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New biomarker for fatal prostate cancer identified

natasa778

Senior Member
Messages
1,774
http://www.physorg.com/news153738140.html


In a study that appears in the February issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, researchers confirmed their earlier findings that men who have too much calcium in their bloodstreams subsequently have an increased risk of fatal prostate cancer. Now researchers have also identified an even more accurate biomarker of the fatal cancer: high levels of ionized serum calcium.

"Scientists have known for many years that most prostate cancers are slow-growing and that many men will die with, rather than of, their prostate cancer," said Gary G. Schwartz, Ph.D., senior author of the study and an associate professor of cancer biology at the School of Medicine, a part of Wake Forest University Baptist Medical Center. "The problem is, how can we determine which cancers pose a significant threat to life and need aggressive treatment versus those that, if left alone, are unlikely to threaten the patient's life? These findings may shed light on that problem."

This was the first study to examine fatal prostate cancer risk in relation to prediagnostic levels of ionized serum calcium, and researchers found that men in the highest third of ionized serum calcium levels are three times more likely to die of prostate cancer than those with the least amount of ionized serum calcium. Researchers also confirmed a previous finding of a doubling of risk for fatal prostate cancer among men whose level of total serum calcium falls in the highest third of the total serum calcium distribution.

Ionized serum calcium is the biologically active part of total serum calcium. About 50 percent of total serum calcium is inactive, leaving only the ionized serum calcium to directly interact with cells.

The findings have both scientific and practical implications, said Halcyon G. Skinner, Ph.D., of the University of Wisconsin, the study's lead author. From a scientific standpoint, it helps focus research on what it is about calcium that may promote prostate cancer. On a practical level, the finding may offer some guidance to men trying to decide whether or not to seek treatment for a recent prostate cancer diagnosis. If confirmed, the findings could also lead to the general reduction of over-treatment of prostate cancer.

"Many men with this diagnosis are treated unnecessarily," Schwartz said. "Within months of initial diagnosis of prostate cancer, many men opt to undergo either radiation or radical surgery. The problem is, we don't know who needs to be treated and who doesn't, so we treat most men, over-treating the majority. These new findings, if confirmed, suggest that men in the lower end of the normal distribution of ionized serum calcium are three times less likely than men in the upper distribution to develop fatal disease.

"These men may choose to delay treatment or perhaps defer it altogether," Schwartz added. "It also suggests that medicine may be able to help in lowering the risk of fatal prostate cancer by reducing serum calcium levels."

Schwartz added that much of the ongoing research into the development of prostate cancer is focused on identifying characteristics of aggressive tumors, whereas this research is focused on identifying characteristics of the men who will develop the tumors before they actually develop.

He cautioned that calcium in serum is little influenced by calcium in the diet. Serum calcium levels are controlled genetically and are stable over much of an individual's life, he said.

"These results do not imply that men need to quit drinking milk or avoid calcium in their diets," Schwartz added.

Source: Wake Forest University Baptist Medical Center
 
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76
natasa778 said:
He cautioned that calcium in serum is little influenced by calcium in the diet. Serum calcium levels are controlled genetically and are stable over much of an individual's life, he said.

"These results do not imply that men need to quit drinking milk or avoid calcium in their diets," Schwartz added.

Source: Wake Forest University Baptist Medical Center

Just highlighting these key messages - i think its important with CFS/ME not to limit calcium (unless you have other medical complicatons which require some limitation). If anything, at times my body craves calcium rich foods so i up my intake considerably.
 

JillBohr

Senior Member
Messages
247
Location
Columbus, OH
I wonder if the ionized calcium is a result of XMRV making the serum calcium active and not as a result of genes. I think XMRV activity is a result of genes. I would love WPI to do a study where they tested this for a biomarker in CFS patients and would love NCI to also test this biomarker with prostate cancer patients in conjuction with XMRV. Stupid question (as always) but do we know the patterns of ionized calcium in ME/CFS, autism and other autoimmune disorders?
 
Messages
76
I wonder if the ionized calcium is a result of XMRV making the serum calcium active and not as a result of genes. I think XMRV activity is a result of genes. I would love WPI to do a study where they tested this for a biomarker in CFS patients and would love NCI to also test this biomarker with prostate cancer patients in conjuction with XMRV. Stupid question (as always) but do we know the patterns of ionized calcium in ME/CFS, autism and other autoimmune disorders?

I cant answer your question about the patterns of ionized calcium in CFS, but i remember on several occasions its been said that XMRV is implicated in highly aggressive forms of prostate cancer. On that basis your question seems far from stupid Jill - if there hasnt been anything published already its worth asking a question to Judy M or another of the leading experts id say.
 

JillBohr

Senior Member
Messages
247
Location
Columbus, OH
I wonder if the ionized calcium is a result of XMRV making the serum calcium active and not as a result of genes. I think XMRV activity is a result of genes. I would love WPI to do a study where they tested this for a biomarker in CFS patients and would love NCI to also test this biomarker with prostate cancer patients in conjuction with XMRV. Stupid question (as always) but do we know the patterns of ionized calcium in ME/CFS, autism and other autoimmune disorders?

omg. omg. Oh, Oh, I have seen this paper several times and forgot about it. duh. This is the post-mortem study on ASD. Here is the link:

http://www.ncbi.nlm.nih.gov/pubmed/18607376

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.
 

natasa778

Senior Member
Messages
1,774
Just highlighting these key messages - i think its important with CFS/ME not to limit calcium (unless you have other medical complicatons which require some limitation). If anything, at times my body craves calcium rich foods so i up my intake considerably.

Yes BUT ... True to some extent. Especially where sharp changes in the levels of dietary calcium is concerned, like through supplementation (esp. alongside vitamin D, which will increase gut absorption...).



I wonder if the ionized calcium is a result of XMRV making the serum calcium active and not as a result of genes.

very very likely. def the case with some others, better researched viruses. actually most viruses, including retroviruses, completely highjack various cellular calcium pathways.... (calcium being viral 'energy' currency used for processes such as virion assembly etc)
 

JillBohr

Senior Member
Messages
247
Location
Columbus, OH
I cant answer your question about the patterns of ionized calcium in CFS, but i remember on several occasions its been said that XMRV is implicated in highly aggressive forms of prostate cancer. On that basis your question seems far from stupid Jill - if there hasnt been anything published already its worth asking a question to Judy M or another of the leading experts id say.

Thank you cookie monster. As you know, I am not a scientist and I struggled through my science BERS when I was in school. I did get an A in biology but I have to admit I took it twice.:ashamed: In my defense, I did have a serious health problem the first time I took it but I am still lame when it comes to science. Not in a million years did I think I would be reading up on viruses, genetics, etc. when I was older. Now, as you can see, I see a paper on autism but now to find out about ME/CFS..
 

Rosemary

Senior Member
Messages
193
very very likely. def the case with some others, better researched viruses. actually most viruses, including retroviruses, completely highjack various cellular calcium pathways.... (calcium being viral 'energy' currency used for processes such as virion assembly etc)

This is very interesting Natasa,

Recently, as we now know the twins with NPC tested positive for XMRV and James Hildreth found that cells affected by Niemann-Pick Type C (NPC), which disrupts cholesterol trafficking, were unable to release HIV, suggesting these cells would not spread the virus.

A NPC researcher Frances Platt who has been investigating NPC for years suspects that the dysfunctional NPC1 protein disrupts regulation of calcium in the cell and pharmalogical agents that cause calcium to increase in the cytoplasm could correct this disruption.

Frances Platt found that curcumin could elevate cytosolic calcium so she tested curcumin on NPC mice and found it improved their disease.
 

Rosemary

Senior Member
Messages
193
Niemann Pick Type C disease,is commonly referred to as "Childhood Alzheimer’s"

Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling

Conclusions/Significance
Quote " Numerous genes important for membrane traffic and cellular regulation of calcium, metals and other ions were upregulated."

http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000019

" Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease."

The young twins with NPC take 3,000 mg curcumin daily ....Curcumin inhibits amyloid beta and reduces amyloid

Alzheimer's Disease - Research in animals has demonstrated that curcumin can support both prevention of changes in the brain that lead to Alzheimer's, and reversal of some of the damage already done.(2) A 2005 study done at UCLA found curcumin supported more effective outcomes than some of the drugs being tested for the prevention and treatment of Alzheimer's. (3)

2. Ringman JM, et al. "A potential role of the curry spice curcumin in Alzheimer's disease." Curr Alzheimer Res. 2005;2:131-6.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702408/

3. Yang F, et al. "Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo." J Biol Chem. 2005;280:5892- 901.
http://www.jbc.org/content/280/7/5892.long
 

JillBohr

Senior Member
Messages
247
Location
Columbus, OH
What can we do to decrease calcium?
Great Question Diesel and my answer is "I don't know". According to the paper on post-mortem study on ASD brains, they mentioned not to use calcium chelation because of the danger but did not mention other methods. I found a link to Dr. Myhill's website and she does not seem to know either.

http://www.prohealth.com/library/showarticle.cfm?libid=15030

One of the biochemical problems that John McLaren-Howard** has identified is a tendency for calcium to build up inside cells.

The cells try to chuck the calcium out of the way by sticking it on to calcium-containing proteins, such as calmodulin, calcium-actin or CaATPase. This is OK in the short term, but eventually these mechanisms become saturated, free ionized calcium rises and inhibits many of the mechanisms for energy production in the cell.

This calcium is not responsive to magnesium administration, so what to do about it? We honestly do not know! BUT calcium and hydrogen ions are intimately related and the optimist in me is hoping that an alkaline environment will help correct the biochemical abnormalities. Watch this space
 

guest

Guest
Messages
320
"Mild Hypercalcemia (corrected total serum calcium < 12mg/dL) - Patients usually do not have any symptoms of hyercalcemia when the blood calcium levels are this low. The best option here is to stay well hydrated, exercise and your doctor should follow your blood calcium levels while you are undergoing treatment for your cancer.

Moderate to Severe Hypercalcemia (corrected total serum calcium > 12mg/dL) - Your doctor may prescribe some drugs (biphosphonates) to stabilize the bones and prevent hypercalcemia. Pamidronate (Aredia) and zolendronic acid (Zometa) are the preferred drugs for treating hypercalcemia and maintaining blood calcium levels. These drugs do not decrease calcium rapidly, so other measures may be needed to reduce calcium more quickly. This may mean that you may have to be admitted to a hospital for monitoring and drug therapy. This therapy includes a lot of intravenous fluid (usually a saline solution) along with a diuretic like furosemide (Lasix). The diuretics should not be started however until you have been properly hydrated with the saline solution. Pamidronate or zolendronic acid may be used concurrently and then every month if needed. Sometimes a drug called calcitonin is used to help lower calcium until the biphosphonates start working (around 2 to 4 days). These drugs are not available in oral form so they must be given intravenously. Other medications that are used to treat hypercalcemia are etidronate, clodronate, plicamycin and gallium nitrate, however, they are not as effective, they have more side effects and they are not tolerated very well. Below is a table of the most effective and well-tolerated biphosphonates."

http://www.cancersupportivecare.com/hypercalcemia.html