The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases

Abstract: Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate L-arginine decreases tumor...

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Autores principales: Marullo, Rossella, Castro, Mónica, Yomtoubian, Shira, Calvo Vidal, M. Nieves, Revuelta, María Victoria, Krumsiek, Jan, Cho, Andrew, Cresta Morgado, Pablo, Yang, ShaoNing, Medina, Vanina Araceli, Roth, Berta M., Bonomi, Marcelo, Keshari, Kayvan R., Mittal, Vivek, Navigante, Alfredo, Cerchietti, Leandro
Formato: Artículo
Lenguaje:Inglés
Publicado: American Association for the Advancement of Science 2022
Materias:
METASTASIS
CEREBRO
TUMORES
ARGININA
RADIACION
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14019
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-14019
record_format dspace
spelling I33-R139-123456789-140192024-03-07T11:49:46Z The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases Marullo, Rossella Castro, Mónica Yomtoubian, Shira Calvo Vidal, M. Nieves Revuelta, María Victoria Krumsiek, Jan Cho, Andrew Cresta Morgado, Pablo Yang, ShaoNing Medina, Vanina Araceli Roth, Berta M. Bonomi, Marcelo Keshari, Kayvan R. Mittal, Vivek Navigante, Alfredo Cerchietti, Leandro METASTASIS CEREBRO TUMORES ARGININA RADIACION Abstract: Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate L-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of L-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that L-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes. 2022-05-24T15:19:06Z 2022-05-24T15:19:06Z 2021 Artículo Marullo, R. et al. The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases [en línea]. Science Advances. 2021, 7 (45). doi: 10.1126/sciadv.abg1964. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14019 2375-2548 (online) https://repositorio.uca.edu.ar/handle/123456789/14019 10.1126/sciadv.abg1964 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science Science Advances Vol.7, No.45, 2021
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic METASTASIS
CEREBRO
TUMORES
ARGININA
RADIACION
spellingShingle METASTASIS
CEREBRO
TUMORES
ARGININA
RADIACION
Marullo, Rossella
Castro, Mónica
Yomtoubian, Shira
Calvo Vidal, M. Nieves
Revuelta, María Victoria
Krumsiek, Jan
Cho, Andrew
Cresta Morgado, Pablo
Yang, ShaoNing
Medina, Vanina Araceli
Roth, Berta M.
Bonomi, Marcelo
Keshari, Kayvan R.
Mittal, Vivek
Navigante, Alfredo
Cerchietti, Leandro
The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
topic_facet METASTASIS
CEREBRO
TUMORES
ARGININA
RADIACION
description Abstract: Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate L-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of L-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that L-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.
format Artículo
author Marullo, Rossella
Castro, Mónica
Yomtoubian, Shira
Calvo Vidal, M. Nieves
Revuelta, María Victoria
Krumsiek, Jan
Cho, Andrew
Cresta Morgado, Pablo
Yang, ShaoNing
Medina, Vanina Araceli
Roth, Berta M.
Bonomi, Marcelo
Keshari, Kayvan R.
Mittal, Vivek
Navigante, Alfredo
Cerchietti, Leandro
author_facet Marullo, Rossella
Castro, Mónica
Yomtoubian, Shira
Calvo Vidal, M. Nieves
Revuelta, María Victoria
Krumsiek, Jan
Cho, Andrew
Cresta Morgado, Pablo
Yang, ShaoNing
Medina, Vanina Araceli
Roth, Berta M.
Bonomi, Marcelo
Keshari, Kayvan R.
Mittal, Vivek
Navigante, Alfredo
Cerchietti, Leandro
author_sort Marullo, Rossella
title The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
title_short The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
title_full The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
title_fullStr The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
title_full_unstemmed The metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
title_sort metabolic adaptation evoked by arginine enhances the effect ofradiation in brain metastases
publisher American Association for the Advancement of Science
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14019
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