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Hailong Li, Jiye Li, Gang Cheng, Jianning Zhang, Xuezhen Li
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O(6)-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis...
October 12, 2016: Clinical Neurology and Neurosurgery
Shigeo Ohba, Joydeep Mukherjee, Tor-Christian Johannessen, Andrew Mancini, Tracy T Chow, Matthew Wood, Lindsey Jones, Tali Mazor, Roxanne E Marshall, Pavithra Viswanath, Kyle M Walsh, Arie Perry, Robert J A Bell, Joanna J Phillips, Joseph F Costello, Sabrina M Ronen, Russell O Pieper
Mutations in the isocitrate dehydrogenase gene IDH1 are common in lower-grade glioma where they result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation and gliomagenesis. IDH1 mutations also co-segregate with mutations in the ATRX gene and the TERT promoter, suggesting that IDH mutation may drive the creation or selection of telomere-stabilizing events as part of immortalization/transformation process. To determine if and how this may occur, we investigated the phenotype of pRb/p53-deficient human astrocytes engineered with IDH1 wild-type (WT) or R132H mutant (IDH1mut) genes as they progressed through their lifespan...
October 6, 2016: Cancer Research
Vaidas Vicka, Laurynas Rimsevicius, Alvita Gincaite, Diana Sukackiene, Marius Miglinas
OBJECTIVE: Water balance and blood pressure (BP) alterations are strongly associated in haemodialysis (HD) patients. Aim of this study was to determine whether bioelectrical impedance analysis (BIA) parameters can be used as predictors of intradialytic hypotension (IDH). DESIGN AND METHOD: We conducted an observational study of chronic HD patients. BIA was measured before the HD procedure using InBody S10 (Biospace, Seoul, Korea) body composition analyzer. Intracellular water (ICW), extracellular water (ECW), total body water (TBW), ECW/TBW ratio and phase angle (PhA) were selected as markers of hydration state and thus possible predictors of IDH...
September 2016: Journal of Hypertension
Hyeon Chang Kim
Cardiovascular disease is the leading cause of death worldwide. Fortunately, cardiovascular mortality has been decreasing in high-income countries, but the rate is still increasing in some middle-income and low-income countries. Even within the Asian region, cardiovascular disease mortality is decreasing in some countries but increasing in others. However, population ageing is common to all Asian countries, and East Asia is among the most aged region in the world. Accordingly, cardiovascular disease prevention in the elderly is becoming more and more important public health issue in East Asia...
September 2016: Journal of Hypertension
Andreas Maus, Godefridus J Peters
Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer's biology is a key for the development of more effective therapy approaches...
October 17, 2016: Amino Acids
Eugene J Vaios, Brian V Nahed, Alona Muzikansky, Amir T Fathi, Jorg Dietrich
OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS])...
October 14, 2016: Journal of Neurosurgery
Shilpa Rao, Palavalasa Sravya, Chitra Chandran, Jitender Saini, Sampath Somanna, Vani Santosh
Oligodendrogliomas are diffuse gliomas characterised by IDH mutation and 1p/19q co-deletion. Classical oligodendrocytes, minigemistocytes, gliofibrillary oligodendrocytes, granular cells, and mucocytes are morphologic cell types described in oligodendroglioma. Even though the occurrence of granular cells in oligodendroglioma is known, exact nature of these cells and their molecular characteristics remain undetermined. We describe a case of oligodendroglioma with granular cells, in which we have attempted to molecularly characterise the granular cells...
October 13, 2016: Brain Tumor Pathology
B C Medeiros, A T Fathi, C D DiNardo, D A Pollyea, S M Chan, R Swords
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation, and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (TCA, also called the 'citric acid' or Krebs) cycle...
October 10, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Andrew L Lin, Michael White, Michelle M Miller-Thomas, Robert S Fulton, Christina I Tsien, Keith M Rich, Robert E Schmidt, David D Tran, Sonika Dahiya
During the 6 month period following chemoradiotherapy, gliomas frequently develop new areas of contrast enhancement, which are due to treatment effect rather than tumor progression. We sought to characterize this phenomenon in oligodendrogliomas (OG) and mixed oligoastrocytomas (MOA). We reviewed the imaging findings from 143 patients with a WHO grade II or III OG or MOA for evidence of pseudoprogression (PsP) or early tumor progression. We characterized these cases for 1p/19q codeletions by FISH, IDH1 R132H mutation by immunohistochemistry, and TP53, ATRX, and EGFR mutations by next generation sequencing...
October 4, 2016: Journal of Neuro-oncology
Wen Cheng, Xiufang Ren, Chuanbao Zhang, Jinquan Cai, Sheng Han, Anhua Wu
Isocitrate dehydrogenase (IDH)1 mutation is one of the most important genetic aberrations in glioma. Even several genetic events have refined its prognostic value, the genome-wide expression alteration has not been systematically profiled. In this work, RNA-seq expression data from 310 patients in the Chinese Glioma Genome Atlas database were included as training set, while another 297 patients with microarray data were used as internal validation set. An independent cohort of GSE16011 (n = 205) constituted an external validation set...
September 30, 2016: Molecular Neurobiology
Jonathan G Thomas, Ganesh Rao, Yvonne Kew, Sujit S Prabhu
OBJECTIVE Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that are difficult to resect and for GBMs that recur despite standard therapies. The authors reviewed their institutional experience of using laser interstitial thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs. METHODS This study reports on the pre-LITT characteristics and post-LITT outcomes of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who underwent LITT...
October 2016: Neurosurgical Focus
Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Guy Kantor, Martin J B Taphoorn, Mohamed Ben Hassel, Christian Hartmann, Gail Ryan, David Capper, Johan M Kros, Sebastian Kurscheid, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frederic Dhermain, Jacoline E Bromberg, Loic Feuvret, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Nicolas Dif, Carmen Balana, Jose Bravo-Marques, Paul M Clement, Christine Marosi, Tzahala Tzuk-Shina, Robert A Nordal, Jeremy Rees, Denis Lacombe, Warren P Mason, Roger Stupp
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration...
September 26, 2016: Lancet Oncology
Anthony J Zera, Rebecca Clark, Spence Behmer
The influence of variable nutritional input on life history adaptation is a central, but incompletely understood aspect of life history physiology. The wing-polymorphic cricket, Gryllus firmus, has been extensively studied with respect to the biochemical basis of life history adaptation, in particular, modification of lipid metabolism that underlies the enhanced accumulation of lipid flight fuel in the dispersing morph [LW(f)=long wings with functional flight muscles] relative to the flightless (SW=short-winged) morph...
September 28, 2016: Journal of Insect Physiology
Andreas F Hottinger, Monika E Hegi, Brigitta G Baumert
PURPOSE OF REVIEW: The management of patients suffering from low-grade gliomas (LGGs) remains a challenge in absence of a definite curative therapy. The median survival is highly variable, from 2 years (high-risk disease) to over 15 years (low risk). The aim of this review is to provide a practical step-by-step evaluation of the available treatment options for patients with LGGs. RECENT FINDINGS: Next to clinical prognostic markers, both the isocitrate dehydrogenase (IDH) mutation status and the status of 1p/19q codeletion are key prognostic factors for the optimal management of patients with LGG...
September 26, 2016: Current Opinion in Neurology
Dong-Ju Yun, Sang-Jin Lee, Sang-Joon Park, Hyeong Seok Oh, Young Jae Lee, Hyun Min Oh, Sang-Ho Lee
BACKGROUND: A new zero-profile, standalone device (Zero P) was recently developed and has shown a lower incidence rate of complications and competitive clinical outcomes compared to CP in single and multi-level ACDF. However, there is still concern whether Zero P is appropriate for multi-level ACDF. In addition, there have been few reports of contiguous two-level ACDF used in conjunction with Zero P. METHODS: We reviewed contiguous two-level ACDF performed from December 2006 to February 2015...
September 23, 2016: World Neurosurgery
Yang Yuan, Mao Yunhe, Wang Xiang, Liu Yanhui, Liang Ruofei, Luo Jiewen, Mao Qing
BACKGROUND: Tumor location, which serves as a prognostic factor for high-grade gliomas, may reflect the molecular and genetic phenotype of tumor initiate cells and thus predict tumor origin. Therefore, the purpose of this study was to combine radiographic atlases and tumor biomarkers through a voxel-based neuroimaging approach. METHODS: Preoperative MRIs were collected from 65 newly diagnosed patients with histologically confirmed high-grades gliomas. These samples were analyzed for TP53 mutations and MMP-9...
November 2016: Clinical Neurology and Neurosurgery
Alvaro Lassaletta, Michal Zapotocky, Eric Bouffet, Cynthia Hawkins, Uri Tabori
Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies...
October 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Gaurav Verma, Suyash Mohan, MacLean P Nasrallah, Steven Brem, John Y K Lee, Sanjeev Chawla, Sumei Wang, Rajakumar Nagarajan, M Albert Thomas, Harish Poptani
BACKGROUND: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism...
2016: Journal of Translational Medicine
Apurva Jain, Lawrence N Kwong, Milind Javle
Biliary tract cancers are relatively uncommon, have an aggressive disease course and a dismal clinical outcome. Until recently, there have been very few clinical advances in the management of these patients and gemcitabine-based chemotherapy has been the only widely accepted systemic therapy. The advent of next generation sequencing technologies can potentially change the treatment paradigm of this disease. Targeted therapy directed against actionable mutations and identification of molecular subsets with distinct prognostic significance is now feasible in clinical practice...
November 2016: Current Treatment Options in Oncology
Vaidas Vicka, Laurynas Rimsevicius, Alvita Gincaite, Diana Sukackiene, Marius Miglinas
OBJECTIVE: Water balance and blood pressure (BP) alterations are strongly associated in haemodialysis (HD) patients. Aim of this study was to determine whether bioelectrical impedance analysis (BIA) parameters can be used as predictors of intradialytic hypotension (IDH). DESIGN AND METHOD: We conducted an observational study of chronic HD patients. BIA was measured before the HD procedure using InBody S10 (Biospace, Seoul, Korea) body composition analyzer. Intracellular water (ICW), extracellular water (ECW), total body water (TBW), ECW/TBW ratio and phase angle (PhA) were selected as markers of hydration state and thus possible predictors of IDH...
September 2016: Journal of Hypertension
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