Optimization of 177Lu-octreotate treatment of neuroendocrine tumours
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PROVIDER: PRJNA317642 | ENA |
REPOSITORIES: ENA
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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: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
Project description:The management of neuroendocrine tumors (NETs) is very variable, depending on many specific aspects, such as the type of tumor, spread and patient general health. Several advances have been made with the newly developed somatostatin analogues to cure this type of malignancies. Somatostain analogues such as octreotide have been used in clinic to treat patients with neuroendocrine tumors (NETs). However, the molecular mechanism leading either to successful therapy or acquired resistance to the analogues is still to large extent unclear. Patients develop drugs resistance during a long term treatment. Therefore, to identify the pivotal regulatory genes involved in the development of drug resistance is an actual challenge. We studied five human neuroendocrine tumor cell lines, CNDT2.5, KRJ1, QGP-1, NCI H720 and NCI H727. We also investigated a long-term treated CNDT2.5 by using octreotide. We performed gene expression profiling in all the human neuroendocrine cell lines. Keywords: Gene Expression profiling, treatment comparison We investigated 5 human neuroendocrine cell lines, CNDT2.5 and KRJ1, established from ileum NETs, QGP1 by a pancreatic NET, NCI H720 and NCI H727 from bronchopulmonary NETs. CNDT2.5 cell were constantly treated with 1M-BM-5M octreotide for 10 and 16 months. We isolated total RNA (Ambion, PARISM-bM-^DM-" Kit) from 5 WT cell lines and CNDT2.5 treated with octreotide (Santostatin, Novartis). Total RNA was hybridized onto the Affymetrix Human Gene 1.0 ST Array by Affymetrix Uppsala Platform, UU. SE (Uppsala, Sweden). We first wanted to verify whether the different cell lines may become reliable models to study neuroendocrine signaling pathways. The main objective of this project aimed at understanding the mechanisms by which octrotide (Sandostatin, Novartis) alter cellular growth and differentiation of CNDT2.5 cells. We therefore focused on intermediate (10 months) and long stimulation (16 months) events triggered by sandostatin, which lead variation of CNDT.2.5 cells gene expression to identify potential pivotal genes involved in the development of drug resistance in neuroendocrine cells.
2012-12-12 | E-GEOD-24358 | biostudies-arrayexpress
Project description:The management of neuroendocrine tumors (NETs) is very variable, depending on many specific aspects, such as the type of tumor, spread and patient general health. Several advances have been made with the newly developed somatostatin analogues to cure this type of malignancies. Somatostain analogues such as octreotide have been used in clinic to treat patients with neuroendocrine tumors (NETs). However, the molecular mechanism leading either to successful therapy or acquired resistance to the analogues is still to large extent unclear. Patients develop drugs resistance during a long term treatment. Therefore, to identify the pivotal regulatory genes involved in the development of drug resistance is an actual challenge. We studied five human neuroendocrine tumor cell lines, CNDT2.5, KRJ1, QGP-1, NCI H720 and NCI H727. We also investigated a long-term treated CNDT2.5 by using octreotide. We performed gene expression profiling in all the human neuroendocrine cell lines. Keywords: Gene Expression profiling, treatment comparison
2012-12-12 | GSE24358 | GEO