**3. Bioelectromagnetic selection – To select or not to select?**

22 Hyperthermia

radiation of the mercury-plasma

excited electrons

fluorescent or LED light-sources.

**Figure 19.** Fluorescent technology. The energy is liberated by micro-"explosions", excited by an UV

**Figure 20.** LED technology. The energy is liberated by micro-"explosions" by using the energy of the

This way, the more intensive light (virtually higher temperature micro-explosions) need less energy by the block of the wasted energy to heat up the environment instead of the visible light emission: the same light-emission needs 60W, 13 W and 5 W in cases of incandescent,

The present main-stream thinking of oncological hyperthermia is a typical loss of aims by illusions: the temperature only makes conditions that are implements and not the aim. The question "Tool or goal?" has become relevant to study the temperature alone. By a simple example of mixing the tool and the goal in our everyday life: the graduation is a tool for our In hyperthermia applications the macroscopic heating centers on the equal (homogeneous) temperature of the entire targeted volume, irrespective of its content and the ratio of the tumor-cells in the target, (see Figure 21**.**/a.). However, the target volume has only a small fraction of active malignant cells, and the heating process would be enough for those alone, avoiding heating (and wasting energy) to the other part of the target-volume. The microheating concept works differently, and heats the selected malignant cells only absorbing the energy non-equally in the target (see Figure 21/b.*)*.

**Figure 21.** The schematics of macroscopic and microscopic heating of tumor

In this case, the lost energy is minimal; the efficacy of the energy utilization and its control is maximal. The energy is concentrated in this case directly to the chemical reactions and does not involve the above listed losses. The energy liberated by the micro reactions is used for the desired job in full, while the explosion-like, huge energy-supply in short time cannot be used optimally, due to the intensity of the immediate offer for the available energy is too much for prompt use. This causes a large demand of waste and a low efficacy of the desired effect. The problem of the heating, however, is that it shows a false, specious effect of applications in biology. When the liberated energy is not used as active biochemical or biophysical driving-force then the waste appears as a simple growth of the temperature in the target. This deceptive illusion seems to have higher efficacy. This, of course, heats everything in the target. The excess energy is wasted in the neighborhood of the malignancy and gaining the average energy of all the parts in the target, irrespective its malignancy or its electrolyte state. This is a typical wasting of energy, using it for the actually not-necessary energizing of healthy parts. This massive heating forces the homeostatic feedback mechanisms acting against the growth of drastic temperature growths.

The oncological hyperthermia application, which uses the nano-scale heating technology (called oncothermia, [160]); the radiofrequency (RF) current flows through the chosen volume of the body (see Figure 22.), heating up the cell-membrane individually (see Figure 23.). The cell-membrane is a good isolator and so the current is most dense at the extracellular electrolyte in the immediate vicinity of the cells. Of course, when the absorbed energy is too much, the individual cellular-heating does not work, all the volume will be equally heated. This is again the declaration of the well- known rule: "the difference between the poison and the medicament is only their dose".

Local Hyperthermia in Oncology – To Choose or not to Choose? 25

**3.1. Selection by Warburg's effect (conductivity selection)** 

obtained from the high efficacy process.

**glucose**

**Figure 24.** Differences in healthy and malignant cells

•Low glucose influx •Normal ECM

•High membrane potential

As Otto Warburg discovered, the malignant cells behave completely differently from their healthy counterparts, [161], having mitochondrial dysfunction to produce ATP. (For this discovery a Nobel-prize was granted for him.) Warburg's work nowadays has its renaissance [162], [163]; showing the validity of the dominance of non-mitochondrial (fermentative) way of ATP production. The fermentative way of the metabolic ATP production is anyway "ancient" chemical reaction, which was characteristic at the beginning of the evolution of life, when the oxygen, the general electron acceptor was available only in a small amount in the atmosphere. It is the fermentative way to utilize the energy of glucose

converting it into lactic acid (*CH3CHOHCOOH*), producing only 2 ATPs in one cycle.

**Healthy cell Malignant cell** glucose 6O2 6CO2 36ATP glucose 2lactic acid 2ATP

**glucose**

The metabolism in healthy cells is mainly governed by the convertible energy-source of ATP. The citrate (Krebs) cycle by mitochondria, the "energy plant" in cells, produces 36 ATPs with excellent efficacy with the help of oxygen (see Figure 24/a.). The fermentative ATP production is a low efficacy process in malignant cells, (see Figure 24/b.*),* however, (due to its simplicity) it can occur in large amount, its overall energy-flux can be higher than

The malignant cells are in frequent and permanent cellular-division. The energyconsumption for the intensive division is higher than the energy requirement for the healthy cells in homeostasis. This is available only when the glucose intake is at least 18 times higher, because its ATP production is 18 times less than normal. This allows the cell to supply energetically all the normal processes and make the differentiation and development, the adaptation and evolution possible. This is a huge additional part of the glucose influx to the anyway high Warburg process. The higher glucose metabolism can be measured by positron emission tomography (PET) [164]. When we take the higher

•High glucose influx •High ion-concentration in ECM •Low membrane potential

**Figure 22.** Both electrodes are always active, independently of its size or form. The current starts in one and ends on the other. The energy density is different, and many safety functions differ

**Figure 23.** The selection mechanism of the optimally applied RF-current targets the cellular membrane, concentrates the energy in nano-range of the cell

Generally, a certain power interval is necessary for optimal efficacy, both the too high and the too low are non-optimal. The cars form a trivial example: the cold engine needs more fuel to be heated up for its optimal use, but it must be cooled down and kept in a definite range of temperature by a cooling system for its optimal work.

The average heating cannot produce high-efficacy. The high efficacy requests high selectivity for the accurate control of the process. The simple control of the average wastes a part of energy. This "waste" is expended energizing the particles, which are not involved in the desired process. The particles in the targeted process, which would like to have more power for the actual effect, have also the average only. Simple examples could be quoted from the everyday life again: when I would like to honor somebody's excellent work, it would be inefficient to honor everybody in average, being sure that the person whom the honor is due is also among the members of the group.

The proper selection has to choose not only the cells in general from the heated volume, but especially the malignant cells have to be selected from the target. This task could be solved using the specialties of malignant cells in comparison with their healthy counterparts.
