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Genetics

Talk about anything and everything related to lipomas and related healthcare issues here.

Moderator: matt

Laura

Genetics

Post by Laura » Mon Aug 22, 2011 4:55 pm

I found this article, rather old, but promising. This paper is about gene structure and lipomas.

An excerpt:

Role of the high mobility group A* proteins in human lipomas
Monica Fedele1, Sabrina Battista1, Guidalberto Manfioletti2, Carlo Maria Croce3, Vincenzo Giancotti2 and Alfredo Fusco1,4,5
Received February 20, 2001.
Accepted May 22, 2001.
Revision received May 15, 2001.
...
Transgenic mice carrying a truncated HMGA2 gene develop abdominal/pelvic lipomatosis
Subsequent to these findings, two independent groups generated transgenic mice carrying a truncated HMGA2 construct. In fact, transgenic mice provide a powerful experimental approach to define the role of oncogenes in neoplastic processes in vivo.
...
The dramatic expansion of the adipose tissue observed in HMGA2/T mice suggests that HMGA2 rearrangements play a pivotal role in the generation of human lipomas. Moreover, the giant phenotype shown by the HMGA2/T mice is the mirror image of that of the HMGA2 null mice. In fact, these mice are characterized by a pigmy phenotype with a reduction of the adult body weight, mainly as a result of a decrease in fat tissue (55). Based on these data, we suggest that the truncation of the HMGA2 gene leads to an increased activity of the HMGA2 protein, which in turn stimulates adipocyte cell growth.
HMGA1 alterations in human lipomas
Recent studies have demonstrated that also the HMGA1 gene is rearranged in the benign tumors characterized with 6p21 chromosome aberrations (114–117).
...
more at thisl link http://carcin.oxfordjournals.org/conten ... /1583.full
Laura

Re: Genetics

Post by Laura » Mon Aug 22, 2011 4:57 pm

Important conclusion in the paper. We should contact the authors.

"These data would suggest that the regulation of adipocytic cell proliferation could result from the balance of HMGA1a/b and HMGA2 protein functions: a gain in HMGA2 protein activity induces adipocyte cell hyperproliferation, whereas the dominance of HMGA1a/b has an opposite effect. Therefore, even though the mechanisms underlying the counteracting activity of HMGA1a/b and HMGA2 proteins needs to be defined, it is reasonable to think that any modification of this balance, by impairing the HMGA1a/b activity or by increasing the HMGA2 function, may affect adipocytic cell growth resulting in the generation of lipomas. "
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Re: Genetics

Post by matt » Mon Aug 22, 2011 6:55 pm

Thanks Laura, very interesting!
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by sjohn » Tue Aug 23, 2011 2:50 am

Yeah we need to make some DNA mapping studies on people that have FML so we can study their sequences. Unfortunatelly such an evaluation has not been undertaken to date.

We need a person with FML who wont have a problem to spend some tenths of thousands of dollars to make it. I am definetly not the one! :lol:

Btw around 2015 they say it will cost less than 1000 usd to make yours!
Laura

Re: Genetics

Post by Laura » Sun Sep 25, 2011 3:03 am

sjohn wrote:Yeah we need to make some DNA mapping studies on people that have FML so we can study their sequences. Unfortunatelly such an evaluation has not been undertaken to date.

We need a person with FML who wont have a problem to spend some tenths of thousands of dollars to make it. I am definetly not the one! :lol:

Btw around 2015 they say it will cost less than 1000 usd to make yours!
What I'm thinking is that there are and have been researchers interested in this issue.
Its a start.

My brother and I both have these, my two sisters do not. We each have our own household and lifestyles, we don't eat the same food.

I am very worried because suddenly I am getting alot more lipomas and also the existing ones are growing.

I believe there are alot more of us out there, and the folks want help. We just need to organize a bit more.
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Re: Genetics

Post by matt » Tue Oct 04, 2011 12:01 pm

I'm still buzzled whether mutated genes are the reason for lipomas or are they rather the result?

This is because of epigenetics, a controversial subject even today, which I have studied some.

Think if your bad habits mean that your children and even their children end up with a psychiatric disorder? Or if the things you eat makes your grand children obese and diabetic? These are some of the implications of a study in rodents that suggests poor diet and parental neglect can leave their mark on the genes of your children and your children's children.

A cryptic epigenetic code added to the DNA of mice shows for the first time that changes in gene activity can pass down three generations. It is likely that the same mechanisms are at work in humans.

We are used to think that genes are something we cannot interact with. This is definitely not the case. Genes are constantly turned on and off. How do we know this? Because of identical twins who have the exactly same DNA. Still, twin studies have shown that people with schizophrenia and bipolar disorder have changes in gene activity caused by their environment. This means that one of the twins has schizophrenia while other one doesn't.

Researchers found out that there was a difference in how the "epigenetic" factors leave chemical marks on genes that dictate how active they are. In this case, the genes were the same that are thought to be linked with bipolar and schizophrenia.

So what if some of us have "inherited" lipomas from their parents or even granparents and some of us have been influenced by environmental things like Agent Orange, steroids, alcohol, hypothyroidism, etc...

I believe that all lipoma cases or "bloodlines" are relatively short aged. This means that you either inherited lipomas from near past relative or you were influenced by some environmental factor. Why? Because there's no sense that nature would continue a "bloodline" that has no life improving quality. Sooner or later these genes will be shut down or otherwise dealed with in an unnecessary bloodline.

The same applies to cancer and many other diseases which can be "inherited" because your inherited genes may be more prone to some external stimulus. But in the long run these bloodlines will always be adjusted if the mutations have no beneficial properties to the species.

So in a way both are correct: our genes may cause lipomas and our environmental factors may cause lipomas. It's individual which is the correct path to your lipomas.

After all this, do I still think all lipomas and related conditions are curable?

The answer is YES. Genes are never actually the cause of anything. They are like a guidebook what should be done but they are influenced by external things, like food. So for example by eating certain kind of food, you may be able to shut down the genes that are no longer needed to create lipoma cells.

What originally triggers the genes that will create lipomas?

That we do not yet know but there are multiple things pointing to microbial causes. The more I study the more things I find - that cause cancer and tumors - which are also related by one way or another to microbies, like fungus and virus. Most of the discussion going on here on this board is about different sides of the coin pointing to one single direction. These include hypothyroidism, iodine, uric acid, genes, fungi, pine bark extract, apricot seeds, resveratrol, heavy metals, green tea, ozone therapy, turmeric, herbal remedies, lemon juice, beta glucan, sodium bicarbonate, etc... All these pop up often both in tumor and microbial literature and studies.

I believe it's these microorganisms that influence to our DNA either by purpose or because of it's our body's natural way to surround and packet the external organisms. I'm starting to think it's the latter. How this kind of DNA mutation could be delivered to offspring, I have no idea yet?

Other treatments like surgery, liposuction, lipolysis or steroid injections will probably not cure the underlying cause and thus shut down the genes which are responsible for creating lipoma cells.
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by matt » Fri Nov 11, 2011 9:28 am

This article shows evidence of an epigenetic drug therapy towards cancer cells. This is to say that scientists have discovered that they can revert or alter the functioning of some tumorgenic genes in the cancer cell by applying a certain drug. In this article they speak about a combination of drugs azacitidine and entinostat.

In tumors, the cell growth limiting genes are silenced.

Azacitidine works by removing gene-silencing markers known as methyl groups from the genes and entinostat inhibits histone deacetylation, a closely related process that also contributes to gene-silencing.

The treatment actually looks to have cured at least one patient's lung cancer and many other patients experienced tumor shrinkage and clearance of metastases. Patients' cancer had progressed after earlier standard therapies.

Adding methyl groups to a substrate or replacing an atom or a atom group is called methylation. This is considered to be the way of epigenetic "memory" of the genes. DNA methylation is the way how the genes control their activity. DNA methylation is also thought to be responsible of silencing the viral and other foreign unwanted genetic code. Some methylation modifications that regulate gene expression are inheritable.

Methylation is normal for every living cell in some degree but it has been discovered that increased transfer of a methyl group to DNA is typical for tumor growth.

Assuming that if bacteria were the cause of lipomas it appears that bacteria hold a specific restriction modification system. This is a system that has evolved to bacteria as a defense mechanism towards foreign DNA, such as viral DNA. Yes, viruses can attack also bacteria.

A simple discription of how the system works is that certain restriction enzymes cut the bacteria DNA periodically in order to determine whether the DNA is bacteria's own DNA or foreign. Bacteria separate their own DNA from the foreign DNA by attaching methyl groups into their own DNA. This separation is not perfect though and sometimes the two DNA can mix.

Now given that the above produces DNA with methyl groups, it might explain why methyl group removal by azacitidine and entinostat could limit the tumor growth - by destroying the bacteria's DNA...
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by sjohn » Fri Dec 23, 2011 4:46 am

An interesting video

Guest

Re: Genetics

Post by Guest » Tue Feb 28, 2012 3:18 am

sjohn wrote:Yeah we need to make some DNA mapping studies on people that have FML so we can study their sequences. Unfortunatelly such an evaluation has not been undertaken to date.

We need a person with FML who wont have a problem to spend some tenths of thousands of dollars to make it. I am definetly not the one! :lol:

Btw around 2015 they say it will cost less than 1000 usd to make yours!

Sjohn: Hi. I was commenting on another thread and Matt asked me to comment on this thread as well. There are tons of published articles in which the genes of lipoma sufferers have been mapped. In the U.S., people have this done at local clinics. It is not tens of thousands of dollars. People are usually looking for worse disease than lipomatosis, but these labs are happy to check for lipomatosis. I don't advise that people should have this done, because it is unnecessary. But I do know people who have had this done.
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Re: Genetics

Post by Guest » Tue Feb 28, 2012 3:25 am

Laura wrote:Important conclusion in the paper. We should contact the authors.

"These data would suggest that the regulation of adipocytic cell proliferation could result from the balance of HMGA1a/b and HMGA2 protein functions: a gain in HMGA2 protein activity induces adipocyte cell hyperproliferation, whereas the dominance of HMGA1a/b has an opposite effect. Therefore, even though the mechanisms underlying the counteracting activity of HMGA1a/b and HMGA2 proteins needs to be defined, it is reasonable to think that any modification of this balance, by impairing the HMGA1a/b activity or by increasing the HMGA2 function, may affect adipocytic cell growth resulting in the generation of lipomas. "

Laura: Hi. Matt asked me to comment on this thread. First my complements to you. So many people have posted misinformation on this site that it refreshing to see someone has posted some real scientific research. But I don't know why you feel we should contact the authors. What do you expect them to tell you?

Anyway, this article that you have posted is not unique. There have been many similar studies. Some go into more specifics than this article. But this article is not obsolete. There has been less in the way of new discoveries in the past ten or fifteen years.

If more people could understand this and other similar articles, then they would be less easy prey to the people hawking herbs or apple peel as miracle cures.
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Re: Genetics

Post by Guest » Tue Feb 28, 2012 3:40 am

matt wrote:I'm still buzzled whether mutated genes are the reason for lipomas or are they rather the result?

This is because of epigenetics, a controversial subject even today, which I have studied some.

Think if your bad habits mean that your children and even their children end up with a psychiatric disorder? Or if the things you eat makes your grand children obese and diabetic? These are some of the implications of a study in rodents that suggests poor diet and parental neglect can leave their mark on the genes of your children and your children's children.

A cryptic epigenetic code added to the DNA of mice shows for the first time that changes in gene activity can pass down three generations. It is likely that the same mechanisms are at work in humans.

We are used to think that genes are something we cannot interact with. This is definitely not the case. Genes are constantly turned on and off. How do we know this? Because of identical twins who have the exactly same DNA. Still, twin studies have shown that people with schizophrenia and bipolar disorder have changes in gene activity caused by their environment. This means that one of the twins has schizophrenia while other one doesn't.

Researchers found out that there was a difference in how the "epigenetic" factors leave chemical marks on genes that dictate how active they are. In this case, the genes were the same that are thought to be linked with bipolar and schizophrenia.

So what if some of us have "inherited" lipomas from their parents or even granparents and some of us have been influenced by environmental things like Agent Orange, steroids, alcohol, hypothyroidism, etc...

I believe that all lipoma cases or "bloodlines" are relatively short aged. This means that you either inherited lipomas from near past relative or you were influenced by some environmental factor. Why? Because there's no sense that nature would continue a "bloodline" that has no life improving quality. Sooner or later these genes will be shut down or otherwise dealed with in an unnecessary bloodline.

The same applies to cancer and many other diseases which can be "inherited" because your inherited genes may be more prone to some external stimulus. But in the long run these bloodlines will always be adjusted if the mutations have no beneficial properties to the species.

So in a way both are correct: our genes may cause lipomas and our environmental factors may cause lipomas. It's individual which is the correct path to your lipomas.

After all this, do I still think all lipomas and related conditions are curable?

The answer is YES. Genes are never actually the cause of anything. They are like a guidebook what should be done but they are influenced by external things, like food. So for example by eating certain kind of food, you may be able to shut down the genes that are no longer needed to create lipoma cells.

What originally triggers the genes that will create lipomas?

That we do not yet know but there are multiple things pointing to microbial causes. The more I study the more things I find - that cause cancer and tumors - which are also related by one way or another to microbies, like fungus and virus. Most of the discussion going on here on this board is about different sides of the coin pointing to one single direction. These include hypothyroidism, iodine, uric acid, genes, fungi, pine bark extract, apricot seeds, resveratrol, heavy metals, green tea, ozone therapy, turmeric, herbal remedies, lemon juice, beta glucan, sodium bicarbonate, etc... All these pop up often both in tumor and microbial literature and studies.

I believe it's these microorganisms that influence to our DNA either by purpose or because of it's our body's natural way to surround and packet the external organisms. I'm starting to think it's the latter. How this kind of DNA mutation could be delivered to offspring, I have no idea yet?

Other treatments like surgery, liposuction, lipolysis or steroid injections will probably not cure the underlying cause and thus shut down the genes which are responsible for creating lipoma cells.

Matt: You asked me to comment on this thread. See my other posts here. Now, to answer some of your questions:

1. The mutated genes are definitely the cause of the tumors, not vice versa.
2. No there is no microbial cause.
3. The environmental factors that you mention do not affect the tumor formation. There are internal factors that can cause differences in the clinical expression of a genetic defect. (But this is a very complex subject.)

If you could read through an article such as the one that Laura posted, and really understand it, then you would find a lot of the answers that you are seeking. What you won't find is a cure, because even with this knowledge of what really causes lipomatosis, it is an extremely difficult problem to solve. But at least you would be better able to recognize BS. For example, as I mentioned on the other thread, lipomatosis has nothing to do with lipid metabolism. So anyone who writes about lipoma "cures" that relate to relate to metabolic pathways is just flat wrong.
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Re: Genetics

Post by caribou » Tue Feb 28, 2012 7:51 am

I believe that all lipoma cases or "bloodlines" are relatively short aged. This means that you either inherited lipomas from near past relative or you were influenced by some environmental factor. Why? Because there's no sense that nature would continue a "bloodline" that has no life improving quality. Sooner or later these genes will be shut down or otherwise dealed with in an unnecessary bloodline.
I don't know if the bloodlines are relatively short-aged, they might be if the mutation is 'new'. But lipomatosis doesn't really affect evolution, because most people will already have children by the time they get affected by it (at least before when people got children in their early 20s). So nature doesn't really care as long as there's still offspring. Of course if around half of the gametes have an unbalanced translocation mutation that doesn't result in viable fetuses, it does have an effect on fertility, but perhaps not to a great enough extent for 'evolution' to prune out the mutation from the gene pool.

I also don't believe that apple peel extract could cure lipomatosis. The most probable treatment there is is to find a way that could remove existing lipomas easily with little damage to the rest of the body. Or possibly gene therapy (on existing lipomas), but that is going to take some time. The only thing we can do right now is live as healthily as we can if that would somehow prolong the development of new lipomas, and excise the lipomas that bother us. I'd like to know more about injections, although I have no idea what they actually do to a lipoma and how they might work (or not work), but noninvasive removal of lipomas would of course be wonderful if it's possible. And new discoveries are made all the time, maybe something will be invented to treat cancer or diseases like Huntington's that could be effectively used for lipomatosis.
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Re: Genetics

Post by matt » Tue Feb 28, 2012 8:23 am

Dear Guest,

Thank you for posting.

First of all I think I asked you to reply on the cause of lipomatosis thread but it doesn't matter.

Second, you sound so confident, so I guess you must have some kind of background in the field to back you up? I would have appreciated some links or other referencies.

1. The mutated genes are definitely the cause of the tumors, not vice versa.

I pretty much agree with you on this, but if you read carefully what I have written you will see that the whole point is WHY DO THE GENES MUTATE? I have never said that the tumors would cause the genes to mutate. And if you have studied the subject at all, you must know that bacteria, viruses, fungi and environmental factors such as radiation are more than capable of mutating the DNA.

2. No there is no microbial cause.

Umm.. Why? I take it you have read that tumors can be caused by a microbe? Warts and Kaposi's sarcoma are caused by Human herpesvirus. Stomach cancer is sometimes caused by Helicobacter pylori. There are many other microbes known to cause tumorous growths, like the larvae Schistoma haematobidium (bladder cancer), Opisthorcis sinensis and O. viverrini (liver cancer). Your certainty astonishes me. :shock:

3. The environmental factors that you mention do not affect the tumor formation. There are internal factors that can cause differences in the clinical expression of a genetic defect. (But this is a very complex subject.)

Again, I'm baffled. I'm not sure to which environmental factors you refer but if you mean Agent Orange, steroids, alcohol and hypothyroidism then at least alcohol is connected with tumor formation. Alcohol causes breast cancer in women. Oh, and alcohol also increases the risk of cancers of the mouth, esophagus, pharynx and larynx, colorectal cancer, liver cancer, stomach and ovaries.

Agent Orange was used by the US military in the Vietnam as a part of its herbicidal warfare program. Agent Orange includes dioxin, a known strong carcinogenic. Dioxin causes a variety of cancers in the lungs, larynx, and prostate.

And I'm sure you have heard that excessive amounts of e.g estrogen and testosterone are linked with breast and prostate cancers among others?

Hypothyroidism is known to enchance tumor invasiveness and metastasis.

Maybe you could educate me on how these examples correlate to your statements? I do not want to sound I know it all but anyone can see that there's more to it than what you have stated.

What you won't find is a cure

Even if that was true, what kind of an attitude is that? I mean, I think it's ok to investigate and ask questions?

lipomatosis has nothing to do with lipid metabolism. So anyone who writes about lipoma "cures" that relate to relate to metabolic pathways is just flat wrong

Can you back this up somehow? Can you explain why you think so? I'm not saying that they do have a relationship but at the moment I can't say there isn't.

Sources
http://en.wikipedia.org/wiki/Helicobacter_pylori
http://en.wikipedia.org/wiki/Kaposi%27s_sarcoma
http://cmr.asm.org/content/12/1/97.full
http://en.wikipedia.org/wiki/Opisthorchis_viverrini
http://en.wikipedia.org/wiki/Alcohol_and_cancer
http://en.wikipedia.org/wiki/Agent_Orange
http://www.ejnet.org/dioxin/#cancer
http://en.wikipedia.org/wiki/Testosterone
http://www.plosone.org/article/info:doi ... ne.0006428
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by matt » Tue Feb 28, 2012 8:52 am

Hi caribou,
The most probable treatment there is is to find a way that could remove existing lipomas easily with little damage to the rest of the body
I think these do exist already. At least the best possible invasive method so far is the minimally invasive technique - I do hope they will teach that to you guys in the medical school! 8-)

You believe that one day a gene therapy might work for lipomatosis. Can you explain how gene therapy works?

Because what I have understand in the gene therapy you'd try to correct or replace genes that have changed and to control their expression. You can also try to control the signaling between the cells or to regulate how the immune system works. In addition you could try to get the tumor cells to have an apoptosis (cell death).

Hmm.. Isn't this pretty much the same what many of the proposed treatments here are trying to do?

In gene therapy you actually inject viruses into the body. The viruses have been genetically altered so that the virus can deliver the "correct" gene to the cells. It's pretty interesting that they use these kinds of methods to alter the DNA but some state that tumors can't be caused by microbes, eventhough they admit that mutated genes can cause tumors. :roll:

To be fare there are non-viral gene therapies being studied but I do not know about those too much. I think they are still just under development rather than in active use.

I think the best injection therapy for lipomas so far is the collagenase injection. One injection of collagenase to a lipoma reduced the lipoma by 93 %. Nice, huh?

Of course there's the question what actually happens. Collagenase is the substance which breaks up collagen (the main substance in the connective tissue). So I wonder whether the lipoma cells are just released to float around in the body and thus possible causing new tumors to form?

Another injection which is know to work for lipomas is the deoxycholate injection.
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by Guest » Tue Feb 28, 2012 12:48 pm

Matt:

Sorry, my response to you was unclear on one point: I was referring only to lipoma tumors, not other tumors or cancer.
Of course you are correct that environmental factors can cause gene mutations. In many cases in which we say that something is a "carcinogen", it absolutely is causing genetic mutations. This can also be the case with some benign tumors and some non-tumor disorders. But we are talking about lipomatosis here. The specific type of mutation that causes lipomatosis is not caused by environmental factors. There are different types of mutations. If you read up on the lipomatosis mutation, you will see why it is not something that can not be caused by exogenous variables. If we see a dented car fender, it is clearly not caused by rust. Sorry to speak in analogies, but this would take several paragraphs to explain.

Can environmental factors play a role in the expression (not the cause) of the lipomatosis mutation? Conceivably, but In all of the studies of lipomatosis this has never been found.

Regarding lipomatosis and lipid metabolism, again if you read through the research (Not quacks, but articles such as Laura posted here) you will see the real tumor formation mechanism. Cell division coding is not a metabolic process. Once you understand that, then you will more easily recognize why certain quack cures have no hope of working.
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Re: Genetics

Post by matt » Tue Feb 28, 2012 1:42 pm

Guest,
If you read up on the lipomatosis mutation, you will see why it is not something that can not be caused by exogenous variables.
Trust me, I've read some about lipomatosis. I disagree with you. Explanations given in the the cause of lipomatosis thread. If you still think differently, please educate me with referencies.

Now you see why I asked you to reply on the other thread because if you had read it you would already know there isn't any specific type of mutation. There are many different mutations linked with lipomatosis. Sure, there can be mutations which occur more often but sometimes there are no mutations at all. And when some people have the mutation supposed to cause lipomatosis, they have zero lipomas.
Can environmental factors play a role in the expression (not the cause) of the lipomatosis mutation? Conceivably, but In all of the studies of lipomatosis this has never been found.
I wonder how many lipomatosis studies you have read? Alcoholism can induce lipomatosis. Some AIDS drugs may cause lipomatosis. Also if you read the other thread you'll see that a fungus is known to induce lipomatosis to a deer.

Next time I hope you could post some links so I'd know what you are talking about.

Thanks.
Hi I'm Matt - the creator and owner of this site. I have dozens of small nasty lipomas all over. I've tried many treatments including surgery and Lipostabil injections. See my lipoma prevention supplement recommendations and please consider donating a small amount via PayPal (click the Donate button) to keep this site up and running. Thx!
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Re: Genetics

Post by caribou » Tue Feb 28, 2012 4:21 pm

I think these do exist already. At least the best possible invasive method so far is the minimally invasive technique - I do hope they will teach that to you guys in the medical school!

You believe that one day a gene therapy might work for lipomatosis. Can you explain how gene therapy works?
Interesting. If I ever get my lipomas excised, I will definitely try to get it done with the minimally invasive technique. I'd like to see what kind of a scar is left behind though.

I don't know about gene therapy more than you do at the moment. A few months in a medical school hardly makes me an expert in anything yet. :) You basically just explained what I've read on the subject.

Yeah, collagenase breaks down collagen. There are many different types of collagen in tissues (all in all 28 different types have been discovered), in different concentrations. E.g. cartilage has mostly type II collagen (also others), whereas bone and ligaments, tendons etc have mainly type I collagen (in addition to others). Adipose tissue is composed of fat cells i.e. adipocytes and loose connective tissue, which has mostly type I collagen (also type III collagen). And type XXII collagen has been found in metastatic tumor cells, according to my histology book (Ross, M.: Histology: A Text and Atlas, if you're interested), but I guess it's not related to lipomas. I would imagine that all the different types of collagen have their respective types of collagenase.

My histology book says (this is my own summary):
Secreted collagen fibers can be degraged through the activity of matrix metalloproteinases (MMPs), which include collagenases (that degrade type I, II, II and X collagens) and which are normally excreted by a variety of connective tissue cells. Also collagen fibers can be phagocytosed (eaten and destroyed) by fibroblasts or macrophages.

So, I would assume that in the study they used at least type I collagenase, possibly some others, to treat lipomas. Several people here have mentioned there being a fibrous 'capsule' outside a lipoma, but my histology book doesn't mention it. It merely says that a conventional lipoma usually consists of mainly mature white adipocytes, whereas a fibrolipoma has adipocytes surrounded by an excess of fibrous tissue, and an angiolipoma has adipocytes separated by an unusually large number of vascular channels. In any case, I suppose the capsule would be type I collagen (though this is merely an educated guess :oops:), and then type I collagenase would break it down.
Of course there's the question what actually happens. Collagenase is the substance which breaks up collagen (the main substance in the connective tissue). So I wonder whether the lipoma cells are just released to float around in the body and thus possible causing new tumors to form?
Yeah, that is a good question. This is something that we can only guess, we would need trials on animals to find out what happens. I would be quite impressed if simply collagenase could get rid of lipomas by degrading the collagen fibrils in the tumour or in the surrounding capsule. Maybe the lipoma comes back after a while, maybe multiple small lipomas come back? Actually that would seem more logical instead of the lipoma disappearing for good, but who knows. We'd need more research.

Wikipedia also said that collagenase can cause indirect tissue damage, so injecting collagenase into one's adipose tissue could be somewhat risky. It should at least be properly tested on animals before doing any experiments on humans.
Last edited by caribou on Tue Feb 28, 2012 4:54 pm, edited 2 times in total.
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Re: Genetics

Post by caribou » Tue Feb 28, 2012 4:47 pm

Now you see why I asked you to reply on the other thread because if you had read it you would already know there isn't any specific type of mutation. There are many different mutations linked with lipomatosis. Sure, there can be mutations which occur more often but sometimes there are no mutations at all. And when some people have the mutation supposed to cause lipomatosis, they have zero lipomas.
Is this well documented that some people that actually have the same mutation don't get lipomas?
Because, well, I agree with 'guest' in that it does appear as if lipomatosis is caused by genes, and by a specific mutation (/mutations) in genes. It seems the most likely explanation when there are families with people getting several (even numerous) lipomas in their lifetime, whilst most of the general population never get lipomas or only get one in their lifetime. Lipomatosis patients aren't sporadic cases, but it's present in every generation of that family with FML. This really would imply dominant inheritance. Even if we can't find the mutation, it merely implies that it hasn't been found, not that it's not there (in my opinion). Of course there might be other ways of getting lipomatosis such as alcoholism, but that doesn't exclude the genetic factor with those families, who most likely aren't all alcoholics or subjected to the same environmental issues that could possibly also cause lipomatosis.

Then of course environmental factors have an effect on how the disease progresses, but they're still not the primary cause, the mutation is. That doesn't mean that environmental factors aren't important of course - maybe hunter-gatherers with the mutation only got a few of lipomas in their lifetime, but we with the current (unhealthy) environment and the mutation can get hundreds. Who knows. Still the primary cause would be the mutation, not lifestyle or diet or environment.

I guess we don't know about lipomatosis that much yet. I suspect that it's very underdiagnosed, and the true frequency is very hard to estimate. Maybe it's a bit like Huntington's disease, with everyone with the gene getting affected by it eventually. Maybe it's a bit like the Breast Cancer Mutation, that makes a person very susceptible to getting breast cancer in their lifetime - still only 80% with the mutation get breast cancer, and 20% don't. Researchers can't explain why. Still, the primary cause for breast cancer in those cases would be genetic, even if environmental factors might affect who those lucky 20% are. And in the same way, if there happen to be some people who don't get lipomas despite having the mutation, that doesn't let genes off the hook.
Last edited by caribou on Tue Feb 28, 2012 4:59 pm, edited 1 time in total.
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Re: Genetics

Post by matt » Tue Feb 28, 2012 4:59 pm

Thanks, that was a huge load of info there! :)

I didn't know that there were so many different types of collagen and that you have to have a certain kind of collagenase but it figures. It's never as easy as one might expect.

To be honest I'm not sure which lipoma has a fibrous surrounding and which does not. It's has just sort of started to circulate when people are trying to separate borderless lipomatous masses (e.g. Multiple Symmetric Lipomatosis) from ordinary lumpy lipomas.

Perhaps you could research this in some point some more? When you have time I mean.

Collagenase has already been tested in humans by Biospesifics with quite promising results:
Human Lipoma:

There are 575,000 U.S. patients diagnosed annually.

An open-label Phase I clinical trial has been completed for treatment of lipomas utilizing a single injection of collagenase. This trial was designed based on observations made during preclinical studies that a collagenase injection decreased the size of fat pads in animals. Favorable initial results, demonstrating that 10 out of 12 patients had a 50-90% reduction in the size of the lipoma, were presented at a meeting of the American Society of Plastic Surgeons.

BioSpecifics will initiate a 14 patient, single center dose escalation study for the treatment of human lipomas shortly.
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Re: Genetics

Post by caribou » Tue Feb 28, 2012 5:02 pm

Well, that is encouraging. :) Maybe there is some potential in the treatment! I hope they would've noticed if dissolving a lipoma with collagenase brings about many more smaller lipomas elsewhere near the original one. >__> Or if the lipoma grows back.

Maybe I could research lipomas and their capsules more when I have the time, but honestly I wouldn't know where to find any information of that sort. When I've advanced in my studies, then hopefully yes. Part of the reason why I decided to get a medical education (on top of being a hypochondriac and interested in medicine) was the fact that I knew there was this syndrome in my family that could affect my life later, and I wanted to be knowledgeable and find out if there was a chance of some kind of treatment.
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