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https://www.readbyqxmd.com/read/28435518/sparc-overexpression-alters-microrna-expression-profiles-involved-in-tumor-progression
#1
Bhavesh K Ahir, Nasya M Elias, Sajani S Lakka
Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28432426/posterior-cranial-fossa-tumours-in-children-at-national-cancer-institute-sudan-a-single-institution-experience
#2
Moawia Mohammed Ali Elhassan, Haytham Hussein Mohammed Osman, Jeannette Parkes
BACKGROUND: Posterior cranial fossa tumours (PCF) comprise 54-70% of childhood brain tumours. The clinical profile and outcomes of these tumours differ in area of the world. The aim of this study is to describe clinical characteristics, treatment and outcome of posterior cranial fossa tumours in Sudan. MATERIAL AND METHODS: A retrospective study of children diagnosed with posterior cranial fossa tumours and treated between January 1998 and December 2015 at National Cancer Institute, Sudan...
April 21, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28431179/mirna-regulation-in-gliomas-usual-suspects-in-glial-tumorigenesis-and-evolving-clinical-applications
#3
Heather Ames, Marc K Halushka, Fausto J Rodriguez
In recent years, an increasing role for noncoding small RNAs (miRNA) has been uncovered in carcinogenesis. These oligonucleotides can promote degradation and/or inhibit translation of key mRNAs. Recent studies have also highlighted a possible role for miRNAs in adult and pediatric brain tumors, including high- and low-grade gliomas, medulloblastoma, ependymoma, and neoplasms associated with neurofibromatosis type 1. Gliomas represent the most common category of primary intraparenchymal brain tumors, and, for example, manipulation of signaling pathways, through inhibition of PTEN transcription appears to be an important function of miRNA dysregulation through miR-21, miR-106b, and miR-26a...
April 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28429760/corrigendum-selective-targeting-of-hdac1-2-elicits-anticancer-effects-through-gli1-acetylation-in-preclinical-models-of-shh-medulloblastoma
#4
Sonia Coni, Anna Barbara Mancuso, Laura Di Magno, Giulia Sdruscia, Simona Manni, Silvia Maria Serrao, Dante Rotili, Eleonora Spiombi, Francesca Bufalieri, Marialaura Petroni, Monika Kusio-Kobialka, Enrico De Smaele, Elisabetta Ferretti, Carlo Capalbo, Antonello Mai, Pawel Niewiadomski, Isabella Screpanti, Lucia Di Marcotullio, Gianluca Canettieri
No abstract text is available yet for this article.
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#5
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28427187/rita-displays-anti-tumor-activity-in-medulloblastomas-independent-of-tp53-status
#6
Aline Gottlieb, Kristina Althoff, Laura Grunewald, Theresa Thor, Andrea Odersky, Marc Schulte, Hedwig E Deubzer, Lukas Heukamp, Angelika Eggert, Alexander Schramm, Johannes H Schulte, Annette Künkele
Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#7
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28417956/establishment-and-characterization-of-an-orthotopic-patient-derived-group-3-medulloblastoma-model-for-preclinical-drug-evaluation
#8
Emma Sandén, Cecilia Dyberg, Cecilia Krona, Gabriel Gallo-Oller, Thale Kristin Olsen, Julio Enríquez Pérez, Malin Wickström, Atosa Estekizadeh, Marcel Kool, Edward Visse, Tomas J Ekström, Peter Siesjö, John Inge Johnsen, Anna Darabi
Medulloblastomas comprise a heterogeneous group of tumours and can be subdivided into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct prognosis, biological behaviour and implications for targeted therapies. Few experimental models exist of the aggressive and poorly characterized Group 3 tumours. In order to establish a reproducible transplantable Group 3 medulloblastoma model for preclinical therapeutic studies, we acquired a patient-derived tumour sphere culture and inoculated low-passage spheres into the cerebellums of NOD-scid mice...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416738/differential-expression-of-folate-receptor-1-in-medulloblastoma-and-the-correlation-with-clinicopathological-characters-and-target-therapeutic-potential
#9
Hailong Liu, Qianwen Sun, Mingshan Zhang, Zhihua Zhang, Xinyi Fan, Hongyu Yuan, Cheng Li, Yuduo Guo, Weihai Ning, Youliang Sun, Yongmei Song, Chunjiang Yu
Medulloblastoma is the most common malignant brain tumor in children. Folate receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies. However the expression profile and the role of clinicopathological significance and therapeutic target potential in medulloblastoma still remain elusive. Currently we detected the expression of Folr1 in medulloblastoma and identified the diagnostic application by evaluating the clinical, pathological and neuroimaging values. Then we developed a target therapeutic compound with Folr1, which exhibited promising efficiency in treatment of medulloblastoma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415684/the-long-noncoding-rna-linc-ned125-controls-the-expression-of-medulloblastoma-driver-genes-by-microrna-sponge-activity
#10
Pietro Laneve, Agnese Po, Annarita Favia, Ivano Legnini, Vincenzo Alfano, Jessica Rea, Valerio Di Carlo, Valeria Bevilacqua, Evelina Miele, Angela Mastronuzzi, Andrea Carai, Franco Locatelli, Irene Bozzoni, Elisabetta Ferretti, Elisa Caffarelli
Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413799/lomustine-induced-acute-pulmonary-toxicity-in-a-pediatric-medulloblastoma-survivor
#11
Venkatraman Radhakrishnan, Jayachandran Perumal, Shirley Sundersingh, Tenali Sagar
No abstract text is available yet for this article.
January 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28411324/determinants-of-social-competence-in-pediatric-brain-tumor-survivors-who-participated-in-an-intervention-study
#12
Maru Barrera, Eshetu G Atenafu, Fiona Schulte, Ute Bartels, Lillian Sung, Laura Janzen, Joanna Chung, Danielle Cataudella, Kelly Hancock, Amani Saleh, Douglas Strother, Dina McConnell, Andrea Downie, Juliette Hukin, Shayna Zelcer
PURPOSE: This prospective study describes disease/treatment, personal characteristics, and social/family contextual variables as risk and resilience factors that predict social competence in pediatric brain tumor survivors (PBTS). METHODS: Ninety-one PBTS (51% male, mean age 11.21 years, off-treatment, attending a regular classroom >50% of the time) participated. PBTS and their primary caregivers (proxy) completed the Social Skills Rating System (SSRS) to assess social competence at baseline, 2, and 8 months follow-up...
April 14, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28409891/functional-validation-of-the-oncogenic-cooperativity-and-targeting-potential-of-tuberous-sclerosis-mutation-in-medulloblastoma-using-a-myc-amplified-model-cell-line
#13
Jacob J Henderson, Jacob P Wagner, Nicolle E Hofmann, Christopher A Eide, Yoon-Jae Cho, Brian J Druker, Monika A Davare
Medulloblastoma is the most common malignant brain tumor of childhood. To identify targetable vulnerabilities, we employed inhibitor screening that revealed mTOR inhibitor hypersensitivity in the MYC-overexpressing medulloblastoma cell line, D341. Concomitant exome sequencing unveiled an uncharacterized missense mutation, TSC2(A415V) , in these cells. We biochemically demonstrate that the TSC2(A415V) mutation is functionally deleterious, leading to shortened half-life and proteasome-mediated protein degradation...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28405869/long-term-neuropsychological-follow-up-of-young-children-with-medulloblastoma-treated-with-sequential-high-dose-chemotherapy-and-irradiation-sparing-approach
#14
Taryn B Fay-McClymont, Danielle M Ploetz, Don Mabbott, Karin Walsh, Amy Smith, Susan N Chi, Elizabeth Wells, Jennifer Madden, Ashley Margol, Jonathan Finlay, Mark W Kieran, Douglas Strother, Girish Dhall, Roger J Packer, Nicholas K Foreman, E Bouffet, Lucie Lafay-Cousin
High-dose chemotherapy (HDC) strategies were developed in brain tumor protocols for young children to prevent neuropsychological (NP) impairments associated with radiotherapy. However, comprehensive NP evaluations of these children treated with such strategies remain limited. We examined the long-term neurocognitive outcomes of young children (<6 years) with medulloblastoma, treated similarly, with a HDC strategy "according to" the chemotherapy regimen of the protocol CCG 99703. This retrospective study included young children less than 6 years of age at diagnosis of medulloblastoma treated from 1998 to 2011 at 7 North American institutions...
April 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28401061/transcription-factor-gfi1b-in-health-and-disease
#15
REVIEW
Eduardo Anguita, Francisco J Candel, Alberto Chaparro, Juan J Roldán-Etcheverry
Many human diseases arise through dysregulation of genes that control key cell fate pathways. Transcription factors (TFs) are major cell fate regulators frequently involved in cancer, particularly in leukemia. The GFI1B gene, coding a TF, was identified by sequence homology with the oncogene growth factor independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is essential for neutrophil differentiation in mice...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28401018/otx2-expression-contributes-to-proliferation-and-progression-in-myc-amplified-medulloblastoma
#16
REVIEW
Yining Lu, Collin M Labak, Neha Jain, Ian J Purvis, Maheedhara R Guda, Sarah E Bach, Andrew J Tsung, Swapna Asuthkar, Kiran K Velpula
Medulloblastoma is one of the most prevalent pediatric brain malignancies, accounting for approximately 20% of all primary CNS tumors in children under the age of 19. OTX2 is the member of a highly conserved family of bicoid-like homeodomain transcription factors responsible for the regulation of cerebellar development and of current investigational interest in the tumorigenesis of medulloblastoma. Recent studies have revealed that Group 3 and Group 4 medulloblastomas show marked overexpression of OTX2 with a concurrent amplification of the MYC and MYCN oncogenes, respectively, correlating with anaplasticity and unfavorable patient outcomes...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28400607/pid1-increases-chemotherapy-induced-apoptosis-in-medulloblastoma-and-glioblastoma-cells-in-a-manner-that-involves-nf%C3%AE%C2%BAb
#17
Jingying Xu, Xiuhai Ren, Anup Singh Pathania, G Esteban Fernandez, Anthony Tran, Yifu Zhang, Rex A Moats, Gregory M Shackleford, Anat Erdreich-Epstein
Phosphotyrosine Interaction Domain containing 1 (PID1; NYGGF4) inhibits growth of medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumor cell lines. PID1 tumor mRNA levels are highly correlated with longer survival in medulloblastoma and glioma patients, suggesting their tumors may have been more sensitive to therapy. We hypothesized that PID1 sensitizes brain tumors to therapy. We found that PID1 increased the apoptosis induced by cisplatin and etoposide in medulloblastoma and glioblastoma cell lines...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398210/out-of-field-doses-from-pediatric-craniospinal-irradiations-using-3d-crt-imrt-helical-tomotherapy-and-electron-based-therapy
#18
Marijke De Saint-Hubert, Dirk Verellen, Kenneth Poels, Wouter Crijns, Federica Magliona, Tom Depuydt, Filip Vanhavere, Lara Struelens
Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e craniospinal irradiation (CSI). This is associated with significant exposure of large volumes of healthy tissue with a growing concern regarding treatment associated side effects. The current study compares out-of-field organ doses in children receiving CSI with three-dimensional-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, including as well radiation doses resulting from imaging performed during treatment...
April 11, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28395087/retrospective-analysis-of-molecular-and-immunohistochemical-characterization-of-381-primary-brain-tumors
#19
Leomar Y Ballester, Gregory N Fuller, Suzanne Z Powell, Erik P Sulman, Keyur P Patel, Rajyalakshmi Luthra, Mark J Routbort
The classification of brain tumors has traditionally depended on microscopic examination of hematoxylin and eosin-stained tissue sections. The increased understanding of clinically relevant genetic alterations has led to the incorporation of molecular signatures as part of the diagnosis of brain malignancies. Advances in sequencing technologies have facilitated the use of next-generation sequencing (NGS) assays in clinical laboratories. We performed a retrospective analysis of sequencing results for 381 brain tumors tested by NGS at our institution using a validated, commercially available panel...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28394352/spatial-heterogeneity-in-medulloblastoma
#20
A Sorana Morrissy, Florence M G Cavalli, Marc Remke, Vijay Ramaswamy, David J H Shih, Borja L Holgado, Hamza Farooq, Laura K Donovan, Livia Garzia, Sameer Agnihotri, Erin N Kiehna, Eloi Mercier, Chelsea Mayoh, Simon Papillon-Cavanagh, Hamid Nikbakht, Tenzin Gayden, Jonathon Torchia, Daniel Picard, Diana M Merino, Maria Vladoiu, Betty Luu, Xiaochong Wu, Craig Daniels, Stuart Horswell, Yuan Yao Thompson, Volker Hovestadt, Paul A Northcott, David T W Jones, John Peacock, Xin Wang, Stephen C Mack, Jüri Reimand, Steffen Albrecht, Adam M Fontebasso, Nina Thiessen, Yisu Li, Jacqueline E Schein, Darlene Lee, Rebecca Carlsen, Michael Mayo, Kane Tse, Angela Tam, Noreen Dhalla, Adrian Ally, Eric Chuah, Young Cheng, Patrick Plettner, Haiyan I Li, Richard D Corbett, Tina Wong, William Long, James Loukides, Pawel Buczkowicz, Cynthia E Hawkins, Uri Tabori, Brian R Rood, John S Myseros, Roger J Packer, Andrey Korshunov, Peter Lichter, Marcel Kool, Stefan M Pfister, Ulrich Schüller, Peter Dirks, Annie Huang, Eric Bouffet, James T Rutka, Gary D Bader, Charles Swanton, Yusanne Ma, Richard A Moore, Andrew J Mungall, Jacek Majewski, Steven J M Jones, Sunit Das, David Malkin, Nada Jabado, Marco A Marra, Michael D Taylor
Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy...
April 10, 2017: Nature Genetics
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