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Title: Renin-Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids.
Austin Authors: Riddiough, Georgina E ;Fifis, Theodora;Muralidharan, Vijayaragavan ;Christophi, Christopher ;Tran, Bang M;Perini, Marcos V ;Vincan, Elizabeth
Affiliation: Surgery (University of Melbourne)
Infectious Diseases
Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institute, Melbourne, VIC 3000, Australia.;Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute, Melbourne, VIC 3000, Australia.;Curtin Medical School, Curtin University, Perth, WA 6102, Australia.
Issue Date: 14-Mar-2024
Date: 2024
Publication information: International Journal of Molecular Sciences 2024-03-14; 25(6)
Abstract: The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin-angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients' parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM.
DOI: 10.3390/ijms25063282
ORCID: 0000-0003-0687-5177
Journal: International Journal of Molecular Sciences
PubMed URL: 38542253
ISSN: 1422-0067
Type: Journal Article
Subjects: colorectal liver metastasis
renin–angiotensin inhibitors
Colorectal Neoplasms/pathology
Neoplasm Recurrence, Local/pathology
Liver Neoplasms/secondary
Appears in Collections:Journal articles

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