Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo

Lærum, Ole Didrik; Rajewsky, Manfred F.; Schachner, Melitta; Stavrou, D.; Haglid, Kenneth G.; Haugen, Åsmund

doi:10.1007/bf00283783

Cited by 102 publications

(48 citation statements)

References 39 publications

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“…BHK-21 cells (ATCC CCL-10) and BT4C rat glioma cells 18 were grown in high-glucose Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine and 50 lg/l gentamicin. Human lung adenocarcinoma cell line A549 (ATCC CCL-185), human squamous cell lung cancer SW-900 (ATCC HTB-59) and human large cell lung cancer cell line NCI-H661 (ATCC HTB-183) were cultured in media recommended by ATCC.…”

Section: Cell Lines and In Vitro Experimentsmentioning

confidence: 99%

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Määttä

Liimatainen

Wahlfors

et al. 2007

Intl Journal of Cancer

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Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested. ' 2007 Wiley-Liss, Inc.

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Section: Cell Lines and In Vitro Experimentsmentioning

confidence: 99%

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Määttä

Liimatainen

Wahlfors

et al. 2007

Intl Journal of Cancer

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“…BT4C cells have been characterized elsewhere. 16 The cells were grown in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal calf sera, 1% penicillin/streptomycin, and nonessential amino acids (Life Technologies, Paisley, UK). A total of 1.2 kb of HSV-tk cDNA 17 (GenBank accession no.…”

Section: Cell Lines and Viral Vectorsmentioning

confidence: 99%

Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: Effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions

et al. 2000

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Herpes simplex virus thymidine kinase (HSV-tk) gene transfer and ganciclovir (GCV) administration have been suggested for the treatment of malignant gliomas. To understand tissue responses and possible ways to improve the treatment effect, we studied tumor growth, tissue reactions, and survival time after HSV-tk/GCV treatment in a syngeneic BT4C rat glioma model by mixing various ratios of stably transfected HSV-tk-expressing BT4C-tk glioma cells with wild-type BT4C glioma cells (percentage of BT4C-tk cells: 0%, 1%, 10%, 30%, 50%, and 100%), followed by injection into BDIX rat brains (n ϭ 79). With the exception of some animals with end-stage tumors, very little astroglia or microglia reactivity was detected in the wild-type tumors as analyzed by immunocytochemistry using glial fibrillary acid protein (GFAP)-, vimentin-, human histocompatibility leukocyte antigen-DR-, OX-42-, and CD68-specific monoclonal antibodies. After 14 days of GCV treatment, tumors induced with Ն10% BT4C-tk cells showed a significant reduction in tumor size (P Ͻ .05) and prolonged survival time (P Ͻ .01). Astrogliosis, as indicated by a strong GFAP and vimentin immunoreactivity, was seen in the tumor scar area. GFAP and vimentin reactivity was already present after the GCV treatment in tumors induced with 1% BT4C-tk cells. Much less human histocompatibility leukocyte antigen-DR-positive microglia was seen in the treated animals, indicating low microglia reactivity and immunoactivation against the tumor. However, GCV-treated tumors were positive for apoptosis, indicating that apoptosis is an important mechanism for cell death in the BT4C-tk glioma model. Our results suggest that Ն10% transfection efficiency is required for a successful reduction in BT4C glioma tumor size with HSV-tk/GCV treatment in vivo. Tissue reactions after 14 days of GCV treatment are characterized by astrogliosis and apoptosis, whereas microglia response and immunoactivation of the brain cells appear to play a minor role. Stimulation of the microglia response by gene transfer or other means might improve the efficacy of the HSV-tk/GCV treatment in vivo. Cancer Gene Therapy (2000) 7, 413-421

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“…BT4C rat glioma cells (Laerum et al, 1977;Sandmair et al, 2000) were obtained from Ark Therapeutics (London, UK). BT4C glioma cells were inoculated intracranially in inbred male BDIX rats aged 3-4 months (Charles River Laboratories, Lille, France) as described previously (Tyynelä et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

Brain Pharmacokinetics of Ganciclovir in Rats with Orthotopic BT4C Glioma

et al. 2014

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Ganciclovir (GCV) is an essential part of the Herpes simplex virus thymidine kinase (HSV-tk) gene therapy of malignant gliomas. The purpose of this study was to investigate the brain pharmacokinetics and tumor uptake of GCV in the BT4C rat glioma model. GCV's brain and tumor uptakes were investigated by in vivo microdialysis in rats with orthotopic BT4C glioma. In addition, the ability of GCV to cross the blood-brain barrier and tumor vasculature was assessed with in situ rat brain perfusion. Finally, the extent to which GCV could permeate across the BT4C glioma cell membrane was assessed in vitro. The areas under the concentration curve of unbound GCV in blood, brain extracellular fluid (ECF), and tumor ECF were 6157, 1658, and 4834 mM×min, respectively. The apparent maximum unbound concentrations achieved within 60 minutes were 46.9, 11.8, and 25.8 mM in blood, brain, and tumor, respectively. The unbound GCV concentrations in brain and tumor after in situ rat brain perfusion were 0.41 and 1.39 nmol/g, respectively. The highly polar GCV likely crosses the fenestrated tumor vasculature by paracellular diffusion. Thus, GCV is able to reach the extracellular space around the tumor at higher concentrations than that in healthy brain. However, GCV uptake into BT4C cells at 100 mM was only 2.1 pmol/mg of protein, and no active transporter-mediated disposition of GCV could be detected in vitro. In conclusion, the limited efficacy of HSV-tk/GCV gene therapy may be due to the poor cellular uptake and rapid elimination of GCV.

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Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo

Cited by 102 publications

References 39 publications

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: Effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions

Brain Pharmacokinetics of Ganciclovir in Rats with Orthotopic BT4C Glioma

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