Single-agent obatoclax (GX15-070) potently induces apoptosis and pro-survival autophagy in head and neck squamous cell carcinoma cells.

ObjectivesMore than half of head and neck squamous cell carcinoma (HNSCC) patients are initially treated with curative intent, but will relapse over the course of their disease and have poor prognosis with a median survival of approximately 6months. Novel therapeutic approaches are in desperate need for this patient population. The anti-apoptotic BCL-2 family proteins such as BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a small-molecule antagonist of the BH3-binding groove of anti-apoptotic BCL-2 family. We evaluated the activity of obatoclax against 4 HNSCC cell lines (UMSCC-1, Cal33, 1483, UMSCC-22A).MethodsCell viability was determined by MTT assay, cell cycle status by propidium iodide staining, and apoptosis by Annexin-V staining and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting.ResultsAll four HNSCC cell lines were highly sensitive to single-agent obatoclax with IC50's ranging from 46 to 177nM. Obatoclax induced apoptosis in all four HNSCC cell lines as evidenced by increases in sub-G1 DNA content, Annexin-V staining, and PARP cleavage. In addition, obatoclax induced autophagy in all 4 cell lines, and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity.ConclusionOur findings demonstrate potent monotherapeutic activity of obatoclax against HNSCC cells, and enhancement of this activity in the presence of chloroquine. This preclinical study suggests that obatoclax might have therapeutic value in the treatment of HNSCC, either alone or in combination with inhibitors of autophagy

Single-agent obatoclax (GX15-070) potently induces apoptosis and pro-survival autophagy in head and neck squamous cell carcinoma cells.

ObjectivesMore than half of head and neck squamous cell carcinoma (HNSCC) patients are initially treated with curative intent, but will relapse over the course of their disease and have poor prognosis with a median survival of approximately 6months. Novel therapeutic approaches are in desperate need for this patient population. The anti-apoptotic BCL-2 family proteins such as BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a small-molecule antagonist of the BH3-binding groove of anti-apoptotic BCL-2 family. We evaluated the activity of obatoclax against 4 HNSCC cell lines (UMSCC-1, Cal33, 1483, UMSCC-22A).MethodsCell viability was determined by MTT assay, cell cycle status by propidium iodide staining, and apoptosis by Annexin-V staining and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting.ResultsAll four HNSCC cell lines were highly sensitive to single-agent obatoclax with IC50's ranging from 46 to 177nM. Obatoclax induced apoptosis in all four HNSCC cell lines as evidenced by increases in sub-G1 DNA content, Annexin-V staining, and PARP cleavage. In addition, obatoclax induced autophagy in all 4 cell lines, and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity.ConclusionOur findings demonstrate potent monotherapeutic activity of obatoclax against HNSCC cells, and enhancement of this activity in the presence of chloroquine. This preclinical study suggests that obatoclax might have therapeutic value in the treatment of HNSCC, either alone or in combination with inhibitors of autophagy

Ellis-van Creveld Syndrome: Mutations Uncovered in Lebanese Families

Background. Ellis-van Creveld (EvC) syndrome is a rare, autosomal recessive disorder characterized by short stature, short limbs, growth retardation, polydactyly, and ectodermal defects with cardiac anomalies occurring in around 60% of cases. EVC syndrome has been linked to mutations in EVC and EVC2 genes. Case Presentation. We report EvC syndrome in two unrelated Lebanese families both having homozygous mutations in the EVC2 gene, c.2653C>T (p.(Arg885*)) and c.2012_2015del (p.(Leu671*)) in exons 15 and 13, respectively, with the latter being reported for the first time. Conclusion. Although EvC has been largely described in the medical literature, clinical features of this syndrome vary. While more research is required to explore other genes involved in EvC, early diagnosis and therapeutic care are important to achieve a better quality of life

Propiedades Psicométricas del Inventario de Personalidad (PAI) en México

No obstante que el Inventario de Evaluación de la Personalidad (PAI) se ha convertido en una opción importante alrededor del mundo, se necesita una versión adaptada y válida de este instrumento psicológico para México. Este estudio presenta las propiedades psicométricas preliminares del PAI en México. Un total de 961 personas, de cuatro Ciudades Mexicanas (Aguascalientes, Distrito Federal, Mazatlán y Pachuca Hidalgo), contestaron la versión en “Español para México” del PAI, adaptado y reproducido mediante un permiso especial otorgado por la Editorial PAR. La media de edad fue 23,5 años con una D. E. de 9,63 años. Los procedimientos psicométricos estandarizados que se siguieron fueron: capacidad discriminativa de reactivos; confiabilidad por Alfa de Cronbach; Análisis Factorial exploratorio y finalmente Análisis Factorial Confirmatorio con AMOS. Basados en los resultados de AMOS de la muestra mexicana, se eliminaron 123 reactivos porque no tuvieron valores estadísticos que les permitiera ser incluidos en el modelo. Como resultado se obtuvo una versión recortada (adaptada y valida) del PAI con 221 reactivos. Concluimos que las traducciones transculturales del PAI deben ser revisadas cuidadosamente a la luz del Análisis Factorial Confirmatorio