Zebrafish, or Danio rerio, is a freshwater fish which lately has become the most used animal model for laboratory studies in the world, thanks to its particular characteristics. At specific times of the growth of Zebrafish embryos, it is possible to obtain, using sophisticated techniques, an entire epigenetic code capable of reprogramming human cells and differentiating them.
The latest scientific discoveries have highlighted and clarified the biochemical mechanisms controlling cell proliferation and differentiation. While the four transcription factors Oct4, Sox2, Klf4 and cMyc have shown to be sufficient to induce pluripotency in fibroblasts, there has in addition a lot of research studying the mechanisms of cell differentiation and the specific properties of stem cells, in particular their plasticity and capacity for trans-differentiation.
These researches have been fundamental in the field of reparative, regenerative and transplant medicine. In fact the genetic engineering production of regulatory factors identified through such research, has allowed the production of new tissues and a new category of cell therapy products, in which the main biological action is carried out by cells or tissues, even if in the presence of organic or inorganic matrices or coatings. Examples of this type of product are in vitro cultivated skin, products made of cellular elements for the reconstruction of bones, cartilages, teeth, etc. Even more important is the fact that a very analytical and detailed characterization of stem cells allowed the comprehension of tumor cell behaviors, that have a crucial role in determining their malignancy.
The malignant behavior of cancer cells can be attributed to the presence of cells with characteristics similar to those of stem cells. As consequence cancer research have been conceived to identify the metabolic pathways common to tumor and stem cells. This will in turn cast light on which micro-environment factors can direct these pathways towards differentiation and induce tumor cells to behave less aggressively.
Recently there has been a lot of studies which were very important to understand the role of embryonic micro-environment in controlling tumor cell behavior and to revert cancer cells towards normal phenotypes. This research is now underway, and they represent the main subject of this website.
New Paradigm in Medicine
It is important to note that research into the possibility of reprogramming cancer stem cells needs a complex approach to the issue. In fact, the problem requires the study of networks of substances and genes involved in the reprogramming phase, demanding skills in a variety of different areas of research, not simply of medical/biological, but also mathematical and modeling, in view of the complexity and non-linearity of the processes being studied.
This means to change the scientific paradigm and shift from reductionism that studies only single molecules or single mechanism to complexity, as described in the article about the new paradigm in medicine.
The future will witness our engagement in increasing numbers of scientific studies requiring a complex vision of life.
New Paradigm Medicine
Conventional medicine uses chemotherapy and other treatments to kill the damaged cells.
Whereas, in this new medicine, malignant or dysfunctional cells are reprogrammed rather than killed.
Without adverse side effects.
a) morular stage, characterized by merely multiplicatory events and therefore made of totipotent embryo stem cells,
b) medium-blastula/gastrula (50% epiboly), where the totipotent embryo stem cells differentiate into pluripotent ones,
c) five somite stage and
d) 20 somite stage, where important differentiation events, characterizing the intermediate and final embryo differentiation, take place.
All cancer cell lines have shown a significant slowdown in the growth curve when treated with factors drawn during the above-mentioned cell differentiation stages, with inhibition percentages ranging from 73% of the glioblastoma and 26% of the melanoma.
Objective tumor response median overall survival and performance status have been evaluated. Results showed a 19.8% patients who experienced a regression and 16% patients who experienced a stabilization with an overall survival of more than 60% of responsive patients after 40 months, against 10% of non responsive ones.
A wide improvement of performance status has been registered in a great majority of patients (82.6%).
Pier Mario Biava, an occupational doctor, graduated in Medicine at the University of Pavia, specializing first in occupational medicine at the University of Padua and later in hygiene at the University of Trieste. He has been studying the relationship between cancer and cell differentiation for several years: he has isolated stem growth and differentiation factors that can inhibit or slow down the growth of various types of human tumors and, in general, direct the fate of normal and pathological stem cells. This is of a significant importance in the field of prevention and treatment of various types of diseases such as chronic degenerative diseases, as well as in the field of regenerative medicine in renewal and regeneration of tissues. This research can also have positive effects in the field of integrative treatments of stem cell transplants and, in the future, may even replace them.
Having been a Professor at the School of Specialization in Occupational Medicine in Trieste for many years, he currently works at the Institute of Research and Treatment Multimedica of Milan.
He is the author of over 100 scientific publications and several books such as: ” L’Aggressione Nascosta – Limiti Sanitari di Esposizione ai Rischi ” published by Feltrinelli, ” Complessità e Biologia” published by Bruno Mondadori and ” Il Cancro e la Ricerca del Senso Perduto” published by Springer,” Il Senso Ritrovato “edited by Ervin Laszlo and published by Springer and “Dal segno al simbolo – The manifesto of the new paradigm in medicine” written with Diego Frigoli and Ervin Laszlo and published by Persiani.
He also takes part in the Scientific Committees of several international journals in the field of oncology and epidemiology.
Scientific responsible for formation of the occupational health service in South America founded in Quito from 1984 to 1990
Member of the WWF Italia Scientific Committee from 1986 to present (still in office), Vice President WWF Italy 2006 -2009
Member of the CDA Unicredit Foundation from 2002 to 2005 where he leaded planning of all health cooperation interventions in Africa.
Dr. Pier Mario Biava on Telomeres:
“Telomeres get shorter each time the cells divide. When the telomere becomes too short, the chromosome reaches a critical length and the cell can no longer replicate. This means that the cell ages and dies. However, GROWTH and DIFFERENTIATION FACTORS can be a very effective tool to promote cellular senescence antagonists in a physiological way. The result is a healthy cell and potentially an inversion of the aging process”
TELOMERS are essential parts of human cells that influence the way we age. Telomeres represent sort of a “cap” of DNA that protects cells from errors during their replication. Over time this hood tends to shorten and lose its protective properties. Thanks to the factors of Zebrafish this problem can be prevented by preserving telomers.
5 PHASES OF CELLULAR DEVELOPMENT
It helps the stem cells to grow and reproduce
are only of differentiation, thus of physiological programming
LASZLO: " Biava and I had a very different starting points.
Biava started from trying to find a cure to cancer,
and I from trying to see what fundamental insights
underline current findings in the sciences.
At the end we reached the same conclusions:
BIAVA: "Cells communicate with one another
by using codes of meaning:
this is true in a literal and not in a metaphorical sense"