RESUMO

The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs' WT1-treated cells when compared with controls, resulting in a loss of the cell's viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.

RESUMO

Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966-76. ©2017 AACR.

Assuntos

RESUMO

Heterotopic salivary gland tissue is the presence of salivary tissue outside of the salivary glands. It is an uncommon condition but it can be the source of the full spectrum of salivary gland diseases. We present a rare case of pleomorphic adenoma developing from heterotopic salivary gland tissue in an upper neck lymph node not related to the major salivary glands. This article reviews the difficulty of the differential diagnosis with other cervical masses, embryogenesis, clinical manifestations and treatment of this condition.

La presencia de tejido salival fuera de las glándulas salivales se denomina heterotopía salival. Es poco frecuente, pero puede ser asiento de todo el espectro de patologías de las glándulas salivales. Se presenta un caso poco común de un adenoma pleomorfo en la región superior del cuello, desarrollado sobre una inclusión de tejido salival en un linfonodo, de manera independiente a las glándulas salivales. Se revisa la dificultad del diagnóstico diferencial dentro de las masas cervicales, su embriogénesis, manifestación clínica y tratamiento.

Assuntos

Assuntos

Assuntos

RESUMO

Introducción: el síndrome de apnea/hipopnea del sueño infantil se asocia a numerosos resultados adversos a nivel cognitivo y conductual. El factor de riesgo más comúnmente identificado para presentar síndrome de apnea/hipopnea del sueño es la hipertrofia adenoamigdaliana, para el cual el tratamiento primario es la adenoamigdalectomía. Objetivo: evaluar la eficacia de la adenoamigdalectomía temprana versus la conducta expectante, en lo que respecta a factores cognitivos, conductuales, calidad de vida y sueño, en niños con síndrome de apnea/hipopnea del sueño. Pacientes y método: se analiza críticamente el artículo de Marcus (2013), estudio multicéntrico, enmascarado simple, aleatorizado, controlado, en siete centros de estudio del sueño. Resultados: en un seguimiento a siete meses, la proporción de remisión espontánea en el grupo control de parámetros polisomnográficos sugiere que 46 por ciento de los niños revierten espontáneamente las alteraciones, efecto que se observó en 79 por ciento de los niños en el grupo intervenido. Conclusión de los revisores: la cirugía adenoamigdaliana para el tratamiento de la apnea obstructiva del sueño en escolares no mejora significativamente la atención o la función ejecutiva, pero sí mejora algunos desenlaces de comportamiento, calidad de vida y variables polisomnográficas. Sin embargo, esta mejoría se aprecia en una alta proporción de niños que no recibieron el tratamiento, mejoría principalmente evidenciada en las variables polisomnográficas. Por lo tanto, no sería un requisito indispensable el realizar esta cirugía para revertir dicho cuadro clínico.

Introduction. Obstructive sleep apnea hypopnea syndrome (OSAHS) in children is associated with numerous adverse cognitive and behavioral consequences. The most common risk factor identified for OSAHS is tonsillar enlargement, and primary treatment is adenotonsillectomy. Aim. To compare the efficacy of early adenotonsillectomy versus watchful waiting, on cognitive, behavioral, quality of life and sleep outcomes in children with OSAHS. Patients and Methods. We critically appraised the Marcus (2013) article, a multicenter, single masked, randomized, controlled study in seven sleep centers. Results. After a seven month follow-up, the rate of spontaneous remission in polysomnographic parameters control group shows that 46 percent of children spontaneously revert untoward outcomes, compared to 79 percent of children in the intervention group. Reviewer’s conclusion. Adenotonsillar surgery for the treatment of obstructive sleep apnea in school-age children does not significantly improve attention or executive function, but it does improve some behavioral outcomes, quality of life, and polysomnographic variables. However, this improvement was also observed in a high proportion of children who received no treatment, mainly regarding polysomnographic variables. Thus surgery does not appear to be necessary to reduce symptoms.

Assuntos

RESUMO

Introducción: el delirium es un síndrome neuropsiquiátrico común entre adultos mayores. Se asocia a mayor mortalidad, deterioro cognitivo y aumentos en costos en salud. Las intervenciones multicomponentes parecen ser eficaces en prevenir el delirium. Objetivo: evaluar la evidencia disponible respecto del uso de intervenciones multicomponentes para prevenir delirium entre adultos mayores hospitalizados. Metodología: se realizó una revisión de la literatura en cinco bases de datos, en búsqueda de revisiones sistemáticas que informaran la utilidad de las intervenciones multicomponentes para reducir el delirium incidente. Las revisiones fueron evaluadas en cuanto a su calidad sobre la base de los criterios de la Colaboración Cochrane. Resultados: se detectaron tres revisiones sistemáticas. La estrategia de búsqueda fue adecuada en todas, aunque dos de ellas incluyeron ensayos no aleatorizados en el análisis. Los programas evaluados fueron heterogéneos, por lo que no se realizó metaanálisis en ninguna de ellas. Sin embargo, fueron descritos resultados benéficos en todas ellas. Discusión: existe evidencia de moderada calidad que sugiere que las intervenciones multicomponentes son eficaces para reducir el delirium incidente. Es necesario realizar nuevas revisiones sistemáticas restringidas a ensayos aleatorizados para obtener una respuesta definitiva sobre su utilidad.

Introduction. Delirium is a common neuropsychiatric syndrome arising among elderly inpatients. It has been associated with increased mortality, cognitive decline and increased healthcare costs. Multicomponent interventions might be useful in preventing incident delirium. Objectives. To assess the available evidence regarding multicomponent interventions in preventing incident delirium among elderly inpatients. Methods. A literature review was conducted in 5 databases in search for systematic reviews evaluating multicomponent interventions in preventing incident delirium. Included reviews were assessed by using the criteria recommended by the Cochrane Collaboration. Results. Three systematic reviews were found. All described adequate searching methods, but two considered non-randomized designs for analyses. Important heterogeneity was seen among studies, precluding meta-analyses. However, beneficial effects were described regarding incident delirium prevention. Discussion. Moderate-quality evidence suggests that multicomponent interventions are useful in preventing delirium. New systematic reviews should restrict their methods to randomized trials in order to allow a definitive conclusion to be made.

Assuntos

RESUMO

PURPOSE: To study the role of survivin and its splice variants in taxane-resistant ovarian cancer. EXPERIMENTAL DESIGN: We assessed the mRNA levels of survivin splice variants in ovarian cancer cell lines and ovarian tumor samples. siRNAs targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA) in vitro and orthotopic murine models of ovarian cancer. The mechanism of cell death was studied in taxane-resistant ovarian cancer cells and in tumor sections obtained from different mouse tumors. RESULTS: Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared with -sensitive cells. Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B-siRNA incorporated into DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) nanoliposomes resulted in significant reduction in tumor growth (P < 0.05) in orthotopic murine models of ovarian cancer, and these effects were similar to T-siRNA-DOPC. The antitumor effects were further enhanced in combination with docetaxel chemotherapy (P < 0.01). Finally, we found a significant association between survivin 2B expression and progression-free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery. CONCLUSIONS: These data identify survivin 2B as an important target in ovarian cancer and provide a translational path forward for developing new therapies against this target.

Assuntos