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Radiotherapy induces an immediate inflammatory reaction in malignant glioma : a clinical microdialysis study

Tabatabaei, Pedram; Visse, Edward LU ; Bergström, Per; Brännström, Thomas; Siesjö, Peter LU and Bergenheim, A. Tommy (2017) In Journal of Neurooncology 131(1). p.83-92
Abstract

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2–3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and... (More)

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2–3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cytokine, Glioblastoma, Inflammation, Microdialysis, Radiotherapy
in
Journal of Neurooncology
volume
131
issue
1
pages
10 pages
publisher
Springer
external identifiers
  • scopus:84988693211
  • wos:000393065400010
ISSN
0167-594X
DOI
10.1007/s11060-016-2271-1
language
English
LU publication?
yes
id
1b03b39b-23b9-4c80-adca-8f8e638aa3b1
date added to LUP
2016-10-28 15:30:03
date last changed
2018-06-24 05:06:49
@article{1b03b39b-23b9-4c80-adca-8f8e638aa3b1,
  abstract     = {<p>The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2–3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.</p>},
  author       = {Tabatabaei, Pedram and Visse, Edward and Bergström, Per and Brännström, Thomas and Siesjö, Peter and Bergenheim, A. Tommy},
  issn         = {0167-594X},
  keyword      = {Cytokine,Glioblastoma,Inflammation,Microdialysis,Radiotherapy},
  language     = {eng},
  number       = {1},
  pages        = {83--92},
  publisher    = {Springer},
  series       = {Journal of Neurooncology},
  title        = {Radiotherapy induces an immediate inflammatory reaction in malignant glioma : a clinical microdialysis study},
  url          = {http://dx.doi.org/10.1007/s11060-016-2271-1},
  volume       = {131},
  year         = {2017},
}