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Increased effect of...
Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma
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- Ahlstedt, Jonatan (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups
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- Konradsson, Elise (author)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Ceberg, Crister (author)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Redebrandt, Henrietta Nittby (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups
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(creator_code:org_t)
- 2020-05-29
- 2020
- English.
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Abstract
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- Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration of 1-methyl tryptophan (1-MT), and radiotherapy (RT) was delivered in doses of 8Gy. Results The expression of IDO1 was increased on gene level in glioblastoma stem cells. Tumor size was significantly reduced in animals treated with 1-MT+RTx 2 (both long and short intervals, i.e. 7 and 4 days between the treatments) as compared to control animals, animals treated with only 1-MT or animals treated with 1-MT+RTx1. Serum levels of IL-1A were significantly altered in all treated animals as compared to control animals. Survival was significantly increased in the animals treated with 1-MT+RTx2 (7-day interval) compared to control animals. Conclusions Addition of two-fraction RT to IDO1 inhibition with 1-MT significantly reduced tumor size in animals with glioblastoma. Survival was significantly increased in animals treated with twofractioned RT+1-MT as compared to untreated controls increased significantly. Advances in knowledge The currently used combination of only two fractions of radiotherapy and immune therapy is a promising area of research, increasing efficacy compared to single fraction irradiation, while potentially lowering radiation side effects compared to radiation in current clinical practice.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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