Epigenetic modulation of a miR-296-5p:HMGA1 axis regulates Sox2 expression and glioblastoma stem cells.

Solid malignancies contain subsets of multipotent cells that grow as spheres and efficiently propagate tumors in xenograft models, reflecting a stem-like, self-renewing and tumor-propagating phenotype. These cancer 'stem cells (SCs)' have been shown to maintain tumor growth, contribute to resistance and drive tumor recurrence. Cancer cell stemness is dynamically influenced by epigenetic mechanisms and differentially regulated coding and noncoding RNAs. How these mechanisms specifically contribute to the generation and/or maintenance of cancer SCs remains unclear. This study identifies a novel epigenetically regulated circuit that integrates microRNA, chromatin remodeling and the reprogramming transcription factor Sox2 to regulate glioblastoma (GBM)-propagating SCs. We show that miR-296-5p expression is repressed in a DNA methylation-dependent manner under conditions that promote GBM cell stemness and that miR-296-5p inhibits GBM cell stemness and their capacity to self-renew as spheres and propagate glioma xenografts in vivo. We show that the chromatin remodeling protein HMGA1 functions as a downstream effector of these biological responses to miR-296-5p and regulates Sox2 expression, a master driver of cell stemness, by modifying chromatin architecture at the Sox2 promoter. These results show for the first time that miR-296-5p inhibits transcriptional mechanisms that support GBM SCs and identify a miR-296-5p:HMGA1:Sox2 axis as a novel regulator of GBM SCs and candidate pathway for targeting therapies directed at depleting tumors of their tumor-propagating stem cell subsets.

DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2.

Cancer stem-like cells represent poorly differentiated multipotent tumor-propagating cells that contribute disproportionately to therapeutic resistance and tumor recurrence. Transcriptional mechanisms that control the phenotypic conversion of tumor cells lacking tumor-propagating potential to tumor-propagating stem-like cells remain obscure. Here we show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs (miRNAs). We show that one such downregulated miRNA, miRNA-148a, inhibits glioblastoma cell stem-like properties and tumor-propagating potential. This study identifies a novel and targetable molecular circuit by which glioma cell stemness and tumor-propagating capacity are regulated.

Use of self-expanding vascular endoprostheses in superior vena cava syndrome.

INTRODUCTION: Superior vena cava syndrome (SVCS) is associated to a malignant tumor in more than 90% of cases; being the lung cancer the most frequent (80%). SVCS has a benign cause in less than 5% of cases. Endovascular stenting has been proposed as the primary treatment of choice. We report our experience in SVC recanalization through the use of self-expanding vascular stents as treatment of life-threatening SVCS of benign and malignant etiology. MATERIALS AND METHODS: Between January 1994 and April 2002 44 patients with critical SVCS, were treated at the Hospital Italiano de Buenos Aires. Forty nine self-expanding endovascular metallic stents were percutaneously placed in the SVC. Thirty-one (70%) patients were male and 13 (30%) were female. The mean age was 55.6 years (range: 21-77). The etiology of SVCS was malignant in 40 cases and benign in 4. The malignant causes included lung cancer: 37 (37/44 - 92.5%), lymphoma: 1 (2.5%), chondrosarcoma 1 (2.5%), melanoma 1 (2.5%). The benign etiology corresponded to central catheters (N: 2) and post-radiation fibrosis (N: 2). Cavography showed complete occlusion of SVC in 12 cases (27%) and significant partial stenosis in 32 cases (73%). Thrombi associated with tumor stenosis were present in 25 (57%) patients. RESULTS: All procedures were technically successful. No stent migration was observed. Thirty-two patients with malignant tumor ultimately died due to the progression of the disease. Mean survival time was 193 days (range: 25-578). SVCS recurrence was observed on six occasions. In four patients a new stent was placed. Symptomatic improvement was dramatically seen within 24-48 h after stent placement in 40 patients (90.9%) and 83.3% out of the cases (38/44) were symptoms-free during the rest of the disease. Three patients died in the 7 following days. CONCLUSION: The use of self-expanding vascular endoprostheses in the recanalization treatment of SVC in SVCS due to a malignant or benign etiology offers excellent results with rapid and prolonged remission of symptoms.

Trombólisis y trombectomía endovascular selectiva en trombosis venosa profunda / Thrombolysis and selective endovascular thrombectomy in deep venous thrombosis

Se efectuó trombólisis y/o trombectomía selectiva en una serie de pacientes con trombosis axilosubclavia (n=13), trombosis en vena cava (n=10), trombosis en venas ileofemorales (n=15) y en venas braquiales o antebraquiales de los miembros superiores asociadas a fístulas de diálisis (n=43). Se realizó trombólisis intratrombótica por cateterismo utilizando Urokinasa (UK) 1000U/kg y/o tromboaspiración mecánica con abordaje percutáneo en la sala de angiografía continuando con infusión prolongada.El procedimiento fue técnicamente posible en todos los casos ...La trombólisis endovascular selectiva es una alternativa válida a tratamientos médicos o quirúrgicos clásicos.Realiazada con un equipo angiográfico adecuado y por un equipo médico experimentado en terapia endoluminal venosa, los resultados son muy satisfactorios y las complicaciones infrecuentes

Utilización de "stents" autoexpansibles en el síndrome de vena cava superior / Use of selfexpandable endoprosthesis in upper cava vein syndrome

Antecedentes: el SVCS responde a causas malignas en más del 90 por ciento de los casos. La conjunción de disnea y encefalopatía previene sobre un rápido curso ominoso. El tratamiento con quimio y/o radioterapia (a excepción de los linfomas) no suele tener éxito inmediato. La cirugía de derivación resulta difícil y sumamente riesgosa en pacientes con poca expectativa de supervivencia prolongada. Objetivos: demostrar la utilidad del empleo de endoprótesis auto expansibles para repermeabilizar la VCS. Lugar de aplicación: Centro Asistencial Universitario. Diseño: estudio observacional retrospectivo. Material y método: entre 1994 y 1999 fueron tratados 21 pacientes portadores de SVCS, con endoprótesis autoexpansibles. Hubo 15 hombres y 6 mujeres. La edad media fue 53 años (rango 26-70). La etiología fue benigna en 2 casos (trombosis por catéter) y maligna en 19. Once pacientes fueron tratados previamente con quimio y/o radioterapia. La colocación del "stent" se efectuó por punción percutánea vía femoral en 18 casos y por vena basílica en 3. Se utilizó un introductor 10 F valvulado y pre-dilatación con balón de angioplastía de 8-10 mm de diámetro. Los "stents" implantados fueron del tipo Wallstent Boston Scientific, cuyo diámetro osciló entre 10-16 mm. Quince pacientes efectuaron posteriormente tratamiento con quimio y/o radioterapia. Resultados: todos los procedimientos resultaron técnicamente exitosos, con desaparición de los síntomas dentro de las primeras 24-48 hs. Un paciente en el cual se demoró la indicación falleció después de la implantación del "stent" como consecuencia de insuficiencia respiratoria por neoplasia avanzada. La supervivencia media fue de 7 meses. Conclusiones: la utilización de endoprótesis para recanalización de la VCS ofrece excelentes resultados en manos de equipos experimentados con rápida remisión del cuadro clínico

Implantación de filtros en el sector suprarrenal de la vena cava / Percutaneous placement of suprarenal greenfield vena cava filters

Se presentan dos casos de implantación de filtros en el sector suprarrenal de la vena cava inferior. Este sitio de implantación es infrecuente. La principal indicación es la trombosis aguda de la vena cava extendida hasta el nivel de las venas renales. En ambos casos se implantaron filtros de Greenfield por abordaje percutáneo transyugular. La evolución postoperatoria fue favorable. El seguimiento de 9 y 19 meses respectivamente, demostró vena cava inferior permeable, ausencia de tromboembolismo pulmonar y función renal normal

Síndrome de Wyburn-Mason: imagenología en TC, RM y angiografía digital / Wyburn-Mason syndrome: CT, MR and digital angiography

Se describen los hallazgos de Tomografía Computada, Resonancia Magnética y Angiografía digital en un paciente portador de una rara entidad, conformada por una malformación arteriovenosa retino-encefálica unilateral (Síndrome Wyburn-Mason). La TC y RM mostraron claramente la topografía de la malformación vascular y su relación con el tejido cerebral, en particular el compromiso hipotalámico. La RM demostró en forma superior a la malformación vascular en toda su extensión intra y extracraneal. Es el único método que permite observar claramente la angioarquitectura de la lesión, elemento de fundamental importancia para establecer una eventual estrategia terapéutica

Macrodacriocistografía digital: imágenes digitales de las vías lagrimales / Digital sustraction of dacryocystography of the lachrymal tract

En un estudio prospectivo realizado entre marzo de 1992 y julio de 1994 se estudiaron ochenta pacientes que tuvieron como denominador común epífora. Se evaluó las bondades de un nuevo método para el estudio de las vías lagrimales que incorporó técnicas de computación permitiendo obtener imágenes digitales libres de elementos óseos (sustracción digital)

Ray representation of longitudinal lateral waves in acoustic microscopy.

For object materials having a large enough Rayleigh velocity, the V(z) (where V is the output voltage and z is the defocus distance) variation is mainly due to interference between the fields of the geometrically reflected wave and the leaky Rayleigh wave. However, for materials, such as organic compounds, having a low Rayleigh velocity, the leaky Rayleigh wave is not excited. For this case, the lateral wave resulting from propagation along the surface of the longitudinal wave plays a significant role in determining the V(z) dependence. The effect of the lateral wave contribution on V(z) is studied. Ray optics is to derive an expression giving the influence of the longitudinal lateral wave. Good agreement is found between the theory and measurements for z not near zero. Because of the ease with which the longitudinal wave velocity can be obtained from V(z), one can conveniently determine the elastic constant c(11 ) of isotropic materials using the acoustic microscope.

Birefringent prism couplers for thin-film optical waveguides.

The coupling from a laser to a thin-film optical waveguide by a prism coupler composed of a birefringent material can be strongly dependent on the orientation of the optic axis. It is shown that when the effective index of the wave guided by the film lies between the ordinary and extraordinary refractive indices of the prism, the coupling depends strongly on the orientation of the optic axis. Differences in orientation of only a few degrees separate ranges of orientation in which strong coupling occurs from ranges in which there is no coupling. The orientation dependence of the coupling is considered both for the pure mode case wherein the optic axis lies in the plane of incidence and for the case when the optic axis is rotated out of the plane of incidence, so that mode coupling occurs. When the effective refractive index of the guided wave is less than both the ordinary and extraordinary refractive indices of the prism, the coupling properties are found to be similar to those obtained with an isotropic prism.