Follica - Good News!

[Moomin]

I cannot believe it, I just posted this stuff, I hit the back button by accident and I return to this page and everything I had written has just disappeared. What a b**ch.

Ok here we go again

I have been looking into the processes that would be employed in producing HF from the methods discussed in this forum and I see a problem with it (I’m hoping someone will laugh at what I have to say, call me noob and we can all have a hearty laugh at my reservations). First let me go through the methodology and chemical processes that are involved, and then I’ll state what I find worrying.

Stage 1: Involves wounding skin sufficiently to induce active Stem Cells (SC) in the epidermis.

Satge 2: Apply Canonical Wnt producer (in our case Lithium Chloride, it may not have to be canonical as Wnt7a seems to be specifically mentioned). If I’m not mistaken Wnt is used to signal Tyronise Kinase (TK) activation, for the purpose of upregulating Beta Catenin (BC). The reason for doing so is that it increases expression of BC encouraging SC differentiation into a HF. So TK and BC are important factors in HF, or at least BC is.

Stage 3: Apply EGFR inhibitor in order to prevent wounded skin from producing normal numbers of skin cells for a specified time and in so doing encourage SC to differentiate into HF (I understand what’s being done here, but I don’t know what chemical process is taking place if anyone knows could you post it on the forum or where I might read about it).

Now these 3 stages look simple enough but we seem to be having some difficulty putting it together, namely, why we don’t have an EGFR that doesn’t negatively effect Wnt. I think I have the answer (although I’m still expecting someone to call me a noob, let me run this by you).

Firstly Wnt in whatever form is not the important factor, what is important is the fact that Wnt activates Tyronise Kinase receptors to signal production of Beta Catenin. So lets forget about Wnt for the time being and concentrate on TK and BC as these are the active ingredients (infact BC is the active ingredient). Right hold that thought, I’m now going to discuss EGFR inhibitors. These inhibitors (which are used as cancer drugs) work by covering the receptor that causes cell creation (and everything that goes with it) and cell apoptosis (cell death). The inhibitor that these drugs target is Tyronise Kinase. The EGFR inhibitor blocks the TK pathway preventing it from communicating with the rest of the cell, therefore it is not able to activate upregulation of Beta Catenin, meaning no differentiation from SC to HF can occur. I should also point out that erlotinib, gefitinib and milk thistle are all EGFR’s that inhibit Tyrosine Kinase, infact every EGFR inhibits TK. Could this be the reason why we haven’t yet found an EGFR that doesn’t deleteriously affect “Wntâ€.

Also if the above isn’t bullshit

I’d like to follow this through to what this should mean in practice:

1) People who used skin wounding and Wnt signalling (Lithium Chloride) should see either see meagre to moderate results. The reason is that whilst you are upregulating TK and BC you will produce more HF but also more epidermal skin cells.

2) People who used wounding and EGFR inhibitor would see no results at all. This is because EGFR would have blocked TK resulting in lower concentration of BC than normal.

3) People who used skin wounding and Wnt signaller and EGFR inhibitor should see no results. This is because EGFR would have blocked TK resulting in lower concentrations of BC than normal despite trying to upregulate it with Wnt.

Like I said I’m not sure if this is true, but I’d like to bounce the idea around this forum and see what comments you come up with, then I can go away and look into it some more.

 

[first]

1) People who used skin wounding and Wnt signalling (Lithium Chloride) should see either see meagre to moderate results. The reason is that whilst you are upregulating TK and BC you will produce more HF but also more epidermal skin cells.

2) People who used wounding and EGFR inhibitor would see no results at all. This is because EGFR would have blocked TK resulting in lower concentration of BC than normal.

3) People who used skin wounding and Wnt signaller and EGFR inhibitor should see no results. This is because EGFR would have blocked TK resulting in lower concentrations of BC than normal despite trying to upregulate it with Wnt.

Like I said I’m not sure if this is true, but I’d like to bounce the idea around this forum and see what comments you come up with, then I can go away and look into it some more.

The second and third statements are not true, as the follica experiments have shown.

"EGF receptor inhibitor administration led to generation of more and larger hair follicles compared with control mice that were wounded only [...] The findings of this Example confirm the results of the previous Example, and show that more and larger HF can be generated when EDIHN comprises, or is followed by, administration of EGFR inhibitors, or with compounds with a similar mechanism of action; e.g. Hedgehog protein and androgen antagonists."

If your theory would be true, that experiment would have failed. If your theory is true, it would also mean that for example gefitinib inhibits (or limits) beta-catenin. There are a lot of studies done on these cancer drugs, likely more than on any other drug, yet I do not recall ever reading about them inhibiting beta-catenin. However if they do, you should find such a study very easily.

 

[Moomin]

I know it seems wrong, especially example 2, which is why i'm asking what chemical activity occurs in EGFR inhibitors.

I don't understand how EGFR inhibitors negatviely affect TK but in turn don't affect BC, if anyone knows please tell me. I assume that somehow EGFRs is inhibiting the TK ligand but somehow BC is still being over regulated.

But the really important thing for me is whether it is accepted that EGFR inhibitors prevent downstream communication from Tyrosine Kinase. Thats the question I would like answered, because if it does then how is the Beta Catenin being upregulated??

 

[Moomin]

Also i should point out First that your reading my post incorrectly, my theory suggests that TK is being inhibited or reduced and in turn will affect Beta Catenin if TK is the only protein that cause upregulation of BC. The point being that Wnt in terms of upregulating TK probably isn't that important, seeing as BC is clearly present without TK doings it thing.

The point being, there must be more than way to upregulate BC other than via TK

I await your answer, oh wise one, with trepidation.

 

[harold]

I cannot believe it, I just posted this stuff, I hit the back button by accident and I return to this page and everything I had written has just disappeared. What a b**ch.

Ok here we go again

I have been looking into the processes that would be employed in producing HF from the methods discussed in this forum and I see a problem with it (I’m hoping someone will laugh at what I have to say, call me noob and we can all have a hearty laugh at my reservations). First let me go through the methodology and chemical processes that are involved, and then I’ll state what I find worrying.

Stage 1: Involves wounding skin sufficiently to induce active Stem Cells (SC) in the epidermis.

Kind of. The epidermal cells regress to an embyonic stem cell like state.

Satge 2: Apply Canonical Wnt producer (in our case Lithium Chloride, it may not have to be canonical as Wnt7a seems to be specifically mentioned).

I think you are confused. There is nothing non-canonical about wnt7a as a ligand. In fact I am pretty sure that the ligand itself has nothing to do with amking wnt siganlling canonical or non-canonical.

If I’m not mistaken Wnt is used to signal Tyronise Kinase (TK) activation, for the purpose of upregulating Beta Catenin (BC).

I dont know that there is a tyrosine kinase intermediary. Protein kinases but not neceassarily tyrosine kinases.

The reason for doing so is that it increases expression of BC encouraging SC differentiation into a HF. So TK and BC are important factors in HF, or at least BC is.

B-catenin is. It goes on to bind with TCF/LEF and promote the expression of the genes we want.

Stage 3: Apply EGFR inhibitor in order to prevent wounded skin from producing normal numbers of skin cells for a specified time and in so doing encourage SC to differentiate into HF (I understand what’s being done here, but I don’t know what chemical process is taking place if anyone knows could you post it on the forum or where I might read about it).

I think you have again some misunderstanding though more subtle here. EGF "says" "you stem cell - you are supposed to be a skin cell" which is what would happen in normal

Now these 3 stages look simple enough but we seem to be having some difficulty putting it together, namely, why we don’t have an EGFR that doesn’t negatively effect Wnt. I think I have the answer (although I’m still expecting someone to call me a noob, let me run this by you).

Firstly Wnt in whatever form is not the important factor, what is important is the fact that Wnt activates Tyronise Kinase receptors to signal production of Beta Catenin.

This is what people generally mean when they talk about wnt signalling. That is the canonical path (ignoring tyrosine kinases).

So lets forget about Wnt for the time being and concentrate on TK and BC as these are the active ingredients (infact BC is the active ingredient). Right hold that thought, I’m now going to discuss EGFR inhibitors. These inhibitors (which are used as cancer drugs) work by covering the receptor that causes cell creation (and everything that goes with it) and cell apoptosis (cell death). The inhibitor that these drugs target is Tyronise Kinase. The EGFR inhibitor blocks the TK pathway preventing it from communicating with the rest of the cell, therefore it is not able to activate upregulation of Beta Catenin, meaning no differentiation from SC to HF can occur.

OK firstly there are like hundreds of different tyrosine kinases. Different pathways use different ones. One that inhibits one specific to the
EGF receptor is not necessarily going to inhibt one that wnt pathway uses (...which i am not sure it does at all)

I should also point out that erlotinib, gefitinib and milk thistle are all EGFR’s that inhibit Tyrosine Kinase, infact every EGFR inhibits TK. Could this be the reason why we haven’t yet found an EGFR that doesn’t deleteriously affect “Wntâ€.

gefitinib etc are not EGFRs. EGFR = Epidermal Growth factor Receptor. And not every EGFR inhibitor inhibits tyrosine kinase activity.

Also if the above isn’t bullshit

I’d like to follow this through to what this should mean in practice:

1) People who used skin wounding and Wnt signalling (Lithium Chloride) should see either see meagre to moderate results. The reason is that whilst you are upregulating TK and BC you will produce more HF but also more epidermal skin cells.

lithium should help tip the scales towards hair folicle formation.

2) People who used wounding and EGFR inhibitor would see no results at all. This is because EGFR would have blocked TK resulting in lower concentration of BC than normal.

See above as for why this is not the case in theory and the Follica patent page 62 Example 12 as for why it has been shown to be untrue in practice.

3) People who used skin wounding and Wnt signaller and EGFR inhibitor should see no results. This is because EGFR would have blocked TK resulting in lower concentrations of BC than normal despite trying to upregulate it with Wnt.

Like I said I’m not sure if this is true, but I’d like to bounce the idea around this forum and see what comments you come up with, then I can go away and look into it some more.

I think this is one of the problems that people who are reading in depth in one area of biology or biochemistry sometimes have - the wider perspective on what a lot of these processes, pathways and proteins do in different types of cells and different situations. It is very easy to come to conclusios or make assumptions that aren't true.
hh

 

[harold]

As I forgot to add that study by Benji showed that EGCG was inhibiting wnt signalling by a completely different mechanism than the one you proposed. basically EGCG docks with a repressor of the LEF/TCF transcription site and thus stops Beta-catenin from promoting the expression of these genes if I recall correctly. But it has nothing to do with the way in which they interfere with EGFR activity.
Sometimes things have a lot of different, unrelated effects on different biochemical processses. Half the challenge of drug design and creation is finding drugs that interfere where you want them to and NOT where you dont want them to. EGCG wasn't designed to do anything except perhaps act as an antioxidant in tea leaves and so its no surprise that it does a bunch of stuff. Some we want some we dont.
hh

 

[Moomin]

Hi Harold, as always a very informative post and i thank you greatly for that. I have only been looking at these methods and the chemistry invovled for a week, so you'll have to forgive my ignorance, but this does seem like an ejoyable subject area that can yield many results.

A few things that I would like to clarify:

I dont know that there is a tyrosine kinase intermediary. Protein kinases but not neceassarily tyrosine kinases.

The first is that one way in which BC is expressed is via Tyrosine Kinase (I did say there must be more than way to express this protein otherwise the follica method couldn't work) you can google this fact and find it stated many times.

gefitinib etc are not EGFRs. EGFR = Epidermal Growth factor Receptor. And not every EGFR inhibitor inhibits tyrosine kinase activity.

Happy to hear your comments.

This is my mistake, I forgot to put inhibitor after EGFR, but i can assure you as lame as my seem I do kow what they are.

In relation to the examples i gave, i did say i don't understand how if my understanding was correct that the follica patent could produce these results (in as far as example 2 and 3 is concerned) unless there was another regulator of Beta Catenin. I have since learnt that the only 2 regulators of BC (that i can find) are Tyrosine Kinae and GSK-3. Which i'll discuss in a later post.

you also said this:

As I forgot to add that study by Benji showed that EGCG was inhibiting wnt signalling by a completely different mechanism than the one you proposed. basically EGCG docks with a repressor of the LEF/TCF transcription site and thus stops Beta-catenin from promoting the expression of these genes if I recall correctly. But it has nothing to do with the way in which they interfere with EGFR activity.

As far as i'm aware EGCG does inhibit Tyrosine Kinase, and the following would seem to suggest this also (by the way i'm not going to produce reams pragraphs just salient sentences you can check the websites for your self):

"EGCG also showed strong inhibition of tyrosine kinase and mitogen-activated protein kinase (MAPK) activities, without affecting the kinases in the normal cells."
http://cat.inist.fr/?aModele=afficheN&cpsidt=13560572

"First, Liang et al. [43] demonstrated that EGCG directly blocks EGF binding to the
EGFR and thus subsequently inhibits the tyrosine kinase activity of the receptor in human A431
epidermoid carcinoma cells"
http://216.239.59.104/search?q=cache:8H ... cd=1&gl=uk

"We found that EGCG inhibits the growth of human squamous carcinoma, breast carcinoma and colon carcinoma cells. This is associated with rapid inhibition of activation of the RTKs (receptor tyrosine kinase), EGFR, HER2 and HER3 inhibition of activation or the expression of several downstream signaling molecules involved in cell proliferation and survival and angiogenesis"

all the above examples relate to malignant cells, Nevertheless it shows that EGCG does work on TK and i'm sure it also works in the process you said it does as well. Also if EGFR inhibitors, which all seem to work by binding to EGF receptor sites, how could TK not be affected by all EGFR inhibitors that work in this way. if you could name some inhibitors that don't work in this way please let me know. This would solve a lot of issues I have with putting together a successful process.

 

[Kestrel]

Hi folks,

I just discovered this forum after having watched the Cotsarelis clip from the Today Show. Hopefully, the collaborative efforts here will yield an off-the-shelf formulation and procedure with some efficacy.

I read through the patent, but not having training in the biological sciences I could comprehend the material at an abstract level at best.

Perhaps someone on this board could answer a question for me: If the Follica technique can sort of sidetrack the healing process to spur the genesis of new hair follicles, why would not these follicles be genetically susceptible to the same androgens that cause follicular miniaturization once they reach the terminal stage?

 

[Orin]

I don't think anyone is suggesting they'd be miraculously spared from succumbing to DHT, but if they can grow out to full terminal hair (like the re-awokened hair that I have gotten), chances are they'll atleast stick around for a full hair-cycle, and most likely longer still before becoming very thin again.

So all in all you will, at worst, buy a few years - at which point you should be able to do the procedure again. It's also possible that hair that grow to terminal under very little bombardment of DHT, might be able to endure longer, than the hair that's been bombarded by DHT since you were... I dunno, 14-15 or so?

All in all, if it gives you a pretty good amount of hair for 3-5 years, then that's pretty incredible. With minoxidil, weak lasers and other assorted mediocre tools at our disposal it is certainly nothing to sneeze at (though I am not suggesting you were). I maintain this (all things considered) simple and cheap procedure could turn out to be the most impressive regrower - if not creator - of hair.

Once I get back from my vacation I will repeat my tweezing and light dermabrasion, followed by lithium on the other side of my temple, and if that shows as good results as I have gotten on a tiny patch on my right temple, I might (should I be able to summon up the courage) tweeze a large part of my scalp, shave it clean, dermabrade and put lithium on it.

Plucking hair prior to the procedure is in my opinion a very important step. Who knows what it can add to the procedure if we on top of that find a working EGFR-inhibitor. Since I last checked, it seems my hairgrowth has spread out a full inch along the side, which is well off from the actual dermabrasion site, and all things considered, it's dense enough to make a difference should it be spread all over my scalp. I'm pretty eager to see the results in my front, which as of late (mostly due to my shift from dutasteride which I can't stand, to propecia) has thinned out in a dissapointing pace.

Going just by pattern, hair has awoken following pretty much the exact hairline I had when I was 15 or so, as in almost a straight hairline, and filling in my maturing V-pattern.

I've said it before, but I think doing this procedure this way, even without EGFR-inhibitors, could very well be worth your time. When I did it I felt kinda silly, applying lithium on my newly healed skin, thinking of how unbelievable the whole thought of it is (even though I've done the same thing once before), but a week or two later hair started growing out. Though it is very encouraing after the fact, you truly feel like you've bought into some snake-oil bullcrap.

Doing this all over my scalp is still atleast a month or so away, and I hope I'll have the courage to do so. But it should be good for all of us to know that there is something "in the now" that we can fall back on, and which (hopefully) will give everyone as good results as it has on me (albeit very locally).

 

[superhl]

I am going to try silymarin. I am currently taking silymarin daily. I will dermabrade with sand paper next to my hairline. Wait three days, mix silymarin with ethanol and apply to dermabrade area. Am i doing this right? Am i leaving out any steps?

 

[masculineyourheart]

How are you guys working out the quantities to mix into your topicals and such?

From memory, lithium comes in a powdered form, yeah? and scales that measure in milligrams are damn expensive.
So, how are you a) working out percentages of active ingredient and vehicle; and b) measuring these amounts to the quantities you're after?

 

[first]

How are you guys working out the quantities to mix into your topicals and such?

From memory, lithium comes in a powdered form, yeah? and scales that measure in milligrams are damn expensive.
So, how are you a) working out percentages of active ingredient and vehicle; and b) measuring these amounts to the quantities you're after?

It's not really possible to know the most effective quantity. What people do is figure out at which % it is soluable and to what degree it could possibly be harmful and then work something out from that. With lithium most people seems to be going with a 4%-10% formula, but the optimal % is still very much unknown. How much does Orin use?

 

[masculineyourheart]

Thanks first. So how are you working out the amount of lithium to put into the vehicle to get it to 4-10%?

1 gram of powder in 100ml of solution is 1%, right? So how do you measure this in smaller quantities? Even at 1g it would be difficult to measure because of the inaccuracy of common kitchen scales.

I remember caffeine being effective at about .001% or .01% or something like that, so 1 to 10mg of powder in 100ml of solution. Trying to measure powder in these quantities isn't possible without the use of accurate scales like those used by jewellers or in labs, as far as I can tell. I remember in China they had these awesome old style scales in the tongrentang's I wish I picked up when I was over there, ah well. How are you guys working it out?

 

[first]

I don't own any scales at all, I use various kinds of measuring cups. Sure it won't be entirely accurate but since I don't know the right amount to begin with, that isn't too important.

If I want a really small amount. I'd add for example 1ml (or 1mg) to 10ml of destilled water (or what ever carrier you will use) and then take 1ml of that destilled water, and I would effectively have 10% of the original amount, this can be repeated indefinitely.

 

[Kestrel]

I don't think anyone is suggesting they'd be miraculously spared from succumbing to DHT, but if they can grow out to full terminal hair (like the re-awokened hair that I have gotten), chances are they'll atleast stick around for a full hair-cycle, and most likely longer still before becoming very thin again.

So all in all you will, at worst, buy a few years - at which point you should be able to do the procedure again. It's also possible that hair that grow to terminal under very little bombardment of DHT, might be able to endure longer, than the hair that's been bombarded by DHT since you were... I dunno, 14-15 or so?

Thanks for the follow-up. At worst, even if the new follicles do succumb to DHT over time, as you suggest, minoxidil and/or Propecia may have enough of a mitigating effect. Also, you have an infinite supply of genetically immune follicles from the back and sides of the head. Maybe if the wounding is done close enough to the existing hairline, the new growth can be coaxed into moving toward the vertex of the scalp.

I need to read through all your previous posts. Please keep us updated on your progress.

 

[joemadrid]

Is something better than lithium to up WNT signaling?. Please include expensive drugs or compounds also.

 

[Orin]

I don't think you have to worry too much about quantities if it's just lithium in an ethanol solution. Depending on what kind of lithium you use, you could get a pretty high solution (lithium chloride) or a very low solution (lithium orotate).

I use orotate. I just put a few pills worth of salt into it and mix for all I'm worth. Nobody knows the exact mechanism of this yet, but I think, and it seems (depending on my own results and those of people who have used higher concentrations through lithium chloride), that it's good enough to have "sufficent" levels of these ingredients for the biolgical regeneration/neogenesis to happen.

Excess amounts most likely wil make no difference. It's kinda like how you there is an optimal level of finasteride at about 1.25 miligram or such, and doubling, trippling or making the dose ten times as potent makes very little difference, if any - while taking half of 1.25 miligram makes a significant difference.

So I don't think we really have to worry about doses of lithium right now. A few capsules or "as much as you can dissolve together with potentially additional ingredients" should suffice.

 

[masculineyourheart]

I don't own any scales at all, I use various kinds of measuring cups. Sure it won't be entirely accurate but since I don't know the right amount to begin with, that isn't too important.

If I want a really small amount. I'd add for example 1ml (or 1mg) to 10ml of destilled water (or what ever carrier you will use) and then take 1ml of that destilled water, and I would effectively have 10% of the original amount, this can be repeated indefinitely.

I'm still confused about how you're turning a measurement of weight into one of liquid volume. How do you work out the 1 mg = 1 ml amount to begin with? I'm asking because I want to use a .001 to .005% amount of caffeine in my topical but have no idea how to work out the 3mg of caffeine I'd need to throw in to achieve that. I had a look on ebay and they have dodgy jewellers scales in Hong Kong for $50 but if there's an easier or cheaper way, I'm completely open to it. In the case of caffeine I don't think it's a good idea to overdo it.

Something else I was reading... anyone else heard of nattozimes or serrazimes facilitating wnt?

edit: Found this here website. This saves me the trouble of spending exorbitant amounts of money on Chemistry Lab quality scales. One accurate to .1g should hopefully suffice.

 

[masculineyourheart]

Excess amounts most likely wil make no difference. It's kinda like how you there is an optimal level of finasteride at about 1.25 miligram or such, and doubling, trippling or making the dose ten times as potent makes very little difference, if any - while taking half of 1.25 miligram makes a significant difference.

So I don't think we really have to worry about doses of lithium right now. A few capsules or "as much as you can dissolve together with potentially additional ingredients" should suffice.

I don't know, I reckon it'd cause problems with solubility if you have a few different ingredients in your topical. I'm no chemist but I imagine if you mix junkloads of finasteride or lithium into your vehicle, there's not going to be much room left for whatever else you want to put in there. I hope someone can tell me I'm wrong on this.

I don't see anything wrong with being precise, especially if we want this to help others later on. It'd be good to at least get a reasonable idea of how much of whatever everyone's using.

 

[harold]

Hi Harold, as always a very informative post and i thank you greatly for that. I have only been looking at these methods and the chemistry invovled for a week, so you'll have to forgive my ignorance, but this does seem like an ejoyable subject area that can yield many results.

A few things that I would like to clarify:

I dont know that there is a tyrosine kinase intermediary. Protein kinases but not neceassarily tyrosine kinases.

The first is that one way in which BC is expressed is via Tyrosine Kinase (I did say there must be more than way to express this protein otherwise the follica method couldn't work) you can google this fact and find it stated many times.

Well I think there is some regulation of the pathway by some tyrosine kinases but I think the wnt pathway has a much greater importance in regulating beta-catenin levels and there is no tyrosine kinase involved in this signalling pathway as far as I can tell. If you see otherwise please let me know.

[quote:2ew17kiu]gefitinib etc are not EGFRs. EGFR = Epidermal Growth factor Receptor. And not every EGFR inhibitor inhibits tyrosine kinase activity.

Happy to hear your comments.

This is my mistake, I forgot to put inhibitor after EGFR, but i can assure you as lame as my seem I do kow what they are.
[/quote:2ew17kiu]

Yeah I got the idea you knew what they were. It was just getting a little confusing.

In relation to the examples i gave, i did say i don't understand how if my understanding was correct that the follica patent could produce these results (in as far as example 2 and 3 is concerned) unless there was another regulator of Beta Catenin. I have since learnt that the only 2 regulators of BC (that i can find) are Tyrosine Kinae and GSK-3. Which i'll discuss in a later post.

you also said this:

[quote:2ew17kiu]As I forgot to add that study by Benji showed that EGCG was inhibiting wnt signalling by a completely different mechanism than the one you proposed. basically EGCG docks with a repressor of the LEF/TCF transcription site and thus stops Beta-catenin from promoting the expression of these genes if I recall correctly. But it has nothing to do with the way in which they interfere with EGFR activity.

As far as i'm aware EGCG does inhibit Tyrosine Kinase, and the following would seem to suggest this also (by the way i'm not going to produce reams pragraphs just salient sentences you can check the websites for your self):

"EGCG also showed strong inhibition of tyrosine kinase and mitogen-activated protein kinase (MAPK) activities, without affecting the kinases in the normal cells."
http://cat.inist.fr/?aModele=afficheN&cpsidt=13560572

"First, Liang et al. [43] demonstrated that EGCG directly blocks EGF binding to the
EGFR and thus subsequently inhibits the tyrosine kinase activity of the receptor in human A431
epidermoid carcinoma cells"
http://216.239.59.104/search?q=cache:8H ... cd=1&gl=uk
[/quote:2ew17kiu]

This quote is not saying that EGCG inhibits tyrosine kinase - EGCG "directly blocks EGF binding to the EGFR" and it is only subsequently ie. indirectly that the EGFR mediated tyrosine kinase inhibitor is blocked. So the mechanism of EGCG inhibiting EGFR is not related to EGFR tyrosine kinase.

"We found that EGCG inhibits the growth of human squamous carcinoma, breast carcinoma and colon carcinoma cells. This is associated with rapid inhibition of activation of the RTKs (receptor tyrosine kinase), EGFR, HER2 and HER3 inhibition of activation or the expression of several downstream signaling molecules involved in cell proliferation and survival and angiogenesis"

all the above examples relate to malignant cells,

I havent read all the links you post above but note as I said before that there are many different types of tyrosine kinase. A drug that is going to inhibit the action of one is not necessarily going to inhibit all others. Thats why gefitinib does not inhibit VEGF related tyrosine kinases like gefitinib. This is fundamental to the questions you are having.

Nevertheless it shows that EGCG does work on TK and i'm sure it also works in the process you said it does as well.

I dont recall saying how EGCG works but as the quote above shows it works as an EGFR inhibitor by directly stopping EGF from docking at the receptor.

Also if EGFR inhibitors, which all seem to work by binding to EGF receptor sites, how could TK not be affected by all EGFR inhibitors that work in this way.

Tyrosine kinase would be affected but only in the same sense that androgen receptors are going to be activated less in balding scalp in the presence of finasteride. That doesnt mean that finasteride is an antiandrogen. Again in the same sense I could reduce the ammount of testosterone converted to DHT by 5-ar by castrating someone (thus removing most endogenous testosterone). That doesnt mean that castration is a 5-ar inhibitor.

if you could name some inhibitors that don't work in this way please let me know. This would solve a lot of issues I have with putting together a successful process.