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Cancer: Medulloblastoma

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Total 40 results found since Jan 2013.

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

Pharmacological Inhibition of the Protein Kinase MRK/ZAK Radiosensitizes Medulloblastoma
Medulloblastoma is a cerebellar tumor and the most common pediatric brain malignancy. Radiotherapy is part of the standard care for this tumor, but its effectiveness is accompanied by significant neurocognitive sequelae due to the deleterious effects of radiation on the developing brain. We have previously shown that the protein kinase MRK/ZAK protects tumor cells from radiation-induced cell death by regulating cell-cycle arrest after ionizing radiation. Here, we show that siRNA-mediated MRK depletion sensitizes medulloblastoma primary cells to radiation. We have, therefore, designed and tested a specific small molecule in...
Source: Molecular Cancer Therapeutics - August 2, 2016 Category: Cancer & Oncology Authors: Markowitz, D., Powell, C., Tran, N. L., Berens, M. E., Ryken, T. C., Vanan, M., Rosen, L., He, M., Sun, S., Symons, M., Al-Abed, Y., Ruggieri, R. Tags: Small Molecule Therapeutics Source Type: research

Radiosensitization of Medulloblastoma by Inhibition of MRK
Medulloblastoma is a cerebellar tumor and the most common pediatric brain malignancy. Radiotherapy is part of the standard care for this tumor, but its effectiveness is accompanied by significant neurocognitive sequelae due to the deleterious effects of radiation on the developing brain. We have previously shown that the protein kinase MRK/ZAK protects tumor cells from radiation-induced cell death by regulating cell-cycle arrest after ionizing radiation. Here, we show that siRNA-mediated MRK depletion sensitizes medulloblastoma primary cells to radiation. We have, therefore, designed and tested a specific small molecule in...
Source: Molecular Cancer Therapeutics - August 2, 2016 Category: Cancer & Oncology Authors: Markowitz, D., Powell, C., Tran, N. L., Berens, M. E., Ryken, T. C., Vanan, M., Rosen, L., He, M., Sun, S., Symons, M., Al-Abed, Y., Ruggieri, R. Tags: Small Molecule Therapeutics Source Type: research

Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.
Authors: Shen K, Lu F, Xie J, Wu M, Cai B, Liu Y, Zhang H, Tan H, Pan Y, Xu H Abstract Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mut...
Source: Oncotarget - July 17, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Abstract C25: Targeting cancer stem cells using ALDH-dependent 5-nitrofuran pro-drugs
We hypothesise that cancer stem cells with high aldehyde dehydrogenase (ALDHhigh) activity present a new therapeutic target and will be selectively sensitive to 5-nitrofuran pro-drugs.Cancers are heterogeneous and contain subpopulations of ALDHhigh cells with tumour initiating potential. ALDH enzymes metabolize toxic aldehydes, and are highly expressed in somatic and cancer stem cells (CSCs), although their function in stem cells is not fully understood. In a small molecule screen coupled with target ID, we recently discovered that clinically active 5-nitrofurans (5-NFNs) are substrates of ALDH2 (Zhou et al., 2012). 5-NFNs...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Crispin, R., Spockeli, N., Brunton, V., Carragher, N., Gourley, C., Houston, D., Unciti-Broceta, A., Patton, E. E. Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C195: A Wee1 inhibitor analog of AZD1775 demonstrates synergy with cisplatin with reduced single-agent toxicity in medulloblastoma
Medulloblastoma is the most common primary brain tumor in children. Current treatment for medulloblastoma includes surgical resection, radiation and cytotoxic chemotherapy. Although this approach has improved survival rates, the high doses of chemotherapy required to circumvent drug resistance mechanisms and result in clinical efficacy often give rise to lasting neurocognitive defects, stunted growth, deafness, and even secondary tumors. Therefore, synergistic drug combinations that maintain clinical efficacy, but allow dose reductions of cytotoxic agents limiting their adverse effects would be an attractive approach for p...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Matheson, C. J., Venkataraman, S., Amani, V., Harris, P., Backos, D. S., Foreman, N. K., Vibhakar, R., Reigan, P. Tags: Therapeutic Agents: Small Molecule Kinase Inhibitors: Poster Presentations - Proffered Abstracts 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

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

Abstract 3570: Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer
In this study, we evaluated whether DDX3 also plays a role in the constitutionally activated Wnt-signaling that drives colorectal cancer and therefore could be a potential therapeutic target in this cancer type.To determine if DDX3 is expressed in colorectal cancers, we immunohistochemically stained a cohort of 303 Dutch and German colorectal cancer patients. We found 40.4% of these tumors to overexpress DDX3 in comparison to the surrounding normal tissue. DDX3 expression was found predominantly in the cytoplasm and occasionally in the nucleus. High cytoplasmic DDX3 expression correlated with nuclear Beta-catenin expressio...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Heerma van Voss, M. R., Vesuna, F., Trumpi, K., Brilliant, J., Kodach, L. L., Morsink, F. H. M., Offerhaus, G. J. A., Buerger, H., van der Wall, E., van Diest, P. J., Raman, V. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 3338: Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma
In conclusion, we have developed a new small molecule inhibitor of MRK/ZAK that radio-sensitizes medulloblastoma cells. We hypothesize that combining radio-therapy with M443 will allow us to lower the radiation dose while maintaining therapeutic efficacy, thereby minimizing radiation-induced side effects.Citation Format: Rosamaria Ruggieri, Daniel Markowitz, Caitlin Powell, Nhan Tran, Magimairajanissai Vanan, Mingzu He, Yousef Al-Abed, Marc Symons. Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ruggieri, R., Markowitz, D., Powell, C., Tran, N., Vanan, M., He, M., Al-Abed, Y., Symons, M. Tags: Tumor Biology Source Type: research

Abstract 2090: GLI3 repressor levels determine Hedgehog pathway activity and predict response to Smoothened antagonist in acute myeloid leukemia
The Hedgehog (Hh) signaling pathway is activated in most hematological and solid cancers and is a promising target for therapeutic development. Deletions in the receptor Patched (PTCH) or activating mutations in the upstream positive regulator Smoothened (SMO) have been reported in a few cancers such as basal cell carcinoma and medulloblastoma, but are largely absent in most tumor types; therefore, the mechanism of pathway activation in most cancers remains unknown. In normal tissues, Hh pathway activation via PTCH/SMO causes an increase in the downstream activating transcription factor GLI1 and a decrease in the transcr...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chaudhry, P., Singh, M., Triche, T., Jorapur, A., Gill, P. S., Merchant, A. Tags: Molecular and Cellular 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

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

Cb-19 * pid1, a new growth-inhibitory gene, sensitizes medulloblastoma and glioma cell lines to chemotherapy
CONCLUSIONS: Our data show that PID1 sensitizes glioma and medulloblastoma cell lines to chemotherapy, possibly explaining the correlation between higher PID1 mRNA and longer patient survival. This suggests also that PID1 mimetics may act as chemotherapy sensitizers in brain tumor treatment.
Source: Neuro-Oncology - November 3, 2014 Category: Cancer & Oncology Authors: Xu, J., Ren, X., Tran, A., Erdreich-Epstein, A. Tags: CELL BIOLOGY Source Type: research

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