Tmod-19. properties of cognitive development of children with cerebellar tumor
The aim of the study was to estimate the influence of brain tumor and tumor’s localization on children’s cognitive development. Two groups of children participated in research: 1) children with cerebellar tumor (N=19, aged 10-14); 2) control group of healthy children developing normally (N=30, aged 10-14).METHODS:K-ABC-II (Kaufman Assessment Battery for Children, 2nd Ed.); CANTAB (Cambridge Neuropsychological Test Automated Battery; Cambridge Cognition), selected subtests: SWM (spatial working memory).RESULTS:Analysis of covariance indicated that group of children with cerebellar tumor scored signific...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Chizhova, V., Shcheglova, A. Tags: TUMOR MODELS Source Type: research
Tmod-18. three-dimensional microtumors in physiologic microenvironments maintain brain tumor initiating cells
Elucidation of mechanisms of brain tumor initiating cell (BTIC) maintenance and therapeutic resistance offers great promise for development of novel anti-tumor treatments. Current leading studies rely on BTIC isolation from patient-derived xenografts followed by propagation as neurospheres. As this process is expensive and time-consuming, we determined if three-dimensional microtumors were an alternative in vitro method for modeling tumor growth via BITC maintenance and/or enrichment. Brain tumor cells were grown as neurospheres or as microtumors produced using a human-derived biomatrix HuBiogelTM and maintained with physi...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Gilbert, A., Walker, K., Tran, A., Gillespie, Y., Singh, R., Hjelmeland, A. Tags: TUMOR MODELS Source Type: research
Tmod-17. convergence of bmi1 and chd7 on erk signalling in medulloblastoma
Medulloblastoma is the most common malignant brain tumour of childhood, and a common cause of pediatric morbidity and mortality. Medulloblastomas have been dissected into four distinct molecular subgroups (WNT, SHH, Group 3, Group 4) with divergent clinical and biological profiles. The Polycomb group protein Bmi1 is upregulated in a variety of cancers, has a positive correlation with clinical grade/stage and poor prognosis and it is a highly druggable molecule. Bmi1 is overexpressed across all MB subgroups; the growth of SHH and Group 4 MB is dependent on Bmi1 expression. Genome wide in vivo insertional muta...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Marino, S., Dubuc, A., Da Cunha Jaeger, M., Morrissy, S., Taylor, M., Zhang, X. Tags: TUMOR MODELS Source Type: research
Tmod-16. biomathematical model of proneural tumors suggests best candidates for pdgf-inhibitor therapies
Platelet Derived Growth Factor (PDGF) is often over-expressed in gliomas, where it can drive tumor growth via autocrine stimulation of PDGF receptor (PDGFR) expressing glioma cells and via paracrine stimulation of non-neoplastic oligodendrocyte progenitor cells (OPCs), which also express PDGFRa. To date, the use of PDGF inhibitors has remained largely unsuccessful at improving patient outcomes in glioblastoma; however, this may be due to inadequate targeting of these agents to the best candidates. In particular, these therapies have been given in the recurrent setting, when tumors that had been predominantly comprised by O...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Massey, S., Canoll, P., Swanson, K. Tags: TUMOR MODELS Source Type: research
Tmod-15. mln8237 treatment in an orthoxenograft rodent model for malignant peripheral nerve sheath tumors
This study provides a robust and reproducible MPNST model, allowing for the advancement of MPNST therapy. This study also demonstrates the effectiveness of MLN8237 for MPNST treatment. Together, our data has major implications on the future of MPNST research by providing a robust murine model as well providing evidence that MLN8237 is an effective treatment for MPNSTs. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Mrowczynski, O., Payne, R. Tags: TUMOR MODELS Source Type: research
Tmod-14. establishment and molecular characterization of patient derived cell lines from low grade glioma
CONCLUSION:We have established and characterized LGG cell lines derived from patient tumor material and provided a unique resource to better understand LGG biology and improve targeted treatment strategies whilst also detailing the extent to which in vitro models of patient derived glioma cell lines mimic their tumor of origin. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Zaman, A., Rapkins, R., Nixdorf, S., Teo, C., McDonald, K. Tags: TUMOR MODELS Source Type: research
Tmod-13. simulating patterns of recurrence following ischemia in brain tumors
Glioblastoma Multiforme (GBM) is the most aggressive primary brain tumor with median survival of 14 months from diagnosis. Following resection, GBM recurrence most often occurs locally but can recur distally. Experimentally, hypoxia has been seen to drive infiltrative growth of glioma cells, but its clinical effects are not well understood. However, a recent paper demonstrated that GBM patients with perioperative ischemia are more likely to recur distally than those without, 61% vs 19%. While this is convincing evidence that hypoxia is involved in generating distant recurrences, it does not fully answer the question r...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Curtin, L., Hawkins-Daarud, A., Porter, A., Jacobs, J., Owen, M., van der Zee, K., Aoun, R., Bendok, B., Swanson, K. Tags: TUMOR MODELS Source Type: research
Tmod-12. a novel patient-derived xenograft model of brain metastasis
CONCLUSION:To the best of our knowledge this is the first report in which the cerebral aqueduct has been targeted for metastatic PDX modeling. Our data indicate that intracranial injection of metastatic cells into the cerebral aqueduct is a reproducible model to study both local growth of metastases and leptomeningeal disease. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kassam, A., Lacrosse, A. Tags: TUMOR MODELS Source Type: research
Tmod-11. using the sleeping beauty transposase system to generate mouse models of diffuse intrinsic pontine glioma harboring acvr1 and h3k27m mutations
In conclusion, we used the SB system to develop a mouse model of DIPG. We observed an increase in median survival and some phenotypic differences in tumors harboring the ACVR1 G328V mutation. The loss of Olig2 NRAS/shp53/ACVR1 G328V tumors is interesting because Olig2 has been associated with delayed tumor progression. In the future we aim to elucidate the mechanisms by which ACVR1 and H3.1 K27M mutations contribute to tumor initiation and progression in order to develop targeted therapies for DIPG. Work supported by NIH/NINDs, Leah’s Happy Hearts and Chad Tough Foundations. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Mendez, F. M., Nunez, F. J., Koschmann, C., Calinescu, A., Saxena, M., Kamran, N., Pawar, S., Dzaman, M., Lowenstein, P. R., Castro, M. G. Tags: TUMOR MODELS Source Type: research
Tmod-10. murine avatars permit study of glioblastoma genesis and progression
CONCLUSION:Preoperative identification of targets for tissue harvest and mindful maintenance of the tumor microenvironment throughout the collection and processing steps yields PDX that are highly reflective of the original tumor in regards to molecular and anatomical characteristics. This is critical when using murine avatars to develop treatments for and an understanding of the biology of GBM. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kassam, A., Lacrosse, A. Tags: TUMOR MODELS Source Type: research
TMOD-09. EGFRvIII INCREASES MISMATCH REPAIR PROTEIN EXPRESSION AND IS THEREFORE A PREDICTIVE MARKER FOR TEMOZOLOMIDE RESPONSE IN O6-METHYLGUANINE-DNA METHYLTRANSFERASE NEGATIVE GLIOBLASTOMA CELLS AND TUMORS
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults with an extremely poor prognosis. The standard therapy involves surgery followed by irradiation and temozolomide (TMZ) treatment. Epigenetic silencing of the O6-methylguanine-DNA-methyltransferase (MGMT) gene is the only predictive biomarker that is associated with TMZ response. Hence the establishment of new markers, which predict treatment response is therefore of significant interest. Approximately 20-30% of GBMs display expression of the epidermal growth factor receptor (EGFR) variant III (EGFRvIII), which is constitutively activated. The ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Struve, N., Brend, T., Stead, L., Ott, L., Petersen, C., Rothkamm, K., Short, S. C., Kriegs, M. Tags: TUMOR MODELS Source Type: research
Tmod-08. pdx modeling of recurrent glioblastoma for testing salvage therapies
In this study we have used a previously untreated patient derived xenograft (PDX), established from a GBM, for engrafting intracranial tumors in athymic mice that began receiving RT (2 Gy/day x 5) + TMZ (10 mg/kg x 5) on day 6 post-tumor cell implantation. Control untreated mice succumbed to growing tumor between days 22 and 26 post-tumor cell implantation. Sequential tumor bioluminescence readings revealed tumor regression in mice receiving RT + TMZ therapy. However, RT + TMZ treated tumors recurred between days 37 and 56 post-implantation. At time of tumor recurrence, mice either received no further treatment, ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: James, C. D., Ahmed, A., Raizer, J., Lesniak, M., Horbinski, C., Kumthekar, P. Tags: TUMOR MODELS Source Type: research
Tmod-07. cellular origins of glioblastoma: lessons from mouse models
A central question in glioblastoma research is the identity of the tumor-initiating cell and its contribution to the malignant phenotype and genomic state. We systematically examined the potential of adult CNS progenitors, and immature and mature neurons to induce fully penetrant glioblastoma using lineage-specific inducible cre mice to inactivate the tumor suppressors Nf1, Trp53 and Pten. Adult CNS progenitors give rise to phenotypically and molecularly distinct tumor subtypes, which, despite histologic identity as glioblastoma, are separable based on the lineage of the cell of origin. Mutations induced in adult neurons d...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Llaguno, S. A., Wang, Z., Sun, D., Chen, J., Pedraza, A., Xu, J., Kim, E., Hatanpaa, K., Raisanen, J., Burns, D., Johnson, J., Parada, L. Tags: TUMOR MODELS Source Type: research
Tmod-06. adaptive culture techniques for high grade glioma, meningioma and brain metastasis
CONCLUSION:We have demonstrated a successful close capture non-ablative harvest technique to be able to acquire viable tissue for cell culture of major brain tumors. We believe this represents a critical step toward better understanding the biology and the development of novel therapeutic targets for the treatment of these common brain tumors. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kassam, A., Coley, D. Tags: TUMOR MODELS Source Type: research
Tmod-05. regional astrocyte heterogeneity influences evolution of low-grade glioma during malignant progression
Glioblastoma (GBM) has a dismal median survival of around 15 months. Primary and secondary GBM likely evolve from low-grade precursors, albeit via distinct genetic and kinetic mechanisms. Primary GBM is composed of four transcriptome subtypes with distinct mutations and transcriptomes reminiscent of particular brain cells, suggesting that mutations and cellular origin contribute to GBM heterogeneity. However, the effects of regional heterogeneity among putative cells of origin on GBM pathogenesis remain elusive. We used genetic lineage tracing and fate mapping in conditional, inducible mice to show that inactivating R...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Irvin, D., Vitucci, M., McNeill, R., Bash, R., Miller, C. R. Tags: TUMOR MODELS Source Type: research
