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Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783696/ https://www.ncbi.nlm.nih.gov/pubmed/36555771 http://dx.doi.org/10.3390/ijms232416132 |
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author | Calderón-Montaño, José Manuel Guillén-Mancina, Emilio Jiménez-Alonso, Julio José Jiménez-González, Víctor Burgos-Morón, Estefanía Mate, Alfonso Pérez-Guerrero, María Concepción López-Lázaro, Miguel |
author_facet | Calderón-Montaño, José Manuel Guillén-Mancina, Emilio Jiménez-Alonso, Julio José Jiménez-González, Víctor Burgos-Morón, Estefanía Mate, Alfonso Pérez-Guerrero, María Concepción López-Lázaro, Miguel |
author_sort | Calderón-Montaño, José Manuel |
collection | PubMed |
description | Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy. |
format | Online Article Text |
id | pubmed-9783696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97836962022-12-24 Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma Calderón-Montaño, José Manuel Guillén-Mancina, Emilio Jiménez-Alonso, Julio José Jiménez-González, Víctor Burgos-Morón, Estefanía Mate, Alfonso Pérez-Guerrero, María Concepción López-Lázaro, Miguel Int J Mol Sci Article Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy. MDPI 2022-12-17 /pmc/articles/PMC9783696/ /pubmed/36555771 http://dx.doi.org/10.3390/ijms232416132 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Calderón-Montaño, José Manuel Guillén-Mancina, Emilio Jiménez-Alonso, Julio José Jiménez-González, Víctor Burgos-Morón, Estefanía Mate, Alfonso Pérez-Guerrero, María Concepción López-Lázaro, Miguel Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title | Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title_full | Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title_fullStr | Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title_full_unstemmed | Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title_short | Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma |
title_sort | manipulation of amino acid levels with artificial diets induces a marked anticancer activity in mice with renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783696/ https://www.ncbi.nlm.nih.gov/pubmed/36555771 http://dx.doi.org/10.3390/ijms232416132 |
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