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brain tumour metabolism

Davide Chiasserini, Magdalena Davidescu, Pier Luigi Orvietani, Federica Susta, Lara Macchioni, Maya Petricciuolo, Emilia Castigli, Rita Roberti, Luciano Binaglia, Lanfranco Corazzi
: Glioblastoma (GBM) is the most common and aggressive brain tumours of adults. The metabolic phenotype of GBM cells is highly dependent on glycolysis; therefore, therapeutic strategies aimed at interfering with glycolytic pathways are under consideration. 3-Bromopyruvate (3BP) is a potent antiglycolytic agent, with a variety of targets and possible effects on global cell metabolism. Here we analyzed the changes in protein expression on a GBM cell line (GL15 cells) caused by 3BP treatment using a global proteomic approach...
November 23, 2016: Journal of Proteomics
Hugh Colvin, Naohiro Nishida, Masamitsu Konno, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Koichi Kawamoto, Ayumu Asai, Kenta Tsunekuni, Jun Koseki, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases...
November 8, 2016: Scientific Reports
Yekaterina A Miroshnikova, Janna K Mouw, J Matthew Barnes, Michael W Pickup, Johnathan N Lakins, Youngmi Kim, Khadjia Lobo, Anders I Persson, Gerald F Reis, Tracy R McKnight, Eric C Holland, Joanna J Phillips, Valerie M Weaver
Increased overall survival for patients with glioma brain tumours is associated with mutations in the metabolic regulator isocitrate dehydrogenase 1 (IDH1). Gliomas develop within a mechanically challenged microenvironment that is characterized by a dense extracellular matrix (ECM) that compromises vascular integrity to induce hypoxia and activate HIF1α. We found that glioma aggression and patient prognosis correlate with HIF1α levels and the stiffness of a tenascin C (TNC)-enriched ECM. Gain- and loss-of-function xenograft manipulations demonstrated that a mutant IDH1 restricts glioma aggression by reducing HIF1α-dependent TNC expression to decrease ECM stiffness and mechanosignalling...
November 7, 2016: Nature Cell Biology
Akbar Khan, Douglas Andrews, Anneke C Blackburn
Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death)...
October 16, 2016: World Journal of Clinical Cases
Yingying Liu, Shanshan Fang, Qiushi Sun, Bo Liu
Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner...
October 19, 2016: Biochemical and Biophysical Research Communications
Iris Völker, Iris Schwarze, Tina E Brezina, Saskia Köstlinger, Marion Hewicker-Trautwein
An 8-month-old, male African hedgehog clinically displayed a wobbly walk, anuria, inappetence and apathy, whereupon the suspected diagnosis wobbly hedgehog syndrome was made. After exacerbation, the hedgehog was euthanized. Histologically, a tumour mainly consisting of medium-sized, oval tumour cells and a smaller number of spindeloid cells was found in the cerebrum. The tumour contained neuropil islets and extracellular myxoid material. Immunohistochemically, the tumour cells expressed oligodendroglial (neurite outgrowth inhibitor, Nogo-A; oligodendrocyte transcription factor, Olig-2) and neuronal (neuron-specific enolase, NSE; microtubule-associated protein-2a, MAP-2a; synaptophysin) cell markers...
October 12, 2016: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Ji Liang, Ruixiu Cao, Yajuan Zhang, Yan Xia, Yanhua Zheng, Xinjian Li, Liwei Wang, Weiwei Yang, Zhimin Lu
Many types of human tumour cells overexpress the dual-specificity phosphatase Cdc25A. Cdc25A dephosphorylates cyclin-dependent kinase and regulates the cell cycle, but other substrates of Cdc25A and their relevant cellular functions have yet to be identified. We demonstrate here that EGFR activation results in c-Src-mediated Cdc25A phosphorylation at Y59, which interacts with nuclear pyruvate kinase M2 (PKM2). Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent β-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop...
August 3, 2016: Nature Communications
Jahae Kim, Kang-Ho Choi, Ho-Chun Song, Joon-Tae Kim, Man-Seok Park, Ki-Hyun Cho
PURPOSE: (18)F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of (18)F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischaemic stroke in cancer patients. METHODS: From among cancer patients presenting with various neurological symptoms and hemiparesis, 134 were selected as eligible for this retrospective analysis. A new infarct lesion on brain MRI within 1 year of FDG PET/CT defined future ischaemic stroke...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
Michelle M Kim, Abhijit Parolia, Mark P Dunphy, Sriram Venneti
The revolution in cancer genomics has uncovered a variety of clinically relevant mutations in primary brain tumours, creating an urgent need to develop non-invasive imaging biomarkers to assess and integrate this genetic information into the clinical management of patients. Metabolic reprogramming is a central hallmark of cancer, including brain tumours; indeed, many of the molecular pathways implicated in the pathogenesis of brain tumours result in reprogramming of metabolism. This relationship provides the opportunity to devise in vivo metabolic imaging modalities to improve diagnosis, patient stratification, and monitoring of treatment response...
December 2016: Nature Reviews. Clinical Oncology
Michael Torrens, Julia Malamitsi, Pantelis Karaiskos, Varvara Valotassiou, Fotis Laspas, John Andreou, Christos Stergiou, Vassilis Prassopoulos
AIM: To re-evaluate the role of (18)F-fluoro-deoxy-D-glucose (FDG) positron emission tomography/ computer assisted tomography (PET/CT) co-registered with magnetic resonance imaging (MRI) in differentiating adverse radiation effect (ARE) from tumour recurrence after Gamma Knife radiosurgery of brain tumours. PATIENTS AND METHODS: Twenty-seven PET/CT studies co-registered with MRI were performed on 16 patients after radiosurgery, with 12/16 patients having multiple radiosurgery treatments...
July 2016: In Vivo
Guido Frosina
Thorough imaging is crucial for diagnosis and treatment of high-grade gliomas (HGG), lethal brain tumours with median survival ranging 1-5 years after diagnosis. Positron-emission tomography (PET) is acquiring importance in imaging of HGG since it has the formidable advantage of providing information on tumour metabolism that may be critical for correct diagnosis and treatment planning. Recently employed PET tracers designed for the non-routine investigation of specific aspects of HGG metabolism, including hypoxia, neoangiogenesis, expression of integrins and stem cell markers, are reviewed herein...
July 2016: Anticancer Research
Ahmed Fathy Sharaf, Ehab Shaban Mahmoud Hamouda, Jennifer Gek Choo Teo
We report the neuroimaging findings of a 4-year-old girl with biopsy-proven bilateral thalamic and right fronto-temporo-parietal cortical gliomas, which are uncommon tumours involving the central nervous system. Despite their benignity, the prognosis is usually poor because of involvement of the thalamic nuclei and difficulty in surgical excision. These lesions have limited differential diagnoses that include metabolic, toxic, infective, vascular and neoplastic. Imaging characteristics on conventional Magnetic Resonance (MR), Magnetic Resonance Spectroscopy (MRS) and Diffusion tensor imaging (DTI) can further narrow the differential diagnosis and also provide additional information regarding the degree of involvement of adjacent brain tissue and white matter tracts around the lesions...
January 2016: Journal of Radiology Case Reports
Michael Gottschalk, Irène Troprès, Laurent Lamalle, Sylvie Grand, Jean-François Le Bas, Christoph Segebarth
Short-TE (1) H MRS has great potential for brain cancer diagnostics. A major difficulty in the analysis of the spectra is the contribution from short-T2 signal components, mainly coming from mobile lipids. This complicates the accurate estimation of the spectral parameters of the resonance lines from metabolites, so that a qualitative to semi-quantitative interpretation of the spectra dominates in practice. One solution to overcome this difficulty is to measure and estimate the short-T2 signal component and to subtract it from the total signal, thus leaving only the metabolite signals...
July 2016: NMR in Biomedicine
Felix Behling, Florian Hennersdorf, Antje Bornemann, Marcos Tatagiba, Marco Skardelly
BACKGROUND: 5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue...
August 2016: World Neurosurgery
Sarah M Clark, Ana Pocivavsek, James D Nicholson, Francesca M Notarangelo, Patricia Langenberg, Robert P McMahon, Joel E Kleinman, Thomas M Hyde, John Stiller, Teodor T Postolache, Robert Schwarcz, Leonardo H Tonelli
BACKGROUND: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology...
October 2016: Journal of Psychiatry & Neuroscience: JPN
A Adibfar, M Saleem, K L Lanctot, N Herrmann
Depression, the most common mood disorder, is a leading contributor to the global burden of disease affecting more than 120 million individuals worldwide. Various pathophysiological processes underlie depression; this complexity renders it difficult to identify clinically useful diagnostic and prognostic markers, as well as treatment options. The current state of knowledge driving the management and treatment of depression remains incomplete, which underscores the need for further insight into pathways relevant to depression...
2016: Current Molecular Medicine
M Min, P Lin, M Lee, I Ho Shon, M Lin, D Forstner, M T Tieu, A Chicco, V Bray, A Fowler
AIMS: To evaluate the prognostic utility of 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography (FDG PET-CT) carried out in the third week (iPET) and after completion (pPET) of definitive radiation therapy in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to investigate the optimal visual grading criteria for therapy response assessment. MATERIALS AND METHODS: Sixty-nine consecutive patients with newly diagnosed MPHNSCC treated with radical radiation therapy with or without systemic therapy underwent staging...
June 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Kai J Lorenz, Reiner Schallert, Volker Daniel
INTRODUCTION: In the postoperative phase, the prognosis of multiple trauma patients with severe brain injuries as well as of patients with extensive head and neck surgery mainly depends on protein metabolism and the prevention of septic complications. Wound healing problems can also result in markedly longer stays in the intensive care unit and general wards. As a result, the immunostimulation of patients in the postoperative phase is expected to improve their immunological and overall health...
2015: GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW
Magnus Sabel, Anette Sjölund, Jürgen Broeren, Daniel Arvidsson, Jean-Michel Saury, Klas Blomgren, Birgitta Lannering, Ingrid Emanuelson
PURPOSE: We investigated whether active video gaming (AVG) could bring about regular, enjoyable, physical exercise in children treated for brain tumours, what level of physical activity could be reached and if the children's physical functioning improved. METHODS: Thirteen children, aged 7-17 years, were randomised to either AVG or waiting-list. After 10-12 weeks they crossed-over. Weekly Internet coaching sessions were used to sustain motivation and evaluate enjoyment...
October 2016: Disability and Rehabilitation
Christophe Sandt, Céline Nadaradjane, Rosalie Richards, Paul Dumas, Violaine Sée
Hypoxia is a common feature of solid tumours and is associated with poor prognosis, resistance to radio- and chemotherapy, and tumour aggressiveness. For predictive purposes as well as for improved therapeutic intervention, it is increasingly needed to have direct and specific diagnostic tools in order to measure the extent of, and changes in, tumour hypoxia. In this article, we have investigated the potential of Fourier Transform Infrared (FTIR) microspectroscopy, at cellular and subcellular resolution, for detecting hypoxia-induced metabolic changes in brain tumour (glioblastoma) cell lines and in short term primary cultures derived from patient samples...
February 7, 2016: Analyst
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