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1. de Groot M, Iyer A, Zurolo E, Anink J, Heimans JJ, Boison D, Reijneveld JC, Aronica E: Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy. Epilepsia; 2012 Jan;53(1):58-66
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  • [Title] Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy.
  • We hypothesized that dysfunction in the metabolism of tumor astrocytes is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in patients with tumors.
  • METHODS: We compared ADK expression and cellular distribution in surgically removed tumor tissue (n = 45) and peritumoral cortex (n = 20) of patients with glial and glioneuronal tumors to normal control tissue obtained at autopsy (n = 11).
  • In addition, we compared ADK expression in tumor patients with and without epilepsy.
  • KEY FINDINGS: Immunohistochemistry predominantly showed cytoplasmic labeling in tumors and peritumoral tissue containing infiltrating tumor cells.
  • ADK immunoreactivity was significantly stronger in tumor and peritumoral tissue compared to normal white matter and normal cortex, especially in astrocytoma WHO grade III, as confirmed by Western blot analysis and ADK activity measurements.
  • SIGNIFICANCE: These results suggest a dysregulation of ADK in astrocytic brain tumors.
  • Moreover, the upregulation of ADK observed in peritumoral infiltrated tissue of glioma patients with epilepsy supports the role of this enzyme in tumor-associated epilepsy.

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  • [Copyright] Wiley Periodicals, Inc. ¬© 2011 International League Against Epilepsy.
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  • (PMID = 22092111.001).
  • [ISSN] 1528-1167
  • [Journal-full-title] Epilepsia
  • [ISO-abbreviation] Epilepsia
  • [Language] ENG
  • [Grant] United States / NINDS NIH HHS / NS / R01 NS065957; United States / NINDS NIH HHS / NS / R01 NS061844; United States / NINDS NIH HHS / NS / R01 NS061844-03; United States / NINDS NIH HHS / NS / R01 NS065957-02; United States / NINDS NIH HHS / NS / R01NS061844; United States / NINDS NIH HHS / NS / R01 NS061844-02
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] EC 2.7.1.20 / Adenosine Kinase
  • [Other-IDs] NLM/ NIHMS325774; NLM/ PMC3253237
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2. Engler JR, Robinson AE, Smirnov I, Hodgson JG, Berger MS, Gupta N, James CD, Molinaro A, Phillips JJ: Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas. PLoS One; 2012;7(8):e43339
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  • [Title] Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas.
  • Glioblastoma (GBM) is a highly malignant brain tumor with a dismal prognosis.
  • Gene expression profiling of GBM has revealed clinically relevant tumor subtypes, and this provides exciting opportunities to better understand disease pathogenesis.
  • Results from an increasing number of studies demonstrate a role for the immune response in cancer progression, yet it is unclear how the immune response differs across tumor subtypes and how it affects outcome.
  • Utilizing gene expression data from The Cancer Genome Atlas Project and the Gene Expression Omnibus database, we demonstrate an enrichment of immune response-related gene expression in the mesenchymal subtype of adult GBM (n = 173) and pediatric high-grade gliomas (n = 53).
  • Using novel immune cell-specific gene signatures we demonstrate selective enrichment of microglia/macrophage-related genes in adult and pediatric GBM tumors of the mesenchymal subtype.
  • Furthermore, immunostaining of adult GBM tumors showed significantly higher cell numbers of microglia/macrophages in mesenchymal versus non-mesenchymal tumors (p = 0.04).
  • Interestingly, adult GBM tumors with the shortest survival had significant enrichment of microglia/macrophage-related genes but this was not true for pediatric GBMs.
  • Consistent with an association with poor outcome, immune response-related genes were highly represented in an adult poor prognosis gene signature, with the expression of genes related to macrophage recruitment and activation being most strongly associated with survival (p<0.05) using CoxBoost multivariate modeling.
  • Using a microglia/macrophage high gene signature derived from quantification of tumor-infiltrating cells in adult GBM, we identified enrichment of genes characteristic of CD4 T cells, granulocytes, and microglia/macrophages (n = 573).

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  • (PMID = 22937035.001).
  • [ISSN] 1932-6203
  • [Journal-full-title] PloS one
  • [ISO-abbreviation] PLoS ONE
  • [Language] ENG
  • [Databank-accession-numbers] GEO/ GSE38330
  • [Grant] United States / NCI NIH HHS / CA / CA097257; United States / NINDS NIH HHS / NS / K08 NS063456
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC3425586
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3. Vassella E, Vajtai I, Bandi N, Arnold M, Kocher V, Mariani L: Primer extension based quantitative polymerase chain reaction reveals consistent differences in the methylation status of the MGMT promoter in diffusely infiltrating gliomas (WHO grade II-IV) of adults. J Neurooncol; 2011 Aug;104(1):293-303
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  • [Title] Primer extension based quantitative polymerase chain reaction reveals consistent differences in the methylation status of the MGMT promoter in diffusely infiltrating gliomas (WHO grade II-IV) of adults.
  • Diffusely infiltrating gliomas (WHO grade II-IV) are the most common primary brain tumours in adults.
  • In addition, we show that the degree of promoter methylation correlates with the prevalence of loss of heterozygosity on chromosome arm 1p in the oligodendroglioma group, but not the astrocytoma group.
  • [MeSH-minor] Adult. Chromosomes, Human, Pair 1. Chromosomes, Human, Pair 19. DNA Methylation. Female. Humans. Linear Models. Loss of Heterozygosity. Male. Middle Aged. Polymerase Chain Reaction / methods. Reproducibility of Results. Statistics as Topic

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  • (PMID = 21181234.001).
  • [ISSN] 1573-7373
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] EC 2.1.1.63 / O(6)-Methylguanine-DNA Methyltransferase
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4. Reyes-Botero G, Laigle-Donadey F, Mokhtari K, Martin-Duverneuil N, Delattre JY: Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults. J Neurooncol; 2014 Dec;120(3):581-6
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  • [Title] Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults.
  • Diffuse brainstem glioma is a rare disease in adults.
  • We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT.
  • Fifteen adult patients (median age 34¬†years) fulfilled the inclusion criteria.
  • Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case).
  • TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma.
  • [MeSH-minor] Adult. Aged. Brain Stem / drug effects. Brain Stem / pathology. Brain Stem / radiation effects. Combined Modality Therapy. Databases, Factual. Disease-Free Survival. Female. Humans. Magnetic Resonance Imaging. Male. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / pathology. Neoplasm Recurrence, Local / radiotherapy. Retrospective Studies. Treatment Outcome. Young Adult

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  • [ErratumIn] J Neurooncol. 2014 Dec;120(3):587
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  • (PMID = 25139026.001).
  • [ISSN] 1573-7373
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; YF1K15M17Y / temozolomide
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5. Orr BA, Bai H, Odia Y, Jain D, Anders RA, Eberhart CG: Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth. J Neuropathol Exp Neurol; 2011 Jul;70(7):568-77
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  • We used immunohistochemistry to evaluate nuclear YAP1 expression in the fetal and normal adult human brains and in 264 brain tumors.
  • YAP1 was expressed in fetal and adult brain regions known to harbor neural progenitor cells, but there was little YAP1 immunoreactivity in the adult cerebral cortex.
  • In gliomas, it was frequently expressed in infiltrating astrocytomas and oligodendrogliomas but rarely in pilocytic astrocytomas.
  • High levels of YAP1 messenger RNA expression were associated with aggressive molecular subsets of glioblastoma and with a nonsignificant trend toward reduced mean survival in human astrocytoma patients.

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  • (PMID = 21666501.001).
  • [ISSN] 1554-6578
  • [Journal-full-title] Journal of neuropathology and experimental neurology
  • [ISO-abbreviation] J. Neuropathol. Exp. Neurol.
  • [Language] ENG
  • [Grant] United States / NIDDK NIH HHS / DK / R01 DK081417-02; United States / NINDS NIH HHS / NS / R01 NS055089; United States / NINDS NIH HHS / NS / NS055089-04; United States / NINDS NIH HHS / NS / R01 NS055089-04; United States / NIDDK NIH HHS / DK / R01 DK081417
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / RNA, Messenger; EC 2.7.10.2 / Proto-Oncogene Proteins c-yes; EC 2.7.10.2 / YES1 protein, human
  • [Other-IDs] NLM/ NIHMS297419; NLM/ PMC3130608
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6. Piscione PJ, Bouffet E, Mabbott DJ, Shams I, Kulkarni AV: Physical functioning in pediatric survivors of childhood posterior fossa brain tumors. Neuro Oncol; 2014 Jan;16(1):147-55
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  • Cerebellar astrocytoma (43.3%) and medulloblastoma (40%) were the most common diagnoses.
  • Participants with a non-astrocytoma performed significantly lower than norms in all areas, independent of age at diagnosis.
  • Survivors with tumors infiltrating the vermis demonstrated significantly lower Body Coordination than norms (P < .001).
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Cross-Sectional Studies. Female. Follow-Up Studies. Humans. Infant. Male. Pediatrics. Prognosis. Prospective Studies. Quality of Life. Young Adult

  • MedlinePlus Health Information. consumer health - Brain Tumors.
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  • (PMID = 24305707.001).
  • [ISSN] 1523-5866
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC3870837
  • [Keywords] NOTNLM ; cancer survivor / disability / long-term outcome / pediatric / physical function / posterior fossa brain tumor
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7. Zhu M, Zheng J, Zhu Y, Wan H, Wu Y, Hong D: Diffuse leptomeningeal gliomatosis initially presenting with intraventricular hemorrhage: a case report and literature review. BMC Neurol; 2015;15:77
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  • [Title] Diffuse leptomeningeal gliomatosis initially presenting with intraventricular hemorrhage: a case report and literature review.
  • BACKGROUND: Primary diffuse leptomeningeal gliomatosis (PDLG) is a lethal neoplasm that is characterized by glioma cells exclusively infiltrating into cerebral and spinal meninges.
  • Cerebral CT and MRI showed diffuse patchy signals with enhancement in bilateral cerebellopontine angle cistern, suprasellar cistern, ambient cistern, quadrigeminal cistern, bilateral cerebellum, cerebral hemisphere, and upper cervical cord surface.
  • Immunohistochemistry showed that the cells were positive to glial fibrillary acidic protein (GFAP) with about 5% Ki-67 positive labeling.
  • The pathological findings were consistent with the diagnostic criteria of anaplastic astrocytoma (WHO grade III).
  • CONCLUSION: We reported an interesting case that PDLG initially presented with intraventricular hemorrhage that might be caused by astrocytoma rupturing into pial vessels.
  • [MeSH-minor] Adult. Astrocytoma / diagnosis. Astrocytoma / pathology. Brain / pathology. Glioma / diagnosis. Glioma / pathology. Humans. Magnetic Resonance Imaging. Male. Meninges / pathology. Spinal Cord / pathology

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  • (PMID = 25957575.001).
  • [ISSN] 1471-2377
  • [Journal-full-title] BMC neurology
  • [ISO-abbreviation] BMC Neurol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC4489354
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8. Saetta AA, Levidou G, El-Habr EA, Panayotidis I, Samaras V, Thymara I, Sakellariou S, Boviatsis E, Patsouris E, Korkolopoulou P: Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence, vascular endothelial growth factor, microvascular characteristics and clinical outcome. Virchows Arch; 2011 Jun;458(6):749-59
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  • Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters.
  • [MeSH-major] Astrocytoma / metabolism. Central Nervous System Neoplasms / metabolism. Extracellular Signal-Regulated MAP Kinases / metabolism. Isocitrate Dehydrogenase / metabolism. Neovascularization, Pathologic / metabolism. Proto-Oncogene Proteins c-akt / metabolism. Vascular Endothelial Growth Factor A / metabolism
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / metabolism. Cell Nucleus / metabolism. Cell Nucleus / pathology. Cytoplasm / metabolism. Cytoplasm / pathology. Female. Humans. Male. Middle Aged. Multivariate Analysis. Prognosis. Retrospective Studies. Survival Analysis

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  • (PMID = 21494763.001).
  • [ISSN] 1432-2307
  • [Journal-full-title] Virchows Archiv : an international journal of pathology
  • [ISO-abbreviation] Virchows Arch.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Vascular Endothelial Growth Factor A; EC 1.1.1.41 / Isocitrate Dehydrogenase; EC 1.1.1.42. / IDH1 protein, human; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt; EC 2.7.11.24 / Extracellular Signal-Regulated MAP Kinases
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9. Rao SA, Srinivasan S, Patric IR, Hegde AS, Chandramouli BA, Arimappamagan A, Santosh V, Kondaiah P, Rao MR, Somasundaram K: A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma. PLoS One; 2014;9(1):e85200
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  • [Title] A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.
  • Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas.
  • The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients.
  • Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples.
  • In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM) and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma.
  • Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively.
  • The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT) pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma.
  • In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.
  • [MeSH-major] Astrocytoma / genetics. Astrocytoma / pathology. Gene Expression Profiling. Glioblastoma / genetics. Glioblastoma / pathology. Transcriptome
  • [MeSH-minor] Adult. Aged. Biomarkers, Tumor. Cluster Analysis. Diagnosis, Differential. Gene Regulatory Networks. Humans. Middle Aged. Neoplasm Grading. Prognosis. Reproducibility of Results. Young Adult

  • Genetic Alliance. consumer health - Glioblastoma.
  • Genetic Alliance. consumer health - Anaplastic Astrocytoma.
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  • [CommentIn] Nat Rev Neurol. 2014 Mar;10(3):121 [24514869.001]
  • (PMID = 24475040.001).
  • [ISSN] 1932-6203
  • [Journal-full-title] PloS one
  • [ISO-abbreviation] PLoS ONE
  • [Language] eng
  • [Databank-accession-numbers] GEO/ GSE1993/ GSE4271/ GSE4422
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
  • [Other-IDs] NLM/ PMC3901657
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10. Walker C, Baborie A, Crooks D, Wilkins S, Jenkinson MD: Biology, genetics and imaging of glial cell tumours. Br J Radiol; 2011 Dec;84 Spec No 2:S90-106
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  • Recent research supports the molecular classification of gliomas based on genetic alterations or gene expression profiles, and imaging data supports the concept that molecular subtypes of glioma may be distinguished through non-invasive anatomical, physiological and metabolic imaging techniques, suggesting differences in the baseline biology of genetic subtypes of infiltrating glioma.
  • [MeSH-minor] Adult. Animals. Astrocytoma / diagnosis. Astrocytoma / genetics. Breast / pathology. Child. Gene Expression Profiling. Humans. Mice. Oligodendroglioma / diagnosis. Oligodendroglioma / genetics

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  • (PMID = 22433833.001).
  • [ISSN] 1748-880X
  • [Journal-full-title] The British journal of radiology
  • [ISO-abbreviation] Br J Radiol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC3473897
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