Lack of interferon beta–induced radiosensitization in four out of five human glioblastoma cell lines

Schmidberger, Heinz; Rave-Fränk, Margret; Lehmann, Jöerg; Weiss, Elisabeth; Gerl, Lara; Dettmer, Nadine; Glomme, Sabine; Hess, Clemens F.

doi:10.1016/s0360-3016(02)04575-3

Cited by 10 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, IFN-β did not contribute to radiosensitization of human GBM cell lines [40] or BTPCs [41]. This data is in line with our findings as neither knock-down nor ectopic expression of IFITM3 changed BTPC radio-resistance.…”

Section: Discussionsupporting

confidence: 89%

“…IFN-related genes, and IFITM proteins in particular, have been reported to be upregulated after the IR of cell lines derived from prostate [ 38 ], glioma, breast [ 14 ] and leukemic tumors [ 39 ]. However, IFN-β did not contribute to radiosensitization of human GBM cell lines [ 40 ] or BTPCs [ 41 ]. This data is in line with our findings as neither knock-down nor ectopic expression of IFITM3 changed BTPC radio-resistance.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

No role of IFITM3 in brain tumor formationin vivo

et al. 2016

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is one of the most lethal solid tumors in adults. Despite aggressive treatment approaches for patients, GBM recurrence is inevitable, in part due to the existence of stem-like brain tumor-propagating cells (BTPCs), which produce factors rendering them resistant to radio- and chemotherapy. Comparative transcriptome analysis of irradiated, patient-derived BTPCs revealed a significant upregulation of the interferon-inducible transmembrane protein 3 (IFITM3), suggesting the protein as a factor mediating radio resistance. Previously, IFITM3 has been described to affect glioma cells; therefore, the role of IFITM3 in the formation and progression of brain tumors has been investigated in vivo. Intracranial implantation studies using radio-selected BTPCs alongside non-irradiated parental BTPCs in immunodeficient mice displayed no influence of irradiation on animal survival. Furthermore, gain and loss of function studies using BTPCs ectopically expressing IFITM3 or having IFITM3 down-modulated by a shRNA approach, did affect neither tumor growth nor animal survival. Additionally, a syngeneic model based on the mouse glioma cell line GL261 was applied in order to consider the possibility that IFITM3 relies on an intact immune system to unfold its tumorigenic potential. GL261 cells ectopically expressing IFITM3 were implanted into the striatum of immunocompetent mice without influencing the survival of glioma-bearing animals. Lastly, the vasculature and the extent of microglia/macrophage invasion into the tumor were studied in BTPC and GL261 tumors but neither parameter was altered by IFITM3. This report presents for the first time that IFITM3 is upregulated in patient-derived BTPCs upon irradiation but does not affect brain tumor formation or progression in vivo.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

No role of IFITM3 in brain tumor formationin vivo

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These changes created a microenvironment within the tumor that appeared to be, at least partly, responsible for the radiosensitizing effects of IFN-β. We theorize that it is the increase in tumor oxygenation that enhances the antitumor effect of ionizing radiation, as previous results in vitro have shown that there is a lack of direct radiosensitization by recombinant IFN-β in several glioma cell lines, including U87 (39). The combination of IFN-β and radiation was synergistic supporting the hypothesis that IFN-β has radiosensitizing effects as well as cytotoxic effects.…”

Section: Discussionmentioning

confidence: 91%

Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

McGee¹,

Hamner²,

Williams³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

124

View full text Add to dashboard Cite

Purpose Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, therefore, the anti-glioma efficacy of ionizing radiation. Methods and Materials Orthotopic U87 xenografts were treated with either continuous interferon-beta (IFN-β) or bevacizumab, alone, or in combination with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; tumor vasculature, with immunohistochemical staining; and tumor oxygenation, with hypoxyprobe staining. Results Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percent area of perivascular cell staining while bevacizumab caused a rapid decrease in the percent area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab the effect was transient, being lost by five days. Administration of IFN-β or bevacizumab prior to RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab, or five days after bevacizumab. Conclusions Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the anti-tumor activity of ionizing radiation. Further investigation into the use and timing of these and other agents that modify vascular phenotype, in combination with radiation, is warranted in order to optimize cytotoxic activity.

show abstract

“…The cells were counted under an inverted microscope (Ernst Leitz Wetzlar GmbH, Wetzlar, Germany) using a hemocytometer. 1ϫ10 6 cells from each EAC mice were suspended in 1 ml of 0.15 M Tris-HCl (pH 7.4) with 50 ml of Triton X100 and sonicated on ice for 20 s using a microprobe sonicator (Sonics Vibra-cell, CT, U.S.A.). The sonicated cell suspension was centrifuged at 13000 rpm for 15 min.…”

Section: Biochemical Estimationsmentioning

confidence: 99%

“…However, the side effects of such modes of treatment are severe and have resulted in the occurrence of secondary malignancies. Some agents under test are interferon beta that has cytotoxic synergism with radiation against MO59J cell line in vitro, 6) and MDM2 inhibitors, such as antisense oligonucleotides as radiosensitizer against various neoplastic cell lines in vitro and different tumor xenografts in vivo. 7) Nevertheless efforts to explore better radiosensitizers shall be continued to reduce toxic side effects of combination treatment.…”

mentioning

confidence: 99%

Enhancement of Radiation Effect by <i>Aphanamixis polystachya</i> in Mice Transplanted with Ehrlich Ascites Carcinoma

Jagetia

Venkatesha

2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The effect of radiation on tumor tissue can be optimized by adding radiosensitizing agents, in order to achieve a greater degree of tumor damage than expected from the use of either treatment alone. The ethanolic extract of Aphanamixis polystachya (APE) was tested in Swiss albino mice transplanted with Ehrlich ascites carcinoma (EAC) and exposed to various doses of g g-radiation. EAC mice received 0, 10, 25, 50, 75, 100, 150 or 200 mg/kg body wt APE before exposure to 6 Gy g g-radiation followed by once daily administration for another 8 consecutive days post-irradiation. The optimum radiosensitizing dose was found to be 50 mg/kg APE that was further tested in EAC mice exposed to 0, 1, 2, 4, 6 or 8 Gy hemi body g g-radiation. The best effect of APE and radiation was observed for 6 Gy g g-radiation. The splitting of 50 mg into two equal fractions of 25 mg and administering the split dose with a gap of 8 h on 1, 3, 5, 7 or 9 d of tumor inoculation resulted in an increased survival even when the drug was administered at late stages (day 5) of tumor development. The APE treatment before irradiation elevated lipid peroxidation followed by a reduction in the glutathione contents. Treatment of tumor bearing mice with APE before irradiation further reduced the activities of various antioxidant enzymes like glutathione peroxidase, glutathione-s-transferase, superoxide dismutase and catalase at different post last drug administration (PLDA) times.

show abstract

Lack of interferon beta–induced radiosensitization in four out of five human glioblastoma cell lines

Cited by 10 publications

References 24 publications

No role of IFITM3 in brain tumor formationin vivo

No role of IFITM3 in brain tumor formationin vivo

Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

Enhancement of Radiation Effect by <i>Aphanamixis polystachya</i> in Mice Transplanted with Ehrlich Ascites Carcinoma

Contact Info

Product

Resources

About