Enjoy a contract under the project, and his work focuses on hydration fronts in heterogeneous materials, forming part of a containment of high level radioactive waste. In his paper studies the phenomena of molecular diffusion of a medium in another, and building on similarities that sometimes have physical and biological phenomena of very different nature, almost like a mathematical curiosity, became interested in the dynamics of tumor growth. He realizes that in its opinion:
- There are many theories about the genesis of tumors.
- Many classifications of types and subtypes, depending on the organ it affects.
- Many treatments. Some of dubious effectiveness.
- There is little information on how tumors grow.
Bru begins to investigate this last point. After several years reached the following conclusions (as argued in their work):
- The growth rate of tumors is different from that expected according to a pure duplication dynamics
- Therefore, all the cancer cells do not grow equally in the tumor. Physicist disagrees with the statement of oncologists, which all are equally divided, and therefore their joint development is exponential (although the high mortality nuance that exists between cells in the nucleus that slows down the growth in this area.) Bru asks: "If so, then where is the necrotic tissue? and states that except in very small diameter tumors, the growth by mitosis (cell division) is reduced almost exclusively to the outermost, being the internal state of induced dormancy (note: your job is by no means the first come to this conclusion, and several models and previous experiments recognizes the presence of an outer region of greatest activity) .. The consequence is that the tumors develop in an almost linear. This observation is confirmed by many other groups in the case of colonies in vitro and multicellular spheroids in the laboratory, even though the team of A. Bru and those jobs have proven in the case of actual tumors.
- Notice that the edges of a tumor have fractal properties, mathematical objects found in many fields of biology and science in general.
- Bru finds that the development of tumor response to very specific guidelines. The physicist gets an equation that is compatible with this dynamic.
- He studied many different tumor cell lines in vitro and in vivo, in animals and humans. Check surprised that all tumors follow the same pattern of cell broadcast, which could be explained by an equation based on fourth order derivative.
This would put into question, from a very specific point of view, one of the most current oncology: that cancer is not one disease but many different diseases, each tumor is different and therefore should be treated and medicated so different.
The model and observed by him, which restricts the growth almost at the edge of the tumor, we would interpret why very small tumors can be so evil. Since metastases caused by them are often much more active than the primary tumor. Professor Bru reasons this phenomenon as follows:
- To form a tissue of 1 cm. cubic single cell from a normal 32 divisions enough (2 to 32). Instead, to achieve the same size in tumor tissue, to reproduce only the outer layer, they can take up to 800 divisions.
- Precisely here lies a possible malignancy. In 32 divisions may not have been accumulated many chromosomal aberrations, but 800 is far more likely. The edge of the tumor cells, with many mutations in their DNA, are adopting a more variable behavior, which can make them die either spontaneously or migrate to other areas of the body causing the dreaded metastasis.
In 1998, Antonio Bru publishes the results of their investigations under titles such as Super-Roug Dynamics on Tumor Growth in the prestigious Physical Review Letters, Non-Linear Dynamics in Tumor Processes and Fractal Dimension and Temporal Evolution of the Neurons in the pages of Spanish VIII Meeting on Statistical Physics.
In 2003, informs his work in The Universal Dynamics of Tumor Growth (Biophysical Journal), which applies the theory MBE (Molecular Beam Epitaxy) to the universal dynamics of tumor development. His articles are discussed favorably in publications of the American Institute of Physics and the important The Lancet Oncology. In our country receive the Badge of Honor AEC 2000 of the Spanish Association of Scientists.
As to the form of dissemination of tumor to healthy tissue, and from the microscope images, extracts the following interpretation: the tumor does not invade healthy tissue and then destroyed, as stated in the official oncology. Actually proceeds in reverse, first destroys healthy tissue by a biochemical attack and then took the empty space that has been:
The tumor attack vectors use two main
- The high tumor metabolism generates large amounts of lactic acid. The environment surrounding the tumor is therefore a very low pH and guests healthy cells are adversely affected.
- Tumor cells produce powerful enzymes whose function is to degrade normal cells.
The theory MBE (Molecular Beam Epytaxi), developed in the sixties, it serves to explain a sudden physical movement observed by the author in the outer cells of the tumor. Which, to differentiate themselves as individuals, migrate across the boundary between tumor tissue itself and the sound reaching the inner part of the roughness of the tumor. This will pose some questions broadcaster interesting:
- Why these cells do not remain in the outer parts, where they have more oxygen and more nutrients?
- What compensation are in this new location?
His interpretation of this phenomenon is that the main compensation lies in the physical space to develop, not to biological factors, since it is in these internal cavities where the space is more abundant, being safe from the tissue pressure does affect healthy convex parts. However, even if less important, it also recognizes the fact that collected here is where the new cell is surrounded and protected by the maximum like, and where the body's defenses (white blood cells) penetrate harder.
Another of their performance relates to why they fail chemotherapies such a high percentage. In reality, these drugs based its action in an attack on cells that are proliferating. Naturally, if we listen to classical theory, they represent the whole tumor cells, and therefore should be affected in depth. Experience however shows that chemotherapy often affects only the border cells and although they often get destroy once treatment is completed, wakes up the second layer of cells (something like an orange if you take off the skin, but soon the inner pulp create a new one) These cells are reactivated in a very good position to grow, with organic defenses itself degraded by chemotherapy and with a good gap between them and the host tissue. In this way, would not be unusual cases that shortly after finishing a session with these treatments, the tumor regrowth with greater virulence.
Established hypotheses, Bru and his team to reflect a strategy to prevent malignant cells to find shelter and space they need to reproduce. Ultimately decide to try neutrophils, one of five types of white blood cells that make up the defenses of our body and which are created naturally in the bone marrow.
Neutrophils, also called granulocytes, white blood cells are more abundant, in a proportion ranging from 55% to 75% of the total. Are phagocytic cells, which carried by our alert system through the bloodstream, attack and destroy germs that invade us, for example, by making us a cut on one hand (in fact, caused swelling around a wound is caused by these cells, and represents the struggle we are having with the invasive component).
Bru's team poses a clinical trial with mice, twenty in total, which are injected with Ehrlich tumor in one leg. Subsequently, it is found that the tumors are growing, are separated into two groups: one control, four individuals who were not carried out any treatment, and the remaining sixteen, who are given a dose of 10 micrograms per kilo of body weight per day of GM-CSF (Factor Building granulocyte-macrophage colonies).
After fifteen days, sacrificed six of the treated mice to analyze their tumors. The rest continued on treatment until eight weeks. In the end it is found that in eight of these tumors have decreased in size between 80 and 90%, and the other two, the tumor had complete remission (although this step is largely subjective interpretation, since the mouse model used yields many methodological concerns.)
Under the microscope, the researchers tested as the tumors are completely surrounded by neutrophils, which hold up well in the acidic environment and fill all holes of the roughness, preventing proliferation of cancer cells in physical space are required. It is shown that by being embedded within their progenitor cells and neutrophils, at fourteen days begin to die. Another interpretation is that the very pressure created by the growth of tumor causing anoxia in the innermost parts of the fabric, which also eventually necrotic.
His interpretation is that our own innate defenses attack the cancer cells (this again is not only novel as is sometimes understand. It is known long ago that the innate immune response attacks the tumors, but it is known that the same have mechanisms to evade these attacks). They interpret the problem is that such defenses, for various reasons, are being overwhelmed in their ability to react. This is when the tumor starts to grow uncontrollably.
This essay is published in Physical Review Letters (again a physical magazine) in June 2004 with the title of Tumor Growth by Pinning Enhancement of the Immune Response.
After these results, on two occasions, clinicians come into contact with Bru for a trial in two human patients. This will get two separate permits AGEMED (Spanish Agency of Medicines), which authorizes such action by the Compassionate Treatment procedure for humanitarian reasons.
The patients are a 34 year old woman with stage IV melanoma, who despite not having even poorer quality of life, the short-term forecast is very pessimistic. The second is a man of 56 with liver cancer of 9.5 cm. in diameter, with complications of liver cirrhosis and hepatitis B. Is always in bed with severe pain and quality of life so degraded. In short, both cases were hopeless and irretrievable, with a life expectancy of a few months.
During treatment, both are given the same dose of 10 micrograms per kilo of body weight per day. In this case, use G-CSF (Neupogen, Amgen Laboratory), virtually unchanged from the product used with mice, but more specifically in the creation of neutrophils (and most recommended in the case of liver disease).
Doses, the researchers said, are well tolerated by patients, and the two months that the treatment only once must decrease to maintain the neutrophil count below 60,000. The HCC patient benefits apparently changed dramatically. The tumor markers AFP (alpha fetoprotein, which is a very specific marker in some patients) normal value in a healthy person is less than 10 ng / ml, low of 453 it had at the beginning of treatment, up to 4.7 to 10 weeks.
Subsequent scans with MRI (magnetic resonance imaging) and biopsy by fine needle aspiration, show a significant change. The tumor tissue is gone, replaced by a small cell dysplasia, not malignancy.
The two people were treated to rejoin work. The latest news (a year and a half ago) is still without symptoms or side effects and consistent with all normal. Consequently, the final report is that "could have been healed" (in these cases is to say "might" because a definitive cure cancer is supported only after 5 years).
In May 2005, Bru team published the results of the remission of hepatocarcinoma in the Journal of Clinical Research (the case of melanoma has never been published, official knowledge, news or developments.) Some journalists write articles about Bru, who is also interviewed on television. He does not say at any time to "cure cancer" but that this experience opens a new and promising research in its opinion, and the need to continue with more resources, and offers its cooperation to all levels of the fight against this disease. Da within approximately two years so it can be applied generally, as a treatment protocol. It also calls for calm, saying he understands the urgency of those whose disease is in an advanced state, but they must follow scrupulously the regulatory channels.
Is the outright rejection of the group of oncologists:
- A publication of a single case ... not valid ... there may be errors in the x-rays ... (Dr. Cubedo, University Hospital Puerta de Hierro).
- If the result was spectacular would have appeared in a magazine more upscale ... this drug is already used and have never noticed antitumor effects ... if he is right, hypertensive patients have a lower rate of cancer ... (Joaquín Arribas, Head of the Vall d Cancer Research 'Ebron)
- Lack of credibility ... should do an audit ... (Eduardo Díaz Rubio, Chief of Medical Oncology, Hospital San Carlos)
- Case striking ... no longer a theory ... (Josep M. Borras, Catalan Institute of Oncology)
- We must ensure that no misleading the cancer patient ... no longer a story ... find out if this gentleman has asked the bureaucracy required to carry out a clinical trial ... there are no safety data at these doses of G-CSF (Antonio Antón, the SEOM, Spanish Society of Medical Oncology) The World health supplement, May 31, 2005
- The Strange Case of Dr. Bru ... it is irresponsible to jump to treat patients without sufficient evidence ... his team includes family and friends ... creates false expectations in patients ... (journalist Alejandra Rodriguez) World Health Organization, June 4, 2005
- I dread to see the desire to produce a reputation of a person ... is nonsense ... (Ricardo Cubedo) World Health Organization, June 9, 2005.
- Lack of seriousness alleged healing ... ... a case of spontaneous remission have been orthodox ... no ... the medical journal that published the result was a category ... you may not be cancer, but two cases misdiagnosed ... (Antonio Antón ) The World health supplement 620.
Antonio Bru, at first, try to ignore the criticism and continue working, but check as these statements are closing doors, decides to refute:
- Show legal permits compassionate treatment of AGEMED (Spanish Agency of Medicines), pertaining to the two cases cited.
- Explains point by point his theory of Universal Dynamics of Tumor spread copies of published papers in scientific journals.
- Introduces its entire team, consisting of twelve people, who include physicians, microbiologists, analysts, etc ...
- Explain that if the cancer had been misdiagnosed, it would actually be the fault of the oncologists and the hospital pathology service. Which can also be argued in the case of healing with chemotherapy. In any case, they argue that both the melanoma and the MRI and the patient's liver biopsies were obvious and offered no room for confusion.
- Accept that there are spontaneous remissions, but statistically they represent one in every 60,000, and therefore is highly unlikely that they had no case but two, followed with the same result.
- The drug Neupogen is used since 1991, but only to recover the normal defense level after chemotherapy (dose at which no anti-cancer effects), and never produce the intense neutrophilia underlying the treatment of Bru. The patients tolerated well the dose without significant side effects during the two years. In any case, the Neupogen is also provided to children with congenital neutropenia at higher doses and durations, and no cumulative effects were observed.
- High blood pressure has nothing to do with the pressure at the interfaces of tissues, because it only occurs inside the blood vessels.
- The publication of the case of hepatocellular carcinoma was made in the Journal of Clinical Research simply because other more circulation magazines have waiting periods of several years publishing, apart from charging high amounts for each published page. Some funds that no Bru team walked on. In any case, argues that it is childish attempt to discredit the content to attack the continent.
- If you have started publishing a case is because there is always one that is first. Naturally, it would have been unconscious trying to start three hundred people at once. He argues that before it had just 15 hits in tumors in vitro, of various types, and 10 in laboratory animals (100% of patients).
Antonio Bru repeated again and again that he is willing to sit down with anyone to discuss in scientific terms, and to repeat each and every one of the steps taken so far with independent oversight.
Understood not to be such a radical opposition, but believes that the huge multinational pharmaceutical business, with 12,000 million euros involved in cancer treatment with current therapies (many of which are of doubtful efficacy) can reach to influence many wills.
Explains the life cycle of a drug, the cost of research and those needed to be validated by health authorities can reach amounts up to 500 million euros, and this investment must be recovered in a few years of life commercial. It is therefore not surprising that nobody is interested in the Neupogen, which appeared in the Spanish market in 1991 and whose active ingredient is on the verge of losing the patent to become generic, leave the very expensive obsolete current chemotherapies, or those who are about to be authorized.
Bru says, half jokingly, half seriously, that his problem has been to propose a very simple and inexpensive treatment, if this were complex and expensive probably not receive many objections.
In another order of things must be said that, as of this moment, both the professor and his assistants have to endure a warning followed and coercion. His main collaborator, Dr. Sonia Albertos digestive specialist also forced to leave the Hospital because the expiration of his contract was not renew it. Some partners are quietly away from them to avoid falling victim to the same repression.
After these successful tests, the team's intention is to keep trying Antonio Bru other terminally ill patients of other types of cancer, since according to the physicist, having shown that all solid tumors have the same dynamic of growth, Neutrophil treatment should be effective for any of them (Bru recognize a possible exception in brain tumors, since being an organ enclosed in a bony case, the local inflammation produced by neutrophils might be counterproductive).
However, from this moment, despite the good results obtained, the Spanish Medicines Agency change of attitude and takes the same ruling party that oncologists, denying them any permission to treat terminally ill patients, even the same cancer Experienced.
Researches The team insists. The agency has moderated its refusal, saying that it will consider issuing permits for melanoma and hepatocellular carcinoma if they are requested by their physicians, but does not intend to authorize a treatment for other cancers.
Since then, they have granted sparingly. Some of these patients had a life expectancy so small they have soon begun, without being able to see the results. The reports that the agency delivers to the terminally ill after refusing treatment include arguments like:
- The idea underlying the treatment is far from those accepted in oncology.
- There is only one case study and no conclusions can be drawn.
- Not sure of the quality of life that can lead to treatment for terminal patients.
Dr. Bru now works as Associate Professor in the Department of Applied Mathematics Faculty of Mathematics, University Complutense of Madrid. Thanks to the efforts of the University designed a clinical trial with 25 patients with terminal liver cancer of Ramón y Cajal hospital. The group of Professor Bru passed twice by the Ethics Committee of the hospital without obtaining approval to begin testing. Later, the professor believes that there are no guarantees necessary for carrying out the experience, and decides to withdraw the offer to the hospital (http://www.mat.ucm.es/ ~ abruespi /).
Regarding the dissemination of its research. Once past the short interest in July 2005, the major media seem to have forgotten the news about his case, but one of the largest national daily newspapers regularly published articles contrary to Bru, in they just seem to take place the voices of his detractors.
For its part, the researcher followed by a hectic schedule disclosing, lecturing in many Spanish cities. At this time, oncologists associated with the SEOM (Spanish Society of Oncology) contact with the organizers to try to annul such acts. There is also evidence that other doctors of different specialties, have been threatened with directives from authorities not renewing their contracts if they collaborate with Bru or attend their events.
- On October 21, Antonio Bru is invited to the Congress and Breast Pathology Senology Ourense, with 200 other specialists. However, since the SEOM is vetoed again your participation and Bru conference has to be postponed a few hours after the conference closed, when oncologists have already left (the story appeared in La Voz de Galicia for 22 - 11-2005).
- The next day, 22, delivers another conference in the city of Mahon, invited a sociation of suffering from breast cancer. In the audience that crowded room full of City Hall, there are only two doctors.
- On November 4, the College of Pharmacists of Alicante Bru invited to lecture. The SEOM acts trying to cancel it again. Fails.
Antonio Bru and his top aides continue to progress in their investigation, however, the implementation of their treatment in hospitals has fallen to a minimum. The Spanish Medicines Agency has warned that only grant permission for compassionate treatment for primary liver cancer, melanoma (two types in which he allegedly had some previous experience). In addition, even patients with these conditions often face the almost insurmountable problem that most of their own oncologists refuse absolutely to take the petition.
In early April 2006, the deputy Isaura Navarro, ask the Congress to the Minister of Health on the implementation of therapy Bru. The minister answered once again with the official position of the AGEMED, which will not endorse or promote this treatment because they say that the physicist has never delivered some documents that were asked at the meeting that the agency had with him (Antonio Bru denied categorically that at no time have any documentation requested, on the other hand, by regulations do not require anyone to grant compassionate treatments), and adds the minister to his reasons the fact that there are no clinical trials to support it.
Some patients began a difficult search to procure the Neupogen abroad, and to apply the treatment outside the formal health sector. To do this will require at least the help of a doctor to check the level of neutrophils and the general trend. Optional, having regard to the circumstances of radicalization that emanate from their own environment, are exposed to suffer serious labor problems.
Since the initial outbreak, attention to this work has been diluted, primarily due to the lack of progress in the investigation (slow by necessity) and the absence of news about the outcome in the various uses compassion and treatments performed. Many conferences and many treatments later (in many cases no satisfactory poachers known), this work seems to have decreased, as in many other occasions, academic limbo with a curious and original mathematical model apparently without the proposed therapy is otherwise likely to be effective.
