RESUMEN
BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.
RESUMEN
Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.
Asunto(s)
Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Transducción de Señal , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Caspasa 9/genética , Caspasa 9/metabolismo , Muerte Celular/efectos de los fármacos , Cisteína/análogos & derivados , Cisteína/química , Cisteína/farmacología , Células Hep G2 , Humanos , Niacinamida/farmacología , Óxido Nítrico/química , Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , S-Nitrosotioles/química , S-Nitrosotioles/farmacología , SorafenibRESUMEN
Objetivo. Los defectos óseos mandibulares resultantes de infecciones,traumatismos o resecciones oncológicas, van a producir severos problemas funcionalesy/o estéticos, que van a precisar de un tratamiento complejo. Durante losúltimos años, las aportaciones al terreno de la reconstrucción ósea se han debatidoentre métodos tan dispares como la distracción ósea o la utilización de colgajos libresmicrovascularizados, pasando por un sin fin de biomateriales. El objetivo de este estudiofue comparar la formación de hueso nuevo tras la aplicación de una membranareabsorbible y dos tipos de sustitutivos óseos. Material y método. Se utilizaron 24ratas adultas macho tipo Wistar, en las que se crearon defectos circulares de 4 mmde diámetro en ambos lados de la mandíbula. Se formaron 4 grupos, un grupo controly 3 grupos experimentales. Los animales fueron sacrificados a las 3 y 6 semanasde la cirugía, realizándose un análisis radiológico e histológico. Resultados. Los defectoscontrol no mostraron formación ósea, apareciendo una reparación por tejidofibroso. La membrana de hueso utilizada de forma aislada, actuó como una barreraeficaz excluyendo los tejidos no osteogénicos, pero no se produjo reparación totaldel defecto en ningún caso. El grupo de Colloss® y membrana, mostró una regeneraciónósea completa del defecto a las 6 semanas. El grupo de NovaBone® y membrana,no mostró formación ósea, apareciendo las partículas del biomaterial ocupandoel defecto. Conclusiones. La regeneración ósea fue significativamente mayoren los defectos rellenos con Colloss® y cubiertos con la membrana de Lambone®,comparado con los otros grupos experimentales(AU)
Objective. Mandibular bone defects can occur as a resultof trauma, neoplasm, or infectious conditions. Such conditions oftenare associated with severe funtional and esthetic problems. Correctivetreatment often is complicated by limitations in tissue adaptation.The aim of this study was to compare new bone formation followingapplication of a bioabsorbable membrane and two types of bonesubstitutes. Material and method. In the present study, 24 fourmonth-old male Wistar rats were used. Standardized round throughand-through bone defects (4 mm in diameter) were made in bothmandibles and the rats were divided into four groups: one controlgroup and 3 experimental groups. Animals were killed 3 and 6 weeksafter surgery. Bone defect healing was assessed by radiologic andhistologic analysis. Results. The control defects showed no boneformation; holes were filled with fibrous connective tissue. Bonemembrane alone was an efficient barrier, excluding nonosteogenictissue. However, new bone formation underneath the membranewas incomplete. The Colloss® + membrane group showed completehealing after 6 weeks. The NovaBone® + membrane group showedno bone formation and particles appeared in the defect. Conclusions.The percentage bone regeneration was significantly better in thedefects filled with Colloss® and covered with Lambone® than theother experimental groups(AU)
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Animales , Ratas , Regeneración Tisular Dirigida/métodos , Materiales Biocompatibles/análisis , Traumatismos Mandibulares/cirugía , Experimentación Animal , Colgajos Quirúrgicos , Sustitutos de Huesos/uso terapéutico , Colágeno/uso terapéuticoAsunto(s)
Xantogranuloma Juvenil/diagnóstico , Femenino , Humanos , Lactante , Atención Primaria de SaludAsunto(s)
Tos/etiología , Disnea/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Macroglobulinemia de Waldenström/complicaciones , Tos/diagnóstico , Disnea/diagnóstico , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico por imagen , Leucemia Linfocítica Crónica de Células B/patología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Macroglobulinemia de Waldenström/diagnóstico por imagen , Macroglobulinemia de Waldenström/patologíaRESUMEN
No disponible
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Persona de Mediana Edad , Femenino , Humanos , Tomografía Computarizada por Rayos X , Leucemia Linfocítica Crónica de Células B , Disnea , Tos , Macroglobulinemia de WaldenströmRESUMEN
La intervellositis histiocítica crónica (TVHC) es una infrecuente lesión placentaria, de posible origen inmunológico. Se ha asociado con abortos de repetición y resultados adversos en el embarazo. Se caracteriza por la presencia de un abundante infiltrado inflamatorio en el espacio intervelloso, compuesto principalmente por monocitos y macrófagos. El diagnóstico diferencial incluye varias entidades, y por el momento no pueden descartarse causas infecciosas (AU)
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Adulto , Femenino , Humanos , Placenta/lesiones , Placenta/patología , Inmunohistoquímica/métodos , Complicaciones Parasitarias del Embarazo/diagnóstico , Aborto Habitual/diagnóstico , Aborto Habitual/patología , Vellosidades Coriónicas/anomalías , Vellosidades Coriónicas/fisiopatología , Infecciones/etiología , Infecciones/epidemiología , Enfermedades Placentarias/fisiopatología , Complicaciones del Embarazo/diagnóstico , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/terapia , Diagnóstico DiferencialRESUMEN
This prospective experimental study aimed to assess the regenerative capability of demineralised bone autografts resected and replaced orthotopically, compared with traditional fresh and deep frozen mandibular autografts in rats. In 60 adult Wistar rats, a bone defect 4 x 4 mm was created at the left ascending mandibular ramus and the removed bone was used as a fresh (n = 20), deep frozen (n = 20), or demineralised (n = 20) graft which was implanted orthotopically 2 weeks later. Ten rats in each group were killed at 2 and 6 weeks later. Outcome was measured by cellular proliferation on histological examination. The number of mesenchymal cells was significantly greater (P < 0.05) at both 2 and 6 weeks in the demineralised grafts than in the other two groups. There were no differences between the 2- and 6-week examinations of deep frozen bone, nor between the medullary and peripheral aspects. It was concluded that demineralised bony autografts cause greater osteoinduction both in the short (2 weeks) and the medium (6 weeks) term.
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Trasplante Óseo/métodos , Enfermedades Mandibulares/cirugía , Animales , Médula Ósea/patología , Regeneración Ósea , Trasplante Óseo/patología , División Celular , Criopreservación , Técnica de Descalcificación , Estudios de Seguimiento , Enfermedades Mandibulares/patología , Mesodermo/patología , Osteogénesis , Estudios Prospectivos , Ratas , Ratas Wistar , Conservación de Tejido , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Trousseau's syndrome includes a wide range of coagulation disorders, migratory thrombotic phenomena being the main associated entities. Treatment is difficult and venous gangrene constitutes a rare but deadly final stage that is particularly painful for the patient. The outlook after treatment is poor.
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Adenocarcinoma/complicaciones , Gangrena/etiología , Pierna/irrigación sanguínea , Neoplasias Pulmonares/complicaciones , Tromboflebitis/etiología , Humanos , Masculino , Persona de Mediana Edad , Flebografía , Síndrome , Tromboflebitis/diagnóstico por imagenRESUMEN
Two cases of multiple idiopathic ulcers of the small intestine are reported, which were found in two aged patients with a significant history of vascular pathology. Despite this, the pathological examination of the surgical specimens could not demonstrate a vascular origin of such lesions.