Optimization of 177Lu-octreotate treatment of neuroendocrine tumours
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA317642 | ENA |
REPOSITORIES: ENA
Similar Datasets
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 vitro and preclinical in vivo studies have shown that irradiation can up-regulate the expression of somatostatin receptors and thereby give an increased uptake of 177Lu-octreotate. The cellular processes that underlie positive treatment response to 177Lu-octreotate are otherwise largely unknown. Genome-wide analysis of tumor cell responses in this successful mouse model offers a venue to identify critical treatment parameters and to optimize clinical effectiveness of 177Lu-octreotate therapy. Combining 177Lu-octreotate with other anti-tumor agents has also been proposed as a strategy for optimization. Some studies have shown synergistic effects in tumor cell killing and volume reduction The hedgehog signaling pathway is involved in embryonic development and tissue regeneration and can be/is abnormally activated in various cancers. Inhibition of the hedgehog signaling pathway has yielded promising therapeutic effects on NE tumors and may potentially enhance the effects of 177Lu-octreotate treatment in patients.
2017-03-08 | GSE80022 | GEO
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.
2017-12-31 | GSE80021 | GEO
Project description:Introduction: Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate treatment of neuroendocrine tumors. Treatment with 177Lu-octreotate is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue while allowing higher absorbed doses to the tumor tissue. However, the mechanisms underlying the protective effects of co-administration of 177Lu-octreotate and A1M are still not fully understood. The aim of this study was to examine the proteomic response of mouse kidneys and bone marrow short time after 177Lu-octreotate and/or A1M administration. Methods: C57/6N mice (n=5/group) were injected with 150 MBq 177Lu-octreotate and/or A1M (5 mg/kg). Corresponding control mice (n=5/group) were injected with saline or the A1M vehicle solution. The animals were killed at 24 hours or 7 days post injection, followed by collection of bone marrow, kidney medulla, and kidney cortex samples at resp. time-points. One of the kidneys from each mouse was used for dosimetric assessment by measuring the 177Lu activity concentration in a gamma counter. Differential protein expression was analyzed with tandem mass spectrometry (LC-MS/MS). Ingenuity Pathway Analysis was then used to simulate affected canonical pathways, upstream regulators, and toxicity functions for identified proteins with |fold change| ≥ 1.5. Results: PHLDA3 was the most prominent radiation responsive protein found in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the 177Lu-octreotate and the 177Lu-octreotate+A1M groups. Several canonical pathways were identified in bone marrow, with the majority found in the 177Lu-octreotate+A1M group. Although toxicity functions related to nephrotoxicity were identified in kidney tissue in all groups, the predicted state (activated or inhibited) of these functions could not be determined. Conclusions: These findings demonstrated a tissue-dependent proteomic response following exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not seem to inhibit the radiation induced expressions, short time after exposure. Long term effects of the combination of A1M and 177Lu-octreotate needs to be further studied.
2026-02-23 | PXD029937 | Pride
Project description:We recently demonstrated that therapy with hyperfractionated administration of 177Lu-octreotate gave a larger volume reduction of GOT1 tumors compared to single administration of the same amount of radiopharmaceutical. The molecular mechanisms behind this response need to be examined. Transcriptional response in apoptotic-related genes have been found both early and late after treatment with 177Lu-octreotate suggesting that apoptosis-related responses appear also in tumor regrowth stage after treatment. The aims of this work were to compare the expression of genes involved in apoptosis in GOT1 tumors during growth phase from mice treated with 177Lu-octreotate and from untreated mice, and to compare gene expression in regrown GOT1 tumors from mice treated with single injection and hyperfractionated injections. The study was performed on tumor samples previously collected and analyzed by other methods. BALB/c mice, bearing the small-intestine neuroendocrine tumor GOT1, were divided into groups and treated i.v. with 2x15 MBq or 1x30; 2x30 or 1x60 MBq; 3x40, 2x60, or 1x120 MBq177Lu-octreotate. Controls were given saline. After tumor volume reduction and regrowth, the mice were euthanized and tumors were collected, and one part was prepared for IHC analysis, RNA was extracted from the other tumor tissue sample and analyzed by PCR Array for expression of 84 genes involved in apoptosis. Expression of each gene was compared with that in controls. Pathway analysis was performed from genes exhibiting at least 1.5-fold change in expression. The highest regulated gene, compared to untreated controls, was RIPK2 in the group that received 3x40 MBq of 177Lu-octreotate. The most frequently regulated gene among the groups in the study was the pro-apoptotic TNFSF8. Most genes in the study were upregulated. The │FC│-values were all below 3.5. The study present similarities and differences in molecular response between the groups of different 177Lu-octreotate treatments. The results point to a complexity that these studies bring and may have impact on the optimization of therapy in the future.
2025-12-08 | GSE250008 | GEO
Project description:This work aimed to examine the regulation of apoptosis-related genes in GOT1 tumors one and seven days after administration of 177Lu-octreotate with and without A1M and of A1M alone. At study start, 22 adult female Balb/c GOT1 tumor-bearing mice were divided into four groups of six animals that received 30 MBq 177Lu-octreotate or 5 mg/kg A1M, or co-treatment with both 177Lu-octreotate and A1M by i.v. injection. 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. Tumor tissues were dissected at the time of termination, snap-frozen in liquid nitrogen and stored at -80°C.
2023-04-25 | GSE200449 | GEO
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.
2024-04-01 | GSE200619 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-03-11 | GSE80024 | GEO
Project description:Differentially expressed genes in the stomachs of type-1 gastric neuroendocrine tumour (NET) patients before, during and after treatment with netazepide (YF476)
2018-12-30 | E-MTAB-6473 | biostudies-arrayexpress
Project description:A peptidomic analysis of plasma from patients with well characterised pancreatic neuroendocrine tumours (PNET) was performed. A nano LC-MS analysis identified a number of peptides from the glucagon gene, which were idenfiried in a previous case study using multiple immunoassays. Peptides to other proteins involved in peptide secretion were also identified. Plasma from a second glucagonoma patient was analysed using a high flow approach, and this identified similar peptides to the nano analysis. In order to demonstrate the potential clinical application of LC-MS to characterising neuroendocrine tumours, a large cohort of plasma samples were analysed to demonstrate the ability of this approach to identify glucagonoma patients, and differentiate from a single insulinoma patient
2018-08-31 | MSV000082880 | MassIVE
Project description:A peptidomic analysis of plasma from patients with well characterised pancreatic neuroendocrine tumours (PNET) was performed. A nano LC-MS analysis identified a number of peptides from the glucagon gene, which were idenfiried in a previous case study using multiple immunoassays. Peptides to other proteins involved in peptide secretion were also identified. Plasma from a second glucagonoma patient was analysed using a high flow approach, and this identified similar peptides to the nano analysis. In order to demonstrate the potential clinical application of LC-MS to characterising neuroendocrine tumours, a large cohort of plasma samples were analysed to demonstrate the ability of this approach to identify glucagonoma patients, and differentiate from a single insulinoma patient
2018-06-06 | PXD008465 | Pride