Spanish scientists cure terminal liver cancer

[Menydh]

Spanish scientists cure terminal liver cancer

The Spain Herald
June 1, 2005

Spanish researchers led by professor Antonio Bru, of the applied mathematics department at the Complutense university in Madrid, succeeded in curing a patient in the terminal phase of liver cancer through strengthening the patient's immune system. Bru stated that this form of therapy "opens very hopeful horizons" against all kinds of solid tumors within a short time, as according to his theory they all have a common pattern. The therapy, published today in the Journal ofClinical Research, is the result of twelve years of research. A mathematical solution to liver cancer was considered, equations were analyzed, and experiments on animals were performed. In 1998 a new theory was proposed, according to which solid tumors develop according to a mathematical equation, said the Complutense. Therapy was applied to a terminal patient, given two months to live, with liver cancer, hepatitis C, and cirrhosis. The treatment consisted of bone marrow stimulation and the generation of large amounts of neutrophiles, a kind of leucocyte that impedes tumor development. According to the Complutense, the liver cancer remitted and the patient was able to return to work as a high school teacher within months, suffering only mild side effects. Besides Bru, Sonia Albertos of the San Carlos clinical hospital and Fernando Garcia-Hoz of the Ramon y Cajal hospital in Madrid participated in the research. The treatment took place at the Clinica de Valle in Madrid.


[source]

[Tabitha]

I was aware that immune therapy stimulation was being
trialed for some years now but I wasn't aware that there
had been a report of such a success. I do however think that the
results need to be interpreted with caution.

So far as I can tell from this article this is a phase I
clinical trial which has only involved one patient - or
perhaps more patients, but they have only reported on the
successful case. I would also like to know how they define
a 'cure'. I gather that the patient is back at work but
have they actually gotten rid of all the tumour, or is the
residual disease just too small to be detected
radiologically, something that is not uncommon even with
conventional chemotherapy. Although the article claims to
have cured him, they would need to have followed him up
being disease free for at least 5 years before they could truly make that claim.
I wonder why they decided to try this out in patient with what sounds like a
primary hepatoma, a cancer which is particularly uncommon
in the West? Why not try it out in someone with liver
metastases from colon cancer or breast cancer something
much more clinically relevant in our society.

All in all very interesting and encouraging results, I'd love to read more on this.

[Menydh]

He explains it in an interview here (in Spanish):

Antonio Brú: "Bastaría potenciar el sistema inmune para superar el cáncer"

A translation of a part of the interview:

... what we discovered in vitro is that the dynamics of growth is equal in all tumours. I.e., there exists a dominant mechanism which is the same for all the types of cell lines. Such dynamics has three characteristics, which from the mathematical point of view are in a certain way equivalent:

1. The majority of cell activity in the tumours concentrates in the external part of them.
2. That it takes place what we call superficial difusion on the edge of the tumour. That is to say that the new cells which originate in the division of one of the cells of the edge of the tumour, move through it until they find a concavous position in which they find themselves surrounded by a bigger number of cells than they were in the position where they were generated.
3. That the growth of a cancerigenous colony is constant in time, except in the first phase (when there are few cells) in which the growth is logically exponential.

That the proliferation was restricted to the edge of the colony of tumour cells also meant that the cells of the inside of the colony do not proliferate at the same rythm as the cells of the outside. Which means that there exists a mechanism of cell inhibition of the cancerigenous cells. It is something similar to what is known in the normal (non tumourous) cells, as inhibition through contact (later we observed that in the practice it could be the same mechanism).

The next step was to confirm that this type of mechanisms also govern the growth of the tumour in vivo. We performed a large number of researches over fifteen different types of tumours, of which we obtained different histological section which allowed us to confirm that the most part of this proliferation was nearly always restricted to the edge of the tumour. We also verified in vivo the fundamental characteristics of in vitro growth; ie., that the mechanism was the same that we had observed in vitro. Besides, te morphological parameters that we measured in the colonies reproduced also during the in vivo growth phase. Therefore, in one way or another, we had discovered that there is a dynamic universality in all type of cell proliferation... and also in the tumour proliferation.

Then he goes on to explain:

According to this method of proliferation and growth, tumours must destroy first the tissue of the host in order to be able to invade it and occupy the new free space. The extracell matrix is degraded by the corrosiveness of the acidic environment created by the metabolism of the cells and by other substances released by tumour itself --among which are the metalloproteinases-- because the tumour need to continue degrading the tissue of the host in order to keep growing. No Physical scientist would be surprised from hearing that a mass that grows in the universe, what it needs above anything else is space. This is in contrast with the common belief that tumours invade first the tissue and then they destroy it. We have shown that it is right the opposite way.

And so on and so forth.. Ma'am.

[svin]

Does anyone have full article?

[Tabitha]

Thank you!

[Menydh]

Originally Posted by svin

Does anyone have full article?

I found the full paper in the Biophysical Journal.

The Universal Dynamics of Tumor Growth -- Brú et al. 85 (5): 2948 -- Biophysical Journal

[Tabitha]

Ask and ye shall receive, is that how it works on Stirpes?
In that case size 38 Christian Louboutins or 37 and a half Manolo Blahniks - I'll PM you my address.

Thanks so much for posting this, this field has long been one of my interests and I'm about to pull on my pointy woolen pom pom chapeau and expose my geeky side.

The results are interesting, but with in vivo experiments there are
perils in extrapolating what happens in the test tube into the human
in-vivo situation.

That the majority of cell growth occurs at the periphery
of the tumour is not new or surprising. The central core
of the tumour is often necrotic due to the simple failure
of supply of oxygen. Cell differentiation within the
tumour is chaotic and neovascularisation is particularly
poor. Consequently the majority of oxygen is obtained by
diffusion from the surrounding tissues, much like the
blood suply to a skin graft.

It is therefore not surprising that it is at the periphery of the tumour,
where the suply of nutrients is at it's greatest, that the
greatest amount of proliferation of the tumour occurs and
by the nature of the cancerous cells, invasion of the
surounding tissues occurs.

The observation that the tumour first destroys the
surrounding extracellular matrix before then proliferating
is also interesting and I would be interested in reading
more about how you demonstrated that. I feel that this may
be something of an over-simplification.

I personally envisage a more dynamic process whereby the creation of
the extra space along with the proliferation of tumours
cells occurs simulataneously rather than a monodirectional
process.

I don't know if anyone else here has a love for this sort of thing, but I'd love to hear others' opinions.

And now back to the lowbrow section where I truly belong.
Normal service will be resumed as soon as possible.

[Menydh]

It is how it works with special people, as far as I am concerned. Nothing to do with Stirpes. Although certainly we do not promote egalitarianism of any type.

I wouldn't want to spoil you much, yet. But you are welcome to forward me your address, in case I suffered from a sunstroke during the summer and decided to change my mind.

Clearly you meant in vitro experiments, not in vivo.

Originally Posted by Tabitha

The observation that the tumour first destroys the
surrounding extracellular matrix before then proliferating
is also interesting and I would be interested in reading
more about how you demonstrated that. I feel that this may
be something of an over-simplification.

Well, obviously I didn't demonstrate it, did I? Whatever crossed your mind..

I take it that you are drawing your conclusions from the 2003 paper. The first paper that I have been able to trace from that team is from 1998, which at least it should suggest that some research had been done before, and more until the date of publication of the 2003 paper.

Super-Rough Dynamics on Tumor Growth (1998)

Later to the 2003 paper, I've only been able to find a summary of another paper, published in 2004.

Pinning of tumoral growth by enhancement of the immune response. (2004)

And a response by the same team to a critique to their 2003 paper, published also in the Biophysical Journal in 2005.

Reply to Comments by Buceta and Galeano Regarding the Article “The Universal Dynamics of Tumor Growth” (2005)

I haven't found any more papers from Brú's team later to that date. Nor any further critiques to it. Admittedly, I may not have searched enough.

This other paper from an American team of Phycisists published in 2006, although it doesn't cite the previous, it might be of your interest too. I haven't even read into it though.

Dynamics and Pattern Formation in Invasive Tumor Growth (2006)

Whatever it may be, there seems to have been a growing interest in that approach since Brú published his paper in 1998. You might find more by running the appropriate keywords on a search engine, with the help of the list of papers in Tumor

Originally Posted by Tabitha

I don't know if anyone else here has a love for this sort of thing

I wouldn't call it a love for it, but I developed a certain temporary interest when a very dear friend of mine was diagnosed a cancer years ago, from which he died.

I understand the skepticism around these publications. I've been used to hear the almost automatic academic skeptical criticisms since I was a child.

Incidentally, at the time when my friend had this cancer, I had a conversation with the head of a center of Oncology here about an alternative treatment that he was following in Italy, which if I recall correctly was from an Italo-American Physician (but please, don't quote me on this last part). As I had expected, I met the same skeptical criticism to the method as I was accustomed to.

But my real interest started and, for any practical purposes, ended with his death. Anything beyond that moment is nothing but sheer curiousity, as with many other things.