Infiltration of glioma cells in brain parenchyma stimulated by radiation in the F98/Fischer rat model

Desmarais, Guillaume; Fortin, David; Bujold, Rachel; Wagner, J. Richard; Mathieu, David; Paquette, Benoît

doi:10.3109/09553002.2012.692495

Cited by 44 publications

(30 citation statements)

References 47 publications

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“…In the F98 Fischer rat model, infiltration of GBM cells in the brain parenchyma is somehow limited, when compared to the level of infiltration reaching the contralateral hemisphere observed in some patients [26]. Since an important advantage of opening the BBB is to reach these infiltrating clusters of cancer cells with the chemotherapeutic agent, our animal model of GBM might not be optimal to evaluate the therapeutic gain of platinum drugs after opening of the BBB.…”

Section: Discussionmentioning

confidence: 97%

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

et al. 2013

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Treatment of glioblastoma with platinum compounds modestly improves progression-free survival and may cause toxic effects which prevent use at higher dose that would otherwise improve the antineoplastic effect. To reduce toxicity, we propose to encapsulate the platinum drug in a liposome. We have also tested three methods of drug administration (intra-venous, intra-arterial and intra-arterial combined with blood brain barrier disruption) to determine which one optimizes the tumor cell uptake, limits the toxicity and delivers the best concomitance effect with radiotherapy. Cisplatin, oxaliplatin, their respective liposomal formulations, Lipoplatin ™ and Lipoxal ™ , and carboplatin were assessed in F98 glioma, orthotopically implanted in Fischer rats. We found that the modest accumulation of drugs in tumor cells after intra-venous injection was significantly improved when the intra-arterial route was used and further increased after the transient opening of the blood brain barrier with mannitol. The liposomal formulations have largely reduced the toxicity and have allowed a better exploitation of the anti-cancer activity of platinum agent. Although the liposomes Lipoplatin ™ and Lipoxal ™ have shown a similar ability to CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript that of carboplatin, to accumulate in brain tumors, the highest additive effect with radiotherapy was obtained with carboplatin. We conclude that the intra-arterial infusion of carboplatin or Lipoxal ™ in concomitance with radiation therapy leads to the best tumor control as measured by an increase of mean survival time in Fischer rats implanted with the F98 glioma with a benefit in survival time of 13.4 and 6.5 days respectively compared to intra-venous.

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Section: Discussionmentioning

confidence: 97%

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

et al. 2013

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“…IR-induced secretion of IL-1 is rapid, within 4 h after brain IR, in C3hf/sed/Kam mice and F98/Fischer rat glioma model (Desmarais et al 2012;hong et al 1995). Interestingly, even head-protected peripheral partial-body IR of rats could also induce the expression of IL-1β in the hypothalamus, thalamus, and hippocampus via the vagus nerve, as early as 6 h after IR (Marquette et al 2003).…”

Section: Il-1mentioning

confidence: 98%

“…IL-1β showed a minimal direct effect on the IR sensitivity of glioma cells (Ross et al 1994). Instead, IR-activated IL-1 could enhance infiltration of glioma cells in brain parenchyma (Desmarais et al 2012).…”

Section: Il-1mentioning

confidence: 99%

Cytokines: shifting the balance between glioma cells and tumor microenvironment after irradiation

Zhou

Jiang

et al. 2014

J Cancer Res Clin Oncol

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Malignant gliomas invariably recur after irradiation, showing radioresistance. Meanwhile, cranial irradiation can bring some risk for developing cognitive dysfunction. There is increasing evidence that cytokines play their peculiar roles in these processes. On the one hand, cytokines directly influence the progression of malignant glioma, promoting or suppressing tumor progression. On the other hand, cytokines indirectly contribute to the immunologic response against gliomas, exhibiting pro-inflammatory or immunosuppressive activities. We propose that cytokines are not simply unregulated products from tumor cells or immune cells, but mediators finely adjust the balance between glioma cells and tumor microenvironment after irradiation. The paper, therefore, focuses on the changes of cytokines after irradiation, analyzing how these mediate the response of tumor cells and normal cells to irradiation. In addition, cytokine-based immunotherapeutic strategies, accompanied with irradiation, for the treatment of gliomas are also discussed.

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“…The F98 glioma cells have an infiltrative pattern of growth in the brain and they are weakly immunogenic (Tzeng et al 1969) . This tumour model is often used in studies involving conventional radiotherapy and synchrotron radiation (Gil et al 2011;Desmarais et al 2012Desmarais et al , 2015.…”

Section: Animal Modelmentioning

confidence: 99%

Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation

et al. 2016

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Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signalling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 nu mice after irradiating their brains using pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 days earlier were treated with either MRT or PB.After recovery times of 2, 12 and 48h, the urinary bladders were extracted and cultured as tissue explants for 24h. The growth medium containing the potential signalling factors was harvested, filtered and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signalling potential. The results show that in the tumour free-mice both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay, however the calcium data do not support a calcium channel mediated mechanism.The presence of tumour reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumour bearing animals. We conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells, however a novel mechanism appears to be involved.

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Infiltration of glioma cells in brain parenchyma stimulated by radiation in the F98/Fischer rat model

Cited by 44 publications

References 47 publications

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

Cytokines: shifting the balance between glioma cells and tumor microenvironment after irradiation

Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation

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