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Author Topic: Possible Causal Genes, and a new Treatment  (Read 1730 times)

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Hontas

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Possible Causal Genes, and a new Treatment
« on: January 20, 2019, 08:57:57 AM »

CDKN1A,CDKN1B,CDKN2A,CDKN2B

Heart QRS complex duration:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338195/
https://www.ncbi.nlm.nih.gov/pubmed/25035420

Association with type 2 diabetes:
https://www.ncbi.nlm.nih.gov/pubmed/23707792
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377835/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007643

Fibrosis in wound healing:
https://www.jax.org/news-and-insights/2015/february/cellular-senescence-an-unexpected-advantage-in-wound-healing

Article showing high amounts of CDKN1A activity on surface(probably tunica) tissues of a penis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165732/

Inactivation of CDKN2A promoted cardiac healing:
https://www.ncbi.nlm.nih.gov/pubmed/26239104

CDKN2B on TGF-B SIGNALING:
https://www.ncbi.nlm.nih.gov/pubmed/26596284

PRP effect on MMP-1 and Cyclin-dependent kinase 4(CDK4) elevation:
https://www.ncbi.nlm.nih.gov/pubmed/21964487

MOST IMPORTANTLY, THIS ONE GIVES AN EXAMPLE OF SUCH A FIBROTIC DISEASE:
https://www.ncbi.nlm.nih.gov/pubmed/12239232

This article is about Connective Tissue growth factor, Diabetic nephropathy, CDKN-- genes, Cell cycle, fibrotic disorders, Type 2 diabetes, glucose etc.

You can use some sites to view the full article, but I don't know if it is legal to give the site here or not. You have to read the last article, it is amazing how they are all connected.

FG-3019 antibody:

Apparently this antibody could supress Connective Tissue growth factor(CTGF), and is on its way to solve other disorders:
https://www.ncbi.nlm.nih.gov/pubmed/26965296
https://pulmonaryfibrosisnews.com/fg-3019-idiopathic-pulmonary-fibrosis/
https://www.ncbi.nlm.nih.gov/pubmed/28710437





In conclusion, all these three genes are responsible on the regulation of Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6, which are probably the main antagonists.

It is one of the two most correlated genes with heart disease as well as cell regeneration and apostosis of the unwanted cells. This is it guys, i believe this actually is it.

,
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skunkworks

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Re: Possible Causal Genes, and a new Treatment
« Reply #1 on: January 20, 2019, 09:22:56 AM »

Just posting so I can find this easily again, as soon as I have time I will read through all the links you've posted.

Bubba dawg

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Re: Possible Causal Genes, and a new Treatment
« Reply #2 on: January 20, 2019, 10:34:52 AM »

Ok now what are you going to do with your find?
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5 Rounds of Xiaflex. Good results.

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Gabriel

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Re: Possible Causal Genes, and a new Treatment
« Reply #3 on: January 20, 2019, 11:59:23 AM »

Hey Hontas,

I'm glad to see a Peyronies Disease brother so happy, but I must confess you that, as the majority of the folks here, I can't get sh*t about what you demonstrate  ;D!!

That seems big, but even though I have a solid scientific culture, this is way out of my league... Can you expert guys discuss it and make us a digest of your reasoning when you post important messages??

Sounds enthusiasming anyway :-)!!!
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- 31 yo, very healthy lifestyle, Peyronies Disease with Erectile Dysfunction, pain, distal hourglassing & length loss since 09/01/17, still acute.
- Treatments: all oral meds/supps discussed here; traction/VED; ointments (essential oils, diclofenac); PRP/HA injections (5/6 sessions)

Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #4 on: January 20, 2019, 12:19:01 PM »

Maybe genetic engineering?
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NeoV

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Re: Possible Causal Genes, and a new Treatment
« Reply #5 on: January 22, 2019, 07:37:43 AM »

Great!
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Bubba dawg

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Re: Possible Causal Genes, and a new Treatment
« Reply #6 on: January 22, 2019, 08:58:04 AM »

Ya what insurance company is going to cover experimental gene therapy for peyrones
?
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5 Rounds of Xiaflex. Good results.

I am known to give out false information and post nonsense with little to no evidence to back up my claims.
I have ignored several warnings. Further reports to the moderators or Administrators and I will be banned.

Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #7 on: July 28, 2019, 02:57:43 AM »

I have found some incredibly exciting stuff. I will post more. I have found an interaction between CDKN1A and p53 stabilization which is lacking in even HEALTHY Tunica Albugenia tissues of Peyronies patients suggesting this gene might play a critical role in our body failing to destroy malfunctioning Fibroblasts that is causing fibrosis in extensive tissue growth events(aka healing)


Chromosomal Instability of certain regulators such as p53 in Healthy Tunica cells in Peyronies  patients versus control:

https://www.nature.com/articles/3901170

Colchicine effect on mitosis, useful for finding a good theurapathic range and time frame to use it:

http://jcb.rupress.org/content/jcb/25/1/145.full.pdf

Possible effects of a Microtubule disruptor meds on p53 activity:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125062/

Specific effect of p53 on Peyronies fibroblasts:

https://www.ncbi.nlm.nih.gov/pubmed/21078039

p21(CDKN1A) messes up with p53 stability:

https://www.tandfonline.com/doi/pdf/10.4161/cc.6.12.4313

Overview of genetic effects on peyronies:

https://www.sciencedirect.com/science/article/abs/pii/S2050052115000037?via%3Dihub

ALSO, from the first post i am putting this here again,

Article showing high amounts of CDKN1A activity on surface(probably tunica) tissues of a penis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165732/


Their theory is that even on healthy tunica tissue in patients with peyronies, there are mutations and instability in a really low amount of fibroblast cells(for example one in a billion cell almost being dysfunctional, acting like a benign tumor), thus when a growth is happening these mutated cells(unregulated due to low or dysfunctional p53) exponentially increase and become easily visible under eye(plaque and transformed TA), so the effects become billion times more visible and the cells differentiation can affect the tunica integrity and collagen regulation etc. by more fibroblasts being mutated. I am just starting to read on it and it looks promising to be honest. I would like if you guys also took a look into it.

Its a bit like whole penis having a remission of tumorous tissues waiting to multiply under certain conditions, but is benign and cannot spread to other places.

Non-specific widening of QRS duration is most of the time caused by excessive CDKN1A activity apparently.

Its also said that HER2 upregulates CDKN1A.
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Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #8 on: July 28, 2019, 04:28:54 AM »

p21 and its effects on apostosis in general:

The Role of the Cyclin-dependent Kinase Inhibitor p21 in Apoptosis 1 Supported in part by NIH Grant R01 DK56283 (to A. L. T.) for the p21 research and Campus Research Board and Illinois Department of Public Health Penny Severns Breast and Cervical Cancer… | Molecular Cancer Therapeutics

Cancer Related look on PARC that is seemingly in responsible for the problem in Peyronies Disease patients fibroblasts:

https://www.ncbi.nlm.nih.gov/pubmed/22117079

this article looks important as well

Analysis of Peyronies cell culture:

https://www.nature.com/articles/3900874

They suggest cisplatin helps the cells transport p53 to their nucleus from their cytoplasm, and down regulating PARC, thus inducing apostosis, and since we talked about PARC being the responsible gene in peyronies related p53 dysfunction, cisplatin might be a thing to try?

tl;dr This stuff is probably cancer level difficult, even more so considering there isn't any single lump to destroy but rather a lot of small cells.
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Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #9 on: July 28, 2019, 07:55:08 AM »

CUL9(PARC), p21 and p53 association:

https://www.nature.com/articles/onc2017141
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Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #10 on: July 28, 2019, 01:44:36 PM »

Potential theurapethic agents that work with Desmoid tumors (similar to Peyronies):

https://www.ncbi.nlm.nih.gov/pubmed/23857431

https://www.ncbi.nlm.nih.gov/pubmed/23327547
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diehardpatriot

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Re: Possible Causal Genes, and a new Treatment
« Reply #11 on: July 28, 2019, 08:29:06 PM »

Hontas. This is interesting. What do you suggest we do with these findings? Is your theory that only a medicine that blocks these genes will improve peyronies?
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17 year old who had stable peyronies. Now battling a new acute injury. Don’t know wtf my symptoms r

Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #12 on: July 29, 2019, 04:35:10 AM »

The theoritical cure(as said in one of the articles) would be more similar to taking chemotherapy, or siRNA gene therapy(?) at this point to be honest. I am just trying to work out the exact process, to maybe find a workaround that in turn changes p21 activity

High p21 activity in cytoplasm causes it to make a complex with ASK1 which in turn stops apostosis:

https://www.ncbi.nlm.nih.gov/pubmed/10064589
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Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #13 on: July 29, 2019, 02:09:58 PM »



Cytoplasmic overexpression of p21 causes Cisplatin related apostosis resistance:

https://www.jci.org/articles/view/41939
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diehardpatriot

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Re: Possible Causal Genes, and a new Treatment
« Reply #14 on: July 30, 2019, 02:57:47 AM »

So your hypothesis is that medicine is the only real solution
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17 year old who had stable peyronies. Now battling a new acute injury. Don’t know wtf my symptoms r

Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #15 on: July 30, 2019, 05:47:19 AM »

I mean doctors have to be literally clueless if they think the acute phase is going to pass any time soon for any of the young people. Every time I read about a person with age <30 the disease itself often becomes torture with a long acute phase and the key would be in my opinion p21 protein that is encoded by CDKN1A gene. If you want to check it cheaply, just go get and ECG(Electrocardiograph) and check your QRS duration. If its higher than 110 ms (nonspecific), you also have insulin resistance problems, eczema etc. it all ties back to this. It would make so much more sense to me if people actually went out and tried these things and we could gather at least a bit of data. I am just clinging on one rope at the moment.

That gene halts cell growth and is a key regulator in most cancers and also in desmoid tumors. It wouldn't suprise me if we were more prone to cancer as well, as this is actually about cell cycle and lack of apostosis on cells with damaged DNA. So yeah, some kind of "smart" chemotherapy or other type of drug is the solution.

It doesn't help me and others if we don't actually create like a group to get tested and screened for a bunch of other things. It makes no sense to just sit on our chairs and wait for it to resolve, it wont... I just want a database , man. Or at least gather a group of very young men and fund, and join for a clinical trial that screens our background in terms of risk factors. There are like, 2 or 3 articles at most on the internet at the moment.

Yes either topical, injection or systemic drug. The agent is what is important here

It is so obvious with this article as well, inhibition of p21, i just need to learn a bit more in detail:

https://www.ncbi.nlm.nih.gov/pubmed/25024194
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Hontas

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Re: Possible Causal Genes, and a new Treatment
« Reply #16 on: August 04, 2019, 04:52:03 PM »

Are there literally ZERO Molecular biology or genetics experts in this forum? In order to fund research we first need to find on which topic we should fund it. So i need a help of a genetics expert, and there are a few people messaging me saying they would support the fund and so would i.
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diehardpatriot

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Re: Possible Causal Genes, and a new Treatment
« Reply #17 on: August 06, 2019, 03:22:43 AM »

I’m willing to take blood tests ect to contribute to data
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17 year old who had stable peyronies. Now battling a new acute injury. Don’t know wtf my symptoms r
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