Сергей Алексеевич Шалин
Pathogenesis of cancer
MECHANISM
The mechanism of occurrence, growth and development of Mononuclear oncogenesis is a complex process, when each subsequent action is the result of the previous one, each action has its own distinctive features and oncogenesis can end for one reason or another at each of them. Pretumor diseases of the body and pathological changes in local tissues in the zone of chronic inflammation contribute to the formation of an isolated microcavity as a future “pretumor” bed. The microcavity, isolated from the microenvironment, contains an aggressive specific liquid in an oxygen-free environment. Inflammatory mediators initiate an additional requirement for specific tissue immunocompetent cells, therefore hematopoiesis is stimulated and the production of mononuclear cells in the red bone marrow is enhanced, because They do not form a bone marrow reserve. During the accelerated production of bone marrow mononuclear cells and under carcinogenic influence, genotypic changes in the DNA of the nucleus of hematopoietic stem cells occur, with different levels of potency according to a recessive trait. After entering the tissue, mononuclear cells with genotypic changes in nuclear DNA penetrate into an isolated microcavity, where they are exposed to aggressive liquid in an oxygen-free environment – epigenetic changes appear. During the process of mitosis of a mononuclear cell, which has genotypic and epigenetic changes, a primary malignant stem cell is “born,” which divides to form similar or homogeneous malignant cells and forms a monoclonal malignant “embryo”—a clone of malignant cells within the shell of an isolated microcavity. Subsequent division of malignant cells leads to an increase in their critical mass (number) and is accompanied by an increase in their malignancy (malignant progression), which contributes to the destruction of the shell of the isolated microcavity. The release of malignant cells into the intercellular space and the involvement of the stroma of an organ or tissue in the malignant process means the beginning of the organization of the primary malignant focus. The malignant focus increases in size due to active proliferation, appositional and invasive growth. Active penetration of true malignant cells through tissue barriers (invasive growth), as well as stimulation of the growth of blood vessels (angioneogenesis) contribute to the penetration of malignant cells into the vascular bed and the organization of a secondary malignant focus (metastasis).
FEATURES
A feature of the formation of a “pre-tumor” bed is the obligatory presence of pre-tumor diseases of the body in general and pre-tumor pathological changes in local tissues in particular. In normal healthy tissues, the occurrence of a malignant process is impossible. A feature of preparing a cell for transformation into a malignant cell is the multi-stage process. Moreover, each stage has its own characteristics that determine the possibility of continuing the process, during which decisive genotypic and epigenetic changes can occur. A feature of the “birth” of a primary malignant stem cell is the obligatory entry into the process of mitosis of a cell that has genotypic and epigenetic changes. Only during MITOSIS does the transformation mechanism occur and the level and nature of genotypic changes become manifest. In this case, the transformation mechanism occurs in an isolated microcavity and, thus, escapes the influence and control of local tissues. A feature of the growth of a malignant lesion is its autonomy and ability to self-organize and self-regulate. Using the host organism as the basis for its own development, the malignant process subjugates the normal cellular and non-cellular structures of vital organs and systems. A peculiarity of the mechanism of penetration of mononuclear cells from the vascular bed into the tissue, and of malignant cells from the primary focus into the vascular bed, is the use of the same section of the microvasculature – the postcapillary and venule. Figuratively speaking, “through whatever “doors” the cells came out, through the same ones they returned.” A feature of the development of the malignant process is the perverted repetition of embryonic hematopoiesis. The host organism unconsciously “connects” a false option to enhance its ability to survive by maintaining individual aging organs. In reality, this path is a dead end, and the mechanism is destructive.
RESULT
As a result of pretumor diseases of the body in general and pathological changes in local tissues in particular, an isolated microcavity is formed as a “pretumor” bed. However, pre-tumor changes in local tissues are only the necessary preparation for creating conditions under which a genotypically and epigenetically altered cell can transform into a malignant stem cell. In the red bone marrow, as a result of carcinogenic effects, various genotypic changes occur in the DNA of the nucleus of the pluripotent progenitor cell of the ancestor of myelopoiesis with further development into a monocytic germ or unipotent progenitor cell of the ancestor of Monocytes according to a recessive trait. These changes do not lead to disruption of cell differentiation, but are inherited by more mature cells – Promonocyte and Monocyte. As a result, an initiated cell appears – a genotypically altered mononuclear cell. In an isolated microcavity of a focus of chronic inflammation, initiated cells are exposed to aggressive fluid in an oxygen-free environment. This leads to structural changes in the cell membrane with disruption of its selective permeability and “chemical evolution” in the cell cytoplasm. As a result, epigenetic changes appear in the genotypically altered Mononuclear Cell. As a result of mitosis of a genotypically and epigenetically altered mononuclear cell, the actual transformation mechanism is launched and the primary malignant stem cell is “born,” which divides to form a clone of the same type or homogeneous malignant cells. As a result, a malignant “embryo” is formed – a clone of malignant cells within the shell of an isolated microcavity. The result of malignant cells leaving the shell of the isolated microcavity and involving the stroma of the microenvironment in the malignant process is the organization of a primary malignant focus. The increase in volume is the result of active proliferation, appositional and invasive growth of malignant cells, and penetration into surrounding tissues is the result of invasive growth of true malignant cells. As a result of the active penetration of true malignant cells through tissue barriers (invasive growth), as well as stimulation of the growth of blood vessels (angioneogenesis), malignant cells penetrate into the vascular bed and participate in the organization of a secondary malignant focus (metastasis). As a result of the ability to independently control the proliferation, differentiation and maturation of malignant cells, the spread of malignant cells throughout the host body and the organization of metastases, as well as as a result of the influence on the vital organs and systems of the host body with their subsequent subjugation, the malignant process develops as an independent system.
FUNDAMENTALS
Statement 1: The precursor cell of the primary malignant stem cell of solid tumors is a tissue mononuclear cell (Promonocyte, Monocyte), which has genotypic and epigenetic changes.
Statement 2: The basis for the “generation” of a malignant stem cell is the return of a tissue mononuclear cell, which has genotypic and epigenetic changes, to the embryonic state during mitosis, a block of differentiation at the pluripotent or unipotent level and transformation.
Statement 3: The mechanism of “generation” of a malignant stem cell is a complex multi-stage process, when genotypic changes in a bone marrow mononuclear cell under carcinogenic influence sequentially appear, epigenetic changes in the same but tissue mononuclear cell under the influence of “super conditions” of an isolated microcavity, and mitosis is the starting point for their implementation.
Statement 4: The polymorphism of malignant cells is due to the variety of options for their “nucleation”, maturation and differentiation, as well as their own evolution and the influence of the microenvironment.
Statement 5: A malignant focus is an independent structural and functional formation that has characteristic features and conditionally repeats the structural organization and functioning of the red bone marrow.
Statement 6: The stages of formation and successive change of generations of malignant stem cells conditionally repeat the stages of formation and successive change of generations of stem cells of embryonic hematopoiesis.
Statement 7: The malignant process, as an independent system, is capable of self-organization and self-regulation; many evolutionarily determined mechanisms lie in its occurrence and development.
