Glycine by MR spectroscopy is an imaging biomarker of glioma aggressiveness.


BACKGROUND:High-grade gliomas likely remodel the metabolic machinery to meet the increased demands for amino acids and nucleotides during rapid cell proliferation. Glycine, a non-essential amino acid and intermediate of nucleotide biosynthesis, may increase with proliferation. Non-invasive measurement of glycine by magnetic resonance spectroscopy (MRS) was evaluated as an imaging biomarker for assessment of tumor aggressiveness. METHODS:We measured glycine, 2-hydroxyglutarate (2HG), and other tumor-related metabolites in 35 glioma patients using an MRS sequence tailored for co-detection of glycine and 2HG in gadolinium-enhancing and non-enhancing tumor regions on 3T MRI. Glycine and 2HG concentrations as measured by MRS were correlated with tumor cell proliferation (MIB-1 labeling index), expression of mitochondrial serine hydroxymethyltransferase (SHMT2), and glycine decarboxylase (GLDC) enzymes, and patient overall survival. RESULTS:Elevated glycine was strongly associated with presence of gadolinium enhancement, indicating more rapidly proliferative disease. Glycine concentration was positively correlated with MIB-1, and levels higher than 2.5 mM showed significant association with shorter patient survival, irrespective of isocitrate dehydrogenase status. Concentration of 2HG did not correlate with MIB-1 index. A high glycine/2HG concentration ratio, >2.5, was strongly associated with shorter survival (P < 0.0001). GLDC and SHMT2 expression were detectable in all tumors with glycine concentration, demonstrating an inverse correlation with GLDC. CONCLUSIONS:The data suggest that aggressive gliomas reprogram glycine-mediated one-carbon metabolism to meet the biosynthetic demands for rapid cell proliferation. MRS evaluation of glycine provides a non-invasive metabolic imaging biomarker that is predictive of tumor progression and clinical outcome. KEY POINTS:1. Glycine and 2-hydroxyglutarate in glioma patients are precisely co-detected using MRS at 3T.2. Tumors with elevated glycine proliferate and progress rapidly.3. A high glycine/2HG ratio is predictive of shortened patient survival.


Neuro Oncol




Tiwari V,Daoud EV,Hatanpaa KJ,Gao A,Zhang S,An Z,Ganji SK,Raisanen JM,Lewis CM,Askari P,Baxter J,Levy M,Dimitrov I,Thomas BP,Pinho MC,Madden CJ,Pan E,Patel TR,DeBerardinis RJ,Sherry AD,Mickey BE,Malloy CR,Mahe




Has Abstract


2020-07-07 00:00:00














  • Long-term outcomes of surgical resection with or without adjuvant radiation therapy for treatment of spinal ependymoma: a retrospective multicenter study by the Korea Spinal Oncology Research Group.

    abstract:BACKGROUND:We sought to determine the surgical treatment and functional outcome and identify the predictors of survival in a retrospective cohort of patients with spinal cord ependymoma using data collected from the Korea Spinal Oncology Research Group database. METHODS:The data regarding 88 patients who had been surg...


    pub_type: 杂志文章,多中心研究


    authors: Lee SH,Chung CK,Kim CH,Yoon SH,Hyun SJ,Kim KJ,Kim ES,Eoh W,Kim HJ

    更新日期:2013-07-01 00:00:00

  • In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas.

    abstract::Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited t...


    pub_type: 杂志文章


    authors: Entin-Meer M,Yang X,VandenBerg SR,Lamborn KR,Nudelman A,Rephaeli A,Haas-Kogan DA

    更新日期:2007-04-01 00:00:00

  • Glioma-derived versican promotes tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling.

    abstract:BACKGROUND:Accumulation and infiltration of microglia/brain macrophages around and into glioma tissue promote tumor invasion and expansion. One tumor-promoting mechanism of microglia/brain macrophages is upregulation of membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation of extracellular ma...


    pub_type: 杂志文章


    authors: Hu F,Dzaye O,Hahn A,Yu Y,Scavetta RJ,Dittmar G,Kaczmarek AK,Dunning KR,Ricciardelli C,Rinnenthal JL,Heppner FL,Lehnardt S,Synowitz M,Wolf SA,Kettenmann H

    更新日期:2015-02-01 00:00:00

  • Primary glioblastoma with oligodendroglial differentiation has better clinical outcome but no difference in common biological markers compared with other types of glioblastoma.

    abstract:BACKGROUND:Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinico...


    pub_type: 杂志文章


    authors: Laxton RC,Popov S,Doey L,Jury A,Bhangoo R,Gullan R,Chandler C,Brazil L,Sadler G,Beaney R,Sibtain N,King A,Bodi I,Jones C,Ashkan K,Al-Sarraj S

    更新日期:2013-12-01 00:00:00

  • Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.

    abstract:BACKGROUND:Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METH...


    pub_type: 杂志文章


    authors: Frühwald MC,Hasselblatt M,Nemes K,Bens S,Steinbügl M,Johann PD,Kerl K,Hauser P,Quiroga E,Solano-Paez P,Biassoni V,Gil-da-Costa MJ,Perek-Polnik M,van de Wetering M,Sumerauer D,Pears J,Stabell N,Holm S,Hengartner H,Ge

    更新日期:2020-07-07 00:00:00

  • Temporal changes in magnetic resonance imaging characteristics of Gliadel wafers and of the adjacent brain parenchyma.

    abstract::Carmustine is used in the treatment of glioblastomas as locally applied chemotherapy in the form of biodegradable wafers, which are lined on the walls of the resection cavity at the end of the resection, to increase local concentrations and decrease systemic toxicity. A total of 44 patients with glioblastoma with gros...


    pub_type: 杂志文章


    authors: Ulmer S,Spalek K,Nabavi A,Schultka S,Mehdorn HM,Kesari S,Dörner L

    更新日期:2012-04-01 00:00:00

  • Brain metastases in melanoma: roles of neurotrophins.

    abstract::Brain metastasis, which occurs in 20% to 40% of all cancer patients, is an important cause of neoplastic morbidity and mortality. Successful invasion into the brain by tumor cells must include attachment to microvessel endothelial cells, penetration through the blood-brain barrier, and, of relevance, a response to bra...


    pub_type: 杂志文章,评审


    authors: Denkins Y,Reiland J,Roy M,Sinnappah-Kang ND,Galjour J,Murry BP,Blust J,Aucoin R,Marchetti D

    更新日期:2004-04-01 00:00:00

  • Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells.

    abstract:INTRODUCTION:Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid...


    pub_type: 杂志文章


    authors: Alimova I,Birks DK,Harris PS,Knipstein JA,Venkataraman S,Marquez VE,Foreman NK,Vibhakar R

    更新日期:2013-02-01 00:00:00

  • Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma.

    abstract::Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an ...


    pub_type: 杂志文章


    authors: Schwartzbaum JA,Huang K,Lawler S,Ding B,Yu J,Chiocca EA

    更新日期:2010-04-01 00:00:00

  • Updates in the management of brain metastases.

    abstract::The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survi...


    pub_type: 杂志文章,评审


    authors: Arvold ND,Lee EQ,Mehta MP,Margolin K,Alexander BM,Lin NU,Anders CK,Soffietti R,Camidge DR,Vogelbaum MA,Dunn IF,Wen PY

    更新日期:2016-08-01 00:00:00

  • A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

    abstract:BACKGROUND:Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS:This pivotal phase III ra...


    pub_type: 杂志文章


    authors: Cloughesy TF,Brenner A,de Groot JF,Butowski NA,Zach L,Campian JL,Ellingson BM,Freedman LS,Cohen YC,Lowenton-Spier N,Rachmilewitz Minei T,Fain Shmueli S,GLOBE Study Investigators.,Wen PY

    更新日期:2020-05-15 00:00:00

  • Posttranscriptional deregulation of signaling pathways in meningioma subtypes by differential expression of miRNAs.

    abstract:BACKGROUND:Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the ...


    pub_type: 杂志文章


    authors: Ludwig N,Kim YJ,Mueller SC,Backes C,Werner TV,Galata V,Sartorius E,Bohle RM,Keller A,Meese E

    更新日期:2015-09-01 00:00:00

  • Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies.

    abstract:BACKGROUND:Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS:Patients with CNS ...


    pub_type: 杂志文章


    authors: Garber ST,Hashimoto Y,Weathers SP,Xiu J,Gatalica Z,Verhaak RG,Zhou S,Fuller GN,Khasraw M,de Groot J,Reddy SK,Spetzler D,Heimberger AB

    更新日期:2016-10-01 00:00:00

  • Akt2 and Akt3 play a pivotal role in malignant gliomas.

    abstract::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...


    pub_type: 杂志文章


    authors: Mure H,Matsuzaki K,Kitazato KT,Mizobuchi Y,Kuwayama K,Kageji T,Nagahiro S

    更新日期:2010-03-01 00:00:00

  • Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study.

    abstract:BACKGROUND:The colony stimulating factor 1 receptor (CSF1R) ligands, CSF1 and interleukin-34, and the KIT ligand, stem cell factor, are expressed in glioblastoma (GB). Microglia, macrophages, blood vessels, and tumor cells also express CSF1R, and depletion of the microglia reduces tumor burden and invasive capacity. PL...


    pub_type: 杂志文章,多中心研究


    authors: Butowski N,Colman H,De Groot JF,Omuro AM,Nayak L,Wen PY,Cloughesy TF,Marimuthu A,Haidar S,Perry A,Huse J,Phillips J,West BL,Nolop KB,Hsu HH,Ligon KL,Molinaro AM,Prados M

    更新日期:2016-04-01 00:00:00

  • ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.

    abstract::Glioma is the most common adult primary brain tumor. Its most malignant form, glioblastoma multiforme (GBM), is almost invariably fatal, due in part to the intrinsic resistance of GBM to radiation- and chemotherapy-induced apoptosis. We analyzed B-cell leukemia-2 (Bcl-2) anti-apoptotic proteins in GBM and found myeloi...


    pub_type: 杂志文章


    authors: Day BW,Stringer BW,Spanevello MD,Charmsaz S,Jamieson PR,Ensbey KS,Carter JC,Cox JM,Ellis VJ,Brown CL,Walker DG,Inglis PL,Allan S,Reynolds BA,Lickliter JD,Boyd AW

    更新日期:2011-11-01 00:00:00

  • Feasibility, phase I, and phase II studies of tandutinib, an oral platelet-derived growth factor receptor-β tyrosine kinase inhibitor, in patients with recurrent glioblastoma.

    abstract:Background:Platelet-derived growth factor (PDGF) signaling is important in gliomagenesis and PDGF receptor-β is expressed on most endothelial cells in glioblastoma specimens. Methods:We report the results of feasibility, phase I, and phase II studies of tandutinib (MLN518), an orally bioavailable inhibitor of type III...


    pub_type: 杂志文章,多中心研究


    authors: Batchelor TT,Gerstner ER,Ye X,Desideri S,Duda DG,Peereboom D,Lesser GJ,Chowdhary S,Wen PY,Grossman S,Supko JG

    更新日期:2017-04-01 00:00:00

  • Assessment and treatment relevance in elderly glioblastoma patients.

    abstract::Glioblastoma (GBM) is the most common malignant primary brain tumor. Its incidence continues to increase in the elderly because the older segment of the population is growing faster than any other age group. Most clinical studies exclude elderly patients, and "standards of care" do not exist for GBM patients aged >70 ...


    pub_type: 杂志文章,评审


    authors: Bauchet L,Zouaoui S,Darlix A,Menjot de Champfleur N,Ferreira E,Fabbro M,Kerr C,Taillandier L

    更新日期:2014-11-01 00:00:00

  • Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma.

    abstract::Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported met...


    pub_type: 杂志文章


    authors: Phillips WT,Goins B,Bao A,Vargas D,Guttierez JE,Trevino A,Miller JR,Henry J,Zuniga R,Vecil G,Brenner AJ

    更新日期:2012-04-01 00:00:00

  • Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort.

    abstract:BACKGROUND:The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. METHODS:Included were adult patients with (n = 354, implantation group) and...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Pallud J,Audureau E,Noel G,Corns R,Lechapt-Zalcman E,Duntze J,Pavlov V,Guyotat J,Hieu PD,Le Reste PJ,Faillot T,Litre CF,Desse N,Petit A,Emery E,Voirin J,Peltier J,Caire F,Vignes JR,Barat JL,Langlois O,Dezamis E

    更新日期:2015-12-01 00:00:00

  • Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomas.

    abstract::We have previously demonstrated that chordomas express activated platelet-derived growth factor receptor (PDGFRB) and that treatment with imatinib, which is capable of switching off the activation of various receptor tyrosine kinases (RTKs) including PDGFRB, benefits a number of patients. The aim of this study was to ...


    pub_type: 杂志文章


    authors: Tamborini E,Virdis E,Negri T,Orsenigo M,Brich S,Conca E,Gronchi A,Stacchiotti S,Manenti G,Casali PG,Pierotti MA,Pilotti S

    更新日期:2010-08-01 00:00:00

  • Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma-a meta-analysis.

    abstract:Background:Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods:Cochrane Library, Emba...


    pub_type: 杂志文章,meta分析


    authors: Falk Delgado A,De Luca F,van Westen D,Falk Delgado A

    更新日期:2018-10-09 00:00:00

  • Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway.

    abstract::Neuroblastomas, an embryonic cancer of the sympathetic nervous system, often occur in young children. Honokiol, a small-molecule polyphenol, has multiple therapeutic effects and pharmacological activities. This study was designed to evaluate whether honokiol could pass through the blood-brain barrier (BBB) and induce ...


    pub_type: 杂志文章


    authors: Lin JW,Chen JT,Hong CY,Lin YL,Wang KT,Yao CJ,Lai GM,Chen RM

    更新日期:2012-03-01 00:00:00

  • Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma.

    abstract::Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients wi...


    pub_type: 杂志文章


    authors: Baraniskin A,Kuhnhenn J,Schlegel U,Maghnouj A,Zöllner H,Schmiegel W,Hahn S,Schroers R

    更新日期:2012-01-01 00:00:00

  • Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau disease.

    abstract::To determine the effectiveness of stereotactic radiosurgery (SRS) treatment to central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease (VHL), we analyzed long-term results in VHL patients treated with SRS. Patients were enrolled in a prospective VHL natural history study, undergoing SRS treatment o...


    pub_type: 临床试验,杂志文章


    authors: Asthagiri AR,Mehta GU,Zach L,Li X,Butman JA,Camphausen KA,Lonser RR

    更新日期:2010-01-01 00:00:00

  • Symptom-based interventions to promote quality survivorship.

    abstract::Survival alone is no longer an adequate outcome for persons with brain tumors; the quality of the survivorship experience should be viewed with equal importance. Symptom management is a significant component of quality survivorship care. Regardless of their histology, brain tumors and therapies used to treat them prod...


    pub_type: 杂志文章


    authors: Amidei C

    更新日期:2018-11-09 00:00:00

  • Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

    abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...


    pub_type: 杂志文章


    authors: Cairncross G,Swinnen L,Bayer R,Rosenfeld S,Salzman D,Paleologos N,Kaminer L,Forsyth P,Stewart D,Peterson K,Hu W,Macdonald D,Ramsay D,Smith A,Oligodendroglioma Study Group.

    更新日期:2000-04-01 00:00:00

  • Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma.

    abstract:INTRODUCTION:Surgery is first-line therapy for glioblastoma, and there is evidence that gross total resection is associated with improved survival. Gross total resection, however, is not always possible, and relationships among extent (percent) of resection (EOR), residual volume (RV), and survival are unknown. The goa...


    pub_type: 杂志文章


    authors: Chaichana KL,Jusue-Torres I,Navarro-Ramirez R,Raza SM,Pascual-Gallego M,Ibrahim A,Hernandez-Hermann M,Gomez L,Ye X,Weingart JD,Olivi A,Blakeley J,Gallia GL,Lim M,Brem H,Quinones-Hinojosa A

    更新日期:2014-01-01 00:00:00

  • Gadd45a sensitizes medulloblastoma cells to irradiation and suppresses MMP-9-mediated EMT.

    abstract::Medulloblastomas are the most common malignant tumors of the central nervous system during childhood. Radiation-induced medulloblastoma tumor recurrences are aggressive and metastatic in nature. In the present study, we demonstrate that Gadd45a expression can sensitize medulloblastoma cells to radiotherapy. We have el...


    pub_type: 杂志文章


    authors: Asuthkar S,Nalla AK,Gondi CS,Dinh DH,Gujrati M,Mohanam S,Rao JS

    更新日期:2011-10-01 00:00:00

  • Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas.

    abstract::Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this ...


    pub_type: 临床试验,杂志文章


    authors: Grossman SA,Alavi JB,Supko JG,Carson KA,Priet R,Dorr FA,Grundy JS,Holmlund JT

    更新日期:2005-01-01 00:00:00