Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 07 2021
30 07 2021
Historique:
received:
17
02
2021
accepted:
01
07
2021
entrez:
31
7
2021
pubmed:
1
8
2021
medline:
9
11
2021
Statut:
epublish
Résumé
This study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique.
Identifiants
pubmed: 34330960
doi: 10.1038/s41598-021-94323-0
pii: 10.1038/s41598-021-94323-0
pmc: PMC8324788
doi:
Substances chimiques
Contrast Media
0
Hydralazine
26NAK24LS8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
15553Subventions
Organisme : NCI NIH HHS
ID : R01 CA204446
Pays : United States
Organisme : NIH HHS
ID : S10 OD016310
Pays : United States
Organisme : NIH HHS
ID : S10657301
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB022612
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Int J Oncol. 1997 Nov;11(5):1123-8
pubmed: 21528313
Biology (Basel). 2021 Jan 22;10(2):
pubmed: 33499069
Kidney Int. 2017 Jan;91(1):157-176
pubmed: 27692563
Int J Hyperthermia. 1990 Nov-Dec;6(6):971-83
pubmed: 2286795
Int J Hyperthermia. 2015;31(8):813-22
pubmed: 26540488
J Clin Transl Hepatol. 2018 Mar 28;6(1):69-78
pubmed: 29607307
PLoS One. 2014 Dec 22;9(12):e113586
pubmed: 25532146
Int J Mol Sci. 2018 Apr 12;19(4):
pubmed: 29649096
Theranostics. 2020 Jan 1;10(2):462-483
pubmed: 31903132
Nucleic Acids Res. 2019 Jan 8;47(D1):D1102-D1109
pubmed: 30371825
Int J Hyperthermia. 2011;27(2):156-71
pubmed: 21158487
Hepatobiliary Surg Nutr. 2013 Aug;2(4):184-7
pubmed: 24570943
Hepatology. 2015 Aug;62(2):452-65
pubmed: 25711742
Asian Pac J Cancer Prev. 2019 Aug 01;20(8):2303-2310
pubmed: 31450899
Radiology. 2019 Apr;291(1):232-238
pubmed: 30644817
Med Phys. 2009 May;36(5):1867-74
pubmed: 19544806
Cancers (Basel). 2018 Aug 10;10(8):
pubmed: 30103412
Prog Biophys Mol Biol. 2007 Jan-Apr;93(1-3):212-55
pubmed: 16934858
Genes Cancer. 2010 Mar;1(3):197-209
pubmed: 21779447
Ultrasound Med Biol. 2015 Apr;41(4):905-28
pubmed: 25728459
Drug Intell Clin Pharm. 1988 Jul-Aug;22(7-8):546-50
pubmed: 2843341
Int J Hyperthermia. 1994 Jul-Aug;10(4):457-83
pubmed: 7963805
Nanotheranostics. 2019 Oct 1;3(4):331-341
pubmed: 31687321
Ultrasound Med Biol. 2019 May;45(5):1025-1043
pubmed: 30773377
Med Phys. 2016 Mar;43(3):1539-49
pubmed: 26936737
Tsitologiia. 2012;54(11):837-46
pubmed: 23402001
Mol Reprod Dev. 2015 Jul-Aug;82(7-8):518-29
pubmed: 26153368
Acad Radiol. 2009 Mar;16(3):321-31
pubmed: 19201361
Semin Liver Dis. 2013 Feb;33 Suppl 1:S11-9
pubmed: 23457035
Ultrasound Med Biol. 1999 Jul;25(6):871-87
pubmed: 10461714
Anticancer Res. 2013 Aug;33(8):2989-96
pubmed: 23898051
Int J Hyperthermia. 1989 Mar-Apr;5(2):123-36
pubmed: 2926180
J Vasc Interv Radiol. 2003 Oct;14(10):1267-74
pubmed: 14551273
Natl Cancer Inst Monogr. 1982 Jun;61:333-7
pubmed: 6757750
J Hepatocell Carcinoma. 2016 Oct 05;3:41-53
pubmed: 27785449
Symp Soc Exp Biol. 1987;41:187-211
pubmed: 3332484
Ultrasound Med Biol. 2012 Dec;38(12):2130-7
pubmed: 23062365
Clin Cancer Res. 2003 May;9(5):1596-603
pubmed: 12738711
Int J Radiat Oncol Biol Phys. 1978 Nov-Dec;4(11-12):1029-32
pubmed: 721647
Int J Hyperthermia. 1991 May-Jun;7(3):403-15
pubmed: 1919137
Ultrasound Med Biol. 2006 Mar;32(3):453-61
pubmed: 16530105
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4802-E4811
pubmed: 28566498
Radiat Res. 1999 Jan;151(1):79-84
pubmed: 9973088
Liver Cancer. 2019 Oct;8(5):326-340
pubmed: 31768343
Int J Radiat Oncol Biol Phys. 1991 May;20(5):1001-7
pubmed: 2022499
Int J Hyperthermia. 2005 Dec;21(8):745-53
pubmed: 16338857
J Acoust Soc Am. 1997 Mar;101(3):1734-41
pubmed: 9069639
Pediatr Nephrol. 2009 Oct;24(10):1939-49
pubmed: 17690916
Am J Physiol. 1987 Jul;253(1 Pt 2):R128-35
pubmed: 3605377
Front Oncol. 2020 Oct 29;10:519164
pubmed: 33194582
Ultrasound Med Biol. 2007 Dec;33(12):1901-10
pubmed: 17720299
Pharm Res. 2002 Aug;19(8):1123-9
pubmed: 12240937
J Hepatol. 2004 Nov;41(5):864-80
pubmed: 15519663
Int J Hyperthermia. 1994 May-Jun;10(3):451-5
pubmed: 7930813
Cancer Res. 1990 Jan 1;50(1):15-9
pubmed: 2293549
Acad Radiol. 2008 Sep;15(9):1133-41
pubmed: 18692754
Anticancer Res. 2011 May;31(5):1583-8
pubmed: 21617213
Oncotarget. 2016 Apr 19;7(16):21875-86
pubmed: 26942461
Pathology. 2009 Feb;41(2):168-72
pubmed: 19152189
Oncology. 1994 Jul-Aug;51(4):339-43
pubmed: 8208517
Sci Rep. 2016 Dec 02;6:38072
pubmed: 27909289
J Immunol. 1988 Apr 1;140(7):2197-200
pubmed: 3258330
Hepat Oncol. 2018 Sep 28;5(2):HEP08
pubmed: 31293776
Lancet Oncol. 2018 Aug;19(8):1027-1039
pubmed: 30001990
Med Phys. 2007 Sep;34(9):3436-48
pubmed: 17926945
Int J Hyperthermia. 2004 Nov;20(7):671-7
pubmed: 15675664
Hepatology. 2020 Jan;71(1):183-195
pubmed: 31206715
Biomed Eng Lett. 2017 Apr 5;7(2):115-120
pubmed: 30603158
Semin Intervent Radiol. 2015 Dec;32(4):398-415
pubmed: 26622104
Eur J Cancer Clin Oncol. 1982 Oct;18(10):1027-33
pubmed: 6891638
Cells Tissues Organs. 2013;197(1):14-26
pubmed: 22987069
ChemMedChem. 2009 May;4(5):792-9
pubmed: 19322801
Br J Pharmacol. 2014 Dec;171(24):5507-23
pubmed: 24665826
Anat Rec (Hoboken). 2008 Jun;291(6):721-34
pubmed: 18484619
Int J Radiat Oncol Biol Phys. 1992;22(3):455-8
pubmed: 1735677
Ultrasound Med Biol. 2005 Oct;31(10):1403-10
pubmed: 16223644
Di Yi Jun Yi Da Xue Xue Bao. 2003 Jan;23(1):21-4
pubmed: 12527507
Sci Rep. 2021 Feb 18;11(1):4100
pubmed: 33603035
BMC Gastroenterol. 2020 Nov 19;20(1):390
pubmed: 33213375
Oncotarget. 2017 Apr 13;8(32):52651-52664
pubmed: 28881759
Ultrasound Med Biol. 2010 May;36(5):853-7
pubmed: 20381952
Cancers (Basel). 2019 Jan 09;11(1):
pubmed: 30634444