Tmod-36. gene expression analysis of short and long survival groups of glioblastoma patient-derived orthotopic xenografts
Few molecular markers predictive of glioblastoma patient prognosis are MGMT promoter methylation, IDH1/2 mutation and G-CIMP status. Gene expression, on the other hand, has been less robust in predicting survival, in part due to the influence and variability of the hosts. Here we present analysis of gene expression patterns in relation to glioblastoma tumor aggressivity in uniform murine hosts, using glioblastoma patient-derived xenograft (PDX) models. Neurosphere cultures established from IDH1/2 wildtype glioblastomas were implanted orthotopically in cohorts of 10 to 15 nude mice, for development of PDX. Mice were monitor...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Cherba, D., Poisson, L., Winn, M., Kim, H., Verhaak, R. G. W., Mikkelsen, T., deCarvalho, A. C. Tags: TUMOR MODELS Source Type: research

Tmod-35. primary and recurrent sacral chordoma affects the hind limbs motor and nociceptive function in rats: an orthotopic spine model
CONCLUSIONS:We have developed an orthotopic human chordoma model in rats that reproduces cardinal clinical signs of the human pathology. Such signs include locomotor and sensory deficits present in human patients. The use of a reliable animal model of CHO will be essential for pathophysiology research and the development of new therapeutic strategies. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Sarabia-Estrada, R., Ruiz-Valls, A., R Sha, S., Guerrero-Cazares, H., Jimenez-Estrada, I., Tyler, B., Gallia, G., Gokaslan, Z., Quinones-Hinojosa, A., Sciubba, D. Tags: TUMOR MODELS Source Type: research

Tmod-34. reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model
CONCLUSIONS:This study demonstrates that peri-tumoral astrocytes undergo temporal and spatial changes after surgical tumor resection, and that surgery-induced changes influence the aggressiveness of residual tumor. Gaining a better understanding of the post-surgical microenvironment will allow optimization of therapeutic strategies and facilitate the development of new approaches that ameliorate surgery-mediated effects on recurrent tumors. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Okolie, O., Bago, J., Schmid, R., Irvin, D., Bash, R., Miller, C. R., Hingtgen, S. Tags: TUMOR MODELS Source Type: research

Tmod-32. mathematically modeling perineural spread along peripheral nerves
The perineural spread of cancers to and along the peripheral nerve system is an emerging explanation for neoplastic plexopathy and underestimated source of patient morbidity and mortality. The perineural spread is a slowly growing process and can be difficult to detect without diligence for those at risk. This can lead to significant loss of mobility, function, and reduced quality of life for patients affected. Building on previous results in modeling glioblastoma multiforme, we present a mathematical model for predicting the course and extent of the perineural spread of recurrent tumors. By tracking cancer growth in the l...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Jacobs, J., Capek, S., Spinner, R., Swanson, K. Tags: TUMOR MODELS Source Type: research

TMOD-31. AN INFLAMMATION RESPONSE GENE SIGNATURE IS ASSOCIATED WITH PROGNOSIS OF GLIOMA PATIENTS WITH 1p/19q CO-DELETION TUMORS
Meta-analysis of glioma patients revealed that LOH of 1p/19q (IDH mutant-codel) is associated with favorable progression-free survival (PFS) and overall survival (OS). Heterogeneity in clinical outcomes exists within this subset of glioma. To determine transcriptional biomarkers associated with treatment response, we developed and independently validated a method to determine codel status using gene expression. We screened the transcriptional profiles from 1,828 gliomas to identify 333 cases predicted to harbor 1p/19 co-deletion. In order to identify a prognostic gene signature, we split this dataset into a training datase...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Hu, X., Martinez-Ledesma, E., Zheng, S., Kim, H., Barthel, F., Jiang, T., R Hess, K., Verhaak, R. Tags: TUMOR MODELS Source Type: research

Tmod-30. r206h acvr1 significantly accelerates diffuse intrinsic pontine glioma pathogenesis
Diffuse intrinsic pontine gliomas (DIPGs) comprise 15% of pediatric brain tumors and are the leading cause of death for children with brain tumors. In spite of numerous clinical trials, little progress has been made in prolonging the survival of DIPG patients. As there are currently no effective treatments, it is important to develop mouse models in order to understand the biology of these tumors. Recently we, and others have discovered activating bone morphogenic protein (BMP) pathway mutations in ACVR1, which encodes for the Activin A receptor (ALK-2). ACVR1 mutations are found in 25% of DIPG patients and commonly c...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Hoeman, C., Hu, G., Cordero, F., Becher, O. Tags: TUMOR MODELS Source Type: research

Tmod-29. glioblastoma patient-derived xenograft microtumors as a high throughput preclinical testing platform
CONCLUSION:GBM PDX microtumors are well suited to high throughput therapeutic testing. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Willey, C., Gillespie, Y., Anderson, J., Langford, C., Gilbert, A., Hicks, P., Shevin, R., Singh, R. Tags: TUMOR MODELS Source Type: research

TMOD-28. UNDERSTANDING EGFRvIII GENOMIC BREAKPOINTS THROUGH CRISPR MODELING
Glioblastoma multiforme (GBM) is the most common and aggressive adult intracranial tumor accounting for 50% of diagnosed brain tumors every year. Genotypically, GBM’s express a variety of oncogenic mutations and amplifications including the epidermal growth factor receptor, EGFR. EGFR is the most frequently altered gene in GBM, being focally amplified in 40% of primary tumors. In a majority of these amplified EGFR cases, EGFRvIII is also present. The EGFRvIII mutant receptor is caused by recombination between loci in intron 1 and 7 leading to genomic deletion of exons 2-7, resulting in loss of part of the extracellul...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Jameson, N., Benitez, J., Zanca, C., Koga, T., Furnari, F. Tags: TUMOR MODELS Source Type: research

Tmod-27. autopsy derived orthotopic xenograft (adox) mouse models for terminal pediatric brain tumors
In conclusion, we have demonstrated that a fraction of tumor cells can survive the lengthy period of postmortem anoxia/starvation and regain tumorigenic capabilities in mouse brains; and identified CD57 as a new marker of the therapy-resistant cells. This novel panel of ADOX models should facilitate biological studies and preclinical therapy of pediatric brain tumors. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Qi, L., Baxter, P., Kogiso, M., Du, Y., Lindsay, H., Liu, Z., Su, J., Adesina, A., Walter, A., Murray, J., McNall-Knapp, R., Nazarian, J., Will Parsons, D., Chintagumpala, M., Blaney, S., Li, X.-N. Tags: TUMOR MODELS Source Type: research

Tmod-26. developing patient-derived xenograft models of metastatic cancer to the brain
The estimated annual incidence of cancer metastases to the brain is as high as 300,000, about 10 times the incidence of all primary brain cancers combined. At least 20% of all cancers eventually produce metastases to the brain, and approximately 40% of all patients who die of cancer have metastatic brain disease. Once a cancer metastasizes to the brain, median patient survival is 4-8 months. Paradoxically, only about 5% of all cancer research is devoted towards developing better ways of treating metastases. A major limitation in the field has been the relative lack of robust preclinical models. To address this, w...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kumthekar, P., Ahmed, A., Lesniak, M., James, C. D., Horbinski, C. Tags: TUMOR MODELS Source Type: research

Tmod-25. modeling adult proneural and mesenchymal glioblastoma using rcas/t-va technology
Glioblastoma (GBM) is the most common and aggressive malignant glioma, characterized by genetic heterogeneity, resistance to treatment, and dismal prognosis. The bulk of research in GBM biology utilizes passaged cell lines and xenograft models that may neglect some aspects of the tumor-stroma interactions, particularly the actions of the immune system. Additionally, the standard of care neglects the four subtypes that have been identified through analysis of the Cancer Genome Atlas. In order to advance exact research into GBM tumorigenesis, progression and treatment, we utilized RCAS/t-va technology to develop mouse models...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Herting, C., Hambardzumyan, D. Tags: TUMOR MODELS Source Type: research

Tmod-24. a novel xenograft model reveals a gene cascade defining a mesenchymal transition during the evolution of resistance to anti-angiogenic therapy
CONCLUSION:These results suggest a mesenchymal and pro-angiogenic response to bevacizumab supported by multiple converging pathways involving inflammation, hypoxia, and ECM remodeling. Strategies preventing the evolution of these responses should be developed and tested in the context of our novel xenograft model to improve the durability of therapeutic response. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Jahangiri, A., Chen, W., Yagnik, G., Sidorov, M., Rick, J., Kuang, R., Lay, M. D., Flanigan, P. M., Aghi, M. Tags: TUMOR MODELS Source Type: research

Tmod-22. snail1 regulates gliomagenesis independent of its mesenchymal function
CONCLUSION:Our data confirms a dual role for SNAIL1 in glioma progression, in which it cooperates with oncogenes to promote early transformation while independently also regulating mesechnymal changes at later stages of tumor development. Our platform combining RNAseq expression profiling and computational network analysis with biological validation provides a potentially powerful tool to study mechanistic events as low-grade gliomas become transformed into malignant gliomas. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Nguyen-Tran, D.-H., Kabbout, M., Le, S., Tran, D. Tags: TUMOR MODELS Source Type: research

Tmod-21. defining the growth factor niche that supports gbm initiation
It has been challenging to fully understand the initiation and progression of Glioblastoma Multiforme (GBM), as the early events in tumour development cannot be readily discerned. Although previous work has hypothesized that genetic alterations, such as chromosome 7 gain and chromosome 10 loss, are critical and conserved during tumour initiation in all GBMs, the functional roles of these events have not been characterized. We have developed a murine model which allows us to study the early stages of GBM initiation in vitro and interrogate the role of specific molecular events at different stages of tumour development. This...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Bohm, A., Blough, M., Cairncross, G. Tags: TUMOR MODELS Source Type: research

Tmod-20. establishment of a brain tumor model with dysfunctional tumor immunity in mice as a platform for immunotherapeutic evaluation
In conclusion, this novel mouse model may be useful to screen for novel immune checkpoint inhibitors and combination regimes in the setting of a single dysfunctional CD8 T cell response. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Nakashima, H., Alayo, Q., Penaloza, P., Barouch, D., Chiocca, E. A. Tags: TUMOR MODELS Source Type: research