RESUMEN
Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients.
Asunto(s)
Antígenos de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/inmunología , Células Madre Neoplásicas/metabolismo , Acetilación , Anciano , Animales , Diferenciación Celular , Línea Celular Tumoral , Metilación de ADN , Epigénesis Genética , Femenino , Genes MHC Clase I , Histonas/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/inmunología , Regiones Promotoras GenéticasRESUMEN
RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape.
Asunto(s)
Antígenos de Neoplasias/biosíntesis , Glioma/patología , Linfocitos Infiltrantes de Tumor/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apoptosis , Niño , Femenino , Glioma/inmunología , Glioma/metabolismo , Humanos , Inmunohistoquímica/métodos , Inmunohistoquímica/estadística & datos numéricos , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Antígenos Comunes de Leucocito/análisis , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
BACKGROUND: The primary malignant dural lymphoma of B-cell type is rare. Our review of the literature (24 cases) indicated that patients with this tumor had female predominance, immunocompetency, and longer survival compared with those with primary malignant intracerebral lymphomas. Based on its clinicopathological features, this dural lymphoma may be classified differently from other types of malignant lymphomas in the central nervous system. CASE DESCRIPTION: The authors report an example of a patient who had a favorable course of malignant dural lymphoma. A 59-year-old woman presented with primary malignant dural lymphoma in the frontal area. Histological diagnosis was a diffuse large B-cell-type lymphoma of intermediate malignancy, but MIB-1 index was extremely high. Subtotal tumor removal was followed by 4 courses of chemotherapy. Thirty months after surgery, the patient is asymptomatic with no MRI evidence of recurrence. A combination of subtotal resection and chemotherapy for a primary malignant dural lymphoma is an effective means to attempt cure of this tumor. CONCLUSION: These rare tumors may be managed successfully by subtotal resection and postoperative treatment. We believe that chemotherapy is the treatment of choice after subtotal resection of malignant dural lymphomas, as experienced in our case.
Asunto(s)
Duramadre/patología , Linfoma de Células B/diagnóstico , Neoplasias Meníngeas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/patología , Craneotomía , Descompresión Quirúrgica , Duramadre/diagnóstico por imagen , Duramadre/cirugía , Espacio Epidural/diagnóstico por imagen , Espacio Epidural/patología , Espacio Epidural/cirugía , Femenino , Lóbulo Frontal/patología , Humanos , Linfocitos/patología , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/cirugía , Imagen por Resonancia Magnética , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/cirugía , Persona de Mediana Edad , Radiografía , Cintigrafía , Radioisótopos de Talio , Resultado del TratamientoRESUMEN
Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, (201)TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.
Asunto(s)
Absceso Encefálico/diagnóstico , Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Nocardiosis/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90% of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation.
Asunto(s)
Encéfalo/citología , Movimiento Celular/inmunología , Embrión de Mamíferos/citología , Microglía/citología , Células Madre/citología , Animales , Antígenos CD/biosíntesis , Antígenos de Superficie/biosíntesis , Encéfalo/inmunología , Encéfalo/metabolismo , Diferenciación Celular/inmunología , Línea Celular , Femenino , Proteínas Fluorescentes Verdes/biosíntesis , Proteínas Fluorescentes Verdes/genética , Antígenos de Histocompatibilidad Clase I/biosíntesis , Antígenos de Histocompatibilidad Clase II/biosíntesis , Inyecciones Intravenosas , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/trasplante , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microglía/inmunología , Microglía/trasplante , Trasplante de Células Madre , Células Madre/inmunologíaRESUMEN
This case report describes an 11-year-old boy with primitive neuroectodermal tumor (PNET), which remains the pediatric brain tumor with the worst prognosis despite combination treatment with surgery, irradiation and anti-cancer drugs. The boy was successfully treated with intratumoral administration of interferon-beta (IFN-beta) following surgical resection and irradiation. Two million units of IFN-beta were locally administered into the post-operative cavity through the Ommaya's reservoir every two weeks after discharge. He was managed as an outpatient without serious side-effects to IFN. The patient has shown no tumor recurrence, mental retardation, or neuroendocrine impairment for over three years and has lived a normal school life with a full Karnofsky Performance Status score. The local administration of IFN-beta may be warranted for maintenance therapy in children with PNET.