Mus musculus
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ABSTRACT:
PROVIDER: PRJNA237325 | ENA |
REPOSITORIES: ENA
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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 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: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: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:Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice
| PRJNA191573 | ENA
Project description:Regulation of gene expression in GOT1 midgut carcinoid in nude mice following injection with 177Lu-octreotate
| PRJNA317644 | ENA
Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ⥠1.5 and adjusted p-value ⤠0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp. Total RNA was isolated from fresh-frozen individual thyroid tissue samples (Sprague Dawley rats). Each sample was run once. Four rats received the same treatment. Control samples (from non-irradiated rats) are included.
2016-06-30 | E-GEOD-66623 | biostudies-arrayexpress
Project description:Optimization of 177Lu-octreotate treatment of neuroendocrine tumours
| PRJNA317642 | ENA
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
2021-09-10 | PXD024446 | Pride