Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
2008 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 90, no 1, p. 35-39Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The metabolism of malignant glioma was studied in 13 patients. The main objective was to perform a study of the metabolic pattern of glucose, lactate, pyruvate, glutamate and glycerol in tumour tissue during base-line conditions and to detect any changes in the metabolism during radiotherapy.

METHOD: During a stereotactic biopsy, two microdialysis catheters were implanted: one in tumour and one in peri-tumoural tissue. Fasting samples were analysed daily, before and during 5 days of radiotherapy given with 2 Gy fractions.

RESULTS: Base-line levels of glucose and pyruvate were significantly lower in tumour compared to peri-tumoural tissue (P = 0.04 and 0.023, respectively). The lactate/pyruvate ratio was significantly higher in tumour tissue (P = 0.022). In general, the levels of lactate, glutamate and glycerol were higher in tumour tissue, although not statistically significant. Further, we could not detect any significant changes during the 5 days of radiotherapy in any of the metabolites analysed.

CONCLUSION: Radiotherapy up to 10 Gy given in five fractions does not influence the glucose metabolism nor does it induce any acute cytotoxic effect detected with glutamate or glycerol in malignant glioma, as assessed by microdialysis. The study confirms the glycolytic properties of glucose metabolism in malignant glioma.

Place, publisher, year, edition, pages
Springer, 2008. Vol. 90, no 1, p. 35-39
Keywords [en]
Glucose metabolism, Malignant glioma, Microdialysis, Radiotherapy
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-10389DOI: 10.1007/s11060-008-9625-2ISI: 000258704900006PubMedID: 18563297OAI: oai:DiVA.org:umu-10389DiVA, id: diva2:150060
Available from: 2008-09-03 Created: 2008-09-03 Last updated: 2020-10-19Bibliographically approved
In thesis
1. Stereotactic microdialysis for metabolic assessment and experimental treatment of malignant glioma
Open this publication in new window or tab >>Stereotactic microdialysis for metabolic assessment and experimental treatment of malignant glioma
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Glioblastoma multiforme, the most common primary brain tumor, has a dire prognosis despite multimodal treatments that include surgery and radio-chemotherapy. To improve the outcome of this destructive disease, we need to improve our understanding of its tumor biology. Furthermore, the development of new treatment strategies will improve with a better understanding of the interplay between malignant cells and their direct surrounding microenvironment.

This thesis aims to increase the understanding of the processes within high-grade glioma and its microenvironment during normal conditions as well as during the distress associated with treatment. Specifically, we have investigated the metabolic response to radiotherapy (study I and II), the immunologic response to radiotherapy (study II), and the metabolic response pattern to loco-regional treatment with cisplatin (study III and IV). Using microdialysis, we collected samples from the extracellular space in both normal brain and tumor tissue during radiotherapy (study I and II) and loco-regional cisplatin treatment (study III and IV). Theses samples were analyzed for glucose metabolites, glycerol, and glutamate (study I, II, and III) and for cytokines (study II). In addition, we analyzed the global metabolism with mass spectrometry to identify and assess the response pattern of malignant glioma cells to loco-regional cisplatin treatment (study IV).

In study I and II, we found that malignant glioma cells used glucose at a higher rate than normal cells and preferred glycolysis for glucose metabolism. The given radiation dose (2 Gray (Gy) daily for five days) did not significantly affect glucose metabolism, glycerol levels, or glutamate levels in tumor tissue or the microenvironment. However, in study II, we observed an induced inflammatory effect due to the given radiation dose as several of the cytokines investigated showed significantly increased levels during radiotherapy. In study IV, we observed a complex and strong metabolic response to the loco-regional cisplatin therapy. At baseline, we found a metabolic pattern corresponding well with highly proliferating tumor tissue–i.e., high levels of amino acids, their metabolites, and other metabolic end products and low levels of sugar derivatives, antioxidants, and nucleotides. During the loco-regional therapy, we observed a clearly localized cytotoxic effect within the tumor and a metabolic response pattern corresponding with cisplatin’s complex mechanism of action, affecting several metabolic pathways within the malignant cell. Glutamate and glycerol also increased in tumor tissue following loco-regional treatment, a finding that further supported the observation of local toxicity.

In study III, we investigated microdialysis as a method to assess the microenvironment in high-grade glioma and as a method for drug delivery (retrograde microdialysis). All studies demonstrated the usefulness of microdialysis as a tool for in vivo real-time assessment of molecular events in malignant glioma tissue. Although the method is invasive, no complications related to the surgical procedure or assessment were noted. In study III, we also demonstrated that retrograde microdialysis is a feasible method for locally delivering clinically significant doses of drugs such as cisplatin to tumor tissue in the brain. However, in addition to having a cytotoxic effect on tumor cells, cisplatin may induce clinically significant edema.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2020. p. 71
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2104
Keywords
Brain microdialysis, Glioblastoma multiforme, Malignant glioma, Retrograde microdialysis, Glucose metabolism, Radiotherapy, Chemotherapy, Cytokine.
National Category
Other Clinical Medicine
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-176052 (URN)978-91-7855-402-7 (ISBN)978-91-7855-403-4 (ISBN)
Public defence
2020-11-20, Hörsal B, Unod T9, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Cancer SocietyRegion VästerbottenSwedish Research CouncilCancerforskningsfonden i Norrland
Available from: 2020-10-30 Created: 2020-10-19 Last updated: 2020-10-20Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Tabatabaei, PedramBergström, PerHenriksson, RogerBergenheim, A. Tommy

Search in DiVA

By author/editor
Tabatabaei, PedramBergström, PerHenriksson, RogerBergenheim, A. Tommy
By organisation
NeurosurgeryOncology
In the same journal
Journal of Neuro-Oncology
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 187 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf