Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy.
Biomedical device
Focused ultrasound
Pancreatic cancer
Pre-clinical animal model
Tumor ablation
Xenograft
Journal
Ultrasound in medicine & biology
ISSN: 1879-291X
Titre abrégé: Ultrasound Med Biol
Pays: England
ID NLM: 0410553
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
28
03
2023
revised:
26
07
2023
accepted:
28
07
2023
medline:
19
9
2023
pubmed:
19
8
2023
entrez:
18
8
2023
Statut:
ppublish
Résumé
New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors. Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy. Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor. This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.
Identifiants
pubmed: 37596154
pii: S0301-5629(23)00245-4
doi: 10.1016/j.ultrasmedbio.2023.07.013
pmc: PMC10529075
mid: NIHMS1921481
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2361-2370Subventions
Organisme : NCI NIH HHS
ID : R01 CA269811
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA274439
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB027979
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB028429
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest The authors declare no competing interests.
Références
Front Oncol. 2019 Mar 12;9:144
pubmed: 30915276
Adv Healthc Mater. 2019 Aug;8(16):e1900409
pubmed: 31148393
Ultrasound Med Biol. 2022 Feb;48(2):293-303
pubmed: 34750030
Int J Hyperthermia. 2020;37(1):786-798
pubmed: 32619373
World J Clin Oncol. 2011 Jan 10;2(1):8-27
pubmed: 21603311
World J Gastroenterol. 2021 May 14;27(18):2105-2121
pubmed: 34025067
Sci Rep. 2016 Apr 27;6:25222
pubmed: 27118081
IEEE Trans Biomed Eng. 2020 Sep;67(9):2490-2496
pubmed: 31902753
Oncoimmunology. 2019 Aug 28;8(11):1652532
pubmed: 31646081
Cancer Cell. 2017 Apr 10;31(4):501-515.e8
pubmed: 28399408
Cancers (Basel). 2022 Mar 22;14(7):
pubmed: 35406383
Pancreatology. 2017 Nov - Dec;17(6):962-966
pubmed: 29037917
Int J Hyperthermia. 2021;38(1):561-575
pubmed: 33827375
Sci Rep. 2021 Jun 28;11(1):13436
pubmed: 34183736
Ultrasound Med Biol. 2017 Jun;43(6):1237-1251
pubmed: 28318889
PLoS One. 2020 Sep 21;15(9):e0239391
pubmed: 32956389
Sci Rep. 2021 Apr 7;11(1):7584
pubmed: 33828203
Phys Med Biol. 2022 Jul 19;67(15):
pubmed: 35772383
Phys Med Biol. 2014 Jan 20;59(2):253-70
pubmed: 24351722
Nat Rev Cancer. 2002 Dec;2(12):897-909
pubmed: 12459728
Cancers (Basel). 2021 Dec 20;13(24):
pubmed: 34945001
Theranostics. 2021 Jan 1;11(2):540-554
pubmed: 33391491
Cancers (Basel). 2022 Jan 27;14(3):
pubmed: 35158903
Ther Adv Med Oncol. 2015 Mar;7(2):68-84
pubmed: 25755680
Ultrasound Med Biol. 2013 Mar;39(3):449-65
pubmed: 23380152
Cancers (Basel). 2017 Nov 16;9(11):
pubmed: 29144412
Ultrasound Med Biol. 2013 Aug;39(8):1398-409
pubmed: 23683406
IEEE Trans Ultrason Ferroelectr Freq Control. 2022 Jan;69(1):5-26
pubmed: 34478363
J Cancer Res Ther. 2010 Oct-Dec;6(4):414-20
pubmed: 21358073
IEEE Trans Ultrason Ferroelectr Freq Control. 2014 Feb;61(2):341-52
pubmed: 24474139
Clin Cancer Res. 2019 Apr 1;25(7):2136-2143
pubmed: 30352906
Nat Rev Gastroenterol Hepatol. 2020 Aug;17(8):487-505
pubmed: 32393771
IEEE Trans Ultrason Ferroelectr Freq Control. 2004 Jun;51(6):726-36
pubmed: 15244286
Methods Mol Biol. 2022;2394:883-895
pubmed: 35094364
Radiology. 2018 May;287(2):485-493
pubmed: 29381870
IEEE Trans Ultrason Ferroelectr Freq Control. 2007 Oct;54(10):2091-101
pubmed: 18019247
Ultrasound Med Biol. 2016 Oct;42(10):2466-77
pubmed: 27401956
Gut Liver. 2010 Sep;4 Suppl 1:S57-61
pubmed: 21103296
Front Oncol. 2017 Aug 23;7:190
pubmed: 28879168
J Vasc Interv Radiol. 2023 Mar;34(3):386-394.e2
pubmed: 36503074
Int J Hyperthermia. 2022;39(1):1115-1123
pubmed: 36002243
J Immunother Cancer. 2020 Jan;8(1):
pubmed: 31940590
J Virol. 2018 Oct 12;92(21):
pubmed: 30111571
Biol Reprod. 2014 Sep;91(3):78
pubmed: 25100712
EBioMedicine. 2019 Jun;44:112-125
pubmed: 31130474
J Immunol. 2022 Oct 26;:
pubmed: 36288906
Trends Mol Med. 2001 Nov;7(11):502-7
pubmed: 11689335
Cancers (Basel). 2018 Jan 10;10(1):
pubmed: 29320420
Ultrasound Med Biol. 2021 Dec;47(12):3435-3446
pubmed: 34462159
Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:6064-6067
pubmed: 30441719
Cardiovasc Intervent Radiol. 2021 Oct;44(10):1643-1650
pubmed: 34244841
IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Sep;68(9):2987-3000
pubmed: 33956631
Nat Med. 1995 Mar;1(3):215-20
pubmed: 7585036
Mamm Genome. 2022 Mar;33(1):230-240
pubmed: 34476572
J Nucl Med. 2010 Apr;51(4):501-4
pubmed: 20237033
Ultrasound Med Biol. 2014 May;40(5):947-55
pubmed: 24462161
IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Sep;68(9):2953-2964
pubmed: 33856990