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Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.
- Source :
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Cancer genomics & proteomics [Cancer Genomics Proteomics] 2024 Jul-Aug; Vol. 21 (4), pp. 380-387. - Publication Year :
- 2024
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Abstract
- Background/aim: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.<br />Materials and Methods: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm <superscript>3</superscript> ) or large (700 mm <superscript>3</superscript> ) tumours were imaged, breathing air then 100% O <subscript>2</subscript> , 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N <subscript>2</subscript> , sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.<br />Results: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.<br />Conclusion: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.<br /> (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Female
Pilot Projects
Mice, Nude
Genomics methods
Hypoxia diagnostic imaging
Hypoxia genetics
Tumor Hypoxia genetics
Cell Line, Tumor
Heterografts
Xenograft Model Antitumor Assays
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms diagnostic imaging
Urinary Bladder Neoplasms pathology
Magnetic Resonance Imaging methods
Oxygen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1790-6245
- Volume :
- 21
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer genomics & proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 38944425
- Full Text :
- https://doi.org/10.21873/cgp.20455