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Medulloblastoma

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https://www.readbyqxmd.com/read/28221730/erratum-to-correct-lafay-cousin-et-al-clinical-pathological-and-molecular-characterization-of-infant-medulloblastomas-treated-with-sequential-high-dose-chemotherapy-pediatric-blood-cancer-2016-sep-63-9-1527-34
#1
https://www.readbyqxmd.com/read/28218785/inhibition-of-shh-pathway-mechanisms-by-arsenic-trioxide-in-pediatric-medulloblastomas-a-comprehensive-literature-review
#2
P H S Klinger, A F Andrade, L E A Delsin, R G P Queiroz, C A Scrideli, L G Tone, E T Valera
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28218430/stepwise-assembly-of-functional-c-terminal-rest-nrsf-transcriptional-repressor-complexes-as-a-drug-target
#3
Ken Inui, Zongpei Zhao, Juan Yuan, Sakthidasan Jayaprakash, Le T M Le, Srdja Drakulic, Bjoern Sander, Monika M Golas
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non-neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C-terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes...
February 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28217158/extra-axial-medulloblastoma-in-the-cerebellopontine-angle-report-of-a-rare-entity-with-review-of-literature
#4
Ishita Pant, Sujata Chaturvedi, Vinod K S Gautam, Pranjal Pandey, Rima Kumari
With only 33 cases reported so far, a purely extra-axial position of medulloblastoma at cerebellopontine (CP) angle is quite exceptional. We report a case of extra-axial medulloblastoma in a 15-year-old male child located in the CP angle that was surgically treated with a provisional diagnosis of schwannoma. Histopathological diagnosis of medulloblastoma was made with the routine hematoxylin and eosin stain and immunohistochemical markers. This case report highlights the fact that although extremely rare, the possibility of an extra-axial mass being a medulloblastoma does exist...
October 2016: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/28215670/therapeutic-efficacy-of-combined-pegylated-liposomal-doxorubicin-and-radiofrequency-ablation-comparing-single-and-combined-therapy-in-young-and-old-mice
#5
Alexander V Andriyanov, Emma Portnoy, Erez Koren, Sara Eyal, S Nahum Goldberg, Yechezkel Barenholz
Antitumor therapy in the elderly is particularly challenging due to multiple, often chronic diseases, poly-therapy, and age-related physiological changes that affect drug efficacy and safety. Furthermore, tumors may become more aggressive and drug-resistant with advanced age, leading to poor patient prognosis. In this study, we evaluated in mice bearing medulloblastoma xenografts the effect of age on tumor progression and tumor therapy. We focused on therapeutic efficacy of two treatment modalities alone radiofrequency ablation therapy (RFA), PEGylated liposomal doxorubicin (PLD) equivalent to Doxil, and their combination...
February 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#6
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28205381/the-clinical-significance-of-equivocal-findings-on-spinal-mri-in-children-with-medulloblastoma
#7
Julie Bennett, Ramy Ashmawy, Vijay Ramaswamy, Derek Stephens, Eric Bouffet, Normand Laperriere, Michael Taylor, Manohar Shroff, Ute Bartels
BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification...
February 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28197531/targeting-sox9-for-degradation-to-inhibit-chemoresistance-metastatic-spread-and-recurrence
#8
Aldwin Suryo Rahmanto, Fredrik J Swartling, Olle Sangfelt
Cancer cells with stem-like properties are believed to contribute to treatment resistance, dissemination, and recurrence. SOX9 controls stem cell plasticity and its deregulation may provide a basis for tumor progression. Here, we summarize our findings of targeted SOX9 destruction by SCF(FBW7) (Skp1/Cul1/F-box) in medulloblastoma and its potential for therapeutic intervention.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28192784/extra-axial-cerebellopontine-angle-medulloblastoma-in-an-infant
#9
Mukesh Kumar Bhaskar, Manish Jaiswal, Bal Krishna Ojha, Sunil Kumar Singh, Anil Chandra, Mukta Meel, Mohd Faheem
Medulloblastoma is a common tumor of the posterior fossa, representing 20-25% of all pediatric neoplasms. It commonly occurs in the midline (cerebellar vermis) and rarely at the cerebellopontine angle. Most of them are intra-axial, and an extra-axial location of this tumor is very rare. Extra-axial cerebellopontine angle medulloblastoma is extremely uncommon and has never been reported in an infant. We report an extra-axial cerebellopontine angle medulloblastoma in a 1-year-old child.
February 14, 2017: Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28187964/brain-perfusion-and-diffusion-abnormalities-in-children-treated-for-posterior-fossa-brain-tumors
#10
Matthew D Li, Nils D Forkert, Palak Kundu, Cheryl Ambler, Robert M Lober, Terry C Burns, Patrick D Barnes, Iris C Gibbs, Gerald A Grant, Paul G Fisher, Samuel H Cheshier, Cynthia J Campen, Michelle Monje, Kristen W Yeom
OBJECTIVE: To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. STUDY DESIGN: We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5...
February 7, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28186969/high-oct4a-levels-drive-tumorigenicity-and-metastatic-potential-of-medulloblastoma-cells
#11
Patrícia Benites Gonçalves da Silva, Márcia Cristina Teixeira Dos Santos, Carolina Oliveira Rodini, Carolini Kaid, Márcia Cristina Leite Pereira, Gabriela Furukawa, Daniel Sanzio Gimenes da Cruz, Mauricio Barbugiani Goldfeder, Clarissa Ribeiro Reily Rocha, Carla Rosenberg, Oswaldo Keith Okamoto
Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates...
7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28180935/clinicopathological-features-and-microsurgical-outcomes-for-giant-pediatric-intracranial-tumor-in-60-consecutive-cases
#12
Ailing Guo, Vigneyshwar Suresh, Xianzhi Liu, Fuyou Guo
PURPOSE: Giant pediatric intracranial tumor (GPIT) remains to be a challenging disease with high morbidity and mortality. METHODS: The clinical data of 60 patients under 18 years of age operated on with GPIT (≥5 cm in diameter) were retrospectively analyzed. RESULTS: Gross total resection was achieved in 46 cases (77%) and subtotal resection was obtained in 14 cases (23%). Ninety percent (47/52) of the cases with obstructive hydrocephalus were resolved remarkably and only 10% (5/52) of the patients needed a ventriculoperitoneal shunt after tumor resection...
February 8, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28179300/the-antiproliferative-and-colony-suppressive-activities-of-stat3-inhibitors-in-human-cancer-cells-is-compromised-under-hypoxic-conditions
#13
Jilai Tian, Hui Xiao, Ruohan Wu, Yang Cao, Chenglong Li, Ronald Xu, Christopher R Pierson, Jonathan L Finlay, Fang Yang, Ning Gu, Jiayuh Lin
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors. To examine this, two STAT3 inhibitors were tested to investigate their inhibitory efficacy in cancer cells grown under hypoxic conditions compared with those without hypoxia...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28167297/loss-of-pin1-suppresses-hedgehog-driven-medulloblastoma-tumorigenesis
#14
Tao Xu, Honglai Zhang, Sung-Soo Park, Sriram Venneti, Rork Kuick, Kimberly Ha, Lowell Evan Michael, Mariarita Santi, Chiyoko Uchida, Takafumi Uchida, Ashok Srinivasan, James M Olson, Andrzej A Dlugosz, Sandra Camelo-Piragua, Jean-François Rual
Medulloblastoma is the most common malignant brain tumor in children. Therapeutic approaches to medulloblastoma (combination of surgery, radiotherapy, and chemotherapy) have led to significant improvements, but these are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed. Genetic mutations leading to the activation of the Hedgehog pathway drive tumorigenesis in ~30% of medulloblastoma. In a yeast two-hybrid proteomic screen, we discovered a novel interaction between GLI1, a key transcription factor for the mediation of Hedgehog signals, and PIN1, a peptidylprolyl cis/trans isomerase that regulates the postphosphorylation fate of its targets...
February 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28164435/childhood-neoplasms-presenting-at-autopsy-a-20-year-experience
#15
Victoria A Bryant, John Booth, Liina Palm, Michael Ashworth, Thomas S Jacques, Neil J Sebire
OBJECTIVE: The aims of the review are to establish the number of undiagnosed neoplasms presenting at autopsy in a single centre and to determine the incidence and most common causes of sudden unexpected death due to neoplasia in infancy and childhood (SUDNIC). DESIGN: Retrospective observational study of paediatric autopsies performed on behalf of Her Majesty's Coroner over a 20-year period (1996-2015; n = 2,432). Neoplasms first diagnosed at autopsy were identified from an established database and cases meeting the criteria for sudden unexpected death were further categorised...
February 6, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28159923/the-anti-neoplastic-activity-of-vandetanib-against-high-risk-medulloblastoma-variants-is-profoundly-enhanced-by-additional-pi3k-inhibition
#16
Rogerio B Craveiro, Michael Ehrhardt, Julia Velz, Martin Olschewski, Barbara Goetz, Torsten Pietsch, Dagmar Dilloo
Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28137592/usp7-promotes-medulloblastoma-cell-survival-and-metastasis-by-activating-shh-pathway
#17
Meixiao Zhan, Xiaohan Sun, Jinxiao Liu, Yan Li, Yong Li, Xu He, Zizhang Zhou, Ligong Lu
The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28123507/inhibition-of-the-cyclind1-promoter-in-response-to-sonic-hedgehog-signaling-pathway-transduction-is-mediated-by-gli1
#18
Zhongxiao Lin, Hansong Sheng, Chaoguo You, Ming Cai, Yiping Zhang, Li Sheng Yu, Xiaoming Yu, Jian Lin, Nu Zhang
Medulloblastoma (MB) is the most common malignant tumor of the central nervous system in children. Accumulating evidence suggests a major role for the activation of the sonic hedgehog (SHH) signaling pathway in the development of MB cells; however, the mechanisms underlying the effect of this pathway on tumor survival and growth remain poorly understood. The Gli family zinc finger 1 (Gli1) transcription factor is considered as a mediator of the SHH signaling pathway in MB cells. Therefore, the present study investigated whether the SHH signaling pathway promotes the apoptosis of MB cells via downregulation of Gli1...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28122904/evolution-of-cerebral-microbleeds-after-cranial-irradiation-in-medulloblastoma-patients
#19
Duangnapa Roongpiboonsopit, Hugo J Kuijf, Andreas Charidimou, Li Xiong, Anastasia Vashkevich, Sergi Martinez-Ramirez, Helen A Shih, Corey M Gill, Anand Viswanathan, Jorg Dietrich
OBJECTIVE: To characterize the temporal and spatial pattern of cerebral microbleeds (CMBs) after cranial irradiation in patients with medulloblastoma. METHODS: We retrospectively identified patients with medulloblastoma treated with craniospinal irradiation at the Massachusetts General Hospital between 1999 and 2015. Longitudinal MRI including T2*-weighted gradient-recalled echo (GRE) sequences were reviewed, and the prevalence, spatial pattern, and risk factors associated with CMBs were characterized...
January 25, 2017: Neurology
https://www.readbyqxmd.com/read/28118148/erratum-for-the-paper-kalogeraki-a-tamiolakis-d-mavrigiannaki-p-karvelaskalogerakis-m-datseri-g-agelaki-s-papadopoulos-s-recurrent-cerebellar-desmoplastic-nodular-medulloblastoma-in-cerebrospinal-fluid-csf-in-the-elderly-a-cytologic-diagnosis-rom-j-intern-med
#20
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