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.

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.

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.

Even today, despite the surgery, radiotherapy, and chemotherapy, gliomas prognosis is still poor. There is a great need to develop new therapies. The understanding of the structural and functional characteristics of mitochondrial network (MN) and mitochondriaassociated membranes (MAM) in gliomas is essential for the design of future therapeutic strategies. A huge range of ultrastructural findings is observed in MN and MAM in the human gliomas. These findings imply that a majority of glioma cells are incompetent to produce an adequate amount of energy by means of oxidative phosphorylation and compensatory increases in glycolytic ATP production. Regarding MAM, a "MAM-rich" cell (well-differentiated glioma cells) and "MAM-deficient" cells (glioma like-stem cells) exist. The quantity of MAM could be linked to the functional or metabolic state of the different glioma cells. MAM-resident mTORC2 is a major regulator tumor growth and drug resistance. If sufficient nutrients are present, glioblastoma cells maintain mTORC2 signaling to drive cell proliferation and survival. Consequently, the replacement of fermentable fuels like glucose with non-fermentable fuels like ketone bodies becomes a logical approach. The vision must be targeting the cellular signaling pathways and metabolic reprogramming. Whatever the modality, a holistic and feasible approach must be developed.