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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 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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1 University of Gothenburg, Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); University of Gothenburg, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
2 Sahlgrenska University Hospital, Department of Clinical Pathology, Gothenburg, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)
3 Lund University, Department of Clinical Sciences, Infection Medicine, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361)
4 Lund University, Neonatology Unit, Department of Clinical Sciences, Pediatrics, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361)
5 University of Gothenburg, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); University of Gothenburg, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
6 University of Gothenburg, Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); University of Gothenburg, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Sahlgrenska University Hospital, Medical Physics and Biomedical Engineering, Gothenburg, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)