Tmod-04. naturally occurring canine glioma as a model for novel therapeutics
CONCLUSIONS:This abstract offers descriptive data for a naturally occurring canine glioma model, which can be used to test different therapies prior to human trials. The classification of tumor grading did correlate with median survival after surgery. The survival did not correlate with age, sex, or breed. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy immunotherapy, or other targeted therapies. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Hubbard, M., Arnold, S., Bin Zahid, A., McPheeters, M., Pluhar, E., Hunt, M. Tags: TUMOR MODELS Source Type: research
Tmod-03. cell-of-origin for gbm and its application for translational research
Glioma is a devastating disease because low-grade tumors inevitably progress into incurable high-grade GBMs. Among all probable explanations, such progressive nature could be attributed to the innate properties of its cell-of-origin. An ideal approach to identify the cell-of-origin for glioma is to analyze growth advantages of mutant cells in each brain cell types prior to malignancy. Our lab models glioma using a mouse genetic system called Mosaic Analysis with Double Markers (MADM), which generates GFP-labeled TSG-null cells and RFP-labeled sibling wildtype cells. By design, increased ratio of green-to-red cell numbers (...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kim, J. Tags: TUMOR MODELS Source Type: research
TMOD-02. Developing models of therapy resistance for the identification of treatment-refractory cell population(s) in human glioblastoma
In this study, we have developed a novel model to profile the clonal evolution of treatment naïve brain tumour initiating cell (BTIC) enriched hGBMs through chemoradiotherapy using: stem cell assays, BTIC marker expression and transcriptome analysis, immunohistochemistry, and cellular DNA barcoding technology. We report that treatment of hGBM BTICs leads to increased self-renewal capacity and higher transcript expression of stem cell genes Bmi1 and Sox2. Based on global transcriptome analysis of the in vitro treated hGBM, we also identify a hyper-aggressive form of glioma. Using our therapy-adapted hGBM-mouse xenog...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Qazi, M., Vora, P., Venugopal, C., Bakhshinyan, D., Nixon, A., Brown, K., Subapanditha, M., Chokshi, C., Murty, N., Moffat, J., Singh, S. Tags: TUMOR MODELS Source Type: research
Tmod-01. functional kinome characterization of a diverse panel of glioblastoma models
Glioblastoma (GBM) is the most common malignant primary brain tumor. Treatments are limited and clinical efficacy of kinase inhibitors has been disappointing. The molecular heterogeneity of GBM is well characterized, but knowledge of the GBM kinome is limited. To this end, we utilized a chemical proteomics method consisting of multiplex inhibitor beads and mass spectrometry (MIB-MS) to assess the functional state of tumor kinomes en masse, both in the presence (dynamic profiling) and absence (baseline profiling) of kinase inhibitors. Baseline kinome profiling of patient derived xenografts, established cell lines (ECL), iso...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: McNeill, R., Stuhlmiller, T., Bash, R., Khagi, S., Johnson, G., Ryan Miller, C. Tags: TUMOR MODELS Source Type: research
Tmic-30. role of matrix metalloproteinase 9 (mmp9) in resistance to anti-angiogenic therapy
CONCLUSIONS:These findings challenge the ideas that gelatinases are solely downstream targets of higher level regulators and that neutrophils are passive inflammatory bystanders, instead defining neutrophil-secreted MMP9 as an early activator responsible for downstream effects driving resistance to anti-angiogenic therapy. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Yagnik, G., Kuang, R., Jahangiri, A., Chen, W., Aghi, M. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-29. distinct molecular signatures of microglia and bone-marrow macrophages in the glioma perivascular niche
Tumor associated macrophage (TAM) infiltration correlates with glioma grade and invasiveness. TAMs are comprised of brain-resident microglia and bone-marrow monocyte derived cells, which extravasate the blood-brain barrier. Study of the distinct roles of these two populations of TAMs has been confounded by their overlapping and inducible gene expression profiles. To identify durable and specific gene-expression signatures for TAMs of microglial and bone-marrow origin respectively, we profiled regional biopsies of primary, untreated gliomas using single-cell and bulk sequencing. In 4 glioblastomas and 2 low-grade gliomas, w...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Muller, S., Kohanbash, G., Liu, S., Carrera, D., Aghi, M., Lim, D., Okada, H., Diaz, A. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-28. heterogeneous glioblastoma cell responses to tnf depend on molecular subtype
We examined how GBM molecular subtype and differentiation status influence invasive behaviors. The microglia/macrophages associated with GBM secrete a number of proinflammatory cytokines including tumor necrosis factor (TNF). In vitro, TNF up-regulates expression of the adhesion molecule VCAM-1 (Mahadev et al., PLoS One 9: e95123; 2014). We utilized a cohort of patient-derived primary glioma cell lines characterized by TCGA signature gene expression as PN or Mes (Brown et al., PLoS One 8: e7769; 2013), grown in culture with stem-like or differentiated cell properties (Brown et al., Cancer Res 69: 8886-8893; ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Barish, M., Mizes, A., Brewster, B., Baghdadchi, N., Brown, C. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-27. contact-induced bi-directional pro-survival signaling between endothelial cells and cancer stem-like cells in glioblastoma
We have demonstrated previously that direct contact between brain endothelial cells (ECs) and cancer stem-like cells (CSCs) from glioblastoma (GBM) significantly enhances endothelial cell migration and angiogenesis through a distinct signaling pathway (Burgett et al, Oncotarget 2016; doi: 10.18632/oncotarget.9700). To determine whether this contact promotes bi-directional signaling that regulates survival, we co-cultured ECs with CSCs on laminin in neurobasal media (NBM) without growth factors (3 hrs) and analyzed the mRNA expression of genes regulating survival and apoptosis with comparison to the mRNA levels found f...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Burgett, M., Nowacki, A., Lathia, J., Rich, J., Gladson, C. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-26. exploration of tryptophan metabolism via the kynurenine pathway in human gliomas
CONCLUSIONS:The increased staining of KP enzymes, as well as the diminished proliferation with the inhibitors, suggests that the KP plays a role in malignant gliomas, and may offer novel therapeutic targets for a patient population with highly limited treatment options. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Guastella, A. R., Kiousis, S., Klinger, N. V., Michelhaugh, S. K., Mittal, S. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-25. the inflammatory landscape of glioblastomas is heterogeneous and may correlate with patient outcome
CONCLUSION:Our preliminary analysis suggests that expression of immune-related genes in specific tumor regions may associate with patient outcomes. Further analysis of these patterns may provide insight into potential therapeutic targets and help predict sensitivity to immune modulatory therapies for glioblastoma. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kersch, C., Claunch-Rabe, C. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-24. the contribution of vascular co-option and tumor-derived endothelial cells to gbm recurrence
Despite aggressive treatment, the prognosis for glioblastoma (GBM) is very poor. The rate of recurrence is nearly 100%, and the recurrent tumor is usually more aggressive and resistant to treatment. The presence of a small population of tumor-initiating cells, the glioma stem cells (GSCs), has been associated with tumor recurrence and resistance to further therapy. To understand the role of GSCs on recurrence, we performed gene expression analysis on human-derived GBM xenografts (PDX) in both primary and recurrent models in vivo. The analysis indicated 3 angiogenesis-associated genes in recurrent GBM samples: CD34, CD105, ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Auffinger, B., Hasan, T., Lee, G., Tobias, A., Deheeger, M., Han, Y., Guo, D., Lesniak, M., James, C. D., Ahmed, A. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-23. differential expression of therapeutic targets across tumor microenvironments and at infiltrative margins in glioblastoma
We present differential protein expression patterns among specific tumor microenvironments as potential therapeutic targets. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Ross, J., Brat, D., Hadjipanayis, C., Cooper, L., Wiliams, M., Bouras, A., Kaluzova, M., Dunn, W., Gutman, D., Duong, D., McCrary, M. Tags: TUMOR MICROENVIRONMENT Source Type: research
TMIC-22. ENRICHMENT OF GLIOBLASTOMA STEM CELLS IN PNIPAAm SCAFFOLDS
Glioblastoma (GBM), the most common and lethal classification of primary adult brain tumor, is maintained by a subpopulation of GBM stem-like cells (GSCs) that exhibit a capacity for indefinite self-renewal and are capable of multipotent differentiation. GSCs are also more tumorigenic, invasive, and resistant to clinical therapies than differentiated GBM cells. Like neural stem cells, it is well-appreciated that GSCs are maintained by a local niche microenvironment that regulates stem-like phenotypes via soluble signaling factors and interactions with components of the extracellular matrix. GSCs are typically propagated in...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Heffernan, J., Bowen, S., Borwege, S., Szeto, E., McNamara, J., Vernon, B., Sanai, N., Mehta, S., Sirianni, R. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-21. kinomic profiling of glioblastoma cells reveals plcg1 as a common pro-survival signaling node under restricted glucose
Understanding the effects of tumor microenvironments on glioblastoma (GBM; grade IV astrocytoma) is required to develop anti-tumor treatments that will be effective in vivo. Physiologic levels of glucose are not modeled in traditional cell culture conditions and can be restricted in tumor niches. Our prior data demonstrated that nutrient restriction promotes phenotypes associated with a highly tumorigenic and therapy resistant subset of GBM cells called brain tumor initiating cells (BTICs). We therefore sought to profile the differences in kinase activity in GBM cells cultured in restricted glucose to identify pathways tha...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Walker, K., Boyd, N. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-20. stem-cell phenotype with dna hypomethylation is induced by hypoxia in glioblastoma
We examined the correlation between the methylation status of stem cell-related genes and the treatment outcomes in patients with glioblastoma (GBM) with special reference to the pseudopalisading necrosis. Tumor cells around necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor-β (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significan...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Iwadate, Y., Matsutani, T. Tags: TUMOR MICROENVIRONMENT Source Type: research
