Differential Gene Expression in Post-Finasteride Syndrome Patients - Dr. Khera - Baylor

Science PFS Research
#224

It could certainly be the truth, hopefully we’ll get a study done on prostate tissue next. I think it would be possible to donate some tissue without damage?

“The de-differentiation/lineage plasticity of androgen receptor (AR)-positive to AR-negative disease is likely dependent on the extent of AR inhibition (duration and/or type of inhibitors) and the existence of genetic and epigenetic adaption mechanisms”

This coupled with the two studies we have on penile skin makes me think we haven’t lost AR signaling. Maybe it’s on par with the castration resistant type, where AR is amplified.

I re-read it today and yes it’s interesting, but not much is revealed that could be used clinically.

#225

That would be nice to have that result especially of a male specific organ.

Finasteride Upregulates Expression of Androgen Receptor in Hyperplastic Prostate and LNCaP Cells: Implications for Chemoprevention of Prostate Cancer

https://www.researchgate.net/publication/51112409_Finasteride_Upregulates_Expression_of_Androgen_Receptor_in_Hyperplastic_Prostate_and_LNCaP_Cells_Implications_for_Chemoprevention_of_Prostate_Cancer

Finasteride Treatment Alters Tissue Specific Androgen Receptor Expression in Prostate Tissues


In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner.

The impact of finasteride and dutasteride treatments on proliferation, apoptosis, androgen receptor, 5α-reductase 1 and 5α-reductase 2 in TRAMP mouse prostates

Finasteride and dutasteride treatments resulted in nonsignificantly decreased AR expression in tumors in most groups, which is not consistent with increased AR expression in castrated TRAMP mice small and large tumors [45], tumors from men who received androgen deprivation therapy for prostate cancer [46], and LNCaP human prostate cancer cells treated with finasteride [47].

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#226

“We show that decreased expression of the androgen receptor in luminal cells of human BPH specimens correlates with a higher degree of regional prostatic inflammation.”

“This inflammatory microenvironment promotes AR-independent prostatic epithelial proliferation, which can be abolished by ablating IL-1 signaling or depleting its major cellular source, the macrophages.”

https://www.sciencedirect.com/science/article/pii/S1097276516304129

Many people here have prostate inflammation, so maybe there is a loss of AR.

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#227

It would be interesting if someone like moonchild before made an appointment with Khera to discuss these findings…Moonchild said khera told him before he believed genes were “off”.

So I would be curious to hear his thoughts now as well as awors…Also there could be other facts that were not published or disclosed or other opinions that have lead to a more firm conclusion especially about DNA Aspects…

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#228

Our focus should be on getting word out and the attention of experts. Developing our own theories on what PFS is and how it might be treated is mental masturbation and accomplishes nothing. We will die on this hill if we can’t learn from the lesson of the last 15 years, and fast.

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#229

In terms of direct action, it would be greatly appreciated if you could complete the patient survey.

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#230

I agree. Hearing Khera’s thoughts after having spent more than half a decade investigating it would be interesting and useful I’d imagine. I mean he’d be one of the best authorities on PFS as far as doctors and researchers go.

#231

If he’s smart (and I’m sure he is) he won’t say much.

Even though he might have his own theories, when you’re a person with authority you have to be careful if you don’t have proof.

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#232

If somebody is paying him 500 dollars for a consult perhaps he’ll be valuable. I don’t see why his offering of advice would be that risky. It’s not a question of rubbishing Merck but bringing about symptomatic relief.

#233

Looking at the “Dollars for Docs” database, the reason why it took so long for M. Khera to publish the Baylor paper was maybe that he received funding from Merck in 2013 and 2014, so he would need 5 more years before publishing an article without having to declare a conflict of interest:


He didn’t receive funding from Merck after 2015, and usually journals ask for the data from the last 5 years.

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#234

The study took so long because it took years to recruit 26 patients, and Khera himself did not perform the gene expression analysis, which is a highly specialised skill. It has nothing to do with receiving a small sum of money years ago.

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#235

Even if it isn’t the prostate tissue

The interesting part is the reversing AR signal loss

I’m assuming those compounds can work in different tissues

#236

i imagine its something he would talk in private about like if you scheduled a meeting with in person or over the phone. but he’d make it clear that its his opinion

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#237

Anyone have access to a Geneticist? Lol…

#238

idk, this is why I posted the study that I posted.
When you see AR overexpression, this doesnt seem to indicate there is signaling loss, in fact quite the opposite.
Though the author of the Baylor study did wonder about AR expression in areas other than the skin, but we have also seen AR overexpression in the brain as well post Fin.
The prostate would be another good site to look at.

“It is now understood that persistent activation of the androgen receptor (AR) signaling pathway often underlies the development of castration-resistant prostate cancer (CRPC). Perhaps not surprisingly, evidence points to persistent AR signaling as one of the key drivers by which resistance develops. In this context, activation of the AR signaling program can occur through a number of molecular adaptations, including alterations leading to persistent canonical AR signaling (e.g., AR amplification/overexpression,”

Adding to this,
“The incredible amount of molecular redundancy by which a malignant prostate cell is able to keep AR signaling engaged remains a critical barrier to the wide deployment of targeted, precision oncology.
A key issue not addressed in past trials is the issue of cross talk between pathways other than the AR.”

Adding my own 2 cents, there is little indication that there is any type of continued androgen deprivation, meaning hormonal blood levels have recovered in most.
The AR gene maybe needs to be tamed but again idk if this is an androgen mediated disease.
The author has said as much as well.

#239

When did we see this?

#240

The rat brain study during and then post Fin. Ive linked it now a few times.

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex , an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma).

^Except we do know dht blood levels mostly return to normal at some point post Fin right?

#241

We also know DHT levels are pretty much nonexistant in the CSF, but an increase in T.

But it’s not due to methylation of 5ARD2, so the question is why 5AR ain’t doing it’s job in the brain? When it seems to work in the peripherals.

The increase in T is likely an adaptation, to compensate for the lack of DHT. But T can never compensate for DHT fully, it’s just not potent enough.

#242

Is this PFS specifically? Remember that the vast majority of Finasteride users don’t end up with PFS.

#243

Well if a person can be damaged from just one pill, I think a study like this should be kept in mind for those that dont recover. This is evidence of adverse effects during and after the drug.
You only have so much you can look at at this point.
You could also make the argument maybe as your saying that PFS has less to do with the drug itself and more the person.
I have seen countless studies on Accutane that dont remain true when it comes to long term side effects.
Some have to though. There has to be some evidence.

Im also the one that said lets just throw out all the drugs, start from scratch and see what we have in common. Maybe we’ll go farther. Then we will backtrack to the drug and see why it had a negative effect based on our predisposition.