Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

Abstract 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 adminis...

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Autores principales:	Mrigendra B. Karmacharya, Laith R. Sultan, Stephen J. Hunt, Chandra M. Sehgal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43bd32a8a8d44abab708d0fc1b9ba52a
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spelling	oai:doaj.org-article:43bd32a8a8d44abab708d0fc1b9ba52a2021-12-02T16:30:09ZHydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma10.1038/s41598-021-94323-02045-2322https://doaj.org/article/43bd32a8a8d44abab708d0fc1b9ba52a2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94323-0https://doaj.org/toc/2045-2322Abstract 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.Mrigendra B. KarmacharyaLaith R. SultanStephen J. HuntChandra M. SehgalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mrigendra B. Karmacharya Laith R. Sultan Stephen J. Hunt Chandra M. Sehgal Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
description	Abstract 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.
format	article
author	Mrigendra B. Karmacharya Laith R. Sultan Stephen J. Hunt Chandra M. Sehgal
author_facet	Mrigendra B. Karmacharya Laith R. Sultan Stephen J. Hunt Chandra M. Sehgal
author_sort	Mrigendra B. Karmacharya
title	Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
title_short	Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
title_full	Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
title_fullStr	Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
title_full_unstemmed	Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
title_sort	hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/43bd32a8a8d44abab708d0fc1b9ba52a
work_keys_str_mv	AT mrigendrabkarmacharya hydralazineaugmentedultrasoundhyperthermiaforthetreatmentofhepatocellularcarcinoma AT laithrsultan hydralazineaugmentedultrasoundhyperthermiaforthetreatmentofhepatocellularcarcinoma AT stephenjhunt hydralazineaugmentedultrasoundhyperthermiaforthetreatmentofhepatocellularcarcinoma AT chandramsehgal hydralazineaugmentedultrasoundhyperthermiaforthetreatmentofhepatocellularcarcinoma
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Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

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