Consumption of oxygen:signal of advanced cancer ??

[Henry Campbell]

I found this interesting .... Now could someone explain it to Me ??

Henry

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Consumption of oxygen: A mitochondrial-generated progression signal of advanced cancer, "Beyond the Abstract," by Masahiro Higuchi, PhD

Published on 18 December 2012

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BERKELEY, CA (UroToday.com) - Changes in mitochondrial genome such as mutation, deletion, and depletion are associated with cancer, and recent reports demonstrate that mitochondrial genome changes determine aggressive phenotypes of cancer. However, detailed mechanisms of how mitochondrial DNA changes induce aggressive phenotypes have not been elucidated.

In our study, we demonstrate the detailed mechanisms of how mitochondrial DNA changes induce aggressive phenotypes of prostate cancer cells as follows. Mitochondrial DNA changes induce dysfunctional respiratory function. The dysfunction reduces oxygen consumption and shifts intracellular oxygen concentration from hypoxia to normoxia. Hypoxia is known to induce proteasomal degradation of HMGCoA reductase (HMGR). Thus, the hypoxia to normoxia shift induces overexpression of HMGR, activates mevalonate pathway, and induces prenylation of Ras. This event is followed by the localization of Ras to membrane, and Ras is constitutively activated. Finally this event activates following signaling such as activation of AKT, NF-kB, and ERK, leading to an aggressive phenotype of prostate cancer. It is known that mevalonate pathway is responsible for progression to aggressive phenotype of prostate cancer since statin users show reduced frequency of metastatic prostate cancer. Our finding explains how statin users have an advantage of reduced prostate cancer death. We also showed that reduction of mitochondrial DNA content, one of the markers for mitochondrial DNA changes, is associated with aggressive phenotype of prostate cancer.

One of the biggest problems of prostate cancer is that some non-aggressive cancers can shift to aggressive metastatic cancers that need to be treated. If we can predict the patients who will show this shift in the future, we can reduce unnecessary treatment of patients. Changes in mitochondrial DNA content, intracellular oxygen concentration, HMGR expression, Ras expression, and localization, which are responsible for aggressive cancer phenotype, may be used as a marker for poor survival. Additionally, inhibition of sequences of the pathway mentioned above, by certain inhibitors, could work as a new treatment to take aggressive prostate cancer back to a non-aggressive cancer.

Written by: 
Masahiro Higuchi, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

 

Consumption of oxygen: A mitochondrial-generated progression signal of advanced cancer - Abstract

[Patrick OShea]

Henry,

The subject of oxygen in cancer drives me bonkers.

As you may know, there are countless people who believe that oxygen kills cancer.  Almost 4 million hits for "cancer hates oxygen".

Blame Otto Warburg.  He was a Nobel laureate, so presumably has the last word.

So people are out there drinking hydrogen peroxide in the mistaken belief that the blood can be made to carry more oxygen than the lungs can provide.

The fact is that cancer cells like oxygen.  When a tumor grows too big, the oxygen supply becomes limited.  The response is the production of hypoxia-inducible factors [HIF].  Check PubMed for HIF-1alpha.

This turns the cancer into the perfect storm.  The answer to the oxygen dilemma is the induction of angiogenesis [via VEGF].  & the joke is that this happens before the oxygen supply is diminished.  Oxygen is irrelevant early on.

Cancer loves oxygen.  We need to inhibit HIF1alpha.  That is the key.

-Patrick

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Prostate cancer is an exceptionally heterogenous disease. What is good for one man may not be so kind on the next. Be sure to research and test any new supplement or treatment before adopting it - and in any case run it past a medically qualified person for a second opinion.