Ultrastructural characterization of the Mitochondria-associated membranes abnormalities in human astrocytomas: Functional and therapeutics implications.

Mitochondria-associated membranes (MAMs) are currently considered an intracellular organelle "hot spot" for the intracellular signaling. MAMs are thought to function in cellular energy homeostasis, apoptosis, and calcium signaling. MAM ultrastructure in surgical specimens from human astrocytic neoplasms was studied. Abnormalities in respect to density, length, and width were found. Poorly differentiated glioma like-stem cells deficient in MAM and well-differentiated glioma cells abundant in MAM were observed. This finding could be the structural basis of functional role of MAM linked to some metabolic abnormalities in astrocytic tumors associated to mitochondrial dysfunction and the Warburg effect and their therapeutics implications.

Ultrastructural characterization of macrophage-like mononuclear leukocytes in human astrocytic tumors.

The aim of this study was to describe the ultrastructural features of macrophage-like mononuclear leukocytes associated with human astrocytic tumors. Tumoral biopsies of 10 patients with a pathological diagnosis of astrocytic tumor by means of transmission electron microscopy were examined. The macrophage-like mononuclear leukocyte shows ultrastructural characteristics related with the physiologic phenotype of the alternatively activated macrophage (M2), localized principally around of tumoral vasculature and tumor milieu; classically activated macrophages (M1) in surrounding necrosis areas were observed. The presence of these two ultrastructural kinds of macrophage-like mononuclear leukocytes into different areas of the tumor denotes that cellular response of TAMs is dependent of microenvironment stimuli in different parts of a tumor. The process of transvascular emigration of monocyte/macrophage-like mononuclear leukocytes into tumor is presented. The preponderance of alternatively activated macrophage-like mononuclear leukocytes suggests disequilibrium between pro-tumoral leukocytes and anti-tumoral leukocytes. Therefore, macrophage polarization toward anti-tumoral macrophage-like mononuclear leukocytes would be a potential target for therapeutic manipulation in human astrocytic tumors.

Ultrastructural characterization of the new NG97ht human-derived glioma cell line using two different electron microscopy technical procedures.

On the basis of transmission electron microscopy observations in tumor cell lines, oncologists have made innumerous diagnostic and therapeutical progresses. Following this path, the UNICAMP immunopathologies laboratory established the NG97 cell line derived from a human astrocytoma grade III, which when injected to the athymic nude mouse flank developed a grade IV astrocytoma. In this study, we focused on ultrastructural characterization of the NG97 cells after being recovered from xenotransplant (NG97ht). These cells in culture were assayed by two different electron microscopy procedures to characterize ultrastructures related to grade IV astrocytomas and to observe their structures through cell subcultivation. Additionally, comparative morphological descriptions of different cell passages in these technical procedures could be a useful tool for improving electron microscopy cell lineage protocols. Results from many cell passage observations showed ultrastructural similarities, which suggest malignant and glioblastoma phenotypes. In the first procedure, NG97ht cells were harvested and then incorporated into agarose before subjecting them to electron microscopy protocols, whereas in the second one, monolayer cells grew first on cover slides. Comparison among protocols revealed that organelles, cytoplasmatic extensions, spatial conformation of filopodia, and cell attachment to substrate were more preserved in the second procedure. Furthermore, in this latter procedure, a unique ellipsoidal structure was observed, which was already described when dealing with gliosarcoma cell line elsewhere. Therefore, these analyses demonstrated a morphological characterization of a new NG97ht cell line using electron transmission microscopy. Moreover, it has been shown that the second procedure provides more detailed information compared with the first.

Ultrastructural mitochondrial pathology in human astrocytic tumors: potentials implications pro-therapeutics strategies.

This study was realized to illustrate and analyze the ultrastructural mitochondrial pathology in human astrocytic tumors. Tumoral biopsies of 10 patients with pathological diagnosis of astrocytic tumors by means of transmission electron microscopy were examined. Mitochondria exhibits heterogeneous morphology in all the cases. Mitochondrial swelling with partial or total cristolysis was the most constant alteration observed. Mitochondrial fusion-fission phenomena have been demonstrated. These findings suggest that the majority of astrocytoma cells are incompetent to produce adequate amount of energy by means of oxidative phosphorylation. Ultrastructural mitochondrial pathology indicates that possibly both glycolytic inhibition and inhibition or down-regulation of mitochondrial respiration would be a potential tool for future therapeutic strategies in cases of human astrocytic tumors.

Tumoral micro-blood vessels and vascular microenvironment in human astrocytic tumors. A transmission electron microscopy study.

The development of peritumoral edema is thought to be due to extravasation of plasma water and macromolecules through a defective blood-brain barrier (BBB), but the exact mechanism by which occurs is poorly understood. The aim of this study was analyze at submicroscopic level the morphological changes in both micro-blood vessels and vascular microenvironment of astrocytic tumors in an attempt of understanding the pathological aspects that may help in the future researches for the design of future therapeutic strategies. Biopsies of 25 patients with pathological diagnosis of astrocytic tumors were examined with the transmission electron microscope. Both open and close tight junctions were observed in the micro-blood vessels, inclusive in a same tumor. Cytoskeletal disorganization associated with disintegrated perijunctional actin filaments were seen. The paracellular space showed enlargement and commonly occupied by fluid proteinaceous, endothelial cells display oncotic and ischemic changes, basal lamina reveals enlargement, edema, vacuolization and collagen fibers disposed in irregular array. Pericytes exhibited edema and phagocytoced material, astrocytic perivascular-feet showed signs of oncosis and necrosis, co-option vessels totally surrounding by neoplastic cells also were seen. The ultrastructural abnormalities observed in both junctional complexes and vascular microenvironment suggest a multi-factorial pathobiology process, probably hypoxia intratumoral, calcium overload in endothelial cells, and degradative effects of metalloproteinases over the basal membrane appear as determinant factors that leading to structural modifications of junctional complexes, therefore, treatment with both HIF-1alpha and metalloproteinases inhibitors possibly can contribute with the pharmacological handling of the peritumoral edema associated with astrocytic tumors.

Glioma del nervio óptico

Se presenta un revisión clínico-patológica de 8 casos de gliomas del nervio y quiasma ópticos. Seis de los casos ocurrieron en niños y dos en adultos. En dos casos se presentó síndrome diencefálico, uno de ellos se demostró en la autopsia. Se presentan los hallazgos histopatológicos, ultraestructurales e inmunohistoquímicos, con especial atención a las fibras de Rosenthal y a la proteína ácida gliofibrilar. Se menciona la utilidad del empleo de la microscopía electrónica e inmunohistoquímica en el diagnóstico diferencial de estas neoplasias.

Diagnóstico de los tumores endocraneales: tomografía computada, resonancia nuclear magnética, anatomía patológica

Clasificación histológica de los tumores del sistema nervioso central, de acuerdo con la OMS. Nuevos criterios sobre tumores del sistema nervioso en niños. Descripción anatomopatológica de los tumores del sistema nervioso central. Ordenamiento de los tumores endocraneales por frecuencia e incidencia, de acuerdo a edad, sexo y localización. Consideraciones generales sobre el diagnóstico por imágenes de los tumores endocraneales. Estadística de los 765 tumores endocraneales estudiados por tomografía computada, resonancia nuclear magnética, cirugía y anatomía patológica. Descripción de las imágenes de los principales tumores del sistema nervioso central. Biopsia cerebral, guiada por tomografía computada

Diagnóstico de los tumores endocraneales: tomografía computada, resonancia nuclear magnética, anatomía patológica

Clasificación histológica de los tumores del sistema nervioso central, de acuerdo con la OMS. Nuevos criterios sobre tumores del sistema nervioso en niños. Descripción anatomopatológica de los tumores del sistema nervioso central. Ordenamiento de los tumores endocraneales por frecuencia e incidencia, de acuerdo a edad, sexo y localización. Consideraciones generales sobre el diagnóstico por imágenes de los tumores endocraneales. Estadística de los 765 tumores endocraneales estudiados por tomografía computada, resonancia nuclear magnética, cirugía y anatomía patológica. Descripción de las imágenes de los principales tumores del sistema nervioso central. Biopsia cerebral, guiada por tomografía computada

Ependymal astrocytoma: subependyoma or subependymal glomerate astrocytoma.

The histological study of four cases and one by electron microscopy of subependyomomas allowed us to obtain morphostructural characteristics of ependymocytes and astrocytes. Comparing these findings to those of the present day literature, we propose to name these tumours ependymal astrocytomas.