Lipidome Signatures of Metastasis in a Transgenic Mouse Model of Sonic Hedgehog Medulloblastoma.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
TISSUE(S): Brain
DISEASE(S): Cancer
PROVIDER: ST001290 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Medulloblastoma (MB), the most common malignant pediatric brain tumor, has high propensity to metastasize. Currently, the standard treatment for MB patients includes radiation therapy administered to the entire brain and spine for the purpose of treating or preventing against metastasis. Due to this aggressive treatment, the majority of long-term survivors will be left with permanent and debilitating neurocognitive impairment, for the 30-40% patients that fail to respond to treatment, all will relapse with terminal metastatic disease. An understanding of the underlying biology that drives MB metastasis is lacking, and is critically needed in order to develop targeted therapeutics for its prevention. To examine the metastatic biology of sonic hedgehog (SHH) MB, the human MB subgroup with the worst clinical outcome in children, we first generated a robust SmoA1-Math-GFP mouse model that reliably reproduces human SHH MB whereby metastases can be visualized under fluorescence microscopy. Lipidome alterations associated with metastasis were then investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) under positive ionization mode to primary tumor samples collected from mice without (n = 18) and with (n = 7) metastasis. Thirty-four discriminant lipids associated with SHH MB metastasis were successfully annotated, including ceramides (Cers), sphingomyelins (SMs), triacylglycerols (TGs), diacylglycerols (DGs), phosphatidylcholines (PCs), and phosphatidic acids (PAs). This study provides deeper insights into dysregulations of lipid metabolism associated with SHH MB metastatic progression, and thus serves as a guide toward novel targeted therapies.
| S-EPMC7982123 | biostudies-literature
Project description:Application of a melanoma experimental metastasis model to elucidate molecular mediators of melanoma brain metastasis. Malignant melanoma frequently metastasizes to the brain. The molecular mediators of brain metastasis still remains largely unknnown. Two melanoma cell lines (opposing phenotypes in vitro: invasive/proliferative) were injected (L.V) into immune-compromised animals to generate organ-specific in vivo metastatic tumor cells and host tissue. Immunomagnetic separation was applied to separate tumor cells from host stroma. A rat model was applied to generate organ-specific profiles. Subsequently, a mouse model was applied to generate in vivo brain metastatic samples to follow altered gene expression in melanoma colonizing the brain over time. Gene expression data was collected from human and animal host-specific arrays.
2014-02-26 | E-MTAB-2065 | biostudies-arrayexpress
Project description:b'Metabolic alternations were investigated by applying Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS) to mice brain tissue samples collected from SmoA1-Math-GFP mice with (n=18) and without (n=7) metastasis. All samples were analyzed using reverse phase (RP) UPLC-MS analysis in positive and negative ion modes.'
2021-02-15 | MSV000086877 | GNPS
Project description:Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages, and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipids alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.TeaserTime-resolved lipidome remodeling in an ovarian cancer model is studied through lipidomics and machine learning.
| S-EPMC9881992 | biostudies-literature
Project description:Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipid alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.
| S-EPMC10243112 | biostudies-literature
Project description:Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
| S-EPMC10469212 | biostudies-literature
Project description:Cerebral malaria (CM), a fatal complication of Plasmodium infection that affects children, especially under the age of five, in sub-Saharan Africa and adults in South-East Asia, results from incompletely understood pathogenetic mechanisms. Increased release of circulating miRNA, proteins, lipids and extracellular vesicles has been found in CM patients and experimental mouse models. We compared lipid profiles derived from the plasma of CBA mice infected with Plasmodium berghei ANKA (PbA), which causes CM, to those from Plasmodium yoelii (Py), which does not. We previously showed that platelet-free plasma (18k fractions enriched from plasma) contains a high number of extracellular vesicles (EVs). Here, we found that this fraction produced at the time of CM differed dramatically from those of non-CM mice, despite identical levels of parasitaemia. Using high-resolution liquid chromatography-mass spectrometry (LCMS), we identified over 300 lipid species within 12 lipid classes. We identified 45 and 75 lipid species, mostly including glycerolipids and phospholipids, with significantly altered concentrations in PbA-infected mice compared to Py-infected and uninfected mice, respectively. Total lysophosphatidylethanolamine (LPE) levels were significantly lower in PbA infection compared to Py infection and controls. These results suggest that experimental CM could be characterised by specific changes in the lipid composition of the 18k fraction containing circulating EVs and can be considered an appropriate model to study the role of lipids in the pathophysiology of CM.
| S-EPMC9820457 | biostudies-literature
Project description: Not available
| S-EPMC3001020 | biostudies-literature
Project description:Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) is a common finding in human and veterinary patients with endocrinopathies (e.g., hypothyroidism and hypercortisolism (Cushing's syndrome; CS)). Despite emerging use of lipidomics technology in medicine, the lipid profiles of these endocrinopathies have not been evaluated and characterized in dogs. The aim of this study was to compare the serum lipidomes of dogs with naturally occurring CS or hypothyroidism with those of healthy dogs. Serum samples from 39 dogs with CS, 45 dogs with hypothyroidism, and 10 healthy beagle dogs were analyzed using a targeted lipidomics approach with liquid chromatography-mass spectrometry. There were significant differences between the lipidomes of dogs with CS, hypothyroidism, and the healthy dogs. The most significant changes were found in the lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylinositols, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, ceramides, and sphingosine 1-phosphates. Lipid alterations were especially pronounced in dogs with hypothyroidism. Several changes suggested a more atherogenic lipid profile in dogs with HT than in dogs with CS. In this study, we found so far unknown effects of naturally occurring hypothyroidism and CS on lipid metabolism in dogs. Our findings provide starting points to further examine differences in occurrence of atherosclerotic lesion formation between the two diseases.
| S-EPMC9031822 | biostudies-literature
Project description:Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo.
| S-EPMC5091834 | biostudies-other