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Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
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2017 (engelsk)Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 131, nr 1, s. 83-92Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Springer, 2017. Vol. 131, nr 1, s. 83-92
Emneord [en]
Cytokine, Glioblastoma, Radiotherapy, Microdialysis, Inflammation
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-131132DOI: 10.1007/s11060-016-2271-1ISI: 000393065400010PubMedID: 27664151OAI: oai:DiVA.org:umu-131132DiVA, id: diva2:1071794
Tilgjengelig fra: 2017-02-06 Laget: 2017-02-06 Sist oppdatert: 2019-05-09bibliografisk kontrollert

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