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Cancer: Medulloblastoma

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Total 40 results found since Jan 2013.

NT-16 * NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR
Pediatric brain tumors are the leading cause of death in children, and survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP). Therefore, there is an urgent need to develop strategies to enhance the tumoricidal action of RT while sparing adjacent normal tissue. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 acti...
Source: Neuro-Oncology - November 3, 2014 Category: Cancer & Oncology Authors: Kievit, F., Stephen, Z., Wang, K., Dayringer, C., Ellenbogen, R., Silber, J., Zhang, M. Tags: NOVEL THERAPEUTICS (CLINICAL AND/OR LABORATORY RESEARCH) Source Type: research

P10.06 Oxamate attenuates aerobic glycolysis, motility, viability and proliferation of medulloblastoma but LDHA siRNA does not
Conclusions:It is possible that oxamate inhibits multiple LDH family members as the active site for LDH isoenzymes, comprised of LDHA and LDHB subunits are identical. The results of further investigations will be critical as LDHA may prove to be an inadequate target for MB and a broader LDH family inhibitor or lactate inhibitor may be more appropriate. However these studies, combined with extensive research into the literature, support the concept and provide proof of principle that targeting aerobic glycolysis and lactate production in medulloblastoma is worthwhile therapeutic avenue worth pursuing further.
Source: Neuro-Oncology - September 20, 2016 Category: Cancer & Oncology Authors: Valvona, C. J., Pilkington, G. J. Tags: P10 Pediatric brain tumours Source Type: research

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells
Conclusions Necrosis is associated with complement activation in medulloblastoma. Medulloblastoma cells express C3aR, and siRNA-mediated knockdown of C3aR inhibits proliferation of these cells in vitro.
Source: Inflammation Research - January 22, 2015 Category: Research Source Type: research

Abstract 3458: Role of the EphB1 gene in mediating migration, proliferation, and radiosensitization of medulloblastoma cells
Eph/ephrin signaling in a variety of cancers has been reported to promote aspects of tumorigenesis, including proliferation, migration, and angiogenesis. Medulloblastoma is an aggressive primitive neuroectodermal tumor originating in the cerebellum. Recently performed integrative genomic approach to a large cohort of medulloblastomas has identified four subtypes (A-D) based on clinical presentation, transcription profiles, genetic abnormalities, and clinical outcome. We show high levels of EphB1 expression in tumors derived from children with group D medulloblastomas, which are known to exhibit a poorer response to current...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Baig*, N. A., Timofeeva*, O., Dritschilo, A., Pasquale, E., Kool, M., Rood, B., Rodriguez, O., Albanese^, C., Karam^, S. Tags: Molecular and Cellular Biology Source Type: research

Overcoming resistance to sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma
ConclusionsRSK inhibitors are promising because they target RSK which is correlated with SHH patients as well as cause high levels of apoptosis to only MB cells. Importantly, BI‐D1870 crosses the BBB, acting as a scaffold for development of more long‐lived RSK inhibitors. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
Source: Pediatric Blood and Cancer - August 12, 2013 Category: Cancer & Oncology Authors: Mary Rose Pambid, Rachel Berns, Hans H. Adomat, Kaiji Hu, Joanna Triscott, Norbert Maurer, Natalia Zisman, Vijay Ramaswamy, Cynthia E. Hawkins, Michael D. Taylor, Christopher Dunham, Emma Guns, Sandra E. Dunn Tags: Research Article Source Type: research

PAX8 expression is associated with SHH/WNT subtypes, desmoplastic histology and patient survival in human medulloblastomas
ConclusionIn summary, high PAX8 expression is linked to better prognosis in medulloblastomas potentially by suppressing both proliferative and migratory properties of MB cells. The distinct spatio‐temporal expression pattern of PAX8 during brain development might contribute to the understanding of distinct MB subtype histogenesis.
Source: Neuropathology and Applied Neurobiology - October 1, 2014 Category: Neurology Authors: Patrick N. Harter, Peter Baumgarten, Jenny Zinke, Karl Schilling, Stefan Baader, Ann‐Kathrin Hartmetz, Jens Schittenhelm, Rudi Beschorner, Stefan Liebner, Dorothea Schulte, Karl‐Heinz Plate, Paul Gutwein, Andrey Korshunov, Stefan M. Pfister, David T. Tags: Original Article Source Type: research

Abstract LB-207: mTORC2/Akt signaling is modulated by noncanonical mitochondrial Notch1/PINK1 interaction in myc-amplified medulloblastoma tumorigenesis
Medulloblastoma is known to be the most malignant pediatric brain tumor. The armamentarium of targeted therapies to currently treat medulloblastoma and similar pediatric central nervous system malignancies is extremely limited, often necessitating the need to combat such tumors with modified regimens of therapeutic options designed originally to target adult neoplasms. Given such limited therapies, a budding focus on the role of mitochondrial dysregulation in the tumorigenesis of such pathologies merits consideration. Mitochondria are known to play fundamental roles in multiple processes conserved across eukaryotic species...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Feroze, A. H., Lee, K.-S., Gholamin, S., Wu, Z., Weissman, I., Lu, B., Mitra, S. S., Cheshier, S. Tags: Tumor Biology Source Type: research

Paired box gene 8 (PAX8) expression is associated with sonic hedgehog (SHH)/wingless int (WNT) subtypes, desmoplastic histology and patient survival in human medulloblastomas
ConclusionIn summary, high PAX8 expression is linked to better prognosis in MBs potentially by suppressing both proliferative and migratory properties of MB cells. The distinct spatio‐temporal expression pattern of PAX8 during brain development might contribute to the understanding of distinct MB subtype histogenesis.
Source: Neuropathology and Applied Neurobiology - January 29, 2015 Category: Neurology Authors: Patrick N. Harter, Peter Baumgarten, Jenny Zinke, Karl Schilling, Stefan Baader, Ann‐Kathrin Hartmetz, Jens Schittenhelm, Rudi Beschorner, Stefan Liebner, Dorothea Schulte, Karl‐Heinz Plate, Paul Gutwein, Andrey Korshunov, Stefan M. Pfister, David T. Tags: Original article Source Type: research

Abstract 487: Whole genome screen to identify genes targeting MYCN-driven embryonal tumors
MYCN is a driver of neuroblastoma (NB) tumorigenesis and is over-expressed in a number of tumors of embryonal origin, including rhabdomyosarcoma, medulloblastoma and diffuse intrinsic pontine gliomas. We sought to identify regulators of MYCN transcription by performing a whole genome screen (WGS) for regulators of MYCN promoter activity using a NB cell model. A plasmid containing the MYCN promoter (1.3kb upstream of MYCN TSS) fused to luciferase and stably integrated into the genome of NGP NB cells was the readout system. NGP-MYCNpluc, was selected based on MYCN luciferase activity inhibition by ATRA and HDAC inhibitors to...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thiele, C. J., Liu, Z., Veschi, V., Buehler, E., Martin, S. Tags: Tumor Biology Source Type: research

OTX2 is a therapeutic target for retinoblastoma and may function as a common factor between C-MYC, CRX, and phosphorylated RB pathways.
In this study on retinoblastoma, OTX2 was frequently amplified and/or overexpressed in primary tumors and cell lines. Knockdown of OTX2 expression by siRNA or pharmacologic inhibition by all-trans retinoic acid (ATRA) repressed OTX2 expression and cell proliferation and significantly decreased tumor growth in vivo. Loss of OTX2 expression also resulted in decreased expression of C-MYC and CRX, genes previously implicated in retinoblastoma tumorigenesis. Loss of OTX2 expression increased the phosphorylation of RB, a potential mechanism of modulating cell proliferation. Aberrant expression of OTX2 may contribute to the deve...
Source: International Journal of Oncology - September 23, 2015 Category: Cancer & Oncology Authors: Li J, Di C, Jing J, Di Q, Nakhla J, Adamson DC Tags: Int J Oncol Source Type: research

Silencing of DNA repair sensitizes pediatric brain tumor cells to ɣ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - April 28, 2017 Category: Environmental Health Source Type: research

Silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - May 11, 2017 Category: Environmental Health Source Type: research

PID1 (NYGGF4), a new growth-inhibitory gene in embryonal brain tumors and gliomas.
CONCLUSIONS: These data are the first to link PID1 to cancer and suggest that PID1 may have a tumor inhibitory function in these pediatric and adult brain tumors. PMID: 24300787 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - December 3, 2013 Category: Cancer & Oncology Authors: Erdreich-Epstein A, Robison N, Ren X, Zhou H, Xu J, Davidson TB, Schur M, Gilles FH, Ji L, Malvar J, Shackleford GM, Margol A, Krieger MD, Judkins AR, Jones DT, Pfister SM, Kool M, Sposto R, Asgharzadeh S Tags: Clin Cancer Res Source Type: research

Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma
Conclusions: Taken together, these findings highlight mitotic kinases and, in particular, WEE1 as a rational therapeutic target for medulloblastoma.
Source: Molecular Cancer - March 24, 2014 Category: Cancer & Oncology Authors: Peter HarrisSujatha VenkataramanIrina AlimovaDiane BirksIlango BalakrishnanBrian CristianoAndrew DonsonAdrian DubucMichael TaylorNicholas ForemanPhilip ReiganRajeev Vibhakar Source Type: research