Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997) provide evidence of a lack of correlation between these fac...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hamid R Molavian, Mohammad Kohandel, Michael Milosevic, Sivabal Sivaloganathan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f37e7081acc343a980c4edbe539612c2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f37e7081acc343a980c4edbe539612c2
record_format	dspace
spelling	oai:doaj.org-article:f37e7081acc343a980c4edbe539612c22021-11-18T07:32:41ZDeriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.1932-620310.1371/journal.pone.0028101https://doaj.org/article/f37e7081acc343a980c4edbe539612c22011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174768/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997) provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2) are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2) and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process) in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.Hamid R MolavianMohammad KohandelMichael MilosevicSivabal SivaloganathanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28101 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hamid R Molavian Mohammad Kohandel Michael Milosevic Sivabal Sivaloganathan Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
description	Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997) provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2) are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2) and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process) in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.
format	article
author	Hamid R Molavian Mohammad Kohandel Michael Milosevic Sivabal Sivaloganathan
author_facet	Hamid R Molavian Mohammad Kohandel Michael Milosevic Sivabal Sivaloganathan
author_sort	Hamid R Molavian
title	Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
title_short	Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
title_full	Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
title_fullStr	Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
title_full_unstemmed	Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
title_sort	deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f37e7081acc343a980c4edbe539612c2
work_keys_str_mv	AT hamidrmolavian derivingmechanismsresponsibleforthelackofcorrelationbetweenhypoxiaandacidityinsolidtumors AT mohammadkohandel derivingmechanismsresponsibleforthelackofcorrelationbetweenhypoxiaandacidityinsolidtumors AT michaelmilosevic derivingmechanismsresponsibleforthelackofcorrelationbetweenhypoxiaandacidityinsolidtumors AT sivabalsivaloganathan derivingmechanismsresponsibleforthelackofcorrelationbetweenhypoxiaandacidityinsolidtumors
_version_	1718423323723956224

Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

Ejemplares similares