión Sanguínea , Complicaciones Posoperatorias , Estrechez Uretral/etiología
6.
Actas Urol Esp ; 34(8): 713-8, 2010 Sep.
Artículo en Español | MEDLINE | ID: mdl-20800036

RESUMEN

OBJECTIVES: Evaluate the introduction of the enucleation with Holmium laser in our center, including the surgeon's learning curve by the analysis of the patients. MATERIALS AND METHODS: 150 procedures have been analyzed in a retrospective manner with an average follow-up of 11 months. Qmax, IPSS and Qol have been determined before surgery, at 6 months and 12 months, realizing their statistic analysis. PSA was measured before surgery and after 3 months. Complications, surgical time and hospital stay have been analyzed. RESULTS: Average patient age was 72, 4 years. Average prostatic size was of 71,3 gr (18-150). Average hospital stay was of 22 h. Qmax before surgery, 6 months, 12 months was of 7,53 ml/s, 23,24 ml/s and 21,62 ml/s being statistically significant (p<0,01). Transfusion rate was of 1,3% and urethral stenosis rate of 4%. IPSS improvement at 6 and 12 months was statistically significant as well (p<0, 01). CONCLUSIONS: Enucleation with Holmium laser is a safe and effective technique with lower complication rate than TURP, included during the learning curve.


Asunto(s)
Láseres de Estado Sólido/uso terapéutico , Prostatectomía/métodos , Anciano , Anciano de 80 o más Años , Hospitales , Humanos , Curva de Aprendizaje , Masculino , Persona de Mediana Edad , Prostatectomía/efectos adversos , Estudios Retrospectivos
10.
Rev Esp Oncol ; 31(3): 409-14, 1984.
Artículo en Español | MEDLINE | ID: mdl-6546169

RESUMEN

In order to know the behavior of the tissue polypeptide antigen (TPA) as a tumor marker, the authors determine its amount in serum by means of radioimmunoassay (TPA Prolifigen RIA) in 441 patients having respiratory, digestive, urogenital, hematopoietic, mammary and other malignant tumors. The obtained results indicate that: TPA has no tumor specificity; however it increases in tumors without any other known tumor marker. TPA has no diagnostic value, but it is useful for the following up of digestive, mammary, respiratory, ovarian and testicular cancer; amounts of TPA comprised between 90 and 120 U/l are not specific and have no clinical significance; and it is very useful the simultaneous determination of CEA and TPA in the respiratory, digestive and mammary malignant neoplasms to help the clinical data in the evaluation of tumor mass (CEA) and tumor activity (TPA) without indication of tumor localization.


Asunto(s)
Antígenos de Neoplasias/análisis , Neoplasias/inmunología , Péptidos/análisis , Adulto , Antígeno Carcinoembrionario/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Valores de Referencia , Antígeno Polipéptido de Tejido
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