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Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

ABSTRACT: Transcriptomic profiling of normal mouse kidney cortex and medulla following 177Lu irradiation

ORGANISM(S): Mus musculus

PROVIDER: GSE44762 | GEO | 2014/03/05

SECONDARY ACCESSION(S): PRJNA191573

REPOSITORIES: GEO

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Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

Project description:Transcriptomic profiling of normal mouse kidney cortex and medulla following 177Lu irradiation Total RNA was isolated from fresh-frozen tissue samples

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Real-time quantitative PCR analysis of mice kidney after administration of Lu-177-octreotate, Lu-177-octreotate + A1M and A1M

Project description:This work aimed to examine the regulation of apoptosis-related genes in kidney cortex and kindey medulla one and seven days after administration of 177Lu-octreotate with and without A1M and of A1M alone. C57BL/6N mice were injected with either 177Lu-octreotate + PBS, A1M + PBS or 177Lu-octreotate + A1M. Also, a control group was sham-treated with saline. Half of the animals in each treatment and control group were terminated by cardiac puncture one-day post-injection (1 dpi), and the remaining animals were terminated at 7dpi. Kidneys were dissected at the time of termination, snap-frozen in liquid nitrogen and stored at -80°C.

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Project description:Transcriptomic profiling of normal mouse tissue and blood following 177Lu irradiation

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Biomarkers for radiation-induced renal toxicity following 177Lu-octreotate administration in mice

Project description:Transcriptomic profiling of normal mouse tissue and blood following 177Lu irradiation Total RNA was isolated from fresh-frozen tissue samples

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Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu-octreotate administration.

Project description:AimThe aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers.MethodsFemale BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples.ResultsIn total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively). No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways.ConclusionIn conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration.

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Regulation of gene expression in GOT1 midgut carcinoid in nude mice following injection with 177Lu-octreotate

Project description:The radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In xenografted tumors, the human stromal components have been replaced with mouse stroma, which may have an impact in the treatment response of the xenografts.

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