Wednesday, 21 March 2012

Reverse Warburg Effect and Breast Cancer Biomarkers

I have written before about Michael Lisanti’s ‘reverse Warburg effect’ theory, and interviewed one of Lisanti’s collaborators in the UK, Dr Anthony Howell of the Christie Cancer Centre in Manchester. Briefly, the theory states that tumour cells ‘cannibalise’ surrounding tissues by creating highly oxidative conditions which force non-cancerous cells into metabolic states that produce nutrients that the tumour cells feed on. This is in contrast to the ‘classical’ Warburg theory, which states that it is the tumour cells which switch metabolic states.

This new theory radically over-turns the conventional view of tumour metabolism and makes a number of predictions which have direct clinical relevance. It also suggests that the traditional explanation of the Warburg effect is due in part to the in vitro models of cancer that have been used – in other words it’s due in part to scientists having the wrong models of cancer to play with. In the test tube isolated cancer cells do exhibit the ‘classical’ Warburg effect as they adapt to those conditions, but in real tumours the conditions are different and evolutionary pressures leads to this ‘reverse Warburg effect’.

While all of this might be of academic interest to the research scientist, does it have any relevance to the patient or the clinician? And the answer is that yes it does, in two distinct ways. The first is the new theory makes some specific predictions on how tumours behave and on how they interact with the surrounding tissues. In particular the theory suggests some new biomarkers that can be used to identify patients at high risk of early breast cancer recurrence, metastasis, drug and hormone resistance and decreased survival. Secondly, and linked to the first point, the new theory suggests some interesting new avenues to explore for treatment.

In a new paper, Lisanti and his team examined tumour samples from 180 triple negative breast cancer patients looking for specific markers related to his theory. The results of tissue analysis showed that having high levels of MCT4 (a marker of hypoxia, oxidative stress and aerobic glycolysis) in the tumour stroma (the cells that surround the tumour) was highly related to a decreased overall survival rate. This is a significant finding, being able to identify those patients at highest risk is vitally important.


Furthermore, based on the theory and supported by these and other results, there are suggestions that interfering with the reverse Warburg effect can have direct therapeutic benefits. In this latest paper, Lisanti and colleagues list a number of existing drugs that should be explored, including the anti-oxidant N-Acetyl-Cysteine (NAC), the anti-diabetes drug Metformin (and there is already lots of evidence for the anti-cancer effect of this) and Hydroxy-Chloroquine.

This latest paper adds to the growing number of studies that support the new theory, and which are pointing more and more to direct therapeutic benefits.

What we need to see now, as a matter of priority, are the clinical trials necessary to prove that the theory is correct and that the proposed therapies show benefit to patients.

The new paper, fortunately available on open access, is available here: http://www.landesbioscience.com/journals/cc/article/19530/

2 comments:

  1. Warburg, Virchow, Suss, Shapoval and Ferromagnetic Theory of Cancer. German scientist Otto H. Warburg argued, cancer should be interpreted as a type of mitochondrial disease. German pathologist Rudolph C. Virchow remarked that no man, even under torture, could define cancer. German cancer researcher Rudolf Suss (R. Suss; V. Kinzel; J. Scribner; Cancer: Experiments and Concepts / Krebs: Experimente und Denkmodelle; Berlin, Heidelberg, New York, Springer, 1970) described oncology as impassable jungle of incomparable facts and ideas; as an ocean of information. Biblical scientist Vadim I. Shapoval argues, cancer and ALS should be interpreted as intracellular superpara-ferri-ferromagnetic infections. Any human cell should be interpreted as a society of dia-, para-, superpara-, ferri- and ferromagnetic nanoparticles. These nanoparticles have certain local magnetic contacts. Any human organism consists of normal cells (cells with non-numerous superpara-, ferri- and ferromagnetic nanoparticles) and tumor cells (cells with numerous superpara-, ferri- and ferromagnetic nanoparticles). Cancer Mortality Statistics: one in three people develop cancer during their lives; over one in four people die from cancer. Intracellular molecules FeO;Fe2O3;Fe3O4 are the main ‘creators’ of intracellular superpara-, ferri- and ferromagnetic nanoparticles that can chaotically distort DNA and shift chromosomes (by local magnetic fields). Cancer is not a genetic disease. Cancer is not disease caused by errors in DNA. Oncologists must beat cancer (an iron disease) by non-complicated anti-iron methods of The Old Testament. Anti-iron intratumoral injections [sulfur (2%) + olive oil (98%); 36.6C - 39.0C] (by ceramic needles) can suppress tumors and large metastases. Anti-iron accurate slow blood loss (even 75%) [hemoglobin control], anti-iron goat’s milk diet and anti-iron drinking water containing hydrogen sulfide [many metal ions react with hydrogen sulfide to give the corresponding metal sulfides] can neutralize any micro-metastases. Medical News Today explains molecular biological and clinical aspects of the Ferromagnetic Theory-2006 of Cancer / Carcinogenesis / Oncogenesis / Tumorigenesis (Iron Conception) http://www.medicalnewstoday.com/opinions/38197/ ; http://www.medicalnewstoday.com/opinions/69048/ ; http://www.merriam-webster.com/dictionary/oncogenesis ; http://www.mesorfa.org/oncologist/ ; http://www.knowledgerush.com/kr/jsp/db/board.jsp?id=81643 ; http://www.anticancer.org.uk/2012/03/reverse-warburg-effect-and-breast.html ; Vadim Shapoval

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  2. CHROMOTHERAPY IN CANCER
    "Chlorophyll and hemoglobin, pigments life, porphyrin structure, differ only by the green chlorophyll, due to the atom of magnesium, and red hemoglobin, due to iron atoms in the structure - PROOF OF ORIGIN COMMON LIFE". (HEILMEYER)
    "Duality of cytochrome-oxidase. Proliferation (growth) and Differentiation (maturation) cell." Cytochrome-oxidase is present in two forms, depending on the context of acid-base internal environment : 1.- Form acidic (acidosis), which contains two Iron atoms, will be red, will absorb the additional green energy of the hydrogen atom, derived from carbohydrates, with formation of H2O, metabolic context that will promote cell proliferation. 2.-Form alkaline (alkalosis), containing two copper atoms, will be green, will absorb the additional red energy of the carbon atom, derived from carbohydrates, with formation of CO2, metabolic context that will promote cell differentiation. Cytochrome-oxidase structure has two atoms of copper. It is known that in conditions of acidosis (oxidative potential), the principle electronegativity metals, copper is removed from combinations of the Iron. So cytochrome oxidase will contain two atoms of iron instead of copper atoms, which changes its oxidation-reduction potential, but (most important), and color. If the copper was green, the iron is red, which radically change its absorption spectrum, based on the principle of complementary colors. Normality consists of alternating the two forms of cytochrome oxidase by successive passage of acid in the alkaline form, in terms of acid-basic balance maintained within normal limits.
    I SUGGEST TO YOU AN EXPERIMENT : TWO PLANTS, A RED LIGHT ONLY, IN BASIC MEDIUM, WITH ADDED COOPER, WILL GROW, FLOWER AND FRUIT WILL SHORT TIME, AND THE OTHER ONLY LIGHT GREEN , IN AN ACID MEDIUM, WITH ADDED COOPER CHELATOR (CUPRENIL) , WHICH GROWS THROUGHOUT WILL NOT GROW FLOWERS AND FRUIT WILL DO.

    CULTURE OF NEOPLASTIC TISSUE IN A GREEN CONTAINER OR IN A COLOURLESS CONTAINER, IRRADIATED WITH MONOCHROMATIC GREEN LIGHT, IN AN ALKALINE MEDIUM, WITH ADDED COOPER, WILL IN REGRESSION OF THE TISSUE CULTURE.

    CULTURE OF NEOPLASTIC TISSUE IN A RED CONTAINER, OR SINGLE IRRADIATED WITH RED LIGHT, IN AN ACID MEDIUM, WITH ADDED COOPER CHELATOR (CUPRENIL), WILL LEAD TO EXAGERATED AND ANARCHICAL MULTIPLICATION.
    According to the principle electronegativity metals, under certain conditions the acid-base imbalance (acidosis), iron will replace copper in combination , cytocromoxidase became inactive (it contains two copper atoms) leading to changing oxidation-reduction potential, BUT THE COLOR FROM BLUE-GREEN, TO REED, to block the final biological oxidation and the appearance of aerobic glycolysis. In connection with my research proposal, to prove that the final biological oxidation, in addition to an oxidation-reduction process takes place and a photo-chemical process, the first in the electron transfer, the second in the energy transfer. A body with cancer disease will become chemically color "red",ACID (pH, rH, pCO2, alkaline reserve ), and in terms of energy, "green" (X-ray). A healthy body will be in terms of "green",Alkaline (as evidenced by laboratory), and in terms of energy, "red" (visible by X-body-colored-ray). Sincerely yours, Dr. Viorel Bungau

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