Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.
Cancer Genomics Proteomics
; 21(4): 380-387, 2024.
Article
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| MEDLINE
| ID: mdl-38944425
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. MATERIALS ANDMETHODS:
The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm3) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 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 N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.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.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.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Oxígeno
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Neoplasias de la Vejiga Urinaria
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Imagen por Resonancia Magnética
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Genomics Proteomics
Asunto de la revista:
BIOQUIMICA
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GENETICA MEDICA
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NEOPLASIAS
Año:
2024
Tipo del documento:
Article