In vivo MRI visualization of U87 glioblastoma development dynamics in the model of orthotopic xenotransplantation to the SCID mouse

Zavjalov, Evgenii L.; Разумов, И. А.; Gerlinskaya, L. A.; Romashchenko, A. V.

doi:10.1134/s2079059716040225

Cited by 18 publications

(17 citation statements)

References 30 publications

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“…Specifically, similar to other cell-line models, human GBM cell lines exhibit genetic drifts and alterations in their transcriptomes, lose cellular heterogeneity, and lose the ability to invade adjacent tissues following prolonged culturing with serum ( 41 , 42 ). Our results on histological analysis of human GBM U87 MG corresponded to the published data ( 43 , 44 ) and showed a rather homogeneous, compact structure of the tumor without pronounced cellular heterogeneity and nuclear atypia. Tumor vascularization was moderately expressed, and no pseudopalisading necrosis was found.…”

Section: Discussionsupporting

confidence: 90%

Highly Invasive Fluorescent/Bioluminescent Patient-Derived Orthotopic Model of Glioblastoma in Mice

et al. 2022

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Development of the novel diagnostic and therapeutic approaches in neuro-oncology requires tumor models that closely reproduce the biological features of patients’ tumors. Patient-derived xenografts (PDXs) are recognized as a valuable and the most “close-to-patient” tool for preclinical studies. However, their establishment is complicated by the factors related to both the surgical material and technique of the orthotopic implantation. The aim of this work was to develop a patient-derived glioblastoma multiform (GBM) model that stably co-expresses luciferase and a far-red fluorescent protein for monitoring of tumor progression in the brain and, using this model, to validate new diagnostic methods—macroscopic fluorescence lifetime imaging (macro-FLIM) and cross-polarization optical coherence tomography (CP OCT). The established model was similar to the original patient’s GBM in terms of histological and immunohistochemical features and possessed reproducible growth in nude mice, which could be observed by both fluorescence and bioluminescence imaging. Our results demonstrated the high potential of macro-FLIM and CP OCT for intraoperative differentiation of GBM from the white matter. Thus, the dual-labeled PDX model of GBM proved to be an excellent approach for observation of tumor development by optical methods.

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Section: Discussionsupporting

confidence: 90%

Highly Invasive Fluorescent/Bioluminescent Patient-Derived Orthotopic Model of Glioblastoma in Mice

et al. 2022

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“…The main idea of this paper is to estimate dependency between glioma tissue and biomarkers in blood serum, revealed by Raman spectroscopy. We used the most common model of human glioma, when continuous cell lines such as U87, derived from primary human tumor cells, are transplanted intracranially into the mouse brain [ 49 , 76 ]. This model is characterized by rapid glioma growth following the injection of tumor cells into the subcortical structures of the brain.…”

Section: Discussionmentioning

confidence: 99%

“…The study was conducted on 60 male mice of the immunodeficient SCID line at the age 6–7 weeks. The model of orthotopic xenotransplantation of the U87 human glioblastoma cells into mice was used [ 49 , 50 ]. A total of 5 μL of the U87 MG cell suspension (500,000 cells per one injection) was introduced in the subcortical brain structure through a hole in the animal’s cranium.…”

Section: Methodsmentioning

confidence: 99%

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Discovering Glioma Tissue through Its Biomarkers’ Detection in Blood by Raman Spectroscopy and Machine Learning

et al. 2023

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The most commonly occurring malignant brain tumors are gliomas, and among them is glioblastoma multiforme. The main idea of the paper is to estimate dependency between glioma tissue and blood serum biomarkers using Raman spectroscopy. We used the most common model of human glioma when continuous cell lines, such as U87, derived from primary human tumor cells, are transplanted intracranially into the mouse brain. We studied the separability of the experimental and control groups by machine learning methods and discovered the most informative Raman spectral bands. During the glioblastoma development, an increase in the contribution of lactate, tryptophan, fatty acids, and lipids in dried blood serum Raman spectra were observed. This overlaps with analogous results of glioma tissues from direct Raman spectroscopy studies. A non-linear relationship between specific Raman spectral lines and tumor size was discovered. Therefore, the analysis of blood serum can track the change in the state of brain tissues during the glioma development.

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“…The experimental human GBM tumors were induced in the brain of the pre-treated SCID mice by a stereotactic inoculation of U87 cells into the subcortical brain structures ( 50 ). Briefly, mice were placed into a chamber with 1.5% isoflurane and airflow of 450 to 500 ml/min for 3 min, and then transferred onto a 37°C heated operating table and placed under an anesthesia mask with 1.5% isoflurane.…”

Section: Methodsmentioning

confidence: 99%

Chemotherapy-Induced Degradation of Glycosylated Components of the Brain Extracellular Matrix Promotes Glioblastoma Relapse Development in an Animal Model

et al. 2021

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Adjuvant chemotherapy with temozolomide (TMZ) is an intrinsic part of glioblastoma multiforme (GBM) therapy targeted to eliminate residual GBM cells. Despite the intensive treatment, a GBM relapse develops in the majority of cases resulting in poor outcome of the disease. Here, we investigated off-target negative effects of the systemic chemotherapy on glycosylated components of the brain extracellular matrix (ECM) and their functional significance. Using an elaborated GBM relapse animal model, we demonstrated that healthy brain tissue resists GBM cell proliferation and invasion, thereby restricting tumor development. TMZ-induced [especially in combination with dexamethasone (DXM)] changes in composition and content of brain ECM proteoglycans (PGs) resulted in the accelerated adhesion, proliferation, and invasion of GBM cells into brain organotypic slices ex vivo and more active growth and invasion of experimental xenograft GBM tumors in SCID mouse brain in vivo. These changes occurred both at core proteins and polysaccharide chain levels, and degradation of chondroitin sulfate (CS) was identified as a key event responsible for the observed functional effects. Collectively, our findings demonstrate that chemotherapy-induced changes in glycosylated components of brain ECM can impact the fate of residual GBM cells and GBM relapse development. ECM-targeted supportive therapy might be a useful strategy to mitigate the negative off-target effects of the adjuvant GBM treatment and increase the relapse-free survival of GBM patients.

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In vivo MRI visualization of U87 glioblastoma development dynamics in the model of orthotopic xenotransplantation to the SCID mouse

Cited by 18 publications

References 30 publications

Highly Invasive Fluorescent/Bioluminescent Patient-Derived Orthotopic Model of Glioblastoma in Mice

Highly Invasive Fluorescent/Bioluminescent Patient-Derived Orthotopic Model of Glioblastoma in Mice

Discovering Glioma Tissue through Its Biomarkers’ Detection in Blood by Raman Spectroscopy and Machine Learning

Chemotherapy-Induced Degradation of Glycosylated Components of the Brain Extracellular Matrix Promotes Glioblastoma Relapse Development in an Animal Model

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