UMLS:C0017636 - FACTA Search

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Query: UMLS:C0017636 (glioblastoma)
18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within tumours, many non-neoplastic cells such as fibroblasts, endothelial cells, and macrophages assist tumour growth by producing various growth factors and pro-angiogenic cytokines. Various tumour-derived molecules drive tumour-associated macrophages towards an anti-inflammatory phenotype (M2) and thus promoting tumour growth. Here we investigated microglia/macrophage differentiation in glioma tissues by means of immunostaining of paraffin-embedded glioma samples. The number of microglia/macrophages with positive staining for CD163 and CD204, which are believed to be markers for M2 macrophages, was correlated with the histological grade of the gliomas. The ratio of M2 macrophages in the tumour-associated microglia/macrophages was also associated with the histological grade. Culture supernatant from the glioma cell line can stimulate macrophages to develop into the M2 phenotype in vitro. Macrophage colony-stimulating factor (M-CSF), which strongly induces M2 polarization of macrophages, was significantly correlated with histological malignancy and with the proportion of M2 microglia/macrophages in vivo. In addition, the proportion of M2 microglia/macrophages and M-CSF expression in tumour cells correlated well with proliferation of glioblastoma cells. These results suggest that tumour-derived M-CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth. Evaluation of the proportion of M2 microglia/macrophages and M-CSF expression in tumour tissue would be useful for assessment of microglia/macrophage proliferative activity and the prognosis of patients with gliomas.
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PMID:Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. 1855 15

Crow-Fukase syndrome is diagnosed based on the presence of chronic sensori-motor polyneuropathy along with other characteristic generalized symptoms denoted by the acronym of POEMS which stands for polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. In this syndrome, the serum levels of the vascular endothelial growth factor (VEGF) are abnormally elevated, and this is a predictive factor for its diagnosis. Although the causes of CFS/POEMS remain unknown, VEGF is evidently correlated with its pathogenesis. Human glioblastoma cells are known to express VEGF. In models of CFS/POEMS, mice that are peritoneally transplanted with human glioblastomas exhibit high serum levels of VEGF, prominent edema with increased circulation volume, and pathological findings in the liver, spleen, and kidney. VEGF that is highly concentrated in platelets may be released in massive amounts due to coagulation in the peripheral tissue and may thus exert its maximal physiological effects and produce the abovementioned diffuse pathological findings. The correlation between polyneuropathy and elevated VEGF remains unclear. However, VEGF may affect the blood-nerve barrier by increased microvascular hyperpermeability, upregulated cytokines such as matrix metalloproteases may induce blood-nerve barrier breakdown and demyelination of the peripheral nerve. Furthermore, microangiopathy due to proliferative endothelial cells and hypercoagulated occlusion also affect axonal damage. Novel strategies that have recently been proposed for the management of this disease include high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) and molecular-targeted therapy against plasma cells and VEGF. Notably, PBSCT exerts a dramatic effect on polyneuropathy; such an effect has rarely been achieved by the previously described modalities of low-dose melphallan and steroid therapy. PBSCT is observed to induce a rapid and persistent decrease in the serum VEGF levels. In conclusion, VEGF is not only the primary molecule involved in the pathogenesis of CSF, but also an important marker for both the diagnosis and treatment of this disease.
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PMID:[Crow-Fukase syndrome and VEGF]. 1856 56

Methylnaltrexone (MNTX) was recently FDA approved to treat opiate induced constipation. It happens to also indirectly reduce Src activity. Src is a 54 kDa tyrosine kinase, crucial in signaling of, and link between, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). Glioblastomas use both EGF and VEGF signaling to enhance growth and neo-angiogenesis. Stem cell sub-fractions of glioblastomas are enriched for high VEGF synthesizing cells so this is a particularly valuable adjunctive target during cytotoxic treatment with drugs like temozolomide. MNTX does not cross the blood-brain barrier (BBB). Methamphetamine (MA) temporarily opens the BBB and therefore may allow methylnaltrexone entry into glioblastoma tissue. MA is FDA approved, marketed to treat attention problems in children. MA-MNTX combination should be tested as glioblastoma treatment adjunct. Temozolomide CSF levels are 10-20% of blood levels. Thus MA may also allow greater brain tissue temozolomide levels yet with lower systemic exposure.
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PMID:Use of FDA approved methamphetamine to allow adjunctive use of methylnaltrexone to mediate core anti-growth factor signaling effects in glioblastoma. 1932 19

It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.
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PMID:Clinical results of BNCT for malignant brain tumors in children. 1940 52

In vitro, high-resolution (1)H and (31)P NMR based qualitative and quantitative analyses of the lipid components of the tissue, serum, and CSF of patients with primary brain tumors were performed. Proton NMR spectra of the lipid extract of serum (blood specimen collected before the surgical procedure) and surgically discarded tissue showed that the total cholesterol (T.CHOL) and choline containing phospholipids (PL) were significantly higher in quantity in medulloblastoma and glioblastoma multiforme as compared to normal subjects. Serum lipid extracts of grade II/ III gliomas showed a higher quantity of PL than normal subjects. Cholesterol esters (CHOLest) were detectable in the tissue lipid extract of the patients with tumors and absent in normal tissue. There was a reduction in the quantity of CHOLest in the serum lipid extract of the tumor patients as compared to normal subjects. Ratio of PL to T.CHOL in serum lipid extract showed a significant difference between different grades of tumors versus normal subjects, while, a significant difference was observed only in medulloblastoma versus normal subjects in tissue lipid extract. Ratio of CHOL to CHOLest distinguishes the different grades of tumors versus normal subjects as well as between different grades of tumors (except medulloblastoma versus glioblastoma). The ratio of the Ph (total phospholipids except phosphatidylcholine) to PC (phosphatidylcholine) in (31)P NMR based study showed a significant difference in all grades of tumors (except medulloblastoma) in normal subjects in tissue lipid extract as well as between different grades of tumors. Medulloblastoma could be differentiated from glioblastoma as well as from normal subjects in serum lipid extract by the ratio of the Ph to PC. Proton NMR spectra of the lipid extract of CSF showed that the CHOL, CHOLest, and PL were present in the patients with tumors, although these were absent in the patients with meningitis, motor neuron disease, and mitochondrial myopathies as well as in normal subjects. PL and T.CHOL provided discrimination between different grades of tumors (except glioblastoma versus medulloblastoma) in the lipid extract of the CSF. This study suggests the role of lipid estimation in CSF and serum as a complementary diagnostic tool for the evaluation of brain tumors preoperatively. NMR-based lipid estimation of post-surgical tumor tissue may also contribute to differentiating the tumor types.
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PMID:In vitro, high-resolution 1H and 31P NMR based analysis of the lipid components in the tissue, serum, and CSF of the patients with primary brain tumors: one possible diagnostic view. 1977 96

Gliosarcoma is an uncommon variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation in the tumor. These tumors occur mostly in the cerebral hemispheres. Intraventricular location is extremely rare. Extensive review of literature revealed only two cases of intraventricular gliosarcoma. The first case arose by malignant transformation of a preexisting ependymoma. The second case was a gliosarcoma involving the frontal lobe with extension into the lateral ventricle. We report a case of an exclusively lateral ventricular tumor probably arising from the interventricular septum and blocking the CSF pathway. To the best of our knowledge, this is the first reported case of an exclusively intraventricular gliosarcoma.
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PMID:An unusual case of intraventricular gliosarcoma. 1978 54

Glioblastoma (GBM) pathologically is defined as an infiltrative glioma and salvage therapy with bevacizumab is believed to increase the incidence of diffuse and distant invasion as assessed radiographically. Eighty adult patients with glioblastoma were treated with surgery followed by radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). At first recurrence, 80 patients were treated with single agent bevacizumab. At time of progression, 57 patients were treated with bevacizumab and a cytotoxic chemotherapy, cytotoxic chemotherapy alone or on an investigational trial. Magnetic resonance imaging (MRI) were analyzed at four time points in each patient; at presentation, at first, second and third recurrence. Four patterns of radiographic disease were assessed, local (unifocal disease), distant (second lesion noncontiguous with primary lesion), multifocal (>2 lesions including leptomeningeal dissemination) and diffuse. At presentation 87.5% of glioblastoma were local, 6.25% distant, 3.75% multifocal and 2.5% diffuse. At first recurrence following progression on RT/TMZ and before initiation of bevacizumab, 80% were local, 7.5% distant, 6.25% multifocal (including 1 with CSF dissemination) and 6.25% diffuse. At second recurrence following progression on bevacizumab, 71.25% were local, 8.75% distant, 8.75% multifocal (2/7 with CSF dissemination) and 11.25% were diffuse. At third recurrence (57 patients evaluable), 71.25% were local, 7.0% distant, 7.0% multifocal and 14.0% were diffuse. Survival following progression on bevacizumab did not differ by pattern of radiographic recurrence. A majority of adult patients with GBM at diagnosis manifest MRI-defined local disease and maintain this pattern notwithstanding multiple recurrences and treatment with bevacizumab.
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PMID:Radiographic patterns of relapse in glioblastoma. 2105 76

A 65-year-old woman presented with progressive gait disturbance. She complained of appetite loss for 3 months. Her gait gradually became unsteady, and she was admitted to our hospital. On admission, slow mentation, bathyhypesthesia in left upper and both lower extremites, positive Romberg sign and wide-based gait were observed. Gd-enhanced MRI revealed mass lesions in the left temporal fossa and the cervical spinal canal with focal meningeal enhancement. Besides lesions in the central nervous system (CNS), systematic examination detected no additional malignancy. Repeated cytology of the cerebrospinal fluid was negative. After admission, her consciousness became reduced gradually. At 2 months after admission, she died of central respiratory failure. On autopsy, diffuse extension of the tumor cells was observed on the surface of CNS, and the mass lesions observed by MRI were extra-parenchymal On microscopic examination, the mass was consisted of GFAP positive malignant cells, and included perivascular pseudorosette, pseudopalisading necrosis and many mitotic cells. The diagnosis of the case was made as primary diffuse leptomeningeal gliomatosis (PDLG). PDLG is a rare disorder that is difficult to diagnose by CSF cytology. The progress of PDLG is rapid, and appropriate treatment is rarely taken. However, the combination of temozolomide and the radiotherapy performed for a glioblastoma has been reported as a possible treatment for PDLG. We emphasize that, in possible cases of PDLG, a biopsy should be performed in the early stages, especially in cases showing features similar to those of metastatic meningeal carcinomatosis and have no malignant tumors by whole body examination.
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PMID:[A case of primary diffuse leptomeningeal gliomatosis, clinically indistinguishable from metastatic meningeal carcinomatosis]. 2148 65

Glioblastoma multiforme is a deadly cancer for which current treatment options are limited. The ability of glioblastoma tumor cells to infiltrate the surrounding brain parenchyma critically limits the effectiveness of current treatments. We investigated how microglia, the resident macrophages of the brain, stimulate glioblastoma cell invasion. We first examined the ability of normal microglia from C57Bl/6J mice to stimulate GL261 glioblastoma cell invasion in vitro. We found that microglia stimulate the invasion of GL261 glioblastoma cells by approximately eightfold in an in vitro invasion assay. Pharmacological inhibition of epidermal growth factor receptor (EGFR) strongly inhibited microglia-stimulated invasion. Furthermore, blockade of colony stimulating factor 1 receptor (CSF-1R) signaling using ribonucleic acid (RNA) interference or pharmacological inhibitors completely inhibited microglial enhancement of glioblastoma invasion. GL261 cells were found to constitutively secrete CSF-1, the levels of which were unaffected by epidermal growth factor (EGF) stimulation, EGFR inhibition or coculture with microglia. CSF-1 only stimulated microglia invasion, whereas EGF only stimulated glioblastoma cell migration, demonstrating a synergistic interaction between these two cell types. Finally, using PLX3397 (a CSF-1R inhibitor that can cross the blood-brain barrier) in live animals, we discovered that blockade of CSF-1R signaling in vivo reduced the number of tumor-associated microglia and glioblastoma invasion. These data indicate that glioblastoma and microglia interactions mediated by EGF and CSF-1 can enhance glioblastoma invasion and demonstrate the possibility of inhibiting glioblastoma invasion by targeting glioblastoma-associated microglia via inhibition of the CSF-1R.
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PMID:Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. 2229 5

Gliomas attract brain-resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro-invasive cells. M-CSF (macrophage colony-stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM-CSF (granulocyte-macrophage colony-stimulating factor encoded by the CSF2 gene) but not M-CSF when compared to normal astrocytes. Knockdown of GM-CSF in GL261 glioma cells strongly reduced microglia-dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1(+) cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM-CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro-invasive activation in GM-CSF-depleted gliomas. Deficiency of M-CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1(+) cells, but impaired accumulation of Iba1(+) cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and in response to injury. The expression of CSF2 (but not CSF1) was highly up-regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM-CSF triggers and drives the alternative activation of tumour-infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas.
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PMID:Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response. 2352 16

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