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Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.

Aliev G, Obrenovich ME, Tabrez S, Jabir NR, Reddy VP, Li Y, Burnstock G, Cacabelos R, Kamal MA - Oxid Med Cell Longev (2013)

Bottom Line: Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD).One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities.Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.

View Article: PubMed Central - PubMed

Affiliation: GALLY International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, No. 328, San Antonio, TX 78229, USA. aliev03@gmail.com

ABSTRACT
Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We speculate that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Recent studies also demonstrate a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.

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The distribution of NOS1-3 and ET-1 immunopositive gold particles in metastatic tumor vessel endothelium and hepatocytes that determined by using Post-embedding triple immunogold labeling techniques. (a) Clusters of NOS2 positive gold particles (20 nm, thick arrows) but not NOS3 (5 nm, single thin arrow) and ET-1 (10 nm, double arrow) were seen in tumor vessel endothelium. X100,000. (b) The expression of NOS1 (20 nm single arrow) was seen in the matrix of lipid laden hepatocytes in tumor growth area. NOS3 (10 nm) and ET-1 (5 nm) positive gold particles indicated by double and thin single arrow. X100,000. (c) Clusters of ET-1 (20 nm, single arrows) but not NOS1 (10 nm, double arrow) and NOS3 (5 nm, single thin arrow) positive gold particles in the cytoplasmic matrix of hepatocytes were seen. X100,000. (d) EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (10 nm, double arrow). X100,000. Reprinted with permission of J Submicrosc Cytol Pathol [2].
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fig6: The distribution of NOS1-3 and ET-1 immunopositive gold particles in metastatic tumor vessel endothelium and hepatocytes that determined by using Post-embedding triple immunogold labeling techniques. (a) Clusters of NOS2 positive gold particles (20 nm, thick arrows) but not NOS3 (5 nm, single thin arrow) and ET-1 (10 nm, double arrow) were seen in tumor vessel endothelium. X100,000. (b) The expression of NOS1 (20 nm single arrow) was seen in the matrix of lipid laden hepatocytes in tumor growth area. NOS3 (10 nm) and ET-1 (5 nm) positive gold particles indicated by double and thin single arrow. X100,000. (c) Clusters of ET-1 (20 nm, single arrows) but not NOS1 (10 nm, double arrow) and NOS3 (5 nm, single thin arrow) positive gold particles in the cytoplasmic matrix of hepatocytes were seen. X100,000. (d) EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (10 nm, double arrow). X100,000. Reprinted with permission of J Submicrosc Cytol Pathol [2].

Mentions: Our extended study by using postembedding triple immunogold labeling techniques showed that the clusters of NOS2 positive, but no NOS3 and ET-1 immunopositive containing gold particles were seen in tumor vessel endothelium (Figure 6(a)). The expression of NOS1 containing positive gold particles was seen in the matrix of lipid laden hepatocytes in tumor growth area (Figure 6(b)). Very often the clusters of ET-1 but not NOS1 and NOS3 positive gold particles in the cytoplasmic matrix of hepatocytes were seen (Figure 6(c)). EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (Figure 6(d)). Our study highlights mitochondria as a critical constituent responsible for cell viability, which can be considered as a new research focus and of new diagnostic criteria for the earlier detection of tumors as well as treatment strategies at least in some tumors. However, further study needs to be carried out in order to clarify the exact nature of these relationships during the metastases and growth of primary and/or metastatic tumors.


Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.

Aliev G, Obrenovich ME, Tabrez S, Jabir NR, Reddy VP, Li Y, Burnstock G, Cacabelos R, Kamal MA - Oxid Med Cell Longev (2013)

The distribution of NOS1-3 and ET-1 immunopositive gold particles in metastatic tumor vessel endothelium and hepatocytes that determined by using Post-embedding triple immunogold labeling techniques. (a) Clusters of NOS2 positive gold particles (20 nm, thick arrows) but not NOS3 (5 nm, single thin arrow) and ET-1 (10 nm, double arrow) were seen in tumor vessel endothelium. X100,000. (b) The expression of NOS1 (20 nm single arrow) was seen in the matrix of lipid laden hepatocytes in tumor growth area. NOS3 (10 nm) and ET-1 (5 nm) positive gold particles indicated by double and thin single arrow. X100,000. (c) Clusters of ET-1 (20 nm, single arrows) but not NOS1 (10 nm, double arrow) and NOS3 (5 nm, single thin arrow) positive gold particles in the cytoplasmic matrix of hepatocytes were seen. X100,000. (d) EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (10 nm, double arrow). X100,000. Reprinted with permission of J Submicrosc Cytol Pathol [2].
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: The distribution of NOS1-3 and ET-1 immunopositive gold particles in metastatic tumor vessel endothelium and hepatocytes that determined by using Post-embedding triple immunogold labeling techniques. (a) Clusters of NOS2 positive gold particles (20 nm, thick arrows) but not NOS3 (5 nm, single thin arrow) and ET-1 (10 nm, double arrow) were seen in tumor vessel endothelium. X100,000. (b) The expression of NOS1 (20 nm single arrow) was seen in the matrix of lipid laden hepatocytes in tumor growth area. NOS3 (10 nm) and ET-1 (5 nm) positive gold particles indicated by double and thin single arrow. X100,000. (c) Clusters of ET-1 (20 nm, single arrows) but not NOS1 (10 nm, double arrow) and NOS3 (5 nm, single thin arrow) positive gold particles in the cytoplasmic matrix of hepatocytes were seen. X100,000. (d) EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (10 nm, double arrow). X100,000. Reprinted with permission of J Submicrosc Cytol Pathol [2].
Mentions: Our extended study by using postembedding triple immunogold labeling techniques showed that the clusters of NOS2 positive, but no NOS3 and ET-1 immunopositive containing gold particles were seen in tumor vessel endothelium (Figure 6(a)). The expression of NOS1 containing positive gold particles was seen in the matrix of lipid laden hepatocytes in tumor growth area (Figure 6(b)). Very often the clusters of ET-1 but not NOS1 and NOS3 positive gold particles in the cytoplasmic matrix of hepatocytes were seen (Figure 6(c)). EC from metastatic liver microvessels prepared as negative controls (through omission of the primary antibody) showed only the presence of single gold particles (Figure 6(d)). Our study highlights mitochondria as a critical constituent responsible for cell viability, which can be considered as a new research focus and of new diagnostic criteria for the earlier detection of tumors as well as treatment strategies at least in some tumors. However, further study needs to be carried out in order to clarify the exact nature of these relationships during the metastases and growth of primary and/or metastatic tumors.

Bottom Line: Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD).One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities.Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.

View Article: PubMed Central - PubMed

Affiliation: GALLY International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, No. 328, San Antonio, TX 78229, USA. aliev03@gmail.com

ABSTRACT
Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We speculate that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Recent studies also demonstrate a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.

Show MeSH
Related in: MedlinePlus