Human Glioblastoma Organoids to Model Brain Tumor Heterogeneity Ex Vivo

Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs). The resulting formation of hybrid organoids demonstrated an invasive tumor phenotype that was distinct from noncancerous adult neural progenitor (NP) spheroid incorporation into eCOs. These findings provide a basis for the modeling and quantification of the GBM infiltration process using a stem-cell-based organoid approach, and may be used for the identification of anti-GBM invasion strategies.

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IMMU-14. REVEALING THE MANY MYELOID STATES IN HUMAN BRAIN TUMORS AND WAYS TO PERTURB THEM

Neuro-Oncology ◽

10.1093/neuonc/noab196.373 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi94-vi95

Author(s):

Tyler Miller ◽

Chadi El Farran ◽

Julia Verga ◽

Charles Couturier ◽

Zeyu Chen ◽

...

Keyword(s):

Brain Tumor ◽

Tumor Microenvironment ◽

Immune Cells ◽

Ex Vivo ◽

Myeloid Cells ◽

Human Tumor ◽

Myeloid Cell ◽

Low Grade ◽

Tumor Patients ◽

The Many

Abstract Recent breakthroughs in immunotherapy have revolutionized treatment for many types of cancer, but unfortunately trials of these therapies have failed to provide meaningful life-prolonging benefit for brain tumor patients, potentially due to abundant immunosuppressive myeloid cells in the tumor. Our ultimate goal is to reprogram immunosuppressive tumor associated myeloid cells to an antitumor state to enable effective immunotherapy. Towards this goal, we have deeply characterized the immune microenvironment of more than 50 primary high and low grade gliomas using high-throughput single-cell RNA-sequencing to reveal recurrent myeloid cell states and immunosuppressive programs across IDH1 wild-type and mutant tumors. We have also established a brain tumor organoid model from primary patient tissue that maintains all of the tumor microenvironment, including myeloid and other immune cells. We utilize the this model to functionally test data-driven reprogramming strategies and understand how they impact the states of tumor and immune cells in the ex vivo human tumor microenvironment.

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Abstract 3639: Therapeutic targeting of tumorigenic EphA2+/EphA3+ brain tumor initiating cells with bi-specific antibody in human glioblastoma

10.1158/1538-7445.am2017-3639 ◽

2017 ◽

Author(s):

Maleeha Qazi ◽

Parvez Vora ◽

Chirayu Chokshi ◽

Chitra Venugopal ◽

Max London ◽

...

Keyword(s):

Brain Tumor ◽

Specific Antibody ◽

Tumor Initiating Cells ◽

Therapeutic Targeting ◽

Human Glioblastoma ◽

Brain Tumor Initiating Cells

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Face, Content, and Construct Validity of Brain Tumor Microsurgery Simulation Using a Human Placenta Model

Operative Neurosurgery ◽

10.1227/neu.0000000000001030 ◽

2015 ◽

Vol 12 (1) ◽

pp. 61-67 ◽

Cited By ~ 12

Author(s):

Marcelo Magaldi Oliveira ◽

Audrey Beatriz Araujo ◽

Arthur Nicolato ◽

Andre Prosdocimi ◽

Joao Victor Godinho ◽

...

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Construct Validity ◽

Content Validity ◽

Ex Vivo ◽

Subjective Evaluation ◽

Surgical Instruments ◽

Surgical Performance ◽

Human Brain Tumor ◽

Microsurgical Techniques

Abstract BACKGROUND Brain tumors are complex 3-dimensional lesions. Their resection involves training and the use of the multiple microsurgical techniques available for removal. Simulation models, with haptic and visual realism, may be useful for improving the bimanual technical skills of neurosurgical residents and neurosurgeons, potentially decreasing surgical errors and thus improving patient outcomes. OBJECTIVE To describe and assess an ex vivo placental model for brain tumor microsurgery using a simulation tool in neurosurgical psychomotor teaching and assessment. METHODS Sixteen human placentas were used in this research project. Intravascular blood remnants were removed by continuous saline solution irrigation of the 2 placental arteries and placental vein. Brain tumors were simulated using silicone injections in the placental stroma. Eight neurosurgeons and 8 neurosurgical residents carried out the resection of simulated tumors using the same surgical instruments and bimanual microsurgical techniques used to perform human brain tumor operations. Face and content validity was assessed using a subjective evaluation based on a 5-point Likert scale. Construct validity was assessed by analyzing the surgical performance of the neurosurgeon and resident groups. RESULTS The placenta model simulated brain tumor surgical procedures with high fidelity. Results showed face and content validity. Construct validity was demonstrated by statistically different surgical performances among the evaluated groups. CONCLUSION Human placentas are useful haptic models to simulate brain tumor microsurgical removal. Results using this model demonstrate face, content, and construct validity.

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Hierarchical non-negative matrix factorization to characterize brain tumor heterogeneity using multi-parametric MRI

NMR in Biomedicine ◽

10.1002/nbm.3413 ◽

2015 ◽

Vol 28 (12) ◽

pp. 1599-1624 ◽

Cited By ~ 24

Author(s):

Nicolas Sauwen ◽

Diana M. Sima ◽

Sofie Van Cauter ◽

Jelle Veraart ◽

Alexander Leemans ◽

...

Keyword(s):

Brain Tumor ◽

Matrix Factorization ◽

Tumor Heterogeneity ◽

Non Negative Matrix Factorization

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Heterogeneidade dos tumores cerebrais

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0038-1625962 ◽

2018 ◽

Author(s):

Telmo Belsuzarri ◽

Maick Neves ◽

Otávio Costa ◽

Diego Soares ◽

Fernando Melo Filho ◽

...

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Tumor Heterogeneity ◽

Glioma Stem Cells

ResumoHeterogeneidade tumoral significa que diferentes células tumorais levam a lesões morfológicas e fenotípicas distintas, com diferentes morfologias celulares, expressão gênica, metabolismo, microambiente, proliferação e possibilidade de lesões metastáticas. A heterogeneidade dos tumores cerebrais malignos tem sido o foco essencial de pesquisas recentes devido às interações notáveis entre genética, epigenética, microambiente e células-tronco glioma, todas mediadas por inflamação crônica. Tumores cerebrais ainda são um desafio no que tange a medicação e doença, podendo, com a carência de opções terapêuticas aliada a resultados insatisfatórios, ocorrer devido à heterogeneidade do tumor e seus múltiplos mecanismos de resistência à quimio e radioterapia. Foi realizada uma revisão da literatura na base de dados Pubmed usando os termos: brain tumor, heterogeneity, epigenetic, microenvironment, e glioma stem cells.

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