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Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells

BACKGROUND: In malignant melanoma, it has been published that up to 40% of cancer patients will suffer from brain metastasis. The prognosis for these patients is poor, with a life expectancy of 4 to 6 months. Calcium exchange is involved in numerous cell functions. Recently, three types of cellular...

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Detalles Bibliográficos
Autores principales: Embi, Abraham, Scherlag, Benjamin J, Embi, Peter J, Menes, Manuel, Po, Sunny S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541088/
https://www.ncbi.nlm.nih.gov/pubmed/23216811
http://dx.doi.org/10.1186/1475-2867-12-51
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author Embi, Abraham
Scherlag, Benjamin J
Embi, Peter J
Menes, Manuel
Po, Sunny S
author_facet Embi, Abraham
Scherlag, Benjamin J
Embi, Peter J
Menes, Manuel
Po, Sunny S
author_sort Embi, Abraham
collection PubMed
description BACKGROUND: In malignant melanoma, it has been published that up to 40% of cancer patients will suffer from brain metastasis. The prognosis for these patients is poor, with a life expectancy of 4 to 6 months. Calcium exchange is involved in numerous cell functions. Recently, three types of cellular calcium sequestration have been reported in the medical literature. The first describes a transgenic mouse model in which an increase of aberrant calcium channels triggers hypertrophy and apoptosis. The second provides a protective mechanism whereby astrocytes in the brain inhibit apoptosis of tumor cells by moving ionic calcium out of the tumor cells thru gap junctions. The third is via calcium chelation, which causes cell apoptosis by converting ionic calcium into a calcium salt. This process has been shown to operate in atrial myocardial cells, thus not allowing the intracellular calcium stores to flow through the myocytes intercalated discs. Ideally chemotherapeutic agents would be those that initiate apoptosis in tumor cells. PRESENTATION OF THE HYPOTHESIS: We hypothesize that the recent reported intracellular calcium sequestration by oxalate chelation, due to its chemical process of converting ionic calcium into a calcium salt, may inhibit the protective effect of astrocytes on brain tumor metastasized melanoma cells by not allowing free calcium to leave the metastatic cells, simultaneously apoptosis of tumor and some healthy adjacent cells could occur. This hypothesis could be extended to include other cancerous tumors such as skin cancers amongst others. TESTING THE HYPOTHESIS: Using the experimental model showing the protective mechanism of co-cultured reactive astrocytes and tumor cells treated with oxalates could be used to test this hypothesis in vitro. The calcium specific von Kossa technique could be used to confirm the presence of chelated intracellular calcium architecture of the metastatic cells (which is a sign of apoptosis), and extracellular calcium chelation stores of the Astrocytes (which has been shown to slow neural conduction). IMPLICATIONS OF THE HYPOTHESIS: The life expectancy in patients with metastasized malignant melanoma brain tumors could be significantly prolonged if the chemotherapeutic issue of brain metastasis is overcome. Other cancerous tumors can also be treated by this Targeted Chelation Approach. Ionic calcium sequestration using naturally occurring calcium chelators, viz., oxalates, could accomplish this desired outcome.
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spelling pubmed-35410882013-01-11 Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells Embi, Abraham Scherlag, Benjamin J Embi, Peter J Menes, Manuel Po, Sunny S Cancer Cell Int Hypothesis BACKGROUND: In malignant melanoma, it has been published that up to 40% of cancer patients will suffer from brain metastasis. The prognosis for these patients is poor, with a life expectancy of 4 to 6 months. Calcium exchange is involved in numerous cell functions. Recently, three types of cellular calcium sequestration have been reported in the medical literature. The first describes a transgenic mouse model in which an increase of aberrant calcium channels triggers hypertrophy and apoptosis. The second provides a protective mechanism whereby astrocytes in the brain inhibit apoptosis of tumor cells by moving ionic calcium out of the tumor cells thru gap junctions. The third is via calcium chelation, which causes cell apoptosis by converting ionic calcium into a calcium salt. This process has been shown to operate in atrial myocardial cells, thus not allowing the intracellular calcium stores to flow through the myocytes intercalated discs. Ideally chemotherapeutic agents would be those that initiate apoptosis in tumor cells. PRESENTATION OF THE HYPOTHESIS: We hypothesize that the recent reported intracellular calcium sequestration by oxalate chelation, due to its chemical process of converting ionic calcium into a calcium salt, may inhibit the protective effect of astrocytes on brain tumor metastasized melanoma cells by not allowing free calcium to leave the metastatic cells, simultaneously apoptosis of tumor and some healthy adjacent cells could occur. This hypothesis could be extended to include other cancerous tumors such as skin cancers amongst others. TESTING THE HYPOTHESIS: Using the experimental model showing the protective mechanism of co-cultured reactive astrocytes and tumor cells treated with oxalates could be used to test this hypothesis in vitro. The calcium specific von Kossa technique could be used to confirm the presence of chelated intracellular calcium architecture of the metastatic cells (which is a sign of apoptosis), and extracellular calcium chelation stores of the Astrocytes (which has been shown to slow neural conduction). IMPLICATIONS OF THE HYPOTHESIS: The life expectancy in patients with metastasized malignant melanoma brain tumors could be significantly prolonged if the chemotherapeutic issue of brain metastasis is overcome. Other cancerous tumors can also be treated by this Targeted Chelation Approach. Ionic calcium sequestration using naturally occurring calcium chelators, viz., oxalates, could accomplish this desired outcome. BioMed Central 2012-12-08 /pmc/articles/PMC3541088/ /pubmed/23216811 http://dx.doi.org/10.1186/1475-2867-12-51 Text en Copyright ©2012 Embi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hypothesis
Embi, Abraham
Scherlag, Benjamin J
Embi, Peter J
Menes, Manuel
Po, Sunny S
Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title_full Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title_fullStr Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title_full_unstemmed Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title_short Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells
title_sort targeted cellular ionic calcium chelation by oxalates: implications for the treatment of tumor cells
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541088/
https://www.ncbi.nlm.nih.gov/pubmed/23216811
http://dx.doi.org/10.1186/1475-2867-12-51
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