Oxygen Treatment of Cancer
Development of methods and technologies for utilization of O18 as a cytostatic in a novel approach to treatment for cancer.
Tech Area / Field
8 Project completed
Senior Project Manager
Komarkov D A
NIIIT (Pulse Techniques), Russia, Moscow
- Plant of Electro-Mechanical Equipment , Russia, Moscow reg., Protvino\nCancer Research Center, Russia, Moscow
- National Institute of Bioscience & Human-Technology, Japan, Tsukuba\nMax-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC), Germany, Berlin
Project summaryThe project is based on the concept of cytostatic activity of the oxygen heavy isotope O18 and the possibility of utilization of O18-enriched preparations for treatment of oncological diseases put forward by Dr Yu.A.Borschevsky (application for invention certificate No. 93-030287/26 "A method of tumor chemotherapy" of 30 June 1993).
The offered approach is original and has no analogs as confirmed by scientific, technological and patent expertise performed by specialists of the Institute of State Patent Expertise, Rospatent.
For the first time in the world practice we propose to use the stable heavy isotope of oxygen O18 as a cytostatic. Molecular oxygen and/or water enriched with the O18 isotope to a level of 50-500-fold greater than the natural concentration of the isotope in water and atmospheric oxygen, i.e. 50-500-fold higher than the O18 background level (0.1995%) resulting from evolution of living organisms for 4 mlrd years beginning from formation of prebiological structures and habitual for man, will be used as O18 chemotherapeuticals.
It should be emphasized that unlike all chemotherapeuticals foreign to the human body the preparation is a significant component of metabolism of the living organism which is vitally important and absolutely necessary for maintaining life in the animal and human body.
Deceleration of chemical reactions after substitution of heavy stable isotopes of biophilic elements for their lighter variants is a well-known fundamental of the isotope chemistry. But the possibility of producing this effect in biochemical systems, especially in living organisms has practically not been studied so far. The biochemical reactions in the living body are characterized by strict correlation of their rates which is the most important factor determining the normal stable balance of inpidual metabolic cycles and the metabolic system as a who1e.
Basing on these considerations it may be expected that the O18 kinetic effect due to the replacement of the light isotope O16 by the heavy isotope O18 will cause considerable disturbances in the body metabolic balance. First of all it must lead to a considerable slow down in the tissular breathing which is a source of energy and organical substances necessary for maintaining all forms of life. The resulting necessity to overcome the metabolic disbalance will stimulate the body immunity for mobilization of all processes with the aim to distinguish and struggle against alien cells.
As oxygen is one of the most active elements in metabolism, and the relative mass difference of the isotopes O18 and O16 is 12,5% w., there are reasons to expect that O18 can suppress the intense metabolism, inhibit growth and cause death of tumor cells.
Thus, the main objective of the project is to obtain experimental evidence of O18 isotope antitumor activity in tumor cell culture, human tumor bioptic samples and animal models with implanted human tumors.
A concrete program of experimental investigations is proposed for evaluation of cytostatic effect of the oxygen heavy isotope O18 on metabolism of normal and tumor cells.
Molecular oxygen enriched with the O18 isotope is one of the main O18 preparations to be administered by inhalation. The inhaled oxygen as oxyhemoglobin is transported through the circulation to all organs and tissues to participate in tissular breathing. All biochemical processes of cellular metabolism must proceed slower due to O18 and therefore inhibit proliferation of tumor cells and stimulate the immune system to destruct them.
But after the inhalation of O18-enriched molecular oxygen the O18 concentration in the living body falls rapidly due to the oxygen isotope exchange in the system "organical acids-water" and continuous excretion of O18-enriched water during this process.
Therefore to maintain the required therapeutic concentration of O18 in patients, i.e. to increase the intensity and duration of the O18 therapeutic effect O18-enriched water should be drunk.
The project involves a complex of works associated with design, manufacture and testing of atypical apparatus, devices and appliances both for experimental assessment of O18 cytostatic activity on cellular cultures and bioptic specimens of human tumors of various genesis and from different sites, and study of O18 pharmacokinetics in the living organism.
The project also involves scientific investigations and experimental design of hardware and software for oxygen isotopic analysis of O18-enriched preparations and medical biological samples.
Since the living body metabolic system is characterized by stability of the isotope ratio under the normal conditions, the isotope content of oxygen in main metabolites and tissues contains valuable genetical information necessary to establish basic regularities of O18 fractionation at the natural distribution level and to detect metabolic disturbances in the living body under the influence of the O18-enriched preparations.
In order to provide reliable operative monitoring of O18 concentration in the main metabolites and tissues of
the body under natural conditions and under those with artificially increased O18 content during therapy the project involves special methodological and experimental investigations for development of reliable express methods for quantitative (100%) isolation of molecular oxygen from medical and biological specimens to be subjected to precision isotopic mass spectrometry.
The experimental oxygen isotope investigations under the project will be performed on a methodological and technical basis involving a complex of thermochemical techniques of quantitative isolation of oxygen from natural and technical materials for precision mass spectrometry of the isotopes. These techniques were developed at the Laboratory of Isotopic Investigations headed by Yu.A.Borschevsky and have the status of inventions. They have been used for over 25 years to study genetical and diagnostic aspects of biogeochemical and technological processes. The techniques are entitled "A method for Isolation of Oxygen for Isotopic Analysis" - Yu.A.Borschevsky, G.B.Amosova, N.I.Medvedovskaya and others.
- Author's Certificate n 223446 of 12 January 1967;
- Author's Certificate n 972312 of 16 September 1980;
- Author's Certificate n 1089462 of 13 May 1982.
The results of many year research in regularities of stable oxygen and carbon isotope tract toning under the effect of various natural processes obtained at the Laboratory on the basis of methods and technical means also developed at the Laboratory are described in 300 scientific publications and reported at numerous International and All-Union symposia and conferences on problems of stable isotope utilization for solution of theoretical and applied problems of geochemistry and biogeochemistry.
At present the Laboratory of Isotopic Investigations of the Institute of Lithosphere of the RAS is transformed into the Interdepartment (RF Minatom-RAS) Problem Laboratory for novel technologies and materials at the NIIIT (IPL of NIIIT) and is situated at the NIIIT premises.
The complex of methods for specimen chemical preparation for isotopic analysis of oxygen is a reliable basis for successful performance of oxygen isotopic investigations under the project.
However, since these methods were developed for precision mass spectrometry of minor variations in the oxygen isotope composition in natural materials at the natural level of oxygen isotope distribution, a special methodological and experimental research should proceed their employment in oxygen isotope investigations of O18-enriched preparations and medical biological samples.
Of great importance are the experimental investigations intended to study and evaluate various aspects of the effect of O18-enriched preparations on vital organs and functions of the living organism (general metabolic, immunologic, cardiologic and others) that will be performed at the CRC RAMS and MO RAS with participation of world recognized scientists such as Academicians N.N.Trapeznikov, R.V.Petrov, A.S.Spirin and E.I.Chazov. The studies are expected to distinguish fields of clinical oncology in which O18 preparations as biochemical cytostatics will be the most beneficial, and the contribution of O18 therapy to treatment of cancer will be the greatest.
Thus, the main result of the proposed project, which in the opinion of experts, is an up-to-date and promising scientific investigation, will be development of a novel approach to therapy of malignant tumors.
Besides, the original factual data obtained as a result of the experimental isotopic and medical investigations for evaluation of O18 antitumor activity will be of great significance for a number of problems associated with study of peculiarities of biophysical and biochemical processes in the living organism.
Successful fulfillment of the project will allow clinical investigations of O18 antitumor activity in man with the objective to evaluate prospects for use of O18 as a therapeutic factor in treatment of cancer and to develop a novel universal atoxic method of tumor chemotherapy based on utilization of the oxygen heavy isotope O18 as a biological cytostatic.