Therapeutic radiation exposure of the abdomen during childhood induces chronic adipose tissue dysfunction
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PROVIDER: PRJNA763378 | ENA |
REPOSITORIES: ENA
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Project description:Childhood cancer survivors who received abdominal radiotherapy (RT) or total body irradiation (TBI) are at increased risk for cardiometabolic disease, but the underlying mechanisms are unknown. We hypothesize that RT-induced adipose tissue dysfunction contributes to the development of cardiometabolic disease in the expanding population of childhood cancer survivors. We performed bulk RNA-sequencing of abdominal subcutaneous adipose tissue from adult childhood cancer survivors previously exposed to TBI, abdominal RT, or chemotherapy alone, alongside a group of healthy controls. We find that irradiated adipose tissue is characterized by a gene expression signature indicative of a complex macrophage expansion, which is also associated with dysregulated adipokine secretion. The full cohort is 30 subjects; however, 3 participants (2 in CHM group, 1 in CTL group) declined to share their sequencing data in a public database.
2021-09-17 | GSE184148 | GEO
Project description:BACKGROUNDChildhood cancer survivors who received abdominal radiotherapy (RT) or total body irradiation (TBI) are at increased risk for cardiometabolic disease, but the underlying mechanisms are unknown. We hypothesize that RT-induced adipose tissue dysfunction contributes to the development of cardiometabolic disease in the expanding population of childhood cancer survivors.METHODSWe performed clinical metabolic profiling of adult childhood cancer survivors previously exposed to TBI, abdominal RT, or chemotherapy alone, alongside a group of healthy controls. Study participants underwent abdominal s.c. adipose biopsies to obtain tissue for bulk RNA sequencing. Transcriptional signatures were analyzed using pathway and network analyses and cellular deconvolution.RESULTSIrradiated adipose tissue is characterized by a gene expression signature indicative of a complex macrophage expansion. This signature includes activation of the TREM2-TYROBP network, a pathway described in diseases of chronic tissue injury. Radiation exposure of adipose is further associated with dysregulated adipokine secretion, specifically a decrease in insulin-sensitizing adiponectin and an increase in insulin resistance-promoting plasminogen activator inhibitor-1. Accordingly, survivors exhibiting these changes have early signs of clinical metabolic derangement, such as increased fasting glucose and hemoglobin A1c.CONCLUSIONChildhood cancer survivors exposed to abdominal RT or TBI during treatment exhibit signs of chronic s.c. adipose tissue dysfunction, manifested as dysregulated adipokine secretion that may negatively impact their systemic metabolic health.FUNDINGThis study was supported by Rockefeller University Hospital; National Institute of General Medical Sciences (T32GM007739); National Center for Advancing Translational Sciences (UL1 TR001866); National Cancer Institute (P30CA008748); American Cancer Society (133831-CSDG-19-117-01-CPHPS); American Diabetes Association (1-17-ACE-17); and an anonymous donor (MSKCC).
| S-EPMC8663557 | biostudies-literature
Project description:Evaluation of aCGH profile of 32 breast tumors from the childhood cancer survivor study Breast cancer cases, most of them received high-dose chest radiation during childhood for the treatment of their first cancers
2015-10-31 | E-GEOD-62940 | biostudies-arrayexpress
Project description:Radiotherapy is an important therapeutic option for the treatment of primary and metastatic brain tumors, and there is increasing concern about the side effects associated with it as survival time after treatment increases. By far, cognitive dysfunction is the most common radiation-induced central nervous system injury. Studies have shown that the hippocampus is involved in radiation-induced cognitive dysfunction. We constructed a model of radiation-induced cognitive dysfunction by irradiating the whole brain of one-month-old rats with 20 Gy, and analyzed the expression profiles in the hippocampus of rats with radiation-induced cognitive dysfunction using single-cell RNA sequencing (scRNA-seq).
2023-12-12 | GSE249426 | GEO
Project description:Low-LET radiation can cause cardiovascular dysfunctions at high-dose rates. For example, photons used in thoracic radiotherapy are known to cause acute cardiac tissue damage with elevated serum cardiac Troponin I level and long-term cardiac complications when delivered as fractionated exposures at high-dose rates. However, the effects of continuous low-dose rate radiation exposure on the heart, which simulate the space radiation environment, have not been well-studied. In this study, we aim to model low-LET space radiation-induced cardiovascular dysfunction using human induced pluripotent stem cell (iPSC)-derived engineered heart tissues (EHTs) exposed to protracted γ-ray irradiation. The investigation of pathophysiological changes in this model may provide insights and guide the development of countermeasures. As a proof-of-principle for the application of this model in drug development, we also tested the protective effect of a mitochondrial-specific antioxidant, MitoTempo, on irradiated EHTs.
2023-09-05 | GSE242108 | GEO
Project description:FaDu tumors were implanted into Athymic mice then treated with HSP90 inhibitor Onalespib (5 days per week, 55mg/kg for 2 weeks), radiation (3 x 2 Gy for 1 week) or combination (2 week Onalespib, 1 week radiation concurrent) The purpose of this study was to understand short term (1 week and 2 week post treatment) gene changes in FaDu tumors that had been injected into hind limbs of athymic mice. A drug treatment, a radiation treatment, a combination treatment, or sham treatment was used. Mice with untreated tumors required early euthanasia as tumors became too large. Treated tumors were collected 5 and 12 days post treatment start while UNtreated tumors were collected Day 5 and Day 8. Control Day 1 samples (mice euthanized on the start date of treatment) were compared to other groups.
2024-04-10 | GSE230151 | GEO
Project description:Acute radiation syndrome (ARS) is a severe condition that develops after exposure to high doses of ionizing radiation that features immune suppression and organ failure. Currently, there are no diagnostics to identify the occurrence or severity of radiation exposure. There are also no current treatments or preventative strategies to mitigate ARS. Extracellular vesicles (EVs) are mediators of intercellular communication that contribute to immune dysfunction across diseases. We investigated if EV cargo would be able to identify whole body irradiation (WBIR) exposure and if EVs promote ARS immune dysfunction. We hypothesized that beneficial EVs derived from mesenchymal stem cells (MSC-EVs) would blunt ARS immune dysfunction and might serve as prophylactic radioprotectants. Mice received WBIR (2 or 9 Gy) with assessment of EVs at 3 and 7 days after exposure. LC-MS/MS proteomic analysis of WBIR-EVs found dose-related changes as well as candidate proteins that were increased with both doses and timepoints (34 total) such as Thromboxane-A Synthase and lymphocyte cytosolic protein 2. Suprabasin and Sarcalumenin were increased only after 9 Gy suggesting these proteins may indicate high dose/lethal exposure. Analysis of EV miRNAs identified miR-376 and miR-136, which were increased up to 200- and 60-fold respectively by both levels of WBIR and select miRNAs such as miR-1839 and miR-664 that were increased only with 9 Gy. WBIR-EVs (9 Gy) were biologically active and blunted immune responses to LPS in RAW264.7 macrophages, inhibiting canonical signaling pathways associated with wound healing and phagosome formation. Accordingly, WBIR-EVs also blunted RAW macrophage phagocytosis. When given 3 days after exposure, MSC-EVs slightly modified immune gene expression changes in the spleens of mice in response to WBIR and a combined radiation plus burn injury exposure (RCI). MSC-EVs normalized the expression of certain key immune genes such as NFκBia and Cxcr4 (WBIR), Map4k1, Ccr9 and Cxcl12 (RCI) lowered plasma TNFα cytokine levels after RCI, though most gene changes were not influenced. When given prophylactically (24 and 3 hours before exposure), MSC-EVs prolonged survival to the 9 Gy lethal exposure. Thus, EVs are important participants in ARS. EV cargo might be used to diagnose WBIR exposure, and MSC-EVs might serve as radioprotectants to blunt the impact of toxic radiation exposure.
2023-06-30 | PXD041837 | Pride
Project description:Integrating metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction
| PRJNA656037 | ENA