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Review 2
The effects of avemar on the metabolism of cancer cells
The cancer cell's modified genes constantly urge the affected cells to divide. In order to maintain the processes of cell division, cell metabolism must also be changed; the cell needs to adapt to an enhanced synthesis of nucleic acids (RNA/DNA) and other constituents. To fuel these processes, cancer cells need an ab-undance of precursors. Cancer cells adapt their metabolism in a way that enables them to utilize the most abundant resource in circulation: glucose. They do this not only to gain chemical en-ergy, but also to produce structural molecules and metabolically active ones. In order to maintain a continuous proliferation, it is crucial that glucose is utilized continuously for synthetic (ana-bolic) biochemical processes.
Another important fact which distinguishes the metabolism of cancer cells from that of normal cells is the considerably high rate of the non-oxidative steps of the anabolic processes. The fact that this process is typical of and limited to cancer cells makes it a primary target for research into new diagnostic and therapeutic approaches [23].
It is commonly observed that cancer patients experience ra-pid weight loss and a decrease in overall physical fitness. The declining resistance to infect-ions also makes them more vul-nerable.
For patients with malignant tumors, death is almost always caused by the severe deterio-ration of one or more of the vital organs or by a severe and life-threatening weight loss which leads to metabolic col-lapse. The main question one needs to comprehend when dealing with malignant feature - one which is also crucial for understanding how Avemar works - is how tumor cells can maintain their continuous growth in a body which is rapidly and inexorably deteriorating as it ap-proaches death. This can only be possible if the tumor cells use certain essential substances or substrates to support their own growth, something that the body keeps in continuous supply because it is crucial for the survival. One such material, and one which the body attempts to maintain at normal physiological levels in all circumstances, is glucose. It was already known in the early 1930's that tumor cells can adapt to a glucose-based metabolism and are also capable of taking up enormous quantities of this molecule - up to 20-30 times more than normal cells do. One part of this glucose will be used for energy production, while another, significant part will be used for the syntesis of nucleic acids.
Another important fact crucial to the understanding the metabolism of tumor cells is the capability of these cells to pro-liferate and settle in an environment with low oxygen partial pressure, such as it is found in hypoxic conditions. This condition is fulfilled if cells prefer non-oxidative processes rather than oxidative ones during macromolecular synthesis. In tumor cells, these non-oxidative anabolic and catabolic processes are found in the pentose-cycle and in the early stages of glycolysis, where glucose is used to build lactate and ribose. As ribose molecules are the building blocks of RNA and DNA, tu-mor cells need to use their glucose for these processes. Transketolase and trans-aldolase, the two key enzymes capable of converting (6 carbon-atoms) phosphorilated glucose derivatives into ribose (5 carbon-atoms). What makes this process even more specific is that it is completely reversible and only slightly controlled. Moreover, it is also the most efficient way for the tumor cell to produce large quantities of nucleic acid precursors. Syn-thesizing ribose through oxid-ative processes produces re-ductive potential (reduced NADP) as well. The latter is not 'wasted' on fatty acid syn-thesis, but is used for con-verting ribonucleotides into de-oxyribonucleotides (DNA).
Obviously, cancer cells have a fairly primitive, undiffer-entiated structure; owing to reduced fatty acid and amino acid synthesis, cancer cells are unable to produce enough proteins and triglycerides to develop functional receptors, enzymes, structural proteins and membrane components. The cancer cell fulfills a single role, but does so quite efficiently: it multiplies at a phenomenal rate and produces primitive, seriously dysfunctional cells. The above-mentioned description is a basic characteristic of all cancer cells irrespective of their origin (genetic or chemical damage, abnormal response to signal transductory or growth hormones) [25].
As a result, it would seem logical to examine the metabolism of tumor cells by adding isotope-labeled sugar molecules to the cell culture in order to track the intracellular distribution of the isotope both in untreated cultures and in those treated with different doses of Avemar. These experiments were performed by our research team in the medical faculty at the University of California at Los Angeles (UCLA) using two cancer cell lines: aggressively growing pancreatic carcinoma and Jurkat-leuk-emia cells. The results were similar in both cell lines and demonstrated that Avemar significantly inhibits the cancer cells in their effort to phosphorilate glucose, thereby inhibiting its activation. This significantly reduces sugar consumption in tumor cells, with the be-nefit that the body will be capable of using this glu-cose to maintain its normal activities and provide en-ergy for organs still in good functional condition. Even more peculiar is the effect of Avemar on the ribose syn-thesis. Ribose is an essential key element of nucleic acids. Avemar prevents the cancer cells from syn-thesizing ribose - and thus RNA and DNA - from glucose using the non-oxidative pathways of the pentose cycle in a direct dose-dependent manner. In fact, since Avemar also blocks the reduced NADP synthesis of tumor cells, it holds back the de-oxy-ribonucleotide production, and thus DNA synthesis, in not one, but two channels. The cancer cells get bogged down in the S-phase and their division stops. Enzym-ology studies performed at the University of Barcelona have ascertained that these effects of Avemar are highly selective for cancer cells [30].
Dosages of Avemar pre-scribed in humans inhibit the activities of the enzymes hexokinase, glucose-6P-de-hydrogenase, transketolase and lactate-dehydrogenase, but only in tumor cells. Therefore, tumor cells become incapable of utilizing glucose reserves for ribose synthesis. Because of Avemar's interference, the tumor cell will be deprived from ribose and, without ribose or its reduced derivants, and thus without RNA and DNA, proliferation becomes impossible. In normal, healthy cells (as in peripheral lymphocytes), a dose at least 50 times higher is required to achieve the same inhibiting effect. Translating these figures onto a human scale, an average weighing adult would need to consume nearly 0,5 kg (!) of Avemar every day, instead of the usual 9 g, in order to diminish its beneficial selective action.
Another effect observed in Avemar treated tumor cells is that these tumor cells utilized the glucose that they would have normally used for nucleic acid production for fatty acid synthesis. This process significantly improves the differentiation or the maturity grade of the cells, as the cancer cell modifies its metabolism to match that of normal cells and thereby becomes considerably less malignant.
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