Pathogenesis of cancer

— the use of the initiator should be one-time and short-term, and the occurrence of mutations depends on the dose of the initiator — the stronger the effect, the more reliable the result;

— initiation occurs only during cell mitosis, i.e. in the zone of natural intensive proliferation of somatic cells;

— initiation is more likely in the area of chronically increased proliferation, stimulated by external or internal influences;

— initiation is irreversible, i.e. mutations that occur at the level of nuclear DNA cannot be restored to normal;

— taking into account that embryonic features appear in a malignant cell, the proliferating zone must begin from the embryonic period of development of the organism, and also during the period of transformation of a normal proliferating somatic cell into a malignant cell, conditions similar to embryonic ones must be created;

— it is known that malignant cells have different levels of potency: from unipotent to pluripotent, that is, the level of activity of the progenitor cell when it transforms into a primary malignant stem cell must be quite high — unipotent or pluripotent;

— initiation must cease completely before the promoter can take effect, i.e. a change in the state of the cell is necessary: initiation must occur under certain conditions, but further influence (promotion) can be carried out when the cell with an altered genotype is already in other conditions of existence and microenvironment. Thus, a single and short-term carcinogenic effect leads to irreversible genotypic changes in the nuclear DNA of a proliferating somatic cell. However, initiation alone is not enough for the “birth” of a malignant stem cell.

Second stage promotions:

— in an isolated microcavity of a focus of chronic inflammation, an aggressive liquid in an oxygen-free environment affects the cell membrane and cytoplasm of a genotypically altered tissue mononuclear cell. Inside an isolated microcavity under conditions close to embryonic, there is a proliferating cellular composition fixed to the membrane or suspended. Structural changes in the cell membrane occur, with a violation of selective permeability for inorganic ions and “chemical evolution” in the cytoplasm of the genotypically changed Mononuclear cell — epigenetic changes.

Promotion terms:

— promotion is effective only after initiation and, moreover, after the complete cessation of the action of the initiator, i.e. the initiated cell must be in other conditions of existence and microenvironment — in the zone of chronic inflammation;

— the interval between initiation and promotion does not affect the final incidence of malignant neoplasms, i.e. the lifespan of an initiated cell can be different, but it is necessary that it be as long as possible (months);

— the promoter must influence the initiated cell continuously and for a long time, i.e. an initiated cell with a long life cycle must be in certain isolated conditions (super conditions), in which the aggressive effect on it can continue for a relatively long period (months);

— the promoter can influence the initiated cell in different ways, including the structure of the cell membrane with changes in selective permeability, the chemical state of the cytoplasm, cell differentiation, the possibility of blocking intercellular connections, etc.;

— promotion is reversible at the initial stage, i.e. early manifestations of promoter effects may disappear and the cell will return to its original state;

— genotypic and epigenetic changes in a proliferating somatic cell prepare the mechanism of transformation into a malignant stem cell and simultaneously trigger it. A prerequisite for the implementation of the transformation mechanism is sufficient isolation from the influence of the host organism;

— in an isolated microcavity of chronic inflammation, mitosis of a cancer cell precursor cell occurs, which has genotypic and epigenetic changes, and its transformation into a primary malignant stem cell. During mitosis, the transformation mechanism is realized as a continuous process consisting of two parts: the manifestation of the level of genotypic changes and the manifestation of the nature of genotypic changes;

— at the same time, an unstable active system is “born” — a primary malignant stem cell, which has retained many of the basic abilities and capabilities of the mother cell-precursor of the cancer cell, has not completely left the embryonic state and acquires new abilities in its new life.