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Laigle-Donadey, F., et A. Duran-Peña. « Gliomi del tronco cerebrale dell’adulto ». EMC - Neurologia 19, no 2 (mai 2019) : 1–13. http://dx.doi.org/10.1016/s1634-7072(19)42022-9.
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Turazzi, S. « Principi di chirurgia dei gliomi ». Rivista di Neuroradiologia 16, no 1_suppl (mai 2003) : 181–82. http://dx.doi.org/10.1177/19714009030160s171.
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Darlix, A., V. Rigau et H. Duffau. « Neoformazioni intracraniche : gliomi di grado II ». EMC - Neurologia 20, no 4 (octobre 2020) : 1–14. http://dx.doi.org/10.1016/s1634-7072(20)44227-8.
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Roux, A., et J. Pallud. « Gravidanza e gliomi diffusi di basso grado ». EMC - Neurologia 18, no 1 (février 2018) : 1–8. http://dx.doi.org/10.1016/s1634-7072(17)87847-8.
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Bradač, G. B., A. Riva, S. Sales et G. Stura. « Chemioterapia arteriosa nel trattamento dei gliomi maligni ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 193–95. http://dx.doi.org/10.1177/19714009940070s139.
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Smaltino, F., R. Ruggiero, F. Fortunato, O. Catalano et A. Frusciante. « La radiochirurgia stereotassica dei gliomi ad alto grado ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 263–68. http://dx.doi.org/10.1177/19714009940070s151.
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Scerrati, M., P. Montemaggi, R. Roselli, M. Iacoangeli, A. Pompucci et G. F. Rossi. « La brachiterapia interstiziale nel trattamento dei gliomi cerebrali ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 275–76. http://dx.doi.org/10.1177/19714009940070s153.
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Piana, C., U. Pasquini, F. Menichelli, M. De Nicola, F. Bevilacqua et U. Salvolini. « Chemioterapia endoarteriosa con ACNU (Nimustin) nei gliomi cerebrali maligni ». Rivista di Neuroradiologia 5, no 4_suppl (novembre 1992) : 83–89. http://dx.doi.org/10.1177/19714009920050s410.
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Piana, C., U. Pasquini, F. Menichelli, M. De Nicola et F. Bevilacqua. « Chemioterapia endoarteriosa con ACNU (Nimustin) nei gliomi cerebrali maligni ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 189–91. http://dx.doi.org/10.1177/19714009940070s138.
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Ruggiero, G., A. Bacci et R. Ricci. « Identificazione della natura istologica deigliomi cerebrali con tomografia computerizzata ». Rivista di Neuroradiologia 2, no 3 (octobre 1989) : 267–71. http://dx.doi.org/10.1177/197140098900200308.
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Gli autori si propongono di verificare l'utilità rispettiva della biopsia e della radiologia per identificare il grado di malignità dei gliomi cerebrali. L'esame critico della letteratura dimostra che la biopsia effettuata su materiale chirurgico è più affidabile di quella sterotassica, ma che comunque essa non è esente da errori tecnici o diagnostici e da pericoli. La TC è utile e non inferiore, anzi non raramente superiore, alla RM. In una ricerca personale condotta su 123 casi verificati istologicamente, la TC, riesaminata dallo stesso neuroradiologo senza conoscenza della diagnosi, senza e con conoscenza della sintomatologia cliniCa, ha permesso l'identificazione precisa (gradi I-IV della scala di Kernohan) nel 42,8% e l'indicazione più generica di «benignità» (gradi I e II) e malignity (grado III e IV) nell'83%. Questi risultati sono stati ottenuti con esami eseguiti con vari tipi di apparecchi e miglioreranno sicuramente con l'utilizzo di macchine moderne e di una tecnica corretta: ricostruzione su tre piani, sezioni sottili; analisi densitometrica; proiezione extracranica38. Per conseguenza gli Autori propongono di eliminare la biopsia e classificare i gliomi cerebrali soltanto neuroradiologicamente (TC), in due tipi: Tipo B («benigno»), Tipo M (maligno).
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Piana, C., U. Pasquini, M. De Nicola, F. Menichelli, U. Salvolini, F. Rychlicki, F. Pauri et al. « Chemioterapia endo-arteriosa con ACNU (Nimustin) nei gliomi cerebrali maligni ». Rivista di Neuroradiologia 3, no 2 (juin 1990) : 153–63. http://dx.doi.org/10.1177/197140099000300202.
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Brada , G. B., A. Riva, R. Soffietti, G. Stura et D. Schiffer. « Chemioterapia arteriosa selettiva con BCNU nelle recidive dei gliomi maligni ». Neuroradiology Journal 5, no 1 (1 février 1992) : 107–13. http://dx.doi.org/10.1177/197140099200500113.
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Rudà, R., C. Mocellini, R. Soffietti, M. Lanotte, A. Riva, E. Vasario et D. Schiffer. « Trattamento delle recidive di gliomi maligni con radioterapia stereotassica : Risultati preliminari ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 279–80. http://dx.doi.org/10.1177/19714009940070s155.
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Munari, C., D. Hoffmann, P. P. Quarato, S. Francione, G. Lo Russo, S. Grand, E. MacCagnano, A. L. Benadid et B. Pasquier. « Biopsie seriate stereotassiche e correlazioni con TC ed RM nei gliomi a lento accrescimento ». Rivista di Neuroradiologia 7, no 1_suppl (mai 1994) : 75–82. http://dx.doi.org/10.1177/19714009940070s114.
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Colombo, F., A. Benedetti, P. Dettori, L. Bernardi, F. Pozza, C. Marchetti et G. Chierego. « Radiochirurgia con acceleratore lineare : 5 anni di esperienza clinica ». Rivista di Neuroradiologia 1, no 1 (avril 1988) : 17–35. http://dx.doi.org/10.1177/197140098800100104.
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Gli autori utilizzano una tecnica di radiochirurgia con acceleratore lineare dal 1982. La tecnica è basata su irradiazioni multiple ad archi intersecantisi focalizzate stereotassicamente su un bersaglio. Dopo che una valutazione meccanica e dosimetrica ha dimostrato la validità della procedura, la tecnica è stata impiegata su un gruppo selezionato di pazienti. Dal novembre 1982 al marzo 1988 sono stati trattati 155 casi. Tra loro 72 erano affetti da malformazioni arterovenose cerebrali, 16 da gliomi a bassa malignità, 8 da neurinoma dell'acustico, 8 da meningiomi e 11 da tumori maligni radiosensibili: in questi gruppi di pazienti la tecnica si è dimostrata sicura ed efficace. I risultati vengono paragonati a quelli ottenuti con la Gamma Unit di Leksell e col Ciclotrone di Kjellberg.
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Hewer, Ekkehard, Jaison Phour, Marielena Gutt-Will, Philippe Schucht, Matthias S. Dettmer et Erik Vassella. « TERT Promoter Mutation Analysis to Distinguish Glioma From Gliosis ». Journal of Neuropathology & ; Experimental Neurology 79, no 4 (29 janvier 2020) : 430–36. http://dx.doi.org/10.1093/jnen/nlaa004.
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Abstract Among the most challenging diagnostic issues in surgical neuropathology is the distinction between scant infiltration by diffuse gliomas and reactive gliosis. The best documented ancillary marker to establish a definitive diagnosis of glioma in this setting is the identification of hotspot mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes, which is limited, however, by the low prevalence of these mutations in gliomas of elderly adults. Since telomerase reverse transcriptase (TERT) promoter mutations are present in the vast majority of IDH-wildtype diffuse gliomas, we hypothesized that combined analysis of IDH and TERT might overcome these limitations. For this purpose, we analyzed a series of non-neoplastic and neoplastic CNS samples for the prevalence of TERT hotspot mutations. TERT mutations were identified in none out of 58 (0%) reactive gliosis samples, and in 91 out of 117 (78%) IDH-wildtype gliomas. Based on a series of 200 consecutive diffuse gliomas, we found that IDH mutation analysis alone had a sensitivity of 28% (63% and 12%, respectively, in patients below and above age of 50) for detection of gliomas, whereas a combined analysis of IDH and TERT was 85% sensitive (87% and 84%, respectively, below and above age of 50). In sum, our findings suggest that TERT promoter mutation analysis contributes favorably to a molecular panel in cases equivocal for glioma versus gliosis on morphological grounds, especially in patients above age of 50, in which IDH analysis alone performs poorly.
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Floris, R., G. L. Sergiacomi, E. Squillaci, D. Lupoi, M. Crecco, E. Fanucci, M. Guazzaroni et G. Simonetti. « Il ruolo della risonanza magnetica nella diagnosi delle neurofibromatosi ». Rivista di Neuroradiologia 5, no 1_suppl (avril 1992) : 101–4. http://dx.doi.org/10.1177/19714009920050s120.
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Gli autori prendono in considerazione il ruolo diagnostico della risonanza magnetica nella diagnostica delle neurofibromatosi, su una casistica di 13 osservazioni, di cui 9 casi di NF1 e 4 NF2. Lo studio è stato eseguito mediante sistemi RM superconduttivi da 0,5 e 1,5 Tesla, osservando un pattern di aspetti polimorfo comprendente nelle NF1 lesioni multiple insieme in T1 (6 casi), iperintense in T1 (2 casi), sempre iperintense in T2; inoltre si sono riscontrati gliomi delle vie ottiche (3 casi), xantogranulomatosi dei plessi corioidei e neurinomi multipli cervicodorsali. Nelle NF2 si sono invece reperiti schwannomi bilaterali dei nervi acustici (3 casi) e monolaterali (1 caso), meningiomi (4 casi), uno schwannoma del nervo facciale e neurofibromi spinali multipli (2 casi). Secondo la esperienza degli autori, la RM si è rivelata il metodo di scelta nella diagnostica e nel controllo dei pazienti con NF, grazie alla elevata accuratezza e sensibilità della metodica. I risultati ottenuti dimostrano l'elevata accuratezza della metodica e la sua preminenza nella diagnosi e nel controllo di tali forme neoplastiche.
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Ramina, Ricardo, Erasmo Barros Da Silva Júnior, Maurício Coelho Neto, Leonardo Gilmone Ruschel et Felipe Andrés Constanzo Navarrette. « 5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors ». JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA 27, no 1 (16 mars 2018) : 13–19. http://dx.doi.org/10.22290/jbnc.v27i1.783.
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Introduction: In the last two decades the 5-aminolevulinic acid (5-ALA) has been utilized in primary brain lesions and metastases surgery to aid the identification of tumor limits and infiltration. Objectives: In this retrospective study, we demonstrate our experience with the first 41 cases Latin America of surgical resection of central nervous system (CNS) lesions with 5-ALA. Methods: In 41 consecutive patients, we recorded age, sex, histopathological diagnosis, intraoperative 5-ALA fluorescence tumor response, 5-ALA post-resection resection grade through magnetic resonance image (MRI) and other concomitantintra-operative techniques utilized (transoperative imaging, awake surgery, electrophysiological stimulation and monitoring). Results: Twenty seven high-grade gliomas and 4 non-glial lesions were 5-ALA fluorescence positive; 6 low-grade gliomas, 1 high-grade glioma and a hippocampal gliosis were 5-ALA fluorescence negative. In one case of a low-grade glioma, the patient developed a cardiac arrhythmia, probably not related to 5-ALA administration, but the surgery was suspended. Conclusions: 5-ALA fluorescence-guided surgery is a safe and easy technique to be used, increasing tumor total gross resection in glioma cases, proving to be an invaluable neurosurgical tool for intracranial tumor surgery. There was no serious side effect in this series. This dye should be utilized in all cases of high-grade gliomas.
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Piovan, E., A. Beltramello, M. C. Spiller, A. Benati, A. Maschio, S. Perini et L. Rosta. « Tumori della regione pineale. È possibile una distinzione sulla base dell'iconografia ? » Rivista di Neuroradiologia 2, no 1 (février 1989) : 43–53. http://dx.doi.org/10.1177/197140098900200105.
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Gli autori prendono in considerazione il valore degli esami neuroradiologici nella diagnosi delle lesioni espansive della regione pineale. I dati riportati in letteratura vengono confrontati con l'esperienza personale (15 casi) per trarre possibili considerazioni significative per la diagnosi di oncotipo. La prima distinzione va fatta tra le lesioni intrinseche della pineale e quelle delle strutture ad essa circostanti. Inquadrando il caso con considerazioni sul sesso del paziente, la sua età, la frequenza relativa dei vari istotipi tumorali e i segni neuroradiologici rilevati con TC e RM, è possibile operare una ulteriore distinzione: — i gliomi della pineale e i pineocitomi sono molto simili tra loro. La loro origine dalle cellule pineali intrinseche (rispettivamente dagli astrociti e dai pineociti) è testimoniata dalla loro tendenza allo sviluppo di cisti e calcificazioni, reperti molto comuni nella ghiandola pineale normale. — I teratomi e i germinomi sono lesioni che prediligono i giovani maschi. I teratomi sono tumori solidi con componenti calcifiche e grassose, mentre il grasso non è presente nei germinomi che invece sono caratterizzati da un frequente coinvolgimento ependimario e soprasellare. In ogni caso, data la grande varietà di lesioni neoplastiche della regione pineale, una diagnosi differenziale affidabile è possibile solo quando la lesione sia di piccole dimensioni e la sua localizzazione anatomica possa essere precisata con ragionevole sicurezza.
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Xia, He-chun, Zhan-feng Niu, Hui Ma, Shuan-zhu Cao, Shao-cai Hao, Zhong-tao Liu et Fan Wang. « Deregulated Expression of the Per1 and Per2 in Human Gliomas ». Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 37, no 3 (mai 2010) : 365–70. http://dx.doi.org/10.1017/s031716710001026x.
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Background:Growing evidence shows that the deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored.Methods:Using reverse transcription polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, Per1 and Per2, in 33 gliomas.Results:In this study, out of 33 gliomas, 28 were Per1-positive, and 23 were Per2-positive. The expression levels of Per1 and Per2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of Per1 and Per2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was insignificant (P>0.05). While there was no difference in the intensity of immunoactivity for Per2 between high-grade gliomas and low-grade gliomas (r=-0.330, P=0.061), the expression level of Per1 in highgrade gliomas was significantly lower than that in low-grade gliomas(r=-0.433, P=0.012).Conclusions:In this study, we found that the expression of Per1 and Per2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in Per1 and Per2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.
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Kim, Junhyung, Min Woo Park, Young Joon Park, Ju Won Ahn, Jeong Min Sim, Suwan Kim, Jinhyung Heo et al. « miR-542-3p Contributes to the HK2-Mediated High Glycolytic Phenotype in Human Glioma Cells ». Genes 12, no 5 (23 avril 2021) : 633. http://dx.doi.org/10.3390/genes12050633.
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(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.
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Kim, Junhyung, Min Woo Park, Ju Won Ahn, Jeong Min Sim, Suwan Kim, Young Joon Park, Jinhyung Heo et al. « TAMI-47. MIR-542-3P CONTRIBUTES TO THE HK2-MEDIATED HIGH GLYCOLYTIC PHENOTYPE IN HUMAN GLIOMA CELLS ». Neuro-Oncology 23, Supplement_6 (2 novembre 2021) : vi208. http://dx.doi.org/10.1093/neuonc/noab196.830.
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Abstract BACKGROUND The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear. METHODS We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis. RESULTS We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database. CONCLUSIONS miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.
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Comba, Andrea, Patrick J. Dunn, Anna E. Argento, Padma Kadiyala, Maria Ventosa, Priti Patel, Daniel B. Zamler et al. « Fyn tyrosine kinase, a downstream target of receptor tyrosine kinases, modulates antiglioma immune responses ». Neuro-Oncology 22, no 6 (17 janvier 2020) : 806–18. http://dx.doi.org/10.1093/neuonc/noaa006.
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Abstract Background High-grade gliomas are aggressive and immunosuppressive brain tumors. Molecular mechanisms that regulate the inhibitory immune tumor microenvironment (TME) and glioma progression remain poorly understood. Fyn tyrosine kinase is a downstream target of the oncogenic receptor tyrosine kinase pathway and is overexpressed in human gliomas. Fyn’s role in vivo in glioma growth remains unknown. We investigated whether Fyn regulates glioma initiation, growth and invasion. Methods We evaluated the role of Fyn using genetically engineered mouse glioma models (GEMMs). We also generated Fyn knockdown stem cells to induce gliomas in immune-competent and immune-deficient mice (nonobese diabetic severe combined immunodeficient gamma mice [NSG], CD8−/−, CD4−/−). We analyzed molecular mechanism by RNA sequencing and bioinformatics analysis. Flow cytometry was used to characterize immune cellular infiltrates in the Fyn knockdown glioma TME. Results We demonstrate that Fyn knockdown in diverse immune-competent GEMMs of glioma reduced tumor progression and significantly increased survival. Gene ontology (GO) analysis of differentially expressed genes in wild-type versus Fyn knockdown gliomas showed enrichment of GOs related to immune reactivity. However, in NSG and CD8−/− and CD4−/− immune-deficient mice, Fyn knockdown gliomas failed to show differences in survival. These data suggest that the expression of Fyn in glioma cells reduces antiglioma immune activation. Examination of glioma immune infiltrates by flow cytometry displayed reduction in the amount and activity of immune suppressive myeloid derived cells in the Fyn glioma TME. Conclusions Gliomas employ Fyn mediated mechanisms to enhance immune suppression and promote tumor progression. We propose that Fyn inhibition within glioma cells could improve the efficacy of antiglioma immunotherapies.
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Rivera-Zengotita, Marie, et Anthony T. Yachnis. « Gliosis Versus Glioma ? » Advances In Anatomic Pathology 19, no 4 (juillet 2012) : 239–49. http://dx.doi.org/10.1097/pap.0b013e31825c6a04.
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Gisina, Alisa, Irina Kholodenko, Yan Kim, Maxim Abakumov, Alexey Lupatov et Konstantin Yarygin. « Glioma Stem Cells : Novel Data Obtained by Single-Cell Sequencing ». International Journal of Molecular Sciences 23, no 22 (17 novembre 2022) : 14224. http://dx.doi.org/10.3390/ijms232214224.
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Glioma is the most common type of primary CNS tumor, composed of cells that resemble normal glial cells. Recent genetic studies have provided insight into the inter-tumoral heterogeneity of gliomas, resulting in the updated 2021 WHO classification of gliomas. Thorough understanding of inter-tumoral heterogeneity has already improved the prognosis and treatment outcomes of some types of gliomas. Currently, the challenge for researchers is to study the intratumoral cell heterogeneity of newly defined glioma subtypes. Cancer stem cells (CSCs) present in gliomas and many other tumors are an example of intratumoral heterogeneity of great importance. In this review, we discuss the modern concept of glioma stem cells and recent single-cell sequencing-driven progress in the research of intratumoral glioma cell heterogeneity. The particular emphasis was placed on the recently revealed variations of the cell composition of the subtypes of the adult-type diffuse gliomas, including astrocytoma, oligodendroglioma and glioblastoma. The novel data explain the inconsistencies in earlier glioma stem cell research and also provide insight into the development of more effective targeted therapy and the cell-based immunotherapy of gliomas. Separate sections are devoted to the description of single-cell sequencing approach and its role in the development of cell-based immunotherapies for glioma.
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Amin, Samirkumar, Kevin Anderson, Beth Bourdreau, Emmanuel Martínez, Emre Kocakavuk, Kevin C. Johnson, Floris Barthel et al. « GENE-57. COMPARATIVE MOLECULAR LIFE HISTORY OF SPONTANEOUS CANINE AND HUMAN GLIOMA ». Neuro-Oncology 21, Supplement_6 (novembre 2019) : vi110. http://dx.doi.org/10.1093/neuonc/noz175.459.
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Abstract Diffuse gliomas are the commonest of malignant brain tumors with high-grade tumors carrying dismal prognosis. Preclinical models have proven themselves as poor predictors of clinical efficacy, attributed to the lack of a comparable tumor microenvironment. Comparative genomics of canine and human gliomas provide an attractive alternative modality to identify conserved drivers and underlying mutational processes of glioma as well as evaluate life history tradeoffs related to tissue context and aging that can shape type and relative timing of drivers in gliomagenesis. We performed a comparative genomics analysis between whole genome-, exome-, transcriptome- and methylation-sequencing of 77 canine gliomas, and human pediatric (n=217) and adult gliomas (n=822). We found alterations in common with those in human pediatric and adult gliomas in the Tp53 and cell cycle pathways, receptor tyrosine kinase and Idh1 R132 mutations. Canine gliomas showed similarity to human pediatric gliomas in terms of lower mutational rates (0.2–0.29 per megabase), hotspot mutations and amplifications of Pdgfrα, and robust aneuploidy constrained within the syntenic regions of Pdgfrα and Myc, but also in the known pediatric drivers, Hist1 and Acvr1 genes. A mutational signature reflecting homologous repair defect was detected in canine and pediatric but not adult gliomas, potentially resulting in the observed higher rates of genomic instability. Canine gliomas in majority classified as pediatric tumors using a commonly used human brain methylation classifier (Capper et al. 2018) and cell-of-origin analysis by deconvoluting canine transcriptome using lineage-specific gene signatures. By providing a large canine glioma genomic-sequencing dataset and comparing it with human glioma, our study provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations. Further, our results effectively position preclinical models of spontaneous canine glioma for use in understanding glioma drivers, and evaluate novel therapies targeting aneuploidy, especially for pediatric brain tumors.
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Yu, Di, Qiuhui Xuan, Chaoqi Zhang, Chunxiu Hu, Yanli Li, Xinjie Zhao, Shasha Liu et al. « Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses ». Metabolites 10, no 12 (24 novembre 2020) : 478. http://dx.doi.org/10.3390/metabo10120478.
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Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma. In the current study, metabolomics and lipidomics analyses based on chromatography-mass spectrometry were performed on different grades of glioma tissues. Differential metabolites between glioma and para-tumor tissues were studied and used as the basis to explore metabolic alterations related to glioma grading. It was found that short-chain acylcarnitines were elevated, whereas lysophosphatidylethanolamines (LPEs) were decreased in high-grade gliomas. Furthermore, the gene expression of short/branched-chain acyl-coenzyme dehydrogenase (ACADSB), which is involved in fatty acid oxidation, was found down-regulated with glioma progression by analyzing related genes and pathways. In addition, LPE metabolism showed a significant difference among different grades of gliomas. These important metabolic pathways related to glioma progression may provide potential clues for further study on the mechanisms and treatment of glioma.
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Jiang, Chongming, Evelien Schaafsma, Yanding Zhao, Thinh Nguyen, Kenneth Zhu et Chao Cheng. « Abstract LB528 : A microglia associated gene signature predicts survival risk in glioma patients ». Cancer Research 82, no 12_Supplement (15 juin 2022) : LB528. http://dx.doi.org/10.1158/1538-7445.am2022-lb528.
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Abstract Background: Gliomas are common tumors that affect the brain and spinal cord. A complex tumor microenvironment is one of the leading reasons for a poor prognosis in glioma patients. Microglia, as part of the immune microenvironment of gliomas, may facilitate glioma growth and invasion. However, the correlation between the microglia abundance and glioma prognosis has not been clarified. Method: Our goal was to examine the relationship between microglia abundance and glioma prognosis. We analyzed the single-cell RNA sequences of human and mouse glioma cells to identify microglia marker genes. Then, we built a LASSO Cox regression model of microglia abundance signatures in gliomas. The Cancer Genome Atlas (TCGA) dataset (Low-grade gliomas, LGG) was used as the training cohort. The Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset and Chinese Glioma Genome Atlas (CGGA) dataset was used to validate the model as the validation cohorts. Findings: Overall survival was significantly lower in those with a high level of microglia infiltration. Additionally, we found that microglia could interact with the tumor microenvironment and genomic features of gliomas, making microglia abundance negatively associated with the prognosis of glioma patients. Microglia abundance was positively correlated with immune genes expression and immune-related pathways. By applying our LASSO Cox regression model to gliomas, we found that patients with high-risk scores had significantly shorter overall survival (OS) than those with low-risk scores. Conclusions: Taken together, our findings suggest that microglia abundance may be negatively associated with survival in gliomas. Based on the novel microglia abundance signatures, we developed a high accuracy LASSO Cox regression model. In this study, we demonstrated that the model accurately predicted the prognosis of glioma patients and could offer new therapeutic targets for microglial-directed therapies. Keywords: Gliomas; Microglia abundance; LASSO Cox regression; TCGA; Signature.- 1 - Citation Format: Chongming Jiang, Evelien Schaafsma, Yanding Zhao, Thinh Nguyen, Kenneth Zhu, Chao Cheng. A microglia associated gene signature predicts survival risk in glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB528.
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Jaraíz-Rodríguez, Myriam, Rocío Talaverón, Laura García-Vicente, Sara G. Pelaz, Marta Domínguez-Prieto, Andrea Álvarez-Vázquez, Raquel Flores-Hernández et al. « Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo ». Neuro-Oncology 22, no 4 (28 décembre 2019) : 493–504. http://dx.doi.org/10.1093/neuonc/noz243.
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Abstract Background Malignant gliomas are the most frequent primary brain tumors and remain among the most incurable cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor properties of this protein in in vivo glioma models. Methods TAT-Cx43266–283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed. Results While glioma stem cell malignant features were strongly affected by TAT-Cx43266–283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administered TAT-Cx43266–283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266–283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity, TAT-Cx43266–283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore, TAT-Cx43266–283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells. Conclusion TAT-Cx43266–283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this peptide could be considered as a new clinical therapy for high-grade gliomas.
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Nguyen, Hoang Dong, Phedias Diamandis, Michelle S. Scott et Maxime Richer. « Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes ». Journal of Personalized Medicine 12, no 4 (14 avril 2022) : 633. http://dx.doi.org/10.3390/jpm12040633.
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Adult infiltrating gliomas are highly aggressive tumors of the central nervous system with a dismal prognosis despite intensive multimodal therapy (chemotherapy and/or radiotherapy). In this study, we studied the expression, methylation and interacting miRNA profiles of GABA-, glutamate- and calcium-related genes in 661 adult infiltrating gliomas available through the TCGA database. Neurotransmitter-based unsupervised clustering identified three established glioma molecular subgroups that parallel major World Health Organization glioma subclasses (IDH-wildtype astrocytomas, IDH-mutant astrocytomas, IDH-mutant oligodendroglioma). In addition, this analysis also defined a novel, neurotransmitter-related glioma subgroup (NT-1), mostly comprised of IDH-mutated gliomas and characterized by the overexpression of neurotransmitter-related genes. Lower expression of neurotransmission-related genes was correlated with increased aggressivity in hypomethylated IDH-wildtype tumors. There were also significant differences in the composition of the tumor inflammatory microenvironment between neurotransmission-based tumor categories, with lower estimated pools of M2-phenotype macrophages in NT-1 gliomas. This multi-omics analysis of the neurotransmission expression landscape of TCGA gliomas—which highlights the existence of neurotransmission-based glioma categories with different expression, epigenetic and inflammatory profiles—supports the existence of operational neurotransmitter signaling pathways in adult gliomas. These findings could shed new light on potential vulnerabilities to exploit in future glioma-targeting drug therapies.
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Chen, Houminji, Ming Li, Yanwu Guo, Yongsheng Zhong, Zhuoyi He, Yuting Xu et Junjie Zou. « Immune response in glioma’s microenvironment ». Innovative Surgical Sciences 5, no 3-4 (1 septembre 2020) : 115–25. http://dx.doi.org/10.1515/iss-2019-0001.
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Abstract Objectives Glioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment. Content Recent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas. Summary and Outlook The complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas.
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Gupta, Pravesh, Minghao Dang, Krishna Bojja, Tuan Tran M, Huma Shehwana, Carlos Kamiya-Matsuoka, Jianzhuo Li et al. « IMMU-35. TRANSCRIPTIONALLY DEFINED IMMUNE CONTEXTURE IN HUMAN GLIOMAS AT SINGLE-CELL RESOLUTION ». Neuro-Oncology 22, Supplement_2 (novembre 2020) : ii112. http://dx.doi.org/10.1093/neuonc/noaa215.465.
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Abstract The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression and a comprehensive understanding of the glioma-centric immune cell repertoire beyond a priori cell types and/or states is uncharted. Consequently, we performed single-cell RNA-sequencing on ~123,000 tumor-derived immune cells from 17-pathologically stratified, IDH (isocitrate dehydrogenase)-differential primary, recurrent human gliomas, and non-glioma brains. Our analysis delineated predominant 34-myeloid cell clusters (~75%) over 28-lymphoid cell clusters (~25%) reflecting enormous heterogeneity within and across gliomas. The glioma immune diversity spanned functionally imprinted phagocytic, antigen-presenting, hypoxia, angiogenesis and, tumoricidal myeloid to classical cytotoxic lymphoid subpopulations. Specifically, IDH-mutant gliomas were enriched for brain-resident microglial subpopulations in contrast to enhanced bone barrow-derived infiltrates in IDH-wild type, especially in a recurrent setting. Microglia attrition in IDH-wild type -primary and -recurrent gliomas were concomitant with invading monocyte-derived cells with semblance to dendritic cell and macrophage/microglia like transcriptomic features. Additionally, microglial functional diversification was noted with disease severity and mostly converged to inflammatory states in IDH-wild type recurrent gliomas. Beyond dendritic cells, multiple antigen-presenting cellular states expanded with glioma severity especially in IDH-wild type primary and recurrent- gliomas. Furthermore, we noted differential microglia and dendritic cell inherent antigen presentation axis viz, osteopontin, and classical HLAs in IDH subtypes and, glioma-wide non-PD1 checkpoints associations in T cells like Galectin9 and Tim-3. As a general utility, our immune cell deconvolution approach with single-cell-matched bulk RNA sequencing data faithfully resolved 58-cell states which provides glioma specific immune reference for digital cytometry application to genomics datasets. Resultantly, we identified prognosticator immune cell-signatures from TCGA cohorts as one of many potential immune responsiveness applications of the curated signatures for basic and translational immune-genomics efforts. Thus, we not only provide an unprecedented insight of glioma TIME but also present an immune data resource that can be exploited to guide pragmatic glioma immunotherapy designs.
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Tedeschi, G., N. Lundbom, R. Raman, S. Bonavita, J. H. Duyn, J. R. Alger et G. Di Chiro. « L'aumento del segnale di colina coincide con la trasformazione maligna dei gliomi cerebrali : Studio longitidinale con imaging di spettroscopia protonica in risonanza magnetica ». Rivista di Neuroradiologia 10, no 2_suppl (octobre 1997) : 18–19. http://dx.doi.org/10.1177/19714009970100s205.
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We tested the hypothesis that proton magnetic resonance spectroscopic imaging (1H-MRSI) can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of either low-to-high grade malignant transformation or of post-therapeutic recurrence. Twenty-seven patients with histologically verified cerebral gliomas were studied repeatedly with 1H-MRSI over a period of 3.5 years. At the time of each 1H-MRSI study, clinical examination, MRI, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG), and biopsy findings (when available) were used to categorize each patient as being either «stable» or «progressive». Measures of the between-studies percent changes in the choline 1H-MRSI signal intensity, obtained without knowledge of the clinical categorization, segregated the groups with a high degree of statistical significance. All progressive cases showed a between-studies choline signal increase of more than 45%, while all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. We conclude that increased choline coincides with malignant degeneration of cerebral gliomas, and therefore, may possibly be used as a supportive indicator of malignant degeneration of these neoplasms.
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Zhao, Shiguang. « BIOM-63. DIAGNOSIS AND PROGNOSTIC SIGNIFICANCE OF CIRCULATING miR-2276-5p IN PLASMA OF GLIOMA PATIENTS ». Neuro-Oncology 22, Supplement_2 (novembre 2020) : ii15. http://dx.doi.org/10.1093/neuonc/noaa215.060.
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Abstract Circulating microRNAs (miRNAs) in plasma have the potential to become diagnostic and prognostic biomarkers for various cancers. This study hopes to use plasma circulating miRNAs as biomarkers for diagnosis and prognosis of glioma patients. METHOD: In this study, the plasma circulating miRNAs of 124 patients with glioma and 36 controls was collected to detect the relative expression of miR-2276-5p, and the specificity and sensitivity of the diagnosis were verified by ROC curve. The follow-up survival status was analyzed by cox regression analysis. RESULT: In the GSE 139031 database, it was found that the expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of patients with non-gliomas. Using our plasma samples, and it is indicated that the expression of circulating miR-2276-5p in plasma is lower than that of healthy patients, and compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. ROC curve analysis found that the AUC value was 0.851. The low expression of circulating miR-2276-5p in plasma of glioma patients indicates a poor prognosis of glioma patients, After univariate and multifactorial cox regression analysis, which can be used as an independent prognostic risk factor for glioma patients (P< 0.05). CONCLUSION: The expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of the control group, compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. The lower the relative expression of circulating miR-2276-5p indicated that glioma patients had a worse prognosis.
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Wirth, Thomas, Farizan Ahmad, Agnieszka Pacholska, Haritha Samaranayake et Seppo Ylä-Herttuala. « The Syngeneic BT4C Rat Malignant Glioma is a Valuable Model to study Myelomonocytic cells in Tumors ». Cancer Growth and Metastasis 5 (janvier 2012) : CGM.S9314. http://dx.doi.org/10.4137/cgm.s9314.
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Background The impact of infiltrating macrophages on tumor progression in malignant gliomas has been studied extensively. However, there is a lack of animal models for studying the role of infiltrating macrophages in malignant gliomas. Material and methods: The BT4C rat malignant glioma model was characterized by immunohistochemical analysis of inflammatory cell types associated with the tumors. Results BT4C malignant gliomas are highly vascularized tumors with an infiltrative behavior. BT4C gliomas demonstrated a high infiltration rate of macrophages. Particularly, a CD68/VEGFR-1 positive subtype of macrophages was detected at the edges of malignant gliomas. Also, CD133 positive cells were located mainly at the infiltrative edges of gliomas, whereas VEGFR-2 was highly expressed throughout the malignant glioma. Conclusion The immunocompetent BT4C rat malignant glioma model shows features similar to its human counterpart, which makes it a valuable model to study the impact of tumor associated macrophages in the pathology of malignant gliomas.
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Pedersen, L. K. « P05.02.A 18F-FACBC PET/MRI in diagnostic assessment of gliomas ». Neuro-Oncology 24, Supplement_2 (1 septembre 2022) : ii36. http://dx.doi.org/10.1093/neuonc/noac174.121.
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Abstract Background and Theory MRI and histopathological tissue sampling are routinely done as part of the diagnostic work-up of patients with glioma. MRI provides anatomical images with high resolution and excellent soft-tissue contrast. But this modality has limitations in identifying tumor grade, true tumor extension and differentiate viable tumor tissue from treatment induced changes. PET can provide quantitative information of cellular activity and metabolism, and may therefore have additional value compared to MRI alone. Objective The aim of this study was to find the sensitivity of [18F]FACBC PET in gliomas, and evaluate if PET imaging with this tracer can improve differentiation between low-and high-grade gliomas. Methods Patients with suspicion of primary (n=19) or recurrent gliomas (n=8) were recruited to this study from St. Olavs hospital, Trondheim University Hospital, Trondheim, and from the University Hospital of North Norway, Tromsø. PET acquisitions (30-45 min post injection) using the amino acid radiotracer [18F]FACBC (3 MBq/kg) were performed simultaneously to MRI acquisitions (T1 with and without contrast, FLAIR, and UTE for attenuation correction. The sensitivity of [18F]FACBC PET in glioma detection was assessed using histopathology as reference. Tumor-to-background ratios (TBRs) were compared to tumor subtype and grade to assess the diagnostic value of this tracer for glioma diagnostics. Results Histopathology revealed 2 WHO grade 1 gliomas (pilocytic astrocytoma n=1, pilocytic astrocytoma/ganglioglioma n=1), 7 WHO grade 2 gliomas(astrocytoma n=4, oligodendroglioma n=3), 7 WHO grade 3 gliomas(astrocytoma n=5, oligodendroglioma n=2) and 12 WHO grade 4 tumors(astrocytoma n=1, glioblastoma n=11). [18F]FACBC PET provided a sensitivity of 74.1% in the detection of gliomas. PET uptake was observed in all grade 4 tumors, 5/7 grade 3 tumors, 2/7 grade 2 tumors, and all grade 1 tumors. TBRpeak was high with a median value of 9.4 (range: 2.1-34.9) in PET positive tumors. Only tumors with a TBRpeak > 2.0 were detected with [18F]FACBC PET. TBRpeak was highest for grade 1 gliomas with a median value of 20.6, and increased significantly from grade 2 to grade 4 tumors with median values of 1.7 (grade 2), 6.2 (grade 3) and 12.4 (grade 4) (Kruskal-Wallis, p=0.001). Conclusion [18F]FACBC PET demonstrated high uptake in the majority of gliomas, and there was a clear tendency to higher uptake in the higher grade tumors. [18F]FACBC PET may be useful in the differentiation between glioms grades and subtypes. A future study using the same patient data will be performed to evaluate the assessment of [18F]FACBC PET in neurosurgical treatment planning. Image-localized biopsies from different regions of each tumor will be correlated to fused PET/MRI images to evaluate if [18F]FACBC PET can be used to guide surgical resection and to improve accuracy in histopathological tissue sampling.
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Martynov, B. V., V. Ye Parfenov, D. V. Svistov, G. Ye Trufanov, V. A. Fokin, A. I. Kholyavin et V. B. Nizkovolos. « Influence of type and volume of surgical resection on postoperative period in patients with gliomas ». Bulletin of Siberian Medicine 7, no 5-1 (30 décembre 2008) : 231–35. http://dx.doi.org/10.20538/1682-0363-2008-5-1-231-235.
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283 patients with gliomas were included in this study. Age, sex, neurological status and Karnovsky performance were analyzed before and after surgery, also tumor location, type and volume of surgical resection, postoperative complications were considered. Volume of tumor resection did not depend on glioma localization, excluding deep located tumors, in which case stereotactic cryotomy was performed (p < 0,01). In cases of stereotactic cryotomy postoperative neurological deficit worsening was noted in 12,5%, in patients with open biopsy and partial resection — 10,9%, and in case of total or subtotal tumor resection in 7,0% (p > 0,05). Partial gliom resection often related with postoperative complications and neurological deficit worsening then open surgery total tumour resection. Stereotactic cryotomy does not lead to bigger postoperative complications frequency in comparisons with open surgery.
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Gao, Huasong, Bin Yu, Yaohua Yan, Jianhong Shen, Sanhu Zhao, Jianhong Zhu, Wenxin Qin et Yilu Gao. « Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis ». Journal of Neurosurgery 118, no 4 (avril 2013) : 846–53. http://dx.doi.org/10.3171/2012.9.jns112134.
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Object Biomarkers for the diagnosis and prognosis of gliomas are lacking. To elucidate new diagnostic and prognostic targets, a routine method is used to evaluate differences between the protein profile of normal and tumor cells. The object of the current study was to investigate novel differentially expressed proteins and their roles in gliomas. Methods Differences in the protein profile were compared using 2D polyacrylamide gel electrophoresis using C6 glioma cells and rat astrocytes. The mRNA and protein expression of ANXA2, PGAM1, and CALR were analyzed in glioma tissues and normal brain tissues. The expression of ANXA2 in the U87 glioma cell line was interrupted using short interfering RNA duplexes, and the role of ANXA2 in the migration and invasiveness of glioma cells was assessed. The expression of ANXA2, PGAM1, and CALR was examined further by immunohistochemical analysis using 130 glioma samples obtained in patients, and their prognostic roles in gliomas were evaluated using Kaplan-Meier and Cox regression analyses. Results Significantly higher expression levels of ANXA2 and PGAM1 and a lower level of CALR were found in glioma samples than in the normal brain samples. ANXA2, PGAM1, and CALR expression correlated with the grade and survival of patients with gliomas. Multivariate analysis further revealed that ANXA2 was an independent prognostic marker for glioma. After ANXA2 expression was suppressed using short interfering RNA, U87 cells had decreased migratory and invasive capabilities in vitro. Conclusions Protein expression alterations in ANXA2, PGAM1, and CALR were found in gliomas, and ANXA2 provided a novel prognostic value.
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Rao, Aparna, Xiaoran Zhang, Christopher Deibert, Paola Sette, Paola Grandi et Nduka Amankulor. « IDH Mutant Gliomas Escape Natural Killer Cell Immune Surveillance by Downregulation of NKG2D Ligand Expression ». Journal of Immunology 196, no 1_Supplement (1 mai 2016) : 142.11. http://dx.doi.org/10.4049/jimmunol.196.supp.142.11.
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Abstract Background Diffuse gliomas are fatal primary brain tumors that are poorly immunogenic. The basis for insufficient anti-tumor immunity in diffuse gliomas is not understood. Mutations in isocitrate dehydrogenases (IDH1 and IDH2) promote diffuse glioma formation through epigenetic reprogramming of a number of genes, including immune-related genes. Here, we identify epigenetic dysregulation of natural killer (NK) cell ligand genes as significant contributors to immune escape in glioma. Methods We analyzed the TCGA database for immune gene expression patterns in IDH mutant or wild-type gliomas and identified differentially expressed immune genes. NKG2D ligands expression levels and NK cell-mediated lysis were measured in patient-derived glioma stem cells and in genetically engineered astrocytes. Finally, we assessed the impact of hypomethylating agent Decitabine as a potential NK cell sensitizing agent in IDH mutant cells. Results All IDH mutant glioma stem-like cell lines exhibited significantly lower expression of NKG2D ligands compared with IDH wild-type cells. Consistent with these findings, IDH mutant glioma cells and astrocytes were resistant to NK cell-mediated lysis. The hypomethylating agent Decitabine increased NKG2D ligand expression, and restored NK- mediated lysis of IDH mutant cells in an NKG2D-dependent manner. Conclusions IDH mutant glioma cells acquire resistance to NK cells through epigenetic silencing of NKG2D ligands ULBP1 and ULPB3. Decitabine-mediated hypomethylation restores ULBP1 and ULBP3 expression in IDH mutant glioma cells and may provide a clinically useful method to sensitize IDH mutant gliomas to NK cell-mediated immune surveillance in patients with IDH mutated diffuse gliomas.
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Sun, Jin-Zhang, Jin-Hao Zhang, Jia-Bo Li, Feng Yuan, Lu-Qing Tong, Xu-Ya Wang, Lu-Lu Chen et al. « MXRA5 Is a Novel Immune-Related Biomarker That Predicts Poor Prognosis in Glioma ». Disease Markers 2021 (9 juin 2021) : 1–13. http://dx.doi.org/10.1155/2021/6680883.
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Background. Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value. Methods. In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples. Results. We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. Conclusion. Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation.
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Nagashima, Yoshitaka, Yusuke Nishimura, Fumiharu Ohka, Kaoru Eguchi, Kosuke Aoki, Hiroshi Ito, Tomoya Nishii et al. « Driver Genetic Mutations in Spinal Cord Gliomas Direct the Degree of Functional Impairment in Tumor-Associated Spinal Cord Injury ». Cells 10, no 10 (24 septembre 2021) : 2525. http://dx.doi.org/10.3390/cells10102525.
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Genetic analysis in glioma has been developed recently. Spinal cord glioma is less common than intracranial glioma. Thus, the clinical significance of genetic mutations in spinal cord gliomas remains unclear. Furthermore, because the spinal cord is an important communication channel between the brain and the rest of the body, increased attention should be paid to its functional prognosis. In this study, we investigated the functional prognosis and driver genetic mutations in eight patients with spinal cord gliomas (World Health Organization grade I, three cases; grade II, two cases; grade III/IV, three cases). IDH mutations were detected in all grade II cases and H3F3A mutations were detected in all grade III/IV cases. The functional status of grade I and II gliomas remained unchanged or improved 1 year after surgery, whereas grade III/IV gliomas remained unchanged or deteriorated. Spinal glioma progenitor cells with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, which led to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis.
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Sears, Thomas K., Craig M. Horbinski et Kevin D. Woolard. « IDH1 mutant glioma is preferentially sensitive to the HDAC inhibitor panobinostat ». Journal of Neuro-Oncology 154, no 2 (23 août 2021) : 159–70. http://dx.doi.org/10.1007/s11060-021-03829-0.
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Abstract Introduction A large subset of diffusely infiltrative gliomas contains a gain-of-function mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2mut) which produces 2-hydroxglutarate, an inhibitor of α-ketoglutarate-dependent DNA demethylases, thereby inducing widespread DNA and histone methylation. Because histone deacetylase (HDAC) enzymes are localized to methylated chromatin via methyl-binding domain proteins, IDH1/2mut gliomas may be more dependent on HDAC activity, and therefore may be more sensitive to HDAC inhibitors. Methods Six cultured patient-derived glioma cell lines, IDH1wt (n = 3) and IDH1mut (n = 3), were treated with an FDA-approved HDAC inhibitor, panobinostat. Cellular cytotoxicity and proliferation assays were conducted by flow cytometry. Histone modifications and cell signaling pathways were assessed using immunoblot and/or ELISA. Results IDH1mut gliomas exhibited marked upregulation of genes associated with the HDAC activity. Glioma cell cultures bearing IDH1mut were significantly more sensitive to the cytotoxic and antiproliferative effects of panobinostat, compared to IDH1wt glioma cells. Panobinostat caused a greater increase in acetylation of the histone residues H3K14, H3K18, and H3K27 in IDH1mut glioma cells. Another HDAC inhibitor, valproic acid, was also more effective against IDH1mut glioma cells. Conclusion These data suggest that IDH1mut gliomas may be preferentially sensitive to HDAC inhibitors. Further, IDH1mut glioma cultures showed enhanced accumulation of acetylated histone residues in response to panobinostat treatment, suggesting a direct epigenetic mechanism for this sensitivity. This provides a rationale for further exploration of HDAC inhibitors against IDH1mut gliomas.
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Smith, Nataliya, Debra Saunders, Randy L. Jensen et Rheal A. Towner. « Association of decreased levels of lipopolysaccharide-binding protein with OKN-007–induced regression of tumor growth in an F98 rat glioma model ». Journal of Neurosurgery 133, no 6 (décembre 2020) : 1695–703. http://dx.doi.org/10.3171/2019.7.jns182435.
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OBJECTIVEHigh-grade gliomas, such as glioblastoma (GBM), are devastating tumors with a very poor prognosis. Previously the authors have found that the nitrone compound OKN-007 (OKlahoma Nitrone 007; or disodium 4-[(tert-butyl-imino) methyl] benzene-1,3-disulfonate N-oxide) is effective against high-grade gliomas in various GBM rodent and human xenograft models. The purpose of the present study was to assess the levels of the lipopolysaccharide-binding protein (LBP) in rodent gliomas treated with OKN-007 as well as determine the expression of LBP in human gliomas.METHODSMicroarray analysis was done to assess altered gene expression following OKN-007 administration in an F98 glioma model. An enzyme-linked immunosorbent assay was incorporated to assess LBP levels in glioma tissues, as well as blood serum, comparing results in OKN-007–treated and untreated tumor-bearing animals. Immunohistochemistry was used to assess LBP levels in varying grades of human glioma tissue sections.RESULTSUpon further assessment of gene expression fold changes in F98 gliomas in rats that received or did not receive OKN-007, it was found that the gene for LBP was significantly downregulated by OKN-007. Further investigation was done to see whether levels of LBP were affected by OKN-007 treatment in F98 gliomas. It was found that LBP could be detected not only in glioma tissue but also in blood serum of F98 glioma-bearing rats and that OKN-007 decreased the levels of LBP. It was also found that LBP levels are highly expressed in human high-grade glioma tissues.CONCLUSIONSLBP could potentially be used as a serum diagnostic marker of treatment response in high-grade gliomas.
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Yang, Jiaying, Yongjun Yao, Li Tong, Ziwei Zhu, Lei Wang et Jinju Yang. « CD47 is highly expressed in gliomas and targeting CD47 is a promising therapeutic strategy ». European Journal of Inflammation 19 (janvier 2021) : 205873922110008. http://dx.doi.org/10.1177/20587392211000899.
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Gliomas are very malignant brain tumors that are difficult to treat. CD47 is an antiphagocytic molecule that binds to SIPRα on phagocytes. It is overexpressed on the plasma membranes of multiple human tumor cell types and is an important diagnostic and prognostic biomarker in many types of cancer. However, the association between CD47 protein expression in glioma tissue and clinicopathological stage has not been investigated in detail. A total of 80 surgical glioma specimens were stained with anti-CD47 antibody to assess the relationship between CD47 protein expression and clinicopathological stage of the glioma. Wound healing assays were performed to analyze the influence of CD47 on the migration and invasion of glioma cells, and near-infrared fluorescence localization assays in a U-87 MG-bearing xenograft model were used to determine the distribution of anti-CD47 antibody in vivo. MTT assays and administration of anti-CD47 to a U251-bearing xenograft model were used to analyze the inhibitory effects of the antibody on gliomas. CD47 expression was higher in high-grade gliomas than in low-grade gliomas, and high CD47 expression was positively correlated with histology and tumor clinicopathological stage. CD47 over-expression promoted the growth and motility of two glioma cell lines (U-87 MG and U251) and a laboratory-developed anti-CD47 antibody accumulated at the glioma site. Proliferation of U251 and U-87 MG cells was not significantly inhibited by the anti-CD47 antibody in vitro, but the antibody significantly inhibited U251 growth in vivo. It also enhanced inhibition capacity by Taxol. Our results suggest that CD47 plays a critical role in the progression of gliomas from stage I to IV and may be a potential target for the treatment of gliomas. CD47 appears to play a critical role in the progression of gliomas from stage I to IV and an anti-CD47 antibody prepared in the laboratory may inhibit the growth of gliomas.
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Surapaneni, Akhil, Vik Kohli, Yousuf Ahmed, Matthew Seghers et John Kuo. « OPTC-3. Differential Synapse-Related Gene Expression Identifies Glioma Subtypes and Predicts Prognosis ». Neuro-Oncology Advances 3, Supplement_2 (1 juillet 2021) : ii6. http://dx.doi.org/10.1093/noajnl/vdab070.024.
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Abstract Synaptic connectivity between gliomas and adjacent brain was recently implicated in tumorigenesis. However, the interaction of synapse-related genes (SRGs) with patient survival and with established clinical and molecular glioma subtypes merit further study in a large patient cohort. We characterized differential expression of SRGs in gliomas and investigated SRG expression as putative clinical biomarkers in a large glioma cohort. Expression of 1189 SRGs was interrogated via RNA sequencing analysis in 603 gliomas (LGG n=451, GBM n=152) of The Cancer Genome Atlas. SRG expression patterns partitioned gliomas into two clusters that were more distinctive than priorly identified glioma subtypes. The two glioma clusters showed significantly low (14.9 months) or high median survival (105.1 months; Hazard Ratio = 7.1, 95% CI: [5.32, 9.78], p = 1.29e-46 using a log-rank test). The high survival cluster showed overrepresentation of known pro-neural and neural subtypes and IDH-mutated gliomas (p<0.00001). The mesenchymal and classic GBMs and IDH-wild type gliomas were overrepresented in the low survival cluster (p < 0.00001). In addition, an Elastic Net Cox Regression model identified 34 SRGs whose expression significantly predicted differential survival and a prognostic Synapse Gene Score (SGS) was created. Using an accelerated failure time model, SGS predicted survival in the overall gliomas after adjusting for IDH-1 mutation (HR = 2.51, 95% CI: [2.27, 2.7496], p<0.00001), and in the IDH-1 mutant cohort after adjusting for 1p/19q co-deletion (HR = 2.05, 95% CI: [1.73, 2.37], p<0.00001). Our analysis shows that gliomas can be distinctively clustered by differential SRGs expression, suggesting that synapse-related proteins may contribute to tumorigenesis via multiple mechanisms. Furthermore, the potential utility of SRGs as clinical glioma biomarkers is supported by our creation of a prognostic SGS. Future studies elucidating interactions between tumorigenesis and synaptic mechanisms may reveal additional insights for glioma biology and therapeutic targeting.
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Li, shaoqun, Mingyao Lai, Jiangfen Zhou, junjie Zhen et Linbo Cai. « PATH-22. GENETIC VARIATION BETWEEN IDH MUTANT AND IDH WILD-TYPE GLIOMA ». Neuro-Oncology 23, Supplement_6 (2 novembre 2021) : vi119. http://dx.doi.org/10.1093/neuonc/noab196.474.
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Abstract OBJECTIVE The prognosis of IDH mutant glioma was significantly different from that of IDH wild-type glioma. In order to explore the differences between them at the genetic level, we analyzed the genetic results of IDH mutant and IDH wild-type glioma. METHODS This study analyzed the clinical data and genetic results of 45 glioma patients from Jan. 2017 to Dec. 2019, exploring relevant prognostic indicators and the difference in genetic profile between IDH mutant glioma and IDH wild-type glioma. RESULTS 45 patients were included in this study, including 15 IDH mutant glioma patients and 30 IDH wild-type glioma patients. Genetic analysis showed that there was no difference in tumor mutation burden (TMB) and microsatellite instability (MSI) between IDH mutant glioma and IDH wild-type glioma. But somatic mutation between IDH mutant and IDH wild-type glioma was different. The expressions of IDH1, CIC, SYNE1 and TP53 were different in the two groups, among which IDH1 and CIC were more significantly different. Copy number variations (CNV) was also different between IDH mutant glioma and IDH wild-type glioma. STIL occured more frequently in IDH wild-type gliomas. Genetic analysis also showed the difference in variant allel frequence (VAF). IDH mutant gliomas were more likely to be combined with ATRX and TP53 mutations, while IDH wild-type gliomas, in addition to the combination of TP53 mutations, often also combined with the mutations of NF1, BRAF and PTEN. In survival analysis, glioma with IDH mutation has a good prognosis, and IDH wild-type patients have a poor prognosis. In IDH wild-type patients, patients with PTEN mutation have a worse prognosis. CONCLUSION There is an obvious genetic difference between IDH mutation and IDH wild-type glioma, and PTEN mutation is a poor prognostic factor for IDH wild-type patients.
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Javier, Rodrigo, et Craig Horbinski. « TAMI-48. THE KETOGENIC DIET IS INEFFECTIVE IN PRECLINICAL MODELS OF IDH1 WILD-TYPE AND IDH1 MUTANT GLIOMA ». Neuro-Oncology 23, Supplement_6 (2 novembre 2021) : vi208. http://dx.doi.org/10.1093/neuonc/noab196.831.
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Abstract Despite decades of intensive research, infiltrative gliomas are still usually lethal and challenging to treat. A subset of gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut), which disrupts cellular biochemistry; such gliomas are generally less aggressive than their IDH1 wild-type (IDH1wt) counterparts. Some preclinical studies have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial against a variety of cancers, including gliomas. However, not all studies have shown promising results, and to date, no study has addressed the sensitivity of glioma cells to KD in the specific context of the endogenous IDH1mut metabolic landscape. The aim of the current study was to compare the effects of KD in preclinical models to IDH1wt versus IDH1mut gliomas. In vitro treatment of patient-derived IDH1wt and IDH1mut glioma cells with the ketone body β-hydroxybutyrate showed no significant effect on cell proliferation in a low glucose culture environment. Likewise, the in vivo flank growth rates of these patient-derived IDH1wt and IDH1mut glioma xenografts showed no significant difference when mice were fed KD versus regular diet (GBM12 p=0.98, GBM164 p=0.4, GBM196 p=0.11). Finally, KD had no effect on the survival of mice engrafted with isogenic Sleeping-Beauty transposase-engineered IDH1wt (median control survival 22 days versus treatment 23 days, p=0.23) or IDH1mut glioma cells (median control survival 26.5 days versus treatment 26 days, p=0.81). These data suggest that IDH1mut gliomas are not more responsive than IDH1wt gliomas to KD, and that clinical trials further exploring KD in this subset of glioma patients are probably not warranted.
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Obukhova, Larisa, Tatiana Kopytova, Elena Murach, Natalya Shchelchkova, Claudia Kontorshchikova, Igor Medyanik, Natalia Orlinskaya, Artem Grishin, Michael Kontorshchikov et Dariya Badanina. « Relationship between Glutathione-Dependent Enzymes and the Immunohistochemical Profile of Glial Neoplasms ». Biomedicines 10, no 10 (25 septembre 2022) : 2393. http://dx.doi.org/10.3390/biomedicines10102393.
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This research aimed to investigate the relationships between the parameters of glutathione metabolism and the immunohistochemical characteristics of glial tumors. Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed. Bioinformatic analysis of the interactions between the gliomas’ immunohistochemical markers and their glutathione-dependent enzymes was carried out using the STRING, BioGrid, while Signor databases revealed interactions between such glioma markers as IDH and p53 and the glutathione exchange enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase). The most pronounced relationship with glutathione metabolism was demonstrated by the level of the nuclear protein Ki67 as a marker of proliferative activity, and the presence of the IDH1 mutation as one of the key genetic events of gliomagenesis. The glutathione system is an active participant in the body’s antioxidant defense, involving the p53 markers and MGMT promoter methylation. It allows characterization of the gliomal cells’ status at different stages of tumor development.
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Mitsuka, Kentaro, Tomoyuki Kawataki, Eiji Satoh, Takayuki Asahara, Toru Horikoshi et Hiroyuki Kinouchi. « Expression of Indoleamine 2,3-Dioxygenase and Correlation With Pathological Malignancy in Gliomas ». Neurosurgery 72, no 6 (19 février 2013) : 1031–39. http://dx.doi.org/10.1227/neu.0b013e31828cf945.
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Abstract BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme involved in immune tolerance and tumor immune escape processes. Recently, IDO expression has been found to correlate with the prognosis of malignant tumors, but the implication of IDO in glioma progression remains unknown. OBJECTIVE: To investigate the relationship between IDO expression and histological malignancy in gliomas. METHODS: IDO expression was examined in a total of 75 surgical specimens obtained from 68 patients with glioma using immunohistochemical staining. The 75 specimens included 15 diffuse astrocytomas, 21 anaplastic astrocytomas, and 39 glioblastomas. Six of 39 glioblastomas were secondary glioblastomas, transforming from grade II or III gliomas that had been determined at the first surgery. IDO expression rate was compared in each histological grade, and patient survival was analyzed. RESULTS: Expression of IDO was found in 72 of 75 gliomas at varying intensities. Stronger expression of IDO was more likely to be observed in malignant gliomas compared with low-grade gliomas. IDO expression in the 6 cases of secondary glioblastoma was stronger than in the initial low-grade glioma. Survival analysis using the Kaplan-Meier method revealed that grade IV patients with strong IDO expression had significantly worse overall survival rates (P = .04) than patients with weak IDO expression. CONCLUSION: IDO is expressed more strongly in both primary and secondary glioblastoma tissue than low-grade glioma and may affect clinical outcome. If IDO promotes glioma cells to escape from the immune system, IDO may be a crucial therapeutic target for malignant gliomas.
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Aabedi, alexander, Benjamin Lipkin, Jasleen Kaur, Sofia Kakaizada, Jacob Young, Anthony Lee, Saritha Krishna, Edward Chang, David Brang et Shawn Hervey-Jumper. « TAMI-66. FUNCTIONAL ALTERATIONS IN CORTICAL PROCESSING OF SPEECH IN GLIOMA-INFILTRATED CORTEX ». Neuro-Oncology 23, Supplement_6 (2 novembre 2021) : vi212. http://dx.doi.org/10.1093/neuonc/noab196.848.
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Abstract INTRODUCTION Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity, in a manner similar to normal-appearing cortex, but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. METHODS Here, we acquired invasive electrophysiologic recordings to sample both normal-appearing and glioma-infiltrated cortex during speech initiation in order to measure language task-related circuit dynamics of IDH-wild-type glioblastoma patients. We then applied an information theoretical framework to directly compare the encoding capacity and decodability of signals arising from these regions. RESULTS We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex, but recruits a diffuse spatial network. On a temporal scale, we show that glioma-infiltrated cortex has lower capacity for information encoding when performing nuanced tasks such as speech production of monosyllabic versus polysyllabic words. As a result, temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex, but not from glioma-infiltrated cortex. CONCLUSION These findings inform our understanding of cognitive processing in patients with malignant gliomas and have implications for patient survival, neuromodulation, and prosthetics in patients with malignant gliomas.