RESUMEN
In malignant gliomas, invasive phenotype and cancer stemness promoting resurgence of residual tumor cells render treatment very difficult. Hence, identification of epithelial-mesenchymal transition (EMT) factors associated with invasion and stemness of glioma cells is critical. To address the issue, we investigated several EMT factors in hypermotile U87MG and U251 cells, orthotopic mouse glioma model, and human glioma samples. Of several EMT markers, SLUG expression was notably increased at the invasive fronts of gliomas, both in mouse tumor grafts and human glioma samples. The biological role played by SLUG was investigated using a colony-forming assay after chemotherapy and irradiation, and by employing a neurosphere culture assay. The effect of SLUG on glioma progression was examined in our patient cohort and samples, and compared to large public data from the REMBRANDT and TCGA. Genetic upregulation of SLUG was associated with increased levels of stemness factors and enhanced resistance to radiation and temozolomide. In our cohort, patients exhibiting lower-level SLUG expression evidenced longer progression-free survival (P = 0.042). Also, in the REMBRANDT dataset, a group in which SLUG was downregulated exhibited a significant survival benefit (P < 0.001). Although paired glioblastoma samples from our patients did not show a significant increase of SLUG expression, increased mRNA levels of SLUG were found in recurrent glioblastoma from TCGA (P = 0.052), and in temozolomide-treated glioma cells and mouse tumor grafts. SLUG may contribute to glioma progression by controlling invasion at infiltrating margins, associated with increased stemness and therapeutic resistance.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Glioma/metabolismo , Glioma/patología , Factores de Transcripción de la Familia Snail/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Movimiento Celular , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Humanos , Masculino , Ratones Endogámicos C57BL , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Factores de Transcripción de la Familia Snail/genética , Esferoides Celulares/patología , Análisis de SupervivenciaRESUMEN
A 53-year old man who had a left hemiparesis from head injury of traffic accident 20 years ago visited an emergency room with suddenly developed semi-comatose mental status. Brain CT showed 8.6-cm sized solid and cystic mass on right temporal lobe that was associated with hemorrhage. Solid lesion showed a strong enhancement after an administration of contrast media. Because of severe mass effect, emergency operation was performed. The mass was an intraparenchymal lesion with yellowish cystic fluid and the firm reddish-brown solid lesion was hemorrhagic. The lesion was totally resected. Pathologically, anaplastic solitary fibrous tumor/hemangiopericytoma was diagnosed with 70/10 high power fields. Postoperative radiotherapy of 50 Gy was done. Postoperative 2 months later, the patient was recovered to alert mental state. We report this unusual case of non-dural based intraparenchymal solitary fibrous tumor/hemangiopericytoma with high mitotic index and acute massive hemorrhage. Rapid tumor growth of hypervascular tumor might have a chance of bleeding.
RESUMEN
Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer's diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no ß-amyloid pathology.