Beat Cancer Save Life

According US National Cancer Institute (http://www.cancer.gov/cancertopics/causes), food, diet, weight and physical activity are related to cancer. Change lifestyle cuts cancer risk. The New York Times reports some cancers can vanish without treatment (http://www.nytimes.com/2009/10/27/health/27canc.html). Based on our laboratory result and scientific evidences, using the biology inside of our body will stop cancer, and save lifes. Stop Cancer What is Cancer? Cancer is the uncontrolled growth of abnormal cells in the body. Cells are the building blocks of living things. Most cells in our body do not divide, but perform certain functions, I define them as normal functional cells, after service for a while, they die, such as skin cell, red blood cell, etc. There are proliferating cells, which divide and some become (differentiate to) normal functional cells, when the body needs them, they do not multiply when there is enough normal functional cell. Cancer appears to occur when the proliferating cells continue multiplying in the body without becoming normal functional cells. There are many kinds of cancers in almost any organ or tissue with different symptoms, such as the lung, colon, breast, skin, bones, or nerve tissue. Cancer cells are cells in our body. Before cancer is detected, cancer cell could exist in our body for very long time. Many dead people from other diseases without detection of cancer had cancer through posthumous analysis. To stop cancer, we need to distinguish cancer cell from normal functional cell and normal proliferating cell. What cancer cells have differences from other cells? Cancer cells multiply without differentiate. Normal functional cells do not divide. Cell division is difference between cancer cells and normal functional cells. How about normal proliferating cell? The difference between cancer cell and normal proliferating cell Both divide. Normal proliferating cell divides to produce missing normal functional cells, and stop to divide after producing enough normal functional cells to replace the missed. The difference between them is differentiation. Normal proliferating cell differentiate after divide, or switch to dormant. Cancer cell does not. Cancer cell continues to divide to produce more and more without doing any repairing. Those useless cells compete nutritional resource, produce large quantity of lactate acid, and damage surrounding normal cells. Besides the outrage division, the difference also includes: Morphology (pathology under microscope), which is classified by ICD-O code. Genome, in general, there is less than 0.1% difference in genome between cancer cell and normal functional cell. What is the genomic difference of cancer cell and normal proliferating cell? I need new research to show the result. Cell is structured with DNA, RNA, Protein, Lipid, Carbohydrate, Water, etc. Protein is one of the most important molecules in the cell to participate very complex biochemistry reactions. Protein is synthesized according to genetic code, DNA. Gene can influence cell biology only when the gene is active, RNA and protein are synthesized, and changing biochemistry occurs. The difference in genome results in different biochemistry reactions. Since cell has very complex biochemistry reactions, most of the differences are hardly detective, also not significant for a cell's life. Many biochemistry pathways need precious evaluation of its roles and functions for cell or cancer cell survive. In general, besides the differences above, all cancer cells of all cancer types are very similar to their normal proliferating cells in genome, morphology, and biochemistry pathways. Also cancer cell can be dormant in the body for years. To survive, cell needs fuel to produce energy. Energy generation pathway is fundamental biochemistry pathway for all living cells. Without it, no cell can survive. In 1920’s, Dr. Otto Warburg and his research group first observed cancer cells use fermentation for energy efficiency, other than respiration, which produces CO2 and water (reference:1-6). Cancer cells get their energy through fermentation (Glycolysis), other than respiration (Oxidative Phosphorylation). This is the fundamental difference of cancer cells from other cells. Lactate fermentation is the hallmarks of cancer cell (reference 7-10). Normal functional cells get their energy mainly through respiration. Normal proliferating cells depend on fermentation to divide, but switch to respiration after division during differentiation. Cancer cells stick to fermentation. Heiden, et al. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324, 1029 (2009). Normal cell can live with lactate fermentation or oxidative respiration according to its living environment, and switch to one or the other, as it needs. Both cancer cell and proliferating cells mainly depend on lactate fermentation to divide, i.e. the high ratio of fermentation to respiration is essential for cell division. When the respiration goes up, normal proliferating cells stop divide and begin to differentiate to normal function cell or stay dormant. Cancer cells stick with fermentation without increasing the respiration pathway. Regulation and Control of Fermentation and Respiration. Glucose is the universal fuel of human body. Usually, glucose is break down in glycolysis to pyruvate, and pyruvate participates respiration, and is break down to carbon dioxide and water. Respiration occurs in Mitochondria through tricarboxylic acid cycle (TCA cycle, or citric acid cycle). Mitochondria are the main powerhouse of cells in our body. Normal cells have function mitochondria, respiration can be regulated, and cells go through regular life cycle. Cancer cells have mitochondria defects/dysfunctions. Mitochondria respiration is blocked. Then, cancer cells continue to divide. Cells obtain energy through fermentation when it is lack of oxygen. Cancer cell and normal proliferating cell have fermentation for cell division with oxygen present, aerobic glycolysis – Warburg Effect. Increasing cellular respiration will stop cell division, and inhibit cancer. The fact that cancer cells switch to glycolysis and consume more sugar has be used in positron emission tomography (PET scan), a medical imaging technology that enables doctors to visualize the human body's metabolism and identify cancer. Warburg effect is the fundamental and generic phenomenon of cancer. Cancer cells are developed through years genomic and biochemistry changes. The changes in genomic and biochemistry are different from cancer type to cancer type, from patient to patient. Mitochondria are regulated by both nuclear and mitochondria DNA. When defects/dysfunctions occur, it is very hard to be regulated. This is also the reason for failed effort to develop drug to target pathway. Mitochondria Respiration and Cytosolic Respiration Cancer cell has very weak respiration because of mitochondria defects/dysfunctions, or because cell division suppress mitochondria functions. Improving respiration will stop cancer. Figure: Summary of published interactions of mitochondrial metabolism and cancer growth is reffered from Oxidative Metabolism in Cancer Growth. Ristow M. Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):339-45. Review. In cancer cell, pruvate is converted to lactic acid. For mitochondria respiration, besides pyruvate, ketone body from fatty acid oxidation, amino acid from protein, malate, valine, etc. also can be the substances of mitochondria respiration. Increasing those substances will increase mitochondria respiration of the cancer cell, and stop cancer. But if mitochondria function is suppressed by cell division, we need other way to increase respiration. Cell is filled with cytoplasm. Mitochondria are organelles embedded in cytoplasm. Beside mitochondrial respiration, is there Cytosolic Respiration? Bacteria have no mitochondria. Respiration is conducted in cytosol, cytosolic respiration. Does human cell lose the ability of cytosolic respiration? Based on current evolution theory, human cell does not lose cytosolic respiration ability, but it is shadowed by mitochondria respiration. Increasing mitochondria respiration or cytosolic respiration will stop cancer. Stop Cancer Fermentation and respiration are the universal biochemistry pathways in all of human cell, except red blood cell, which is lack of mitochondria. Fermentation and respiration are the fundamental, basic biochemistry pathways in all of human cell. Without fermentation and respiration to provide energy, no human cell can live. Instead of change cancer cell, to increase respiration, the best way is finding the best substance for respiration of cancer cell. Tetrose (C4H8O4) is a monosaccharide – a sugar, including erythrose, erythrulose, and threose; which has 2/3 of weight of glucose. Glucose (C6H12O6) is universal fuel. Erythrose has very similar structure (line or circle) as glucose. Also tetrose is very close to ketone body from fatty acid oxicidation. Tetroses are discovered having strong anti-cancer effect. Among tetroses, D-erythrose is the best anti-cancer agent in tested tetrose (reference). In vitro, 3-4mM erythrose effectively kills cancer cells for tested cell lines such as: lung cancers, breast cancers, colorectal cancers, etc; higher dose is required for some other cancer cell lines, liver and prostate. In mice model test, although there are significant in inhibiting tumor growth, the expected results have not be achieved since it is hardly to maintain erythrose concentration in the mice, because erythrose can be digested very fast, and make the concentration below the effect concentration. Can we provide our body, or body part, with efficacy dose of erythrose to kill cancer? Erythrose exists in human body by participating pentose phosphate pathway. Erythrose can be used as cellular fuel and the final products are carbon dioxide and water (Batt et al. 1960). Tetrose digestion process is very rapid. Maintain effective erythrose around tumour is challenge for the success of the solution. Toxicity of erythroluse, an isomer of erythrose, tested by Australia Government Agent (NICNAS) shows acute oral lethal dose 50 is more than 2g/kg body weight in rat. The toxic is very low. The effective erythrose concentration that kills cancer is about 10-40% of the glucose concentration in people with diabetes (up to 30mM glucose), or 20-40% of the ketone bodies concentration during fasting (up to 15mM ketone body), or similar to lactate concentration after exercise (4mM lactate). Most cancer cell lines die in normal culture media with 3-4mM erythrose. As long as we can provide the condition to tumor in human body, the tumor will be destroyed. Experiment with normal proliferating cell lines (human dermal fibroblasts and human umbilical vein endothelial cells) shows that erythrose has similar effect on cell proliferation and viability as glucose. Preliminary result also shows that erythrose initialize normal proliferating cell line differentiation. The sugar property, nutritional value, and easy distribution in mammals are ideal to treat human cancer rather than traditional cytotoxic agents. Erythrose has far advantage in molecule structure, metabolism pathway, toxicity, and mammal acceptance than any other molecules. As all mammals metabolize sugars in same pathways, it can be used to treat all types of cancer. Erythrose has great potential to treat human cancer. The side effects could be as short-term diabetes, manageable and reversible. Note: Cell line experiment, MTT or MTS assay (the most commonly used methods in research labs, which is read by machine) is interrupted by erythrose. You should use Trypan Blue assay (the original human detect method). If you want to know the best condition to destroy cancer cell in vitro, or tumor in vivo, please contact me for unpublished results. Whole body treatment is very challenge. It is easy to inject into bladder to treat bladder cancer. It is workable to administration erythrose to lung through inhalation. There are many technologies to administrate a sugar and continue maintaining its effective concentration. It is doable. It will workable. Reference: Warburg, O., Biochem. Z., 1923, cxlii, 317. Warburg, O., Posener, K., and Negelein, E., Biochem. Z., 1924, clii, 309. Negelein, E., Biochem. Z., 1925, clviii, 121; 1925, clx, 307. OTTO WARBURG, FRANZ WIND, AND ERWI'N NEGELEIN 1926 THE METABOLISM OF TUMORS IN THE BODY) Warburg O (1930) Metabolism of Tumors. Arnold Constable, London, UK. Warburg O (1956) On the origin of cancer cell. Science 123: 309–314. Mazurek S, Boschek CB, Eigenbrodt E (1997) The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. J Bioenerg Biomembr 29, pp. 315–330. Ristow M (2006) Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care (4): 339–345. Putignani L, Raffa S, Pescosolido R, Aimati L, Signore F, Torrisi MR, Grammatico P (2008) Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria. Breast Cancer Res Treat 110(3): 439-452. Heiden, et al. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324, 1029 (2009). Batt RD, Dickens F, Williamson DH. 1960. Tetrose metabolism 2. The utilization of tetroses and tetritols by rat tissues. Biochem J. 77:281-94. Hiatt HH, Horecker BL. 1956. D-erythrose metabolism in a strain of Alcaligenes faecalis. J Bacteriol. 71(6):649-54. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). Erythrulose. Australia February 11, 2008. Wang X and Wei Y 2010 “Erythrose kill cancer cell in vitro and inhibit tumor growth in vivo” American Association for Cancer Research 101th Conference.