Development of in Vitro Assays for Advancing Radioimmunotherapy Against Brain Tumors

Walter, Yohan; Hubbard, Anne M.; Benoit, Allie; Jank, Erika; Salas, Olivia; Jordan, Destiny; Ekpenyong, Andrew

doi:10.20944/preprints202205.0142.v1

Cited by 4 publications

(2 citation statements)

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“…The α/β showed no significant changes with the addition of pembrolizumab to radiation, suggesting little effect of these agents as radiosensitizers for T98G glioblastoma cells. [43][44][45] (Figures 5 and 6). (those with dividing nuclei) compared to cells with round nuclear was a major quantifying parameter (Figure 6).…”

Section: Radiation Most Significantly Determined Decrease In Cell Sur...mentioning

confidence: 99%

Cellular Biophysical Markers for Rapid Evaluation of Immune Checkpoint Inhibitors in Radioimmunotherapy Against Glioblastomas

Ibironke,

Machida,

Khan

et al. 2023

Preprint

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Cancers of the brain and nervous system account for 1 in every 100 cancer diagnoses in the United States and about 0.3 million diagnoses globally, every year. Surgery, radiotherapy, and chemo-therapy constitute the standard of care. Despite advancements in diagnosis and treatment delivery, mortality rate for these cancers have remained steady for over three decades. Immunotherapy is an emerging fourth treatment modality which has been effective against several cancers but not brain cancers, such as glioblastoma, GBM. Here, we develop in vitro assays to quantify molecular readouts of cell death, cell migration and clonogenicity, and synopsize these as biophysical markers for the rapid evaluation of immune checkpoint inhibitors (ICI), durvalumab and pembrolizumab, alone and in combination with radiotherapy (radioimmunotherapy). We find different trends in their direct action on two GBM cell lines (T98G and U87), even in the absence of immune cells. Radiation alone, and pembrolizumab with radiation, both reduced (p < 0.05) cell-cell adhesion. This reduction suggests increased potential for local invasion. Our assays offer additional insights regarding ICIs, may enable evaluation of their potential efficacy, and could set the stage for pa-tient-specific radioimmunotherapy against brain cancers, engendering improved treatment out-comes.

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Section: Radiation Most Significantly Determined Decrease In Cell Sur...mentioning

confidence: 99%

Cellular Biophysical Markers for Rapid Evaluation of Immune Checkpoint Inhibitors in Radioimmunotherapy Against Glioblastomas

Ibironke,

Machida,

Khan

et al. 2023

Preprint

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show abstract

“…We used tube voltage and current of 100 kVp and 5 mA respectively for target doses of 5, 10, 20 and 50 Gy with post radiotherapy nanoparticle spectroscopy on the 5 and 20 Gy irradiations. Post-radiotherapy NP spectroscopy was carried out mainly on the 5 Gy and 20 Gy irradiations because of our recent findings about increased migration of cells at those doses [27,28].…”

Section: Radiotherapymentioning

confidence: 99%

Simultaneous Assessment of Reactive Oxygen Species and Radiosensitization of Brain Cancer Cells using Nanoparticle Spectroscopy

Djam¹,

Kramer²,

Thiegs³

et al. 2022

Preprint

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Nanoparticle-mediated radiation therapy (NPRT) is an emerging modality for radiosensitization of highly resistant cancers such as brain cancers. This is due to the ability of specific nanoparticles (NPs) to increase physical dose deposition and subsequent direct damage to cells and DNA within their local vicinity, through enhanced generation of reactive oxygen species, ROS. Here, we report the successful use of PEGylated (biocompatible) core-shell quantum dots (QDs) and carbon quantum dots (CQDs) to simultaneously enhance and assess ROS generation while radiosensitizing highly radioresistant brain cancer cell lines: T98G and U87 Glioblastoma cells. Relative peak fluorescence intensity ratio calculations and average intensity comparisons show highly significant (***p&lt;0.001) enhancement of ROS generation, for 5 Gy and 20 Gy irradiation, applied using a Faxitron Cell Irradiator. By quantifying post-radiotherapy cell attachment, proliferation, migration, cell survival and cell death using electric cell-substrate impedance sensing and clonogenic assays, we demonstrate potentially improved in vitro radiotherapeutic outcomes for brain cancer cells radiosensitized using PEGylated CdSe/ZnS QDs and CQDs.

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Simulated Microgravity-Induced Changes to Drug Response in Cancer Cells Quantified Using Fluorescence Morphometry

McKinley

Taylor

Peeples

et al. 2023

Life

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Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.

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Development of in Vitro Assays for Advancing Radioimmunotherapy Against Brain Tumors

Cited by 4 publications

References 0 publications

Cellular Biophysical Markers for Rapid Evaluation of Immune Checkpoint Inhibitors in Radioimmunotherapy Against Glioblastomas

Cellular Biophysical Markers for Rapid Evaluation of Immune Checkpoint Inhibitors in Radioimmunotherapy Against Glioblastomas

Simultaneous Assessment of Reactive Oxygen Species and Radiosensitization of Brain Cancer Cells using Nanoparticle Spectroscopy

Simulated Microgravity-Induced Changes to Drug Response in Cancer Cells Quantified Using Fluorescence Morphometry

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