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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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Synergistic effects of blocking the CXCL2/CXCR2 pathway in combination with Temozolomide therapy in glioblastoma multiforme as a combined therapeutic approach

Synergistische Effekte der Blockade des CXCL2/CXCR2 Signalwegs und gleichzeitiger Temozolomid-Therapie im Glioblastoma multiforme als kombinierter Therapieansatz

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  • presenting/speaker Claudius Jelgersma - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Julia Zollfrank - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Susan Brandenburg - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Peter Vajkoczy - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Güliz Acker - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocP158

doi: 10.3205/20dgnc442, urn:nbn:de:0183-20dgnc4425

Published: June 26, 2020

© 2020 Jelgersma et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Blocking of the CXCL2/CXCR2 pathway has been shown to reduce glioma growth and the standard therapy Temozolomide (TMZ) is known to induce changes in this chemokine network in glioma cell lines. Thus, the aim of our study was to investigate possible synergistic effects of TMZ in combination with CXCR2 antagonist (SB225002).

Methods: GL261 glioma cells were implanted intracranially in C57/B6N mice and the treatments (Control with Aqua ad iniectabilia i.p., SB225002 via osmotic pump, TMZ i.p. and SB225002+TMZ; n= 7-8 per group) were initiated after 14 days and carried out for 7 consecutive days. Tumor volume was verified using MRI before and after the treatment period. Immunofluorescence staining was performed on the tumor tissue with focus on angiogenesis, tumor-associated macrophages (TAMs) and proliferation. One-way Anova with Bonferroni correction was used for statistical analysis (p≤0.05).

Results: Tumor volume was significantly reduced by 61% after TMZ and by 75% after combined treatment in comparison to control tumors on day 21 (mean volumes (in mm3) were: control 30.22 ± 19.64; SB225002 alone: 16.04 ± 6.81; TMZ alone 11.75 ± 6.82; combination: 7.51 ± 2.97). The difference in tumor growth between the combination therapy and TMZ or SB225002 did not reach a significant level. The immunostainings showed significantly reduced proliferation in TMZ and combination group vs. control and combination vs. SB225002. Apoptosis, TAM accumulation and CXCL2/CXCR2 do not seem to be affected significantly by any of the treatments, while SB225002 induced alterations in tumor vascularisation. No side effects were observed amongst all treatment groups.

Conclusion: TMZ in combination with SB225002 was well tolerated and reduced the tumor volume significantly most likely due to impaired proliferation. However, as the impact of the combination therapy in comparison to TMZ alone was not impressive within the observation time, survival experiments are needed to clarify the real benefit of the combination treatment.