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Nasser K Yaghi, Jun Wei, Yuuri Hashimoto, Ling-Yuan Kong, Konrad Gabrusiewicz, Edjah K Nduom, Xiaoyang Ling, Neal Huang, Shouhao Zhou, Brittany C Parker Kerrigan, Jonathan M Levine, Virginia R Fajt, Gwendolyn Levine, Brian F Porter, Eric G Marcusson, Kiyoshi Tachikawa, Padmanabh Chivukula, David C Webb, Joseph E Payne, Amy B Heimberger
BACKGROUND: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. METHODS: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects...
October 8, 2016: Neuro-oncology
Philippe Menei, Anne Clavreul, Jean Michel Lemée
No abstract text is available yet for this article.
October 7, 2016: Neuro-oncology
David Ratel, Boudewijn van der Sanden, Didier Wion
No abstract text is available yet for this article.
October 7, 2016: Neuro-oncology
Kenneth Aldape, Romina Nejad, David N Louis, Gelareh Zadeh
BACKGROUND: Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process...
September 29, 2016: Neuro-oncology
Roger J Packer, Stephan Pfister, Eric Bouffet, Robert Avery, Pratiti Bandopadhayay, Miriam Bornhorst, Daniel C Bowers, David Ellison, Jason Fangusaro, Nicholas Foreman, Maryam Fouladi, Amar Gajjar, Daphne Haas-Kogan, Cynthia Hawkins, Cheng-Ying Ho, Eugene Hwang, Nada Jabado, Lindsay B Kilburn, Alvaro Lassaletta, Keith L Ligon, Maura Massimino, Schouten-van Meeteren, Sabine Mueller, Theo Nicolaides, Giorgio Perilongo, Uri Tabori, Gilbert Vezina, Katherine Warren, Olaf Witt, Yuan Zhu, David T Jones, Mark Kieran
For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management...
September 28, 2016: Neuro-oncology
Tracy T Batchelor, Elizabeth R Gerstner, Xiaobu Ye, Serena Desideri, Daniel G Duda, David Peereboom, Glenn J Lesser, Sajeel Chowdhary, Patrick Y Wen, Stuart Grossman, Jeffrey G Supko
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 receptor tyrosine kinases including PDGF receptor-β, Fms-like tyrosine kinase 3, and c-Kit in patients with recurrent glioblastoma. RESULTS: In an initial feasibility study, 6 patients underwent resection for recurrent glioblastoma after receiving tandutinib 500mg twice daily for 7 days...
September 23, 2016: Neuro-oncology
Jayson Hardcastle, Lisa Mills, Courtney S Malo, Fang Jin, Cheyne Kurokawa, Hirosha Geekiyanage, Mark Schroeder, Jann Sarkaria, Aaron J Johnson, Evanthia Galanis
BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM is a promising strategy due to preclinical efficacy, excellent clinical safety, and its ability to evoke antitumor pro-inflammatory responses. We hypothesized that combining anti- programmed cell death protein 1 (anti-PD-1) blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thus improving therapeutic outcome...
September 23, 2016: Neuro-oncology
Chetan Bettegowda, Stephen Yip, Sheng-Fu Larry Lo, Charles G Fisher, Stefano Boriani, Laurence D Rhines, Joanna Y Wang, Aron Lazary, Marco Gambarotti, Wei-Lien Wang, Alessandro Luzzati, Mark B Dekutoski, Mark H Bilsky, Dean Chou, Michael G Fehlings, Edward F McCarthy, Nasir A Quraishi, Jeremy J Reynolds, Daniel M Sciubba, Richard P Williams, Jean-Paul Wolinsky, Patricia L Zadnik, Ming Zhang, Niccole M Germscheid, Vasiliki Kalampoki, Peter Pal Varga, Ziya L Gokaslan
BACKGROUND: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. METHODS: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP...
September 23, 2016: Neuro-oncology
Haley Gittleman, Daniel Lim, Michael W Kattan, Arnab Chakravarti, Mark R Gilbert, Andrew B Lassman, Simon S Lo, Mitchell Machtay, Andrew E Sloan, Erik P Sulman, Devin Tian, Michael A Vogelbaum, Tony J C Wang, Marta Penas-Prado, Emad Youssef, Deborah T Blumenthal, Peixin Zhang, Minesh P Mehta, Jill S Barnholtz-Sloan
BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor. Nomograms are often used for individualized estimation of prognosis. This study aimed to build and independently validate a nomogram to estimate individualized survival probabilities for patients with newly diagnosed GBM, using data from 2 independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. METHODS: This analysis included information on 799 (RTOG 0525) and 555 (RTOG 0825) eligible and randomized patients with newly diagnosed GBM and contained the following variables: age at diagnosis, race, gender, Karnofsky performance status (KPS), extent of resection, O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status, and survival (in months)...
September 23, 2016: Neuro-oncology
Sophie E van West, Hein G de Bruin, Bart van de Langerijt, Annemarie T Swaak-Kragten, Martin J van den Bent, Walter Taal
BACKGROUND: As the incidence of pseudo-progressive disease (psPD), or pseudoprogression, in low-grade glioma (LGG) is unknown, we retrospectively investigated this phenomenon in a cohort of LGG patients given radiotherapy (RT). METHODS: All MRI scans and clinical data from patients with histologically proven LGG treated with radiation between 2000 and 2011 were reviewed. PsPD was scored when a new enhancing lesion occurred after RT and subsequently disappeared or remained stable for at least a year without therapy, including dexamethasone...
September 21, 2016: Neuro-oncology
Edward K Avila, Marc Chamberlain, David Schiff, Jaap C Reijneveld, Terri S Armstrong, Roberta Ruda, Patrick Y Wen, Michael Weller, Johan A F Koekkoek, Sandeep Mittal, Yoshiki Arakawa, Ali Choucair, Jorge Gonzalez-Martinez, David R MacDonald, Ryo Nishikawa, Aashit Shah, Charles J Vecht, Paula Warren, Martin J van den Bent, Lisa M DeAngelis
Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy...
September 20, 2016: Neuro-oncology
Sabine Wagner, Heinrich Lanfermann, Gerrit Eichner, Hubert Gufler
BACKGROUND: We sought to determine whether radiation-induced injuries could be distinguished from malignancy after stereotactic radiosurgery (SRS) by analyzing time-dependent changes in lesion morphology on sequential MRI for up to 55min. METHODS: In 31 consecutive patients treated with SRS for brain metastases, the time-dependent changes in lesion morphology were analyzed on MRI 2min, 15min, and 55min after contrast administration and on subtraction images. A simultaneous, matched-pairs approach was used for quantitative region of interest analysis of the area of the lesion...
September 15, 2016: Neuro-oncology
Kelly V Pinheiro, Camila Alves, Marienela Buendia, Mirela S Gil, Amanda Thomaz, Gilberto Schwartsmann, Caroline Brunetto de Farias, Rafael Roesler
No abstract text is available yet for this article.
September 14, 2016: Neuro-oncology
Krishna M Talasila, Gro V Røsland, Hanne R Hagland, Eskil Eskilsson, Irene H Flønes, Sabrina Fritah, Francisco Azuaje, Nadia Atai, Patrick N Harter, Michel Mittelbronn, Michael Andersen, Justin V Joseph, Jubayer Al Hossain, Laurent Vallar, Cornelis J F van Noorden, Simone P Niclou, Frits Thorsen, Karl Johan Tronstad, Charalampos Tzoulis, Rolf Bjerkvig, Hrvoje Miletic
BACKGROUND: Invasion and angiogenesis are major hallmarks of glioblastoma (GBM) growth. While invasive tumor cells grow adjacent to blood vessels in normal brain tissue, tumor cells within neovascularized regions exhibit hypoxic stress and promote angiogenesis. The distinct microenvironments likely differentially affect metabolic processes within the tumor cells. METHODS: In the present study, we analyzed gene expression and metabolic changes in a human GBM xenograft model that displayed invasive and angiogenic phenotypes...
September 3, 2016: Neuro-oncology
Soner Gundemir, Alina Monteagudo, Abdullah Akbar, Jeffrey W Keillor, Gail V W Johnson
BACKGROUND: Glioblastomas (GBMs) are a heterogeneous group of primary brain tumors. These tumors are resistant to therapeutic interventions and invariably recur after surgical resection. The multifunctional protein transglutaminase 2 (TG2) has been shown to promote cell survival in a number of different tumors. There is also evidence that TG2 may be a pro-survival factor in GBMs. However, the roles that TG2 plays in facilitating GBM survival and proliferation have not yet been clearly delineated ...
September 2, 2016: Neuro-oncology
Benjamin M Ellingson, Robert J Harris, Davis C Woodworth, Kevin Leu, Okkar Zaw, Warren P Mason, Solmaz Sahebjam, Lauren E Abrey, Dana T Aftab, Gisela M Schwab, Colin Hessel, Albert Lai, Phioanh L Nghiemphu, Whitney B Pope, Patrick Y Wen, Timothy F Cloughesy
BACKGROUND: The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM...
August 31, 2016: Neuro-oncology
Louis-Marie Terrier, Luc Bauchet, Valérie Rigau, Aymeric Amelot, Sonia Zouaoui, Isabelle Filipiak, Agnès Caille, Fabien Almairac, Marie-Hélène Aubriot-Lorton, Anne-Marie Bergemer-Fouquet, Eric Bord, Philippe Cornu, Alain Czorny, Phong Dam Hieu, Bertrand Debono, Marie-Bernadette Delisle, Evelyne Emery, Walid Farah, Guillaume Gauchotte, Catherine Godfraind, Jacques Guyotat, Bernard Irthum, Kevin Janot, Pierre-Jean Le Reste, Dominique Liguoro, Hugues Loiseau, Guillaume Lot, Vincent Lubrano, Emmanuel Mandonnet, Philippe Menei, Philippe Metellus, Serge Milin, Bertrand Muckenstrum, Pierre-Hugues Roche, Audrey Rousseau, Emmanuelle Uro-Coste, Anne Vital, Jimmy Voirin, Michel Wager, Marc Zanello, Patrick François, Stéphane Velut, Pascale Varlet, Dominique Figarella-Branger, Johan Pallud, Ilyess Zemmoura
BACKGROUND: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. METHODS: Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively...
August 30, 2016: Neuro-oncology
Sarah J Nelson, Achuta K Kadambi, Ilwoo Park, Yan Li, Jason Crane, Marram Olson, Annette Molinaro, Ritu Roy, Nicholas Butowski, Soonmee Cha, Susan Chang
BACKGROUND: The heterogeneous biology of glioblastoma (GBM) emphasizes the need for imaging methods to assess tumor burden and assist in evaluating individual patients. The purpose of this study was to investigate early changes in metrics from 3D (1)H magnetic resonance spectroscopic imaging (MRSI) data, compare them with anatomic lesion volumes, and determine whether they were associated with survival for patients with newly diagnosed GBM receiving a multimodality treatment regimen. METHODS: Serial MRI and MRSI scans provided estimates of anatomic lesion volumes and levels of choline, creatine, N-acetylaspartate, lactate, and lipid...
August 30, 2016: Neuro-oncology
Natividad Gomez-Roman, Katrina Stevenson, Lesley Gilmour, Graham Hamilton, Anthony J Chalmers
BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug-radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures. METHODS: We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available...
August 30, 2016: Neuro-oncology
Jeffrey S Wefel, Kyle R Noll, Ganesh Rao, Daniel P Cahill
BACKGROUND: Patients with malignant gliomas present with variation in neurocognitive function (NCF) not attributable to lesion size or location alone. A potential contributor is the rate at which tumors grow, or "lesion momentum." Isocitrate dehydrogenase 1 wild type (IDH1-WT) are more proliferative and aggressive than IDH1-mutant (IDH1-M) tumors. We hypothesized that patients with IDH1-WT would exhibit worse NCF than patients with IDH1-M tumors. METHODS: Comprehensive NCF testing was completed in 119 patients with malignant glioma prior to surgical resection...
August 30, 2016: Neuro-oncology
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