Stmc-15. innate immune signaling via tlr4 suppresses self-renewal in glioblastoma
Multiple cellular and molecular components within the glioblastoma microenvironment work to maintain a balance between immune dampening and inflammation, effectively preventing immune rejection of the tumor. Therefore, revealing the mechanisms that dampen immune signaling is critically important. Immune response initiation can be activated by ligands recognized by the toll-like family of receptors (TLRs). TLR activation limits proliferation in developing neural systems, yet these pathways are generally drivers of proliferation in many tumors including glioblastoma. This functional shift is surprising, considering the numbe...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Lathia, J., Alvarado, A., Vogelbaum, M., Hale, J., Silver, D. Tags: STEM CELLS Source Type: research
Stmc-14. glioblastoma cancer stem cells undergo dynamic state transitions
Glioblastoma (GBM) is a highly malignant brain tumor where no curative treatment is available. According to the cancer stem cell (CSC) hypothesis GBMs rely on a small subpopulation of cancer cells with stem-like properties responsible for tumor progression and recurrence. Recent experimental data from GBM and other cancers however suggest that CSCs cannot be defined by specific marker expression and may in fact not be a stable entity but a population of cells adapting to a changing microenvironment. We have previously shown that glioma CSCs do not represent a genetically homogenous population. Here we examined inter- and i...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Dirkse, A., Brons, N. H. C., Buder, T., Deutsch, A., Leite, S., Sauvageot, N., Senn, S., Herold-Mende, C., Golebiewska, A., Niclou, S. Tags: STEM CELLS Source Type: research
Stmc-13. tumorsphere isolation from who grade iv gliomas according to the weight of fresh specimens
CONCLUSION:Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Sung, K.-S., Shim, J.-K., Lee, J.-H., Kim, S. H., Park, S., Moon, J. H., Kim, E. H., Kim, S. H., Chang, J. H., Kang, S.-G. Tags: STEM CELLS Source Type: research
STMC-12. Sox2 ACTIVATES THE EXPRESSION OF ONCO-miRNA-486-5p
In this study, we identify miRNA-486-5p as a Sox2-induced miRNA that regulates GBM SC self-renewal, through its inhibition of the tumor suppressor gene, FoxO1. Using established glioma cell lines and patient-derived neurospheres as models of GBM, we show that miR-486-5p associates with the GBM SC phenotype and is directly induced by Sox2. Forced expression of miR-486-5p in vitro enhances the self-renewal capacity of GBM neurospheres and inhibition of endogenous miR-486-5p leads to cell death, concomitant with the activation of the miRNA-486-5p target FoxO1. These results suggest that Sox2 regulates the survival of GBM stem...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Michelson, N., Lopez-Bertoni, H., Li, Y., Laterra, J. Tags: STEM CELLS Source Type: research
STMC-11. ANALYSIS OF miRNA EXPRESSION PROFILE REGULATED BY SOX2 IN GLIOMA STEM-LIKE CELLS
This study suggests that miR-425-5p may act as a novel oncogene, providing future novel diagnostic and therapeutic strategies for glioblastoma. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: de la Rocha, A. M. A., Lopez-Bertoni, H., Martinez-Velez, N., Gonzalez-Huarriz, M., Laterra, J., Roldan, M. M. A. Tags: STEM CELLS Source Type: research
STMC-10. STEM CELL-BASED SUICIDE GENE THERAPY FOR MALIGNANT GLIOMA UTILIZING MUSE CELLS TRANSDUCED WITH HSVtk GENE
CONCLUSIONS:These results indicate feasibility and safety of this therapy. We are planning to progress to human clinical trials of allogeneic Muse cell-mediated suicide gene therapy in patients with malignant glioma. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Horikawa, M., Yamasaki, T. Tags: STEM CELLS Source Type: research
Stmc-09. assessment of tumorigenic potential of human induced pluripotent stem cell-derived neural stem/progenitor cells
DISCUSSION:Our research group is working vigorously to pursue a clinical trial for patients with SCI within the next several years. Therefore, it is crucial to establish criteria to choose the "safe" iPSC-NS/PCs. Here, we revealed differences in their SNVs, CNVs and DNA methylation patterns, which enables us to control the quality of iPSC-NS/PCs with respect to their tumorigenicity. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Iida, T., Iwanami, A., Kohyama, J., Nagoshi, N., Matsumoto, M., Okano, H., Nakamura, M. Tags: STEM CELLS Source Type: research
Stmc-08. actin cytoskeleton regulator arp2/3 complex is required for dll1 activating notch1 signaling to maintain the stem cell phenotype of brain tumor initiating cells
Glioblastoma (GBM) is the most common and lethal primary intracranial tumor. Actin cytoskeleton regulator ARP2/3 complex modulates glioma cell invasion and migration. Besides, inside the tumor entity contains brain tumor initiating cells (BTICs), which are resistant to chemical and radiation therapies and form recurrent tumor. It has been shown that NOTCH signaling is essential for BTICs to maintain the stem cell phenotype. But little is known regarding the role of actin cytoskeleton in NOTCH signaling and the stem cell phenotype maintenance. Here, we show ARP2/3 complex is required for NOTCH ligand DLL1 to activate NOTCH1...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Zhang, C., Yang, X. Tags: STEM CELLS Source Type: research
Stmc-07. prmt5-pten molecular pathway regulates senescence and self-renewal of glioblastoma neurospheres
Glioblastoma (GBM) represents the most common and aggressive histologic subtype among malignant astrocytoma and is associated with poor outcomes because of heterogeneous tumor cell population including mature non-stem like cell and immature stem-like cells within the tumor. Thus, it is critical to find new target-specific therapeutic modalities. Protein arginine methyltransferase enzyme 5 (PRMT5) regulates many cellular processes through its methylation activity and its overexpression in GBM is associated with more aggressive disease. Previously, we have shown that silencing of PRMT5 expression in differentiated GBM cell l...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Banasavadi-Siddegowda, Y. K., Russell, L., Frair, E., Karkhanis, V., Relation, T., Yoo, J. Y., Zhang, J., Sif, S., Imitola, J., Baiocchi, R., Kaur, B. Tags: STEM CELLS Source Type: research
Stmc-06. qki deletion enhances self-renewal of glioma stem cells and promotes gliomagenesis
Glioma stem cells (GSCs) have higher self-renewal capacity than neural stem cells (NSCs). However it is still not clear how GSCs enhance their self-renewal and whether or not enhanced self-renewal alone without affecting cell proliferation can promote gliomagenesis. Here we report the generation of a novel conditional KO allele of QKI, a tumor suppressor in GBM with RNA binding motif. When QKI was deleted in NSCs isolated from subventricular zone of Nestin-CreERT2 QKI L/L mice, multiple NSC markers were dramatically increased. When QKI was deleted in adult Nestin-CreERT2 QKI L/L mice, the NSC population, which is chara...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Hu, J., Shingu, T. Tags: STEM CELLS Source Type: research
Stmc-05. neural stem cells and glioblastoma
Glioblastoma multiforme represents one of the most frequent brain cancers, it display a rather heterogeneous cellular composition, as indicated by the term "multiforme". Recently some authors have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumors, even under the challenging settings posed by serial transplantation experiments. Our study focused attention on the distribution of neural cancer stem cells inside the tumour; the study ID divided in three phases: -removal of tumoural specimens ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Rispoli, R., Chirico, A. d., Ciampini, A., Kouleridou, A., Caputo, N., Carletti, S. Tags: STEM CELLS Source Type: research
Stmc-04. the utility of x0-glioma stem cell lines in understanding of gliomagenesis
We have established glioma stem cell lines from patients, named X0-series, representing cancer stem cell features, including self-renewal, multipotential differentiation, and recapitulation, both in vitro and in vivo, and even in long-term cultures (A Inagaki et al. BBRC 2007, N Oka et al. BBRC 2007). We have been providing these cell lines to researchers on request, with material transfer agreement, and they have been studied around the world (4 institutions in Japan, 8 in USA, and 5 in Korea). These researchers have independently investigated their original ideas and published their own results, without sharing...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Soeda, A., Park, D., Iwama, T. Tags: STEM CELLS Source Type: research
Stmc-03. repositioning chlorpromazine against chemoresistant glioma through the inhibition of cytochrome c oxidase
Chlorpromazine (CPZ) is an FDA-approved phenothiazine widely used as psychotropic in clinical practice. The pharmacological mechanism is through blockage of dopamine receptor. Recent reports have demonstrated some anti-proliferative activity against colon and brain tumors. However, the effect of CPZ in chemoresistant glioma has not yet been reported. Chemoresistant patient derived glioma stem cells and glioma cell lines were used to investigate the inhibitory mechanism of CPZ. CPZ effectively inhibited tumor growth and induced cell cycle arrest through the inhibition of cytochrome c oxidase subunit 4 isoform 1. Inhibi...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Griguer, C. E., Oliva, C. Tags: STEM CELLS Source Type: research
STMC-02. TUMOR RECURRENCE FROM CANCER STEM-LIKE CELLS POST-RADIATION IS REGULATED BY THE Shh-YAP-YB1-IGF2 AXIS IN MEDULLOBLASTOMA
Sonic hedgehog (Shh)-mediated medulloblastoma growth requires IGF2 (Insulin-like Growth Factor 2) and we have shown that over-expression of Yes Associated Protein (YAP1) induces IGF2 expression as a part of YAP’s radiation resistance mechanism in mouse Shh-medulloblastoma cells and Shh-induced cerebellar granule neural precursors (CGNPs), proposed cells-of-origin for the SHH molecular subclass of medulloblastoma (1). The peri-vascular niche, a microenvironmental niche proposed to house so-called tumor re-populating cells that survive radiation and contribute to medulloblastoma recurrence, showed high levels of Y...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Dey, A., Malhotra, A. Tags: STEM CELLS Source Type: research
STMC-01. NANOPARTICLE DELIVERY OF miRNAs TO INHIBIT GBM STEM CELLS
Cancer cells arise from multiple complementary genomic and epigenomic abnormalities that deregulate pathways that control cell proliferation and tissue homeostasis. Epigenetic modifications, involving deregulation of non-coding RNAs, are emerging as critical determinants of gene expression and essential drivers of neoplastic phenotypes. Our knowledge of how these complex epigenetic mechanisms operate in the context of cancer cell phenotype regulation remains limited. Non-coding RNAs, in particular miRNAs, are emerging as critical epigenetic regulators of cell fate and oncogenesis. MiRNAs act by selectively inhibiting gene ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Lopez-Bertoni, H. Tags: STEM CELLS Source Type: research
