RESUMEN
INTRODUCTION: Diffusion tensor magnetic resonance (MR) imaging (DTI) can be used to characterize the microstructures of ordered biological tissues. This study was designed to assess histological features of gliomas and surrounding brain tissues in rats using DTI. METHODS: Three types of tumors, a 9L gliosarcoma (n = 8), a F98 glioma (n = 5), and a human glioblastoma xenograft (GBM22; n = 8) were incubated in rat brains and underwent conventional MRI and DTI scanning using a 4.7-T animal MRI system. Fractional anisotropy (FA), isotropic apparent diffusion coefficient, parallel diffusivity (λ//), and perpendicular diffusivity (λâ¥), as well as histological features within several regions of interest were analyzed. RESULTS: All tumor masses consisted of low-FA central zones (tumor center) and high-FA peripheral regions (tumor rim). Histological examination revealed the existence of highly coherent tumor organizations (circular for 9L and F98 or radial for GBM22) in the tumor rims. There were higher apparent diffusion coefficient, λâ¥, and λ// in the peritumoral edema compared to the contralateral gray matter. There were significantly lower FA and higher λ⥠in the ipsilateral white matter than in the contralateral white matter for the GBM22 tumor, whereas there were no differences for the 9L and F98 tumors. Histologic examination showed GBM22 tumor infiltration into the ipsilateral damaged white matter. CONCLUSIONS: Quantitative analysis of DTI indices provides useful information for assessing tumor microstructure and tumor cell invasion into the adjacent gray matter and white matter.
Asunto(s)
Neoplasias Encefálicas/patología , Neoplasias Encefálicas/ultraestructura , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/patología , Glioma/ultraestructura , Animales , Anisotropía , Encéfalo/patología , Encéfalo/ultraestructura , Modelos Animales de Enfermedad , Glioblastoma/patología , Glioblastoma/ultraestructura , Gliosarcoma/patología , Gliosarcoma/ultraestructura , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Ratas , Células Tumorales CultivadasRESUMEN
We present an unusual case of gliosarcoma containing numerous islands of well-differentiated melanocytes in a 65 year-old man. Melanocytic differentiation of medulloblastomas is well described, and it has also rarely been reported in low-grade glial neoplasms. Histologic features and immunophenotyping are helpful in differentiating divergent differentiation in a gliosarcoma from melanoma. To our knowledge, this is the first description of a gliosarcoma with melanocytic differentiation. Awareness of the phenomenon of melanocytic differentiation within primary neuroepithelial and glial neoplasms is important to prevent the misdiagnosis of these tumors such as metastatic melanoma or primary melanocytic neoplasms of the CNS.
Asunto(s)
Neoplasias Encefálicas/ultraestructura , Gliosarcoma/ultraestructura , Melanocitos/ultraestructura , Anciano , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , Diagnóstico Diferencial , Gliosarcoma/metabolismo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Imagen por Resonancia Magnética , Masculino , Melanoma/patología , Microscopía Electrónica de TransmisiónRESUMEN
Amide proton transfer (APT) imaging is a variant of magnetization transfer (MT) imaging, in which the contrast is determined by a change in water intensity due to chemical exchange with saturated amide protons of endogenous mobile proteins and peptides. In this study, eight Fisher 344 rats implanted with 9L gliosarcoma cells and six nude rats implanted with human glioblastoma cells were imaged at 4.7 T. There were increased signal intensities in tumors in the APT-weighted images. The contrast of APT imaging between the tumor and contralateral brain tissue was about 3.9% in water intensity (1.49 +/- 0.66% vs -2.36 +/- 0.19%) for the more uniformly hypercellular 9L brain tumors, and it was reduced to 1.6% (-1.18 +/- 0.60% vs -2.77 +/- 0.42%) for the human glioblastoma xenografts that contained hypocellular zones of necrosis. The preliminary results show that the APT technique at the protein level may provide a unique MRI contrast for the characterization of brain tumors.
Asunto(s)
Amidas/química , Glioblastoma/química , Gliosarcoma/química , Espectroscopía de Resonancia Magnética/métodos , Protones , Animales , Agua Corporal/química , Encéfalo/citología , Encéfalo/patología , Neoplasias Encefálicas/química , Neoplasias Encefálicas/ultraestructura , Línea Celular Tumoral , Medios de Contraste , Imagen Eco-Planar/métodos , Interacciones de Partículas Elementales , Transferencia de Energía , Glioblastoma/ultraestructura , Gliosarcoma/ultraestructura , Humanos , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344 , Ratas Desnudas , Trasplante HeterólogoRESUMEN
Three cases of primary gliosarcoma (GS) were studied by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled fibrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillary acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII-related antigen was negative except for endothelial cells. One tumor exhibited alpha-smooth muscle actin positivity in the SC. Expression of MIB-1 and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB-1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle-shaped fibroblasts in the SC contained well-developed rough endoplasmic reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin-embedded tissue demonstrated single signals for chromosome 10 in 40.6-58.3% of cells and for chromosome 17 in 37.9-48.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/ultraestructura , Gliosarcoma/ultraestructura , Actinas/metabolismo , Adulto , Antígenos Nucleares , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 17/genética , Resultado Fatal , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosarcoma/genética , Gliosarcoma/metabolismo , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ/métodos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
Lipid-coated microbubbles (LCM) administered intravenously (i.v.) to rats bearing brain tumor, specifically enhance tumor visualization by ultrasound [1]. In order to understand the basis for this observation, we have examined the interactions of LCM with glioblastoma (C6) and gliosarcoma (9L) tumor cells in vivo and in vitro. LCM and LCM labeled with the fluorescent lipophilic dye 3,3'-dioctadecyloxacarbocyanine perchlorate (diO) were administered to rats bearing brain tumor. LCM and diO-labeled LCM were found principally at the tumor site with no evidence of label in the surrounding normal brain tissue. Analysis of the tumor by confocal laser scanning microscopy revealed that labeled LCM were inside the tumor cells. Similar analysis of LCM interactions with C6 and 9L cells in culture showed that LCM first adsorb at the surface of the cells, and with time became localized inside the cells. Binding and internalization proceeded faster at 37 degrees C than at room temperature (RT). Staining of live cells with N-(3-((2,4-dinitrophenyl)amino)propyl)-N-(3-aminopropyl) methylamine dihydrochloride (DAMP), a dye that recognizes acidic compartments, showed that the majority of internalized LCM was associated with compartments containing DAMP. If the same uptake mechanism were operative in vivo, it would indicate that a portion of LCM bypasses the reticuloendothelial system and become endocytosed directly by tumor cells.
Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/ultraestructura , Carbocianinas , Craneotomía , Dinitrobencenos , Endocitosis , Colorantes Fluorescentes , Glioma/metabolismo , Glioma/ultraestructura , Gliosarcoma/patología , Gliosarcoma/ultraestructura , Liposomas , Microscopía Confocal , Microscopía Fluorescente , Microesferas , Trasplante de Neoplasias , Orgánulos/ultraestructura , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Coloración y Etiquetado , Células Tumorales CultivadasRESUMEN
Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.