Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “brain microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed2004

p75 neurotrophin receptor functions as a survival receptor in brain-metastatic melanoma cells.

The p75 neurotrophin receptor (p75(NTR)), a common receptor for members of the neurotrophins (NT) family, was previously identified as a molecular determinant of brain metastasis. We have also reported that NT treatment of murine and human brain-metastatic melanoma cells affects their invasive capacities and increases the production of heparanase, an important and unique extracellular matrix (ECM) degradative enzyme. Neurotrophism can be a survival-support mechanism for brain-metastatic cells and a survival assay was devised to mimic the growth limiting conditions of rapidly expanding metastatic tumors prior to neoangiogenesis. We report that p75(NTR) promoted the survival of brain-metastatic melanoma cells but not melanocytes in stress cultures conditions. Secondly, melanoma cells fluorescently sorted for high p75(NTR) expression (p75(NTR-H) cells) had an up to a 15-fold greater survival than those sorted for low p75(NTR) expression (p75(NTR-L) cells). Thirdly, cells overexpressing p75(NTR) associated with the growth fraction and provided these cells with an inherent growth advantage. Finally, we observed an increased survival of sorted p75(NTR-L) cells, dependent upon treatment of NT members whose functional receptors are present on these cells. Together, these results delineate that p75(NTR)-mediated trophic support profoundly affects competitive melanoma-cell survival when the tumor cell microenvironment becomes growth limiting.

Animals↗
PubMed2001

Perspectives on brain tumor formation involving macrophages, glia, and neural stem cells.

The incidence of brain tumors is rising in children and the elderly, but little is known about the mechanisms underlying brain tumor initiation and progression. In the 1940s, Zimmerman and coworkers exploited the tumor-promoting potential of polycyclic hydrocarbons to produce brain tumor models in adult mice that simulated the neuropathology of human brain tumors. Based on these early findings and on recent neurobiological studies of stem cells, I propose that crystalline carcinogenic pellets surgically implanted in the central nervous system establish over time a microenvironment that fosters proliferation and genetic damage in neural stem cells and their progenitors. Moreover, activated glia (microglia and astrocytes) and recruited macrophages mediate these processes. Gradually local tissue fields, which normally restrict stem cell proliferation, become disorganized, leading to further stem cell proliferation, genetic damage, and eventual neoplasia. Depending on age, location, and the state of glial/macrophage activation, the resulting brain tumor may resemble transformed neural progenitors aborted in more or less differentiated states. This hypothesis integrates the general mechanisms by which neural stem cells, glia, and macrophages orchestrate the initiation and progression of brain cancer. Also discussed are implications of these concepts for the diagnosis and therapy of human brain tumors.

Animals↗
PubMed2026

Accurately Deciphering Tissue Heterogeneity From Spatial Multi-Modal and Multi-Omics With STransformer.

Advances in spatially resolved technologies enable the simultaneous acquisition of diverse data modalities within a tissue slice while preserving critical spatial context, which presents unprecedented opportunities to decipher intricate tissue heterogeneity. However, existing computational approaches lack the intrinsic flexibility to universally process both spatial multi-modal and multi-omics data. Here, we introduce STransformer, a unified deep learning framework designed to seamlessly accommodate a comprehensive landscape of spatial data. By simultaneously capturing short-range cellular interactions and tissue-wide semantic patterns, it extracts robust representations to accurately dissect complex tissue heterogeneity. Systematic evaluations across diverse species, tissue types, and data modalities highlight its profound versatility. For spatial multi-modal data, STransformer delineates intricate anatomical structures in the human cortex, uncovers pathological mechanisms in Alzheimer's disease, and characterizes dynamic spatiotemporal developmental trajectories during chicken cardiogenesis. Scaling to spatial multi-omics data, STransformer synergizes spatial transcriptomic and proteomic profiles to decipher intricate immune microenvironments within the human tonsil, and jointly analyzes spatial epigenomic and transcriptomic data to infer regulatory mechanisms in the mouse embryonic brain. Consequently, STransformer serves as a highly versatile and robust analytical framework for advancing our understanding of tissue heterogeneity and disease pathogenesis.

Multiomics↗
PubMed2000

Intratracheal administration to the lung enhances therapeutic benefit of an MBP peptide in the treatment of murine experimental autoimmune encephalomyelitis.

The treatment of autoimmune diseases by targeted down-regulation of autoantigen-specific cells has been accomplished by the administration of high doses of autoantigen. We performed direct comparisons between injection of myelin basic protein peptide and administration by several nonparenteral routes to determine whether route impacted benefit in the treatment of murine allergic encephalomyelitis, a model for multiple sclerosis. The range of effective peptide doses spanned over 1000-fold, and route of delivery played a major role in determining optimal dose. The oral route of administration was the least effective, requiring at least 50- to 100-fold more antigen than subcutaneous injection, which in turn required at least 10-fold more antigen than delivery of peptide to the lung using an intratracheal instillation. Intratracheal delivery was also considerably more effective than inhalation of peptide, and, unlike inhalation, resulted in obvious penetration of delivered material deep into the lung. The increase in therapeutic efficacy did not appear to result from slower systemic delivery of antigen. Accumulation of peptide on antigen presenting cells in the spleen and in the brain was less efficient using the intratracheal route of administration compared to subcutaneous injection, implicating a special role for the lung microenvironment in the induction of immune nonresponsiveness.

Administration, Inhalation↗
PubMed2002

Secondary parathyroid hyperplasia in tuberous sclerosis: report of a case with large eosinophilic ganglion-like cells similar to those of subependymal giant cell astrocytoma, tubers, and atypical angiomyolipoma.

We report a case of secondary parathyroid hyperplasia in a 49-year-old man with tuberous sclerosis. Two parathyroid glands had collections of large, eosinophilic ganglion-like endocrine cells that to our knowledge have not been previously described at this site. These cells are morphologically similar to those of subependymal giant cell astrocytoma, tubers, and atypical angiomyolipoma, all of which may arise in the setting of tuberous sclerosis. These large, eosinophilic ganglion-like cells found in different affected organs appear to be distinctive of tuberous sclerosis. We suggest these large eosinophilic cells arise from a common stem cell precursor that acquires variable phenotypes according to alterations in the cellular microenvironment.

Angiomyolipoma↗
PubMed1991

Neuro-immune network. Basic structural and functional correlates.

The relationship among the nervous, endocrine and immune systems can be addressed in a number of ways. In this minireview, after introducing the immune microenvironment and outlining the principal domains of neuroimmune investigations, the preference was given to the influence of lesioning and stimulation of brain structures on immunological responsiveness; the relationship between micromagnetic fields, brain and immunity; the humoral and cell-mediated immunological features of certain neurological and psychiatric diseases; and the effect of stress on immune reactions. Described phenomena support the contention that there are numerous and continuous intercommunications between the nervous system and the immune system.

Animals↗
PubMed1982

Tumor-selective modification of cellular microenvironment in vivo: effect of glucose infusion on the pH in normal and malignant rat tissues.

The pH distributions in transplanted neural (TV1A, BT1A) and hepatic (HV1A3) tumors and in brain and kidney of BDIX rats were analyzed as a function of serum glucose concentration (SGC), tumor size, and tissue architecture. Tissue damage during pH measurements in vivo could be minimized by the use of pH microelectrodes with tip diameters of less than or equal to 10 micrometers. In normoglycemic rats, the pH in TV1A tumors was only slightly lower than in brain or kidney. However, at 6 hr after the induction of hyperglycemia by continuous i.v. infusion of glucose, the average pH in TV1A tumors had fallen to 6.7 at an SGC of 27 mM and to 6.1 at an SGC of 50 mM. A similar glucose-mediated pH reduction was observed in BT1A and HV1A3 tumors. No significant increase in tissue acidity occurred in brain and kidney. The pH in tumors had reached its minimum at 2 hr after the onset of high-dose glucose infusion (SGC, 50 mM) and could be maintained at this level in hyperglycemic rats for at least 48 hr. In hyperglycemic hosts, an increased retention of acidic metabolites in the tumor tissue with decreasing vascular density was reflected by a tumor size (age)-dependent pH reduction and a higher degree of intratumoral pH variation. In partially necrotic tumors, pH values as low as 5.2 were recorded. Oral administration of NaHCO3 to tumor-bearing rats had no effect on the average pH in TV1A tumors.

Animals↗
PubMed1991

Phosphatidylinositol 4,5-bisphosphate-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum terminal cisternal membranes. Ca2+ flux and single channel studies.

We report here that the inositol 1,4,5-trisphosphate (IP3) precursor, L-alpha-phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent molecule (1 microM) which activates the ryanodine-sensitive Ca2+ release channel from rabbit skeletal muscle terminal cisternae incorporated into a phospholipid bilayer. It also stimulates Ca2+ release from these membrane vesicles. Therefore, it may play a modulating role in excitation-contraction coupling. In the bilayer, PIP2 added on the cytoplasmic side increased the mean channel opening probability 2-12-fold in the presence and absence of physiological Mg2+ and ATP. From flux studies, PIP2-induced Ca2+ release, occurring through the ryanodine-sensitive Ca2+ release channel, displayed saturation kinetics. The rate of Ca2+ release induced by PIP2 was approximately greater than 50% slower than the rates induced by other agents (e.g. caffeine, Ca2+, ATP). PIP2, and not IP3, effectively elicited Ca2+ release from terminal cisternae. On the contrary, IP3, and not PIP2, specifically mediated Ca2+ release from dog brain cerebellum microsomes, where IP3 receptors are known to be found. The PIP2-induced Ca2+ release from muscle membranes was not dependent on medium [Ca2+] (from less than 10(-9) to approximately 10(-4) M). However, IP3 could activate the terminal cisternae Ca2+ channel in the bilayer when there was low Ca2+ (less than 10(-7) M). The data suggest that the ionic microenvironment around the Ca2+ channel may be different for observing the two phosphoinositide actions.

Animals↗
PubMed1993

Organ-specific metastases in immunodeficient mice injected with human melanoma cells: a quantitative pathological analysis.

Pathological and morphometric techniques were used to investigate the potential of two human melanoma cell lines for organ colonization in three different immunodeficient mouse strains; nude (nu/nu), NIH triple immunodeficient (TID: nu/nu, bg/bg, xid/xid) and severe combined immunodeficient (SCID) mice. The MM-RU cell line gave rise exclusively to lung metastases, whereas the MM-AN cell line gave rise to lung and extrapulmonary metastases. Although the TID mice showed more pancreatic and brown fat lesions than nude or SCID mice, the overall pattern of distribution of organ metastases among the strains was similar, suggesting that cellular properties intrinsic to the melanoma cells are important for the colonization of specific organs. The metastatic nodules were well circumscribed in all organs and exhibited peripherally located macrophages, except for brain metastases, where a more invasive pattern along vasculature was observed. The differences in cellular infiltrate and infiltrative patterns of the tumors implicate features of the host microenvironment (organ-specific factors) which are, at least in part, independent of the host's genetic background or degree of immunodeficiency. Our findings suggest that intrinsic malignant cellular properties play an important role in organ-specific colonization by haematogenously metastasizing cells.

Adipose Tissue, Brown↗
PubMed1999

Alterations in blood-brain barrier glucose transport in SIV-infected macaques.

The neurological manifestations of HIV infection may be in part due to alterations in the blood-brain barrier. These may be caused by structural changes in the barrier or may consist of subtle metabolic or biochemical disturbances in barrier function. In the CNS, the family of glucose transporter proteins plays a key role in controlling movement of glucose across cell membranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-brain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulates nonvascular glial glucose uptake. In this study, expression of 55 and 45 kDa forms of GLUT1 in different regions of the brain from 18 SIV-infected macaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is related to altered glucose metabolism at the BBB and in brain parenchyma. An inverse relationship was found between severity of SIV encephalitis and expression of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical grey matter, caudate nucleus, and cerebellum. A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In addition, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques with moderate to severe encephalitis, 55 kDa GLUT1 expression had declined to pre-infection levels. These GLUT1 alterations at the BBB and in glial cells may reflect severe disturbances in the CNS microenvironment that contribute to CNS dysfunction.

Animals↗
PubMed1995

Modulation of synaptic transmission at low temperatures by hibernation-related changes in ionic microenvironment in hippocampal slices of golden hamsters.

In hamsters, the entrance into hibernation is associated with a respiratory acidosis and elevation of the blood plasma concentrations of potassium, calcium, and magnesium. To investigate the effects of presumed hibernation-related ionic changes in the brain interstitium on neuronal function, the transmission properties of hippocampal slices prepared from golden hamsters were studied at low temperatures in vitro. Slices were investigated at 15-20 degrees C in artificial cerebrospinal fluid (ACSF) of variable composition (K+, 3-5 mM; Ca2+, 2-4 mM; Mg2+, 2-4 mM; pH 7.0-7.7). Population action potentials (population spikes, PS) of CA1 pyramidal cells were continuously evoked with 100-microseconds stimulus pulses delivered to the Schaffer collaterals/commissural fibers in intervals of 30 s. The PS amplitude was measured as a function of extracellular ion concentrations at given temperatures or as a function of temperature at a given ACSF composition. Elevation of [K+]o, [Mg2+]o, or [H+]o all reduced the PS amplitude at low temperatures, whereas elevation of [Ca2+]o increased the PS amplitude. In conclusion, changes in the ionic microenvironment occurring during entrance into hibernation presumably result in depression of synaptic transmission at low temperatures in the hamster hippocampus. The modulatory effect of ionic changes may be an important factor supporting a general depression of the brain during entrance into hibernation.

Animals↗
PubMed2001

Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques.

The proliferation marker Ki-67 labels cell nuclei in the G(1), S, M, and G(2) phases of the cell cycle. We used Ki-67 immunohistochemistry to quantify proliferating glial cells in brain tissue sections from twenty-four patients, comprised of multiple sclerosis, normal brains, and other neurological disease controls. Glial proliferation was greatly increased in MS lesions when compared with control brain white matter. Both actively demyelinating/early remyelinating plaques and chronic inactive plaques of long standing often displayed large numbers of glial cells in the proliferative cycle. The bulk of these proliferating cells were of oligodendroglial lineage in the MS plaques. Ki-67 positive macrophage/microglial lineage cells were largely restricted to acute lesions. The finding of increased numbers of proliferating oligodendroglia in most MS plaques, regardless of disease duration or activity state, indicates that the MS brain is capable of recruiting unexpectedly large numbers of new oligodendrocytes over long periods of time. The factors within the MS plaque microenvironment that provoke new oligodendrocyte generation and their subsequent loss still need to be identified.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2004

Hypoxia and hypoxia inducible factors (HIF) as important regulators of tumor physiology.

Regions of low oxygen tension are common findings in malignant tumors and are associated with increased frequency of tumor invasion and metastasis. Indeed, the ability to initiate homeostatic responses and adapt to hypoxia, e.g. by induction of angiogenesis, represents an important and crucial aspect in solid tumor growth. A significant advance in our understanding of the hypoxia response stems from the discovery of the hypoxia inducible factors (HIF) which act as key regulators of hypoxia-induced gene expression. Both, low levels of oxygen, apparently via reduced activity of a recently identified class of 2-oxoglutarate dependent oxygenases, and various tumor specific genetic alterations synergistically act to induce the HIF system. A widespread HIF activation can be observed in a variety of malignant tumors including brain tumors. The HIF system induces adaptive responses including angiogenesis, glycolysis, and pH regulation which confer increased resistance towards the hostile tumor microenvironment. Apart from protumorigenic the wide-ranging HIF pathway is known to harbor antitumorigenic components, which may, however, be disabled by tumor specific genetic alterations. Thus, mounting evidence has identified HIF as a crucial regulator of tumor growth and progression constituting an intriguing and novel target for therapeutic intervention.

DNA-Binding Proteins↗
PubMed1993

Evidence for nonsynaptic serotonergic and noradrenergic innervation of the rat dorsal horn and possible involvement of neuron-glia interactions.

We investigated the synaptic incidence of the contacts established by serotonergic and noradrenergic descending fibers in the dorsal horn of the rat spinal cord. Serial electron microscopic sections were performed. Synapses were scarce. The majority of serotonergic and noradrenergic varicosities (more than 60%) are characterized by nonsynaptic contacts. Numerous glial profiles, and particularly astrocytic profiles, were observed in apposition with serotonergic and noradrenergic varicosities. The proportion of astroglia was higher around serotonergic and noradrenergic varicosities devoid of synaptic specialization. The length of the contact between immunoreactive nonsynaptic varicosities and astrocytes was twice as long as that between synaptic varicosities and astrocytes. Thus, the modulation of sensitive messages by serotonin and noradrenaline through pauci-synaptic varicosities in the dorsal horn of the spinal cord could be an example of the concept of "volume transmission" [Fuxe and Agnati (1991) Volume Transmission in the Brain: Novel Mechanisms for Neural Transmission, Advances in Neuroscience, Vol. 1, pp. 1-9.] in the central nervous system. Analysis of the microenvironment of serotonergic and noradrenergic varicosities led us to make the hypothesis that glial cells, particularly astrocytes, could play some role in volume transmission.

Animals↗
PubMed2000

[Features of the development of homo- and heterotopic allotransplants of rat embryonal neocortex].

Mechanisms of regulation of cell division in the developing neocortex are largely unknown. The aim of the present study was to investigate the influence of a microenvironment on the fetal neocortex histogenesis. The fetal neocortex from 15-day old Wistar rat embryo was grafted into the neocortex, crushed sciatic nerve and anterior chamber of eye of adult rats. A comparative study of graft development was carried out on 1, 3, 7, 10, 30 days using histological (Nissl stain, hematoxylin-eosin) and immunohistochemical (monoclonal antibody to proliferating cell nuclear antigen, and to glial fibrillary acidic protein) methods. Grafted neuroepithelial cells proliferated in grafts that developed in the neocortex and the anterior chamber of eye for 7 days, and in the sciatic nerve for 10 days. In all grafts differentiating neuroblasts, young neurons and mature neurons were observed 7, 10 and 30 days later, respectively. In 10 days, transplants in the nerve have a glial capsule, in contrast to other sites of grafting. The capsule consists of ependymocytes with microvilli and cilia 30 days later. These cells are GFAP-positive. Our results indicate epigenetic influence on the development of neuroepithelial precursors. The microenvironment of the peripheral nerve is suggested to promote glyogenesis in developing grafts. Afferent inputs do not influence the proliferative potency of brain cell precursors.

Animals↗
PubMed1987

Differential localization of alkaline phosphatase in barrier tissues of the frog and rat nervous systems: a cytochemical and biochemical study.

We investigated the localization of alkaline phosphatase (AP) in the peripheral and central nervous systems of the frog (Rana pipiens) and rat. In the frog sciatic nerve, AP reaction product was seen as a precipitate within caveolae and vesicular profiles of perineurial cells, and frequently filled the extracellular space. In the rat peripheral nerve, AP reaction product appeared as small tufts on the cell surfaces and within vesicular profiles of endoneurial blood vessels. AP reaction product was not detected in the rat perineurium or in endoneurial blood vessels of the frog. In the frog central nervous system, AP reaction product was detected in the arachnoid membrane adjacent to the subarachnoid space, but not in the cerebral or pial vessels, whereas in the rat it was detected in the outer arachnoid membrane and in the cerebral and pial blood vessels. Biochemical analysis indicated a sevenfold higher AP activity in the frog perineurium over the endoneurium, whereas in the rat, threefold more activity was measured in the endoneurium over the perineurium. Levamisole, an AP inhibitor, decreased the enzyme activity by 95% in rat tissues, and by 70% in frog tissues and in plasma from both animals. Similar decrements were observed cytochemically. This study suggests that: (1) the distribution of AP varies between species, but that it is always present in at least one component of the blood-brain and blood-nerve barriers, (2) because barrier tissues of the nervous system have enzymatic activity, they may biochemically modify the adjacent environment, (3) vesicular profiles and caveolae in the blood vessels and perineurium may function as microenvironments for enzymatic activity, and (4) in the rat and frog, different isozymes of AP may be present.

Alkaline Phosphatase↗
PubMedDate not supplied

Neural stem cell biology may be well suited for improving brain tumor therapies.

Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel.

Brain Neoplasms↗
PubMed2006

Isolation and culture of microvascular endothelial cells from gliomas of different WHO grades.

Gliomas are the most common intrinsic brain tumors. The degree of vascularization corresponds to malignancy and is related to prognosis. In order to retrieve information about tumor behavior in situ, the use of primary tissue material for experiments is advantageous. With increasing evidence for the importance of microenvironment and vascularization in tumor biology, we concentrated on the isolation of endothelial cells (EC) from primary tumor material to investigate the role of endothelium within tumor tissue. We developed a method for isolation and purification of tumor-derived endothelial cells. EC were isolated and cultivated from normal brain using tissue digestion and Percoll density gradient centrifugation resulting in a <95% of EC culture. For isolation of EC from gliomas of different malignancy grades a combination of tissue digestion, Percoll gradient centrifugation and magnetic bead sorting by anti-CD31, -VE-Cadherin and -CD 105 was employed. This approach provided a purity of <98%. Cells were classified and characterized by testing expression of CD105, CD31, VE-Cadherin, vWF, UEA-1 and measuring DiI-Ac-LDL-uptake. To exclude contamination, staining and negative selection with anti-SMA, -GFAP, and -CD68 was performed. Tumors were histopathologically diagnosed according to WHO classification. We isolated EC from normal brain (NBEC, n = 11), low-grade gliomas WHO II (LGEC, n = 22), and high-grade gliomas WHO III & IV (HGEC, n = 11). There were no clear differences in EC morphology between the different tumor grades. However, a significantly higher proliferation rate of HGEC compared to LGEC was observed as well as distinctive antigen expression. Already in early passages isolated EC showed a rapid change in antigen expression indicating a phenotypic shift under culture conditions. We could establish a protocol for reliable and reproducible isolation and culture of EC from gliomas with different WHO grading. In first phenotypical and functional analyses, NBEC, LGEC and HGEC show remarkable differences. EC from all tumors could be grown in culture. However, passage related changes of EC phenotype demand very early passages to work with.

Brain Neoplasms↗