Tumorcanser129rhdueb_Maria_Sayar[2].pptx

About cancer and tumor

1. Tumors Maria Sayar General Medicine 222i1b Pathophysiology free work

2. Neoplasia is a typical pathological process that does not submit to the regulatory mechanisms of the body and is characterized by unlimited cell proliferation. The formation of tumor tissue is characterized by a disorder of the genetic control of the cell cycle due to the action of various oncogenic factors. Overgrowth of tumor tissue is a local manifestation of a common tumor disease of the body. In general benign tumors are designated by attaching the suffix — oma to the cell type from which they arise (for example, myoma , osteoma , chondroma , fibroma, etc.). Malignant tumors arising from epithelial tissue are called cancer, or carcinoma, from connective tissue — sarcoma. A large number of tumors are called using the organ in which they were formed ( hepatoma , thymoma , etc.). Tumors are divided into benign and malignant

3. Benign tumors consist of differentiated cells, in these tumors, morphological atypicalness occurs only at the tissue level, they do not have cellular atypicalness . Benign tumors grow expansively, their borders are even, smooth, limited by the capsule, they develop slowly, pushing the surrounding tissue, do not penetrate into the tissue, do not metastasize, the metabolism in them does not differ from the metabolism in healthy tissues, rarely recur. Malignant tumors consist of cells with low differentiation or undifferentiated cells; have biochemical, cellular and tissue atypicalness . They are characterized by invasive, rapid growth, they penetrate into surrounding tissues and, due to the absence of capsule, do not have clear borders, give metastases and relapses. Perverted metabolism in the malignant tumors leads to cachexia of the body. There are tumors that occupy an intermediate position between benign and malignant tumors. They are called carcinoma in situ. Carcinoma in situ has a number of atypicalness characteristics of malignant tumors, however, due to the presence of the capsule, it does not grow invasively and does not metastasize. But after a certain time, due to additional mutations, these tumors acquire new properties — invasiveness and the ability to metastasize. Etiology of tumors. The factors that cause the formation of tumors are called carcinogens (forming a tumor). These factors acting on the genes of a normal cell, lead to mutations in the genes involved in cell division. As a result of the action of carcinogenic factors, a normal cell is transformed into a tumor (neoplastic) cell. Exogenous and endogenous carcinogenic factors are distinguished. Exogenous carcinogenic factors include physical, mechanical, chemical, and biological carcinogens. Among the physical carcinogens various types of ionizing radiation (x-rays, gamma rays, etc.) and ultraviolet rays are of great importance. These factors, directly affecting the DNA molecule, disrupt its structure (gene mutation, chromosomal aberration). Regular intake of very hot food (thermal factor) plays a large role in the formation of malignant tumors of the oral mucosa. As a result of prolonged mechanical irritation in the stomach, lungs, rectum and other organs, malignant tumors can form. Among the etiological factors of malignant tumors, chemical carcinogens play a leading role. According to WHO, 80% of all tumors are caused by chemical carcinogens. Chemical carcinogens are compounds that can pass through the cell membrane and, entering the cell nucleus, enter into a chemical reaction with nucleotides.

4. Among the etiological factors of malignant tumors, chemical carcinogens play a leading role. According to WHO, 80% of all tumors are caused by chemical carcinogens. Chemical carcinogens are compounds that can pass through the cell membrane and, entering the cell nucleus, enter into a chemical reaction with nucleotides. Chemical carcinogens are divided into organic and inorganic. Chemical carcinogens are also divided into direct and indirect types of action. Carcinogens that have a direct effect, without undergoing any transformations in the body, directly affect the genetic apparatus of the cell and lead to the development of tumors. Such compounds include chloroethylamines , epoxides, alkylating compounds, some antitumor compounds (for example, cyclophosphamide), acetylating factors (1-acetyl-imidazole) and others. Indirect carcinogens can cause an effect after a series of metabolic transformations in the body. This group of compounds includes polycyclic aromatic hydrocarbons, aromatic amines, nitroso compounds and nitramines , aflatoxins, etc. For example, epoxides are formed from polycyclic aromatic hydrocarbons, hydroxyamines — from aromatic amines, and alkaline radicals — from nitrosamines.

5. The formation of a blood and clot is coagulation associated mechanisms of hemostasis. The basis of the vascular-platelet mechanism is a violation of the integrity of the vessel wall and an increase in the ability of platelets to adhere and aggregate. The main reason for platelet adhesion is deendothelization of the vascular wall as a result of its damage (fig. 9.2). As a result of this, a special protein located on the subendothelial | A layer, von Willebrand factor, connecting with receptors on the surface of platelets (glycoprotein Ib — Gp Ib ), provides platelet adhesion. Activated platelets and from damaged tissues release substances that provide high platelet aggregation ability (ADP, thromboxane Az , etc.). Under the influence of these substances, other receptors located on the platelet surface ( GplIb / IIla ) undergo conformative changes and, through fibrinogen bridges, other platelets are also involved in this process. Thus, a “plug” is formed, consisting of aggregated platelets. Aggregated (activated) platelets _ release procoagulants (thromboplastins), what initiates the stage of coagulation of thrombosis.

6. There are 2 ways of coagulation: intrinsic and extrinsic. The intrinsic pathway begins with the activation of the XII coagulation factor (Hageman’s factor), and the extrinsic pathway begins with the activation of cellular lipoproteins called tissue factor (VII coagulation factor). Both pathways lead to the activation of the X factor, as a result, prothrombin converts to thrombin. In turn, small molecule peptide chains are separated from the fibrinogen molecule under the action of thrombin and it leads to the formation of fibrin. Under the action of the fibrin-stabilizing factor (factor XIII), the formed fibrin monomers polymerize and turn into insoluble fibrin filaments. Then a certain amount of plasma is separated from the thrombus, its volume decreases, i.e. thrombus retraction occurs. Fibrin formed on the damaged areas of blood vessels under the action of fibrinolysin (plasmin) is rapidly hydrolytically cleaved.

7. The DNA gene of oncoviruses , penetrating the genome of the target cell ensures its transformation into a tumor cell. In the genome of RNA containing retroviruses is a gene encoding the enzyme revertase (reverse transcriptase). This enzyme based on the RNA matrix synthesizes a copy of DNA. Such a copy of DNA integrating into the genome of a cell causes expression of the oncogen and transformation into a tumor cell. Viral oncogenesis is realized by two molecular mechanisms: epigenomic and mutational. In the epigenomic mechanism, the virus genome easily binds to the genome of a normal cell and a normal cell transforms into a tumor cell. And in the mutation mechanism viruses after their integration into the genome of a normal cell, subject its proto- oncogen to mutation i.e. turn it into an oncogen and lead to the development of a tumor. Endogenous carcinogenic factors include steroid hormones, particularly estrogens, cholesterol, products of tryptophan and tyrosine metabolism. * virus reception — the interaction of the virus with the receptors of the plasma membrane of a normal cell; * integration — connection of the virus genome with the cell genome. This is the central and crucial stage of viral oncogenesis ; ® virus persistence in the cellular genome. In this case, the virus multiplies with the cell; ® cell transformation; ® promotion; ® tumor progression.

8. The pathogenesis of tumors. The basis of cell transformation is irreversible damage to the DNA molecule. In the occurrence of tumors, the decisive role is played by physical, chemical, biological carcinogenic factors, as well as the conditions and hereditary predisposition that ensure the implementation of their action. A hereditary predisposition to the occurrence of tumor diseases is associated with a mutation of the following genes:proto-oncogenes are the genes of normal cells that control cell proliferation; tumor suppressor genes are a normal cell genes that inhibit cell proliferation; genes that regulate apoptosis; genes for DNA repair (restoration). Proto-oncogenes are involved in the synthesis of a number of substances — growth factors, transcription factors, their receptors, cytoplasmic protein kinases, etc., participating in the cell cycle (fig.15.5). These substances play a role in the reception of mitogenic signals — factors that cause cell division, the transmission of these signals from the surface of cells to the nucleus and the expression of certain groups of genes. Factors that stimulate mitogenic activity include growth factors (growth factor of nerves, fibroblasts, epidermal and platelet growth factors, etc.), hormones (insulin, follicle-stimulating hormone, estrogens, growth hormone), cytokines (interleukins, interferon), neurotransmitters (acetylcholine, norepinephrine, glycine), adhesive proteins ( integrins , cadherins , selectins, etc.), macromolecules located in the intercellular space (fibronectin, laminin , etc.).

9. Tissue atypicalness is characterized by changes that develop in the structure of the tissue. If a tumor develops as a result of the transformation of one cell, it goes by the monoclonal pathway of development, if from several mutated cells — by the polyclonal pathway. In a monoclonal tumor, a transformed cell creates similar clones with the same genotype and phenotype. Tumor tissue that goes through the polyclonal pathway of development consists of cells with different genotypes and phenotypes. A tumor node formed from one transformed cell consists of heterogeneous cell clones. Additional mutations at the stage of tumor progression lead to the formation of new features in tumor cells. Therefore, despite the fact that the tumor has a monoclonal origin, it consists of heterogeneous cells . The growth atypicalness is characterized by an abnormality in the division of tumor cells, impaired differentiation, invasive growth, metastasis and relapse. An abnormality in the division of tumor cells leads to the disappearance of the Hayflick limit. Each cell is characterized by a certain maximum number of divisions, which is genetically programmed and it is unchanged. This is called the Hayflick limit. In tumor cells, this limit is lost and the cell acquires the potential for unlimited division .

10. Invasive growth is the penetration of tumor cells into the surrounding intercellular space. This process is
accompanied by tissue destruction. The invasion of tumor cells into the extracellular matrix (ECM) consists
of four stages separation of tumor cells from each other;
degradation (splitting) of the ECM;
connection of tumor cells with degraded ECM components;
= migration of tumor cells.

11. For the development and metastasis of the tumor, vascularization of the tumor tissue (angiogenesis) is important (fig. 15.11). In tumor tissue, angiogenesis is observed in both primary and metastatic tumors. Tumor cells produce factors that stimulate angiogenesis — angiogens (VEGF, PDGF, FGF, MMPs — matrix metalloprotein), stimulate vascularization and cause a malignancy. The main factor that triggers the release of angiogen is hypoxia. If the tumor cells are located 1-2 mm away from the vessels, their development stops. Relapse is the recurrence of a new tumor with the same histological structure at the site of a removed or destroyed tumor. The cause of relapse is incomplete removal of the tumor, weakening of the anti-blastomic resistance, invasion of tumor cells into the surrounding tissue before tumor resection. In case of relapse, the tumor develops faster.

12. Functional atypicalness of tumor tissue is characterized by a decrease in the function ( hypofunction ) of blast-transformed cells or its qualitative change (dysfunction), and sometimes its increase ( hyperfunction ). For example, in hemoblastoses , leukocytes cannot perform phagocytosis; in liver carcinoma, hepatocytes lose the ability to synthesize albumin; in pheochromocytoma and insulinoma the synthesis of the corresponding hormones by the tumor cells increases. A tumor cell is capable to synthesize the proteins, hormones that are not related to the tissue from which it developed. For example, in small cell lung cancer, blast-transformed epithelial cells of the bronchi synthesize ACTH, and it leads to the development of an ectopic form of Cushing syndrome. In a primary liver tumor, tumor cells intensively synthesize embryonic a-fetoprotein, and in myeloma — Bens-Jones protein. The detection of these substances in blood plasma (tumor markers) is of great importance in the diagnosis of tumor diseases.
Immunological atypicalness of tumor tissue is a change in the antigenic properties of tumor cells.
Tumor antigens include:
antigens formed due to mutations of protooncogenes and tumor suppressor genes;
antigens formed due to mutations of other genes under the influence of various carcinogens;
proteins formed due to over-expression of normal cell genes, or due to aberrantly synthesis of characteristic proteins of some cells in another cells (heteroantigen);
+ antigens caused by viral oncogenes. These antigens are recognized by T-lymphocytes (CD8+)

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