Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas

Feldman, Lisa A.; Fabre, Marie-Sophie; Grasso, Carole; Reid, Dana; Broaddus, William C.; Lanza, Gregory M.; Spiess, Bruce D.; Garbow, Joel R.; McConnell, Melanie J.; Herst, Patries M.

doi:10.1371/journal.pone.0184250

Cited by 19 publications

(15 citation statements)

References 53 publications

(64 reference statements)

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“…Combined, these data implied that BCL6 survival activity is not conserved in the GL261 cells. Thus the animal model, which we and others have used widely [19,31,[38][39][40], would not be useful, beyond demonstrating that DNA damaging therapy did indeed induce BCL6 in vivo as well as in vitro.…”

Section: Plos Onementioning

confidence: 98%

The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy

et al. 2020

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The prognosis for people with the high-grade brain tumor glioblastoma is very poor, due largely to low cell death in response to genotoxic therapy. The transcription factor BCL6, a protein that normally suppresses the DNA damage response during immune cell maturation, and a known driver of B-cell lymphoma, was shown to mediate the survival of glioblastoma cells. Expression was observed in glioblastoma tumor specimens and cell lines. When BCL6 expression or activity was reduced in these lines, increased apoptosis and a profound loss of proliferation was observed, consistent with gene expression signatures suggestive of anti-apoptotic and pro-survival signaling role for BCL6 in glioblastoma. Further, treatment with the standard therapies for glioblastoma-ionizing radiation and temozolomide-both induced BCL6 expression in vitro, and an in vivo orthotopic animal model of glioblastoma. Importantly, inhibition of BCL6 in combination with genotoxic therapies enhanced the therapeutic effect. Together these data demonstrate that BCL6 is an active transcription factor in glioblastoma, that it drives survival of cells, and that it increased with DNA damage, which increased the survival rate of therapy-treated cells. This makes BCL6 an excellent therapeutic target in glioblastoma-by increasing sensitivity to standard DNA damaging therapy, BCL6 inhibitors have real potential to improve the outcome for people with this disease.

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Section: Plos Onementioning

confidence: 98%

The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy

et al. 2020

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“…After the first collection of fecal samples following a 7-day adaptive feeding regime (T0), the allogeneic orthotopic glioma model was constructed by implanting GL261 cells into 1642 the left putamen as described previously. 21 Briefly, after anesthesia by intraperitoneal injection of 2% chloral hydrate (0.2 mL/10g) mice were fixed in stereotaxic apparatus (RWD Life Science, Shenzhen, China). A burr hole was made in the left parietal bone 0.1 mm posterior to the bregma and 2.3 mm lateral to the midline.…”

Section: Gl261 Transplantation and Tmz Treatmentmentioning

confidence: 99%

Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma

Li¹,

Wu²,

Jiang³

et al. 2021

DDDT

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Background: Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood. Methods: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. Results: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium. Conclusion: Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

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“…The use of animal models in oncological research is a key step in the search for new therapeutic strategies. GL261 cells grown in C57BL/6 mice is one of the most investigated immunocompetent models, widely used in GB preclinical studies [ 27 , 28 , 29 , 30 , 31 ]. Wu and Waxman [ 32 ] described an immune friendly cyclophosphamide treatment triggering activation of the immune system against GL261 subcutaneous tumors, which also proved useful with TMZ treatment of an orthotopic GL261 GB model, improving mice survival [ 29 , 33 ] in comparison with previous protocols [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells

Villamañan

Martínez-Escardó

Arús

et al. 2021

IJMS

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Background: The relevance of the cancer immune cycle in therapy response implies that successful treatment may trigger the exposure or the release of immunogenic signals. Previous results with the preclinical GL261 glioblastoma (GB) showed that combination treatment of temozolomide (TMZ) + CX-4945 (protein kinase CK2 inhibitor) outperformed single treatments, provided an immune-friendly schedule was followed. Our purpose was to study possible immunogenic signals released in vitro by GB cells. Methods: GL261 GB cells were treated with TMZ and CX-4945 at different concentrations (25 µM–4 mM) and time frames (12–72 h). Cell viability was measured with Trypan Blue and propidium iodide. Calreticulin exposure was assessed with immunofluorescence, and ATP release was measured with bioluminescence. Results: TMZ showed cytostatic rather than cytotoxic effects, while CX-4945 showed remarkable cytotoxic effects already at low concentrations. Calreticulin exposure after 24h was detected with TMZ treatment, as well as TMZ/CX-4945 low concentration combined treatment. ATP release was significantly higher with CX-4945, especially at high concentrations, as well as with TMZ/CX-4945. Conclusions: combined treatment may produce the simultaneous release of two potent immunogenic signals, which can explain the outperformance over single treatments in vivo. A word of caution may be raised since in vitro conditions are not able to mimic pharmacokinetics observed in vivo fully.

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Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas

Cited by 19 publications

References 53 publications

The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy

The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy

Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma

Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells

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