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Medulloblastoma

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Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth.

Michelle A Francisco, Siyi Wanggou, Jerry J Fan, Weifan Dong, Xin Chen, Ali Momin, Namal Abeysundara, Hyun-Kee Min, Jade Chan, Rochelle McAdam, Marian Sia, Ronwell J Pusong, Shixuan Liu, Nish Patel, Vijay Ramaswamy, Noriyuki Kijima, Lu-Yang Wang, Yuanquan Song, Ran Kafri, Michael D Taylor, Xuejun Li, Xi Huang,

Ion channels represent a large class of drug targets, but their role in brain cancer is underexplored. Here, we identify that chloride intracellular channel 1 (CLIC1) is overexpressed in human central nervous system malignancies, including medulloblastoma, a common pediatric brain cancer. While global knockout does not overtly affect mouse development, ... Read more >>

J. Exp. Med. (The Journal of experimental medicine)
[2020, 217(5):]

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Mini-Symposium in Medulloblastoma Genomics in the Modern Molecular Era.

David W Ellison,

In this mini-symposium, four review articles describe recent advances in our understanding of the pathobiology of medulloblastoma. Medulloblastoma is the commonest malignant brain tumor of childhood and has been the subject of intense scientific investigation over several decades. ... Read more >>

Brain Pathol. (Brain pathology (Zurich, Switzerland))
[2020, :]

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Immunohistochemical and nanoString-Based Subgrouping of Clinical Medulloblastoma Samples.

Colleen E D'Arcy, Liana Figueiredo Nobre, Anthony Arnaldo, Vijay Ramaswamy, Michael D Taylor, Lili Naz-Hazrati, Cynthia E Hawkins,

The diagnosis of medulloblastoma incorporates the histologic and molecular subclassification of clinical medulloblastoma samples into wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3 and group 4 subgroups. Accurate medulloblastoma subclassification has important prognostic and treatment implications. Immunohistochemistry (IHC)-based and nanoString-based subgrouping methodologies have been independently described as options for medulloblastoma subgrouping, ... Read more >>

J. Neuropathol. Exp. Neurol. (Journal of neuropathology and experimental neurology)
[2020, 79(4):437-447]

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Predisposition of Wingless Subgroup Medulloblastoma for Primary Tumor Hemorrhage.

Dominik Reisinger, Johannes Gojo, Gregor Kasprian, Christine Haberler, Andreas Peyrl, Amedeo A Azizi, Lisa Mayr, Monika Chocholous, Marcel Kool, Thomas Czech, Irene Slavc,

BACKGROUND:Primary intratumoral hemorrhage as a presenting sign is rare in children with medulloblastomas but may result in severe complications. Given the distinct properties of molecular medulloblastoma subgroups, the impact on neurosurgical practice has still to be defined. OBJECTIVE:To investigate both clinical and radiological presentation of intratumoral hemorrhage in medulloblastoma patients ... Read more >>

Neurosurgery (Neurosurgery)
[2020, 86(4):478-484]

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Pathology, Diagnostics, and Classification of Medulloblastoma.

Brent A Orr,

Medulloblastoma (MB) is the most common CNS embryonal tumor. While the overall cure rate is around 70%, patients with high risk disease continue to have poor outcome and experience long term morbidity. Medulloblastoma is among the tumors for which diagnosis, risk stratification, and clinical management has shown the most rapid ... Read more >>

Brain Pathol. (Brain pathology (Zurich, Switzerland))
[2020, :]

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Differentiation Between Ependymoma and Medulloblastoma in Children with Radiomics Approach.

Jie Dong, Lei Li, Shengxiang Liang, Shujun Zhao, Bin Zhang, Yun Meng, Yong Zhang, Suxiao Li,

RATIONALE AND OBJECTIVES:Ependymoma (EP) and medulloblastoma (MB) of children are similar in age, location, manifestations and symptoms. Therefore, it is difficult to differentiate them through visual observation in clinical diagnosis. The aim of this study is to investigate the effectiveness of radiomics and machine-learning techniques on multimodal magnetic resonance imaging ... Read more >>

Acad Radiol (Academic radiology)
[2020, :]

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GLI3: a mediator of genetic diseases, development and cancer.

Stephan J Matissek, Sherine F Elsawa,

The transcription factor GLI3 is a member of the Hedgehog (Hh/HH) signaling pathway that can exist as a full length (Gli3-FL/GLI3-FL) or repressor (Gli3-R/GLI3-R) form. In response to HH activation, GLI3-FL regulates HH genes by targeting the GLI1 promoter. In the absence of HH signaling, GLI3 is phosphorylated leading to ... Read more >>

Cell Commun. Signal (Cell communication and signaling : CCS)
[2020, 18(1):54]

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Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data.

Jian Peng, Hao Zhou, Oliver Tang, Ken Chang, Panpan Wang, Xiaowei Zeng, Qin Shen, Jing Wu, Yanhe Xiao, Sohil H Patel, Chongyu Hu, Ke Jin, Bo Xiao, Jerrold Boxerman, Xiaoping Gao, Patrick Y Wen, Harrison X Bai, Raymond Y Huang, Li Yang,

BACKGROUND:Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. METHODS:We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients diagnosed with MBL, ... Read more >>

Neuro-oncology (Neuro-oncology)
[2020, :]

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Effective inhibition of MYC-amplified Group 3 medulloblastoma through targeting translation machinery eIF4F complex

Jie Ma, Yang Zhao, Tiantian Li, Shuaiwei Tian, Wei Meng, Jian Yang, Baocheng Wang, Zhuangzhuang Liang, Heng Zhao, Yipeng Han, Yujie Tang,

<title>Abstract</title> <p> Background: Medulloblastoma (MB) consists of four major molecular subtypes and group 3 subtype (G3) is the most aggressive one. MYC amplification tends to happen in G3 MB and those patients exhibit the worse prognosis and need novel effective therapeutic approach most urgently. MYC has been shown ... Read more >>

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Targeting MYC-driven replication stress in medulloblastoma with AZD1775 and gemcitabine.

Daniel C Moreira, Sujatha Venkataraman, Apurva Subramanian, John Desisto, Ilango Balakrishnan, Eric Prince, Angela Pierce, Andrea Griesinger, Adam Green, Charles G Eberhardt, Nicholas K Foreman, Rajeev Vibhakar,

PURPOSE:MYC-driven medulloblastomas are highly aggressive childhood tumors with dismal outcomes and a lack of new treatment paradigms. We identified that targeting replication stress through WEE1 inhibition to suppress the S-phase replication checkpoint, combined with the attenuation of nucleotide synthesis with gemcitabine, is an effective strategy to induce apoptosis in MYC-driven ... Read more >>

J. Neurooncol. (Journal of neuro-oncology)
[2020, :]

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Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study

Enrico Franceschi, Santino Minichillo, Antonella Mura, Alicia Tosoni, Maurizio Mascarin, Chiara Tomasello, Stefania Bartolini, Alba Ariela Brandes,

<title>Abstract</title> <p> Background : The role of chemotherapy for average-risk adult patients remains controversial. Medulloblastoma is extremely rare in adults. Radical surgery and radiotherapy provide a significant control of disease and a good prognosis but about 25% of average-risk patients have a relapse and die because of disease ... Read more >>

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Molecular Heterogeneity and Cellular Diversity: Implications for Precision Treatment in Medulloblastoma.

Han Zou, Brad Poore, Alberto Broniscer, Ian F Pollack, Baoli Hu,

Medulloblastoma, the most common pediatric malignant brain tumor, continues to have a high rate of morbidity and mortality in childhood. Recent advances in cancer genomics, single-cell sequencing, and sophisticated tumor models have revolutionized the characterization and stratification of medulloblastoma. In this review, we discuss heterogeneity associated with four major subgroups ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(3):]

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Using Fluorescein in the Resection of a Pediatric Posterior Fossa Tumor.

Alysa Almojuela, C Michael Honey, Alwyn Gomez, Mohammed Hasen, Carling MacDonald, Colin Kazina, Demitre Serletis,

Can J Neurol Sci (The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques)
[2020, :1-3]

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Editorial: Pediatric Central Nervous System Tumors: State-of-the-Art and Debated Aspects.

Andrea Carai, Angela Mastronuzzi,

Front Pediatr (Frontiers in Pediatrics)
[2020, 8:91]

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Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.

Kuo-Sheng Wu, Donald Ming-Tak Ho, Shiann-Tarng Jou, Alice L Yu, Huy Minh Tran, Muh-Lii Liang, Hsin-Hung Chen, Yi-Yen Lee, Yi-Wei Chen, Shih-Chieh Lin, Feng-Chi Chang, Min-Lan Tsai, Yen-Lin Liu, Hsin-Lun Lee, Kevin Li-Chun Hsieh, Wen-Chang Huang, Shian-Ying Sung, Che-Chang Chang, Chun Austin Changou, Kung-Hao Liang, Tsung-Han Hsieh, Yun-Ru Liu, Meng-En Chao, Wan Chen, Shing-Shung Chu, Er-Chieh Cho, Tai-Tong Wong,

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(3):]

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MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3).

Ranjana K Kanchan, Naveenkumar Perumal, Pranita Atri, Ramakanth Chirravuri Venkata, Ishwor Thapa, David L Klinkebiel, Andrew M Donson, Deborah Perry, Michael Punsoni, Geoffrey A Talmon, Donald W Coulter, Daniel R Boue', Matija Snuderl, Mohd W Nasser, Surinder K Batra, Rajeev Vibhakar, Sidharth Mahapatra,

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins ... Read more >>

Brain Pathol. (Brain pathology (Zurich, Switzerland))
[2020, :]

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Astrocytes - New Stars In The Medulloblastoma Firmament.

Charles Eberhart,

Neuro-oncology (Neuro-oncology)
[2020, :]

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Phase I study of intraventricular infusions of autologous ex-vivo-expanded NK cells in children with recurrent medulloblastoma and ependymoma.

Soumen Khatua, Laurence J N Cooper, David I Sandberg, Leena Ketonen, Jason M Johnson, Michael E Rytting, Diane D Liu, Heather Meador, Prashant Trikha, Robin J Nakkula, Gregory K Behbehani, Dristhi Ragoonanan, Sumit Gupta, Aikaterini Kotrotsou, Tagwa Idris, Elizabeth J Shpall, Katy Rezvani, Rivka Colen, Wafik Zaky, Dean A Lee, Vidya Gopalakrishnan,

BACKGROUND:Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex-vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies. METHODS:Twelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from ... Read more >>

Neuro-oncology (Neuro-oncology)
[2020, :]

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PET imaging of medulloblastoma with an 18F-labeled tryptophan analogue in a transgenic mouse model.

Yangchun Xin, Xuyi Yue, Hua Li, Zhiqin Li, Hancheng Cai, Arabinda K Choudhary, Shaohui Zhang, Diane C Chugani, Sigrid A Langhans,

In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):3800]

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Proton beam therapy utilization in adults with primary brain tumors in the United States.

William C Stross, Timothy D Malouff, Mark R Waddle, Robert C Miller, Jennifer Peterson, Daniel M Trifiletti,

The utilization of proton beam therapy (PBT) as the primary treatment of adults with primary brain tumors (APBT) was evaluated through query of the National Cancer Database (NCDB) between the years 2004 and 2015. International Classification of Diseases for Oncology code for each patient was stratified into six histology categories; ... Read more >>

J Clin Neurosci (Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia)
[2020, :]

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Population-Based Analysis of Demographic and Socioeconomic Disparities in Pediatric CNS Cancer Survival in the United States.

Robert Fineberg, Shadi Zahedi, Megan Eguchi, Muriel Hart, Myles Cockburn, Adam L Green,

Previous studies have demonstrated effects of racial and socioeconomic factors on survival of adults with cancer. While less studied in the pediatric population, data exist demonstrating disparities of care and survival in pediatric oncology patients based on socioeconomic and racial/ethnic factors. Brain cancers recently overtook leukemia as the number one ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):4588]

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Projected t-SNE for batch correction.

Emanuele Aliverti, Jeff Tilson, Dayne L Filer, Benjamin Babcock, Alejandro Colaneri, Jennifer Ocasio, Timothy R Gershon, Kirk C Wilhelmsen, David B Dunson,

MOTIVATION:Low-dimensional representations of high-dimensional data are routinely employed in biomedical research to visualize, interpret and communicate results from different pipelines. In this article, we propose a novel procedure to directly estimate t-SNE embeddings that are not driven by batch effects. Without correction, interesting structure in the data can be obscured ... Read more >>

Bioinformatics (Bioinformatics (Oxford, England))
[2020, :]

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An Inbred Ecosystem that Supports Medulloblastoma.

Ana de Pablos-Aragoneses, Manuel Valiente,

In a recent issue of Cell, Yao et al. use a unique genetic strategy to study sonic hedgehog-medulloblastoma. Their results reveal a complex network in the tumor microenvironment involving the trans-differentiation of cancer cells into astrocytes to fuel tumor growth. ... Read more >>

Immunity (Immunity)
[2020, 52(3):431-433]

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Heterozygous mutation of sonic hedgehog receptor (Ptch1) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice.

Thomas W Jackson, Gabriel A Bendfeldt, Kelby A Beam, Kylie D Rock, Scott M Belcher,

Sonic hedgehog (SHH) signaling is essential for the differentiation and migration of early stem cell populations during cerebellar development. Dysregulation of SHH-signaling can result in cerebellar overgrowth and the formation of the brain tumor medulloblastoma. Treatment for medulloblastoma is extremely aggressive and patients suffer life-long side effects including behavioral deficits. ... Read more >>

Neurotoxicol Teratol (Neurotoxicology and teratology)
[2020, 78:106866]

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Pediatric medulloblastoma in the molecular era: what are the surgical implications?

Michelle M Kameda-Smith,

Pediatric brain tumors are the leading cause of childhood cancer mortality with medulloblastoma (MB) representing the most frequent malignant tumor. Although standardization of therapy resulted in a 2-fold reduction in mortality in patients with MB by 2002, it became clear that further improvements in clinical outcome would require a deeper ... Read more >>

Cancer Metastasis Rev. (Cancer metastasis reviews)
[2020, 39(1):235-243]

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