IGF-I & Mortality

[pjoshea13]

New study below [1].

The insulin axis is rarely talked about but is very important IMO.

Even back in 2004 there were a lot of insulin-like growth factor-I [IGF-I] studies. Currently 556 hits on PubMed for <prostate "IGF-I">. But who reads them?

I have learned to beware of anything with "growth factor" in the name, since diagnosis.

The simple view of IGF-I is that most of it is normally bound to proteins. There are various IGF binding proteins, but IGFBP-3 may be the most important one. It's common for IGF-I to be higher in PCa, and/or IGFBP-3 levels to be lower. The effect is to increase bioactive IGF-I. {IGF-I can be lowered by selective amino acid restriction - i.e. of one of the essential amino acids for building protein. The body will not commit to growth when it cannot build protein.}

In the new Boston/Montreal study, they looked at:

"Circulating Insulin-Like Growth Factor 1-Related Biomarkers and Risk of Lethal Prostate"

At first it seems that they did a bait & switch:

"Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease."

PAPP-A is pregnancy-associated plasma protein A. What the heck is that?

"Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer "

Wiki: the "main substrate {for PAPP-A} is insulin-like growth factor binding proteins" [IGFBPs]. So PAPP-A is not derived from IGF-I, but from one of its binding proteins. That's one way of reducing IGFBPs.

It's good to have more pregnancy-associated plasma protein A when you are pregnant, but not so much when you are diagnosed with PCa.

Seems to me that it could be used as a biomarker for aggresive treatment. It would be good to have a heads-up at diagnosis.

From 2020 [2] we see that:

"Pregnancy-Associated Plasma Protein-A2 Is Associated With Mortality in Patients With Lung Cancer"

From 2019 [3], a link with inflammation:

"Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-I/PI3K/Akt Pathways"

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/350...

[2] ncbi.nlm.nih.gov/pmc/articl...

[3] ncbi.nlm.nih.gov/pmc/articl...

[MateoBeach]

“You just keep thinking Butch, that’s what you’re good at.” (Sundance Kid). And we are all listening to your thoughts. Mateo

[Graham49]

I'm wondering if high PAPP-A might be associated with low testosterone?

[PhilipSZacarias]

This is getting getting too much into the weeds for me...

[dockam]

Did a quick search and found these:

ascopost.com/news/november-...

endocrinologyadvisor.com/ho...

spandidos-publications.com/...

naturalmedicinejournal.com/...

bbc.com/news/magazine-25549805

translational-medicine.biom...

Btw, I've been on IF(Intermittent Fasting) since the Dx in 01/2015 - 7 years ago!!! and on Metformin since 01/2016

Fight on Brothers

[pjoshea13]

Here is the paper that came out of the ASCO presentation (first link):

ncbi.nlm.nih.gov/pmc/articl...

I'm not convinced by the free-T association. The men do not seem to have had freakishly high levels.

The authors appear to take the view that T (or rather, free-T) initiates PCa. Who believes that, these days. As though virile young men are walking time bombs.

Table 1 shows SHBG to be higher in cases (41.9 versus 39.5) and free-T 200 versus 209.

I must be missing something.

-Patrick