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Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors

Rassol, Nishte ; Andersson, Charlotte ; Pettersson, Daniella ; Al-Awar, Amin ; Shubbar, Emman ; Kovács, Anikó ; Åkerström, Bo LU ; Gram, Magnus LU orcid ; Helou, Khalil and Forssell-Aronsson, Eva (2023) In Scientific Reports 13(1).
Abstract

Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the 177Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of 177Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq 177Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7... (More)

Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the 177Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of 177Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq 177Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after 177Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of 177Lu-octreotate in GOT1 tumors.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
issue
1
article number
6417
publisher
Nature Publishing Group
external identifiers
  • pmid:37076494
  • scopus:85152979450
ISSN
2045-2322
DOI
10.1038/s41598-023-32091-9
language
English
LU publication?
yes
id
08e03ae6-d4ab-4395-a872-57a2d5dfbfbe
date added to LUP
2023-07-12 14:20:57
date last changed
2024-04-19 23:20:07
@article{08e03ae6-d4ab-4395-a872-57a2d5dfbfbe,
  abstract     = {{<p>Recombinant α<sub>1</sub>-microglobulin (A1M) is a proposed radioprotector during <sup>177</sup>Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the <sup>177</sup>Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of <sup>177</sup>Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq <sup>177</sup>Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after <sup>177</sup>Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of <sup>177</sup>Lu-octreotate in GOT1 tumors.</p>}},
  author       = {{Rassol, Nishte and Andersson, Charlotte and Pettersson, Daniella and Al-Awar, Amin and Shubbar, Emman and Kovács, Anikó and Åkerström, Bo and Gram, Magnus and Helou, Khalil and Forssell-Aronsson, Eva}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Co-administration with A1M does not influence apoptotic response of <sup>177</sup>Lu-octreotate in GOT1 neuroendocrine tumors}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-32091-9}},
  doi          = {{10.1038/s41598-023-32091-9}},
  volume       = {{13}},
  year         = {{2023}},
}