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Critical Facts in Cancer Hyperthermia

#KR-1262


Physical Principles of Cancer Hyperthermia in Electromagnetic Fields on the Basic of Phase Transition Theory into the Spectrum of Mutagenic Emission

Tech Area / Field

  • MED-RAD/Radiomedicine/Medicine
  • MED-OTH/Other/Medicine
  • MED-DID/Diagnostics & Devices/Medicine
  • CHE-RAD/Photo and Radiation Chemistry/Chemistry
  • PHY-PLS/Plasma Physics/Physics

Status
3 Approved without Funding

Registration date
29.03.2005

Leading Institute
Kyrgyz-Russian Slavonic University, Kyrgyzstan, Bishkek

Collaborators

  • University Parthenope, Italy, Naples\nSib Tech, Inc., USA, CT, Newington\nFukui University / Biomedical Imaging Research Center, Japan, Fukui\nInstitute of Biophysics Bulgarian Academy of Science, Bulgaria, Sofia\nNational Research Council Canada / Institute for Information Technology, Canada, NB, Fredericton\nUniversity of Cambridge / Unilever Centre for Molecular Informatics, UK, Cambridge\nWashington University School of Medicine, USA, MO, St Louis\nUniversity of Minnesota / Department of Therapeutic Radiology-Radiation Oncology, USA, MN, Minneapolis\nVilnius University / Institute of Materials Science and Applied Research, Lithuania, Vilnius\nVito, Belgium, Mol\nPolitecnico di Milano / Dipartamento di Bioingegneria, Italy, Milan\nUniversity College London / Wolfson Institute for Biomedical Research, UK, London\nUniversitatea Babes-Bolyai, Romania, Cluj-Napoca\nJohann Wolfgang Goethe-Universität / Klinikum der Johann Wolfgang Goethe-Universität, Germany, Frankfurt am Main\nMVIP ImagingProducts GmbH, Germany, Norten-Hardenberg\nUniversity of Brighton / School of Pharmacy and Biomolecular Siences, UK, Brighton\nUniversity of Padova / Chemical Sciences Department, Italy, Padova\nUniversity of Alberta / Department of Anthropology, Canada, AB, Edmonton\nMedical University of South Carolina / MUSC Children's Hospital, USA, SC, Charleston\nKyoto University / School of Health Sciences, Japan, Kyoto\nMichigan State University / Department of Electrical and Computer Engineering, USA, MI, East Lansing\nHospital of Macerata, Italy, Macerata\nUniversity of Arkansas at Little Rock, USA, AR, Little Rock\nBaylor College of Medicine, USA, TX, Houston

Project summary

Effective methods for cancer therapy are hyperthermia and radiotherapy. Hyperthermia use together with: ultrasound, including for cancer diagnostics (G. ter Haar); electromagnetic fields (EF); g-rays; laser, photodynamic, neutrons and chemo- therapy [1]-[7], where main interest is concentrated to theory [5]. At the project #2221 ISTC it is proposed only development of methodic for common hyperthermia. At the represented project, unlike project #KR-1140 ISTC, it had developed the theory of hyperthermia based on theory of phase transitions [8]. Theory was confirmed by the independent experimental data from Canadian scientists [9], negative pi-mesons cancer therapy [3] (JINR, Dubna, Russia) and coherence with mutagenic emission (ME) [10].

For optimal interval (41-42)oC it is precede very danger zone (38-39)oC. At this zone neoformation explosive growth, as under growth temperature T, so under it’s reduction from 42oC till 36.5oC. Because of in during the therapy it is very important the fast transit trough zone (38-39)oC, as for heating, so for cooling. This effect is able only when substance stay near the phase transition point [11]. Inside of zone (38-39)oC such substance is nitrogen protoxide N2O [8].

Researchers [1]-[6] and referred projects ignored the critical effects, i.e. to interaction between emission and substance, when substance is heated to critical temperature Tc [11]. Main result of the works [8] is establishing of the direct dependence cancer hyperthermia: a) from 1 type of phase transitions in N2O and HCl, where Tc=38.75oC for N2O and Tc=51.39oC for HCl; b) from concentration heavy nitrogen 15N in the cell. For instance by the IHS it was established the threshold level for hyperthermia 38.5oC that is less than critical temperature of N2O on 0.25oC. Nitrogen protoxide contain 5-valent 15N an it is strong oxidant and narcotic gas. Under the temperature T>Tc nitrogen protoxide become to gas and partially is retired from the cell together with the 15N. Explosive growth of neoformation under the decreasing of temperature from 42oC to
36.5
oC is able only near the critical point of nitrogen protoxide, if N2O remain inside of the neoformation after hyperthermia. Its were demonstrated by researchers at the different countries and estimate like average survive time after the therapy, approximately equal 1 year [5]. Implicit, that if there is not growth of neoformation, it is estimation of therapy efficiency.

From the data analysis it is implicit, that upper boundary for hyperthermia dependent not only from HCl. Those temperature accordant also phosphony chloride PH4Cl, phosphor and phosphine PH4 with the relative critical temperatures 49.04oC, 50oC and 51.24oC. At the T@50oC white phosphor flame and it is happened 1 type of phase transition with the changes of valence. The growth of temperature from 49.04oC to 51.24oC change the valence of phosphor from 5 to 3. It is destroyed phospholysis and proteins synthesis from amino acids, and chlorine is exclude from biochemical processes.

It is the future in cancer problem the mutagenic emission [10]. It is rays with low intensity in spectrum 190-325 nm, that are emitted by normal cells. In during growth cancer neoformation in the blood it arise anomaly substance, that cancel mutagenic emission. Identification of this substance is very important for earliest diagnostic of cancer. We proofed that mutagenic emission interact with the nitrogen oxides. NO and NO2 absorb mutagenic emission at the interval 190 nm and 325 nm and N2O – at the center of mutagenic emission spectrum at the line 248 nm. Thereby in hyperthermia we have to consider the critical effects.

As known, heavy nitrogen 15N distinctive long time is save in collagen [12]. In researches [9] it was defined concentration of the heavy nitrogen d15N in collagen and apatite of relics of defunct and developing civilizations. It was found, that death boundary approximately equal d15N@11‰. Usually d15N=7.5‰. In the relics of the defunct civilizations d15N>11‰, but in the relic of developing civilizations d15N<11‰. It is condition ate by the food with d15N>11‰, that acted accumulation of the heavy nitrogen and death.

In [8] it was proofed, that pi-mesons, that used in cancer radiotherapy, interacted only with heavy nitrogen nucleus. Under adsorption null-pi-meson energy of 16Nm sufficiently grater than full binding energy of 16N nucleus, because of it 16Nm is decay. It was derive the formula for 16Nm decay and splinter analysis satisfy to experimental data from cancer pi-meson therapy at the particle accelerators. Its are follow products of neoformation’s destruction: neutrons, protons, a-particles, ions of lithium, beryllium, borax and other chemical elements. Since human corps contain 3% of nitrogen, than concentration of 15N, that is in balance with atmosphere concentration, is 10.95‰, that is equal statistical average value [9]. I mean that death boundary is defined by concentration of the heavy nitrogen in the atmosphere, implicit d15N=10.95‰ is critical level for cell’s existence.

As result we derive the law and formula for calculation of the length of macromolecule in dependence from concentration of heavy nitrogen in the cell. This formula we may to use as measure cell’s senescence. Firstly, it is known, that lysine is concentrated in cancer cells, and for completing catalytic function in polypeptide chain it must used remind of serine –Ser. It is allocate at the № 195 from the end of chain: Asp197 – Lys196 – Ser195 – Tyr194 [12]. If d15N=10.83‰, than concentration of 15N (0.361%) is less than in atmosphere (0.365%), implicit, we obtain value 195, that is satisfy Ser195. For d15N=10.95‰ concentration of 15N stay at the balance with atmosphere’s concentration of 15N. It is satisfy value 197.1 and point to Asp197. Secondly, for glycolysis its are need 10 biochemical reactions transformations of the glucose to the lactic acid [12]. Under the mutagenic emission in the glucose and high-molecular carbohydrate it appear destruction of the С–С binding to the two equal remains, each of that is lactic acid. Than, Paster’s effect is deject by the dejection of the mutagenic emission by the nitrogen’s oxides, that together with carbohydrates and lipids perform the low- molecular proteins of the cancer cells. Finally, unknown factor of the clarification in hyperthermia is mutagenic emission [12], because emission at the line 190 nm destruct chilymicrones and pre-b-lipoproteins, that have size 300-1500 nm and 150-300 nm. These facts proof our theory.

Main aim of represented research is theoretical rational of hyperthermia and magnetic cancer therapy on the basic of phase transitions and confirmation of theory by the real experiment.

At the project it used known methods of the physical and chemical analysis, performed at the investigations of the vitamin В12 [7] and investigation of the optical activity of intercellular compounds in the normal and neoformation’s cells. Its are NMR-, EPR- and mass-spectrometry for analysis nitrogen isotopes. Experiments in vitro will carry out by mass- and EPR-spectrometers, for fixing the role of 15N. Main point for using of NMR-tomography is that we developed original methodic for experiment in vivo on the odd-even heavy nitrogen nucleus. Accordingly with this aim its necessary to solve the follow tasks and answer for follow questions:

  1. Find out physical properties of the atom nucleus for normal and neoformation’s cells relatively to heavy nitrogen.
  2. Is Hyperthermia confirmed by theory of phase transitions?
  3. Establish the nature of mutagenic emission on the basic of cancellation of mutagenic emission by the nitrogen oxides.
  4. To held analysis for spectrum of emission and isotope’s content for normal and cancer cells at the different stages of disease.
  5. Experimentally proof, that cause of neoformation’s (cancer) cells is the concentration d15N, equal 10.95‰ inside of its, i.e. proof the formula for calculation of the polypeptide’s length.
  6. Is quantum-mechanical pair 15N with 13C – cyanide.
  7. Develop principally new methods and equipment for diagnostics and cancer thermo-radiotherapy and patented of its.

Answers for these questions in the represented theory were obtained and need in proofing of its by the real experiments in vitro and in vivo, methodic of that we had developed. Experimental proofing of the theory will give to us ability to develop principally new methods and equipment for diagnostics and cancer thermo-radiotherapy. These methods and equipments are know-how for the moment and need in financial support for patents. It is able decreasing of concentration d15N to 5.5‰, i.e. it’s rejuvenation/ Formula for calculation of the polypeptide’s length let us perform biological molecules with sufficient length with the given properties and ability to concatenate with the other macromolecules. Nitrogen oxides are diamagnetic, implicit they extract from space with the maximum of the magnetic induction. It is confirmation the theory of critical effects in hyperthermia and cancer magneto-therapy.

References

  1. Falk M.H, Issels R.D. Hyperthermia in oncology. Int. J. Hyperthermia, 2001, V.17, p. 1-18.
  2. An Introduction to the Practical Aspects of Clinical Hyperthermia. Field, S.B., & Hand J.W., editors. London-New-York: Taylor & Francis, 1990.
  3. Yarmonenko C.P. Radiobiology of Human and Animals. Moscow, 1977.
  4. Komarova L.N., Zhurakovskaya G.P. and Petin V.G. The Dependence of the Synergetic Action of Ultrasound and Hyperthermia on Ultrasound Intensity. Biophysics, RAS, 2000, V.45, No 1, P.125-129.
  5. Osinsky S.P. Hyperthermia in clinical oncology: current state of the problem (conference summary: the 20th annual meeting of the European Society for Hyperthermia Oncology (ESHO)). Oncology, 2002, V.4, No 4, P. 288-292.
  6. Konov V. I., Osiko V. V. and Shcherbakov I. A. Fundamental Achievements in Optics and Laser Physics for Medicine. Herald of the Russian Academy of Sciences. 2004, V 74, No 1, p. 25-37.
  7. Willams D.R. Metals, Ligands and Cancer. Chem. Rev, 1972, V.72, No3, P.202-213.
  8. Tukembaev Ch.A., Vasiliev I.A. The Physics of Hyperthermia and p--Therapy of Cancer. J. of Universities of Kyrgyz Republic, 2003, No 3-4, P. 61-65.
  9. Katzenberg M.A., Weber A.W. Stable isotope ecology and paleolite in the Lake Baikal region of Siberia. J. of Archaeological Science, 1999, No 26 (6), P. 651-659.
  10. Kuzin A.M. Electromagnetic Information in the Phenomenon of Life. Biophysics. RAS, 2000, V.45. No 1, P. 144-147.
  11. Ginzburg V.L. About physics and astrophysics. М.: Science, 1985.
  12. McMurray W.C. Essentials of Human Metabolism. N.Y., 1977.

Result of research will establishing of cancer’s cause and selection of the real way for cancer therapy. Anomaly substance, caused cancer, like implicit from theory, is compound of oxides of heavy nitrogen 15N inside of the corps cells. Since the theory was developed by us, it is necessary real experimental confirmation of the obtained results. At the represented project such experiments in vivo and in vitro are prearranged.


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