Name the basic features of growth of malignant tumours in vivo.

1. Monoclonal origins. The tumour grows "from itself ", so occurs from one transformed cell. Other near located cells in process of tumoral regeneration is not involved.

2. Autonomy of growth - independence of growth of a tumour from regulation influences of an organism (nervous system, hormones, factors of growth, and inhibitors of proliferation). For some tumours such autonomy is not absolute, and relative.

3. Anaplasia - purchase by tumoral cells of properties, characteristic for embryonic stage of development of an organism. In other words, tumoral cells structural, functional, biochemical, immunological properties remind embryonic cells.

4. Occurrence in tumoral cells of a plenty of chromosomal aberrations. In cells of a malignant tumour naturally there are such kinds of chromosomal violations, as translocation, deletion, inversion, duplication (it is detailed see chapter.6).

5. Tumoral progression (see question 16.19 and 16.20).

6. Invasiveness.

7. Metastasis.

16.38. With what speed do malignant tumours grow? What factors is it defined by?

Theoretical calculations have shown, that under condition when all tumoral cells constantly devided, it is possible to allocate two periods of development of a tumour.

The first is the period from occurrence of one tumoral cell before formation of a tumour which contains 10⁹ cells. For this purpose it is necessary 30 doublings so makes 90 days. Weight of such tumour is approximately 1g it is a minimal tumour on size which can be found out in an organism by means of modern methods of research.

The second period is the period during which the quantity of cells in a tumour increases from 10⁹ up to 10¹². For this purpose it is necessary only 10 doublings it should make 30 days. Weight of a tumour in the end of the second period is about 1 kg it is greatest possible on size the malignant tumour still compatible to a life.

However in natural conditions growth rate of a tumour is much less, because not all cells are being proliferate, and many perish. Growth rate of a malignant tumour is influenced by following factors.

1. Duration of mitosis cycle of tumoral cells. For the majority of them it makes from 20 up to 60 hours.

2. Size of proliferative pool (growth fractions) - a parameter reflecting percent of cells of a tumour which stay in a condition of division. In some tumours it reaches 30 %.

3. Speed of destruction of tumoral cells. It is enough greater. There are tumours in which on 100 again formed cells 80-90 victims are necessary.

The reasons of destruction of cells in a tumour are: a) deficiency of nutrients; b) high sensitivity action of damaging factors; destruction by protective antineoplastic systems of an organism.

16.39. What violations of metabolism characterize malignant tumours?

I. Violations of a protein exchange. In cells of a malignant tumour biosynthesis of proteins is perverted: many own proteins disappear, in particular, some superficial antigens, at the same time appear proteins not peculiar to cells viral and embryonic origins, enzymes of ectopic synthesis of hormones. In a tumoral tissue intensity of catabolism of proteins decreases, formation of some amino acids necessary for a tumour, in particular L-asparagine is broken. As the tumour intensively absorbs huge quantity of amino acids from blood, it names a nitrogen ?trap?.

II. Violations of a carbohydrate exchange. For a malignant tumour low intensity of tissue breath, high activity of glycolysis, Pasteur's weakened effect are characteristic. In this connection the tumour requires lots of glucose. Absorbing it from blood, it "robs" an organism that can cause development of hypoglycaemia. In this meaning a malignant tumour name "trap" of glucose.

III. Violations of a fatty exchange. In a tumoral tissue synthesis of fat acids from glucose and acetate decreases. Necessary lipids the tumour receives from blood, absorbing lipoproteins very of low density and complexes of albumins with fat acids.

16.40. What is invasiveness of tumours? How do malignant cells sprout in surrounding tissue?

Invasiveness - it is ability of a malignant tumour to sprout in surrounding tissues.

The basis of invasion is made of three processes.

1. An attachment of tumoral cells to collagen proteins of interstitial tissue. It occurs owing to presence on a surface of tumoral cells of receptors to fibronectin, that promotes formation "of fibronectin bridges" between cells of a tumour and collagen of I and III types.

2. Degradation of interstitial connecting tissue. After an attachment to collagen tumoral cells are activated and start to allocate enzymes: collagenase of I and III types, elastase, cathepsins, plasmine. All of them provide hydrolytic splitting of fibrous structures of a connecting tissue and components of the basic intercellular substance. It creates a way for migration of cells, for their promotion in a healthy tissue.

3. Actually migration of tumoral cells. The pressure created during division, directs tumoral cells in undergone changes interstitial tissue. Besides the part of cells of a tumour has own mobility and possesses property chemotaxis. Them chemotaxis is stimulated with products of degradation of a connecting tissue.

16.41. What is metastasing? How is it carried out?

Metastasing is an ability of a malignant tumour to give secondary tumoral units (metastasises) in the parts of an organism remote from a primary tumour.

Process of metastasing consists of three stages.

I. An output of tumoral cells from a tissue into lymphatic or blood vessels - intravasation. It is preceded with an attachment of tumoral cells to components of basal membranes of vessels. In a basis of such attachment formation "laminine bridges" between a surface of cells of a tumour and collagen of IV type of basal membranes lays. Glycoprotein laminine is a component of intercellular substances of basal membranes. Some most malignant cells are capable to produce this substance. Laminine, on the one hand, cooperates with so-called laminine receptors of tumoral cells, and on the other - with chemical groups of collagen of IV type.

II. Transport of tumoral cells by lymph and blood - dissemination. From cells of a tumour, penetrating in vessels, are formed tumoral embolus. Their formation is connected with aggregation of tumoral cells. In this process take part trombocytes.

III. The output of tumoral cells from vessels in tissues and formation of the secondary neoplasm nodes (metastasises) - extravasation. For localization of metastasises the site of a primary tumour, a way of metastasing (lymphogenous or haematogenous), receptor interaction of tumoral cells with endothelium of vessels matter. By the last the fact of specific localization of metastasises of some tumours (a cancer of prostate into a bone, bronchocarcinoma into a brain and adrenal glands, neuroblastome into a liver, etc.), in particular is explained.

16.42. How do the tumours influence on an organism as a whole? Why cancer cachexy do develops?

Development of a malignant tumour can be shown by three groups of the general violations in an organism.

I. Cancercachexy - the general exhaustion. It is characterized by sharp reduction of weight of a body, weakness, absence of appetite, anaemia. Occurrence of cancer cachexy is explained by the following phenomena:

a) The tumour grasps from blood lots of glucose ("a trap of glucose") therefore develops hypoglycaemia and occurs power "robbing"of an organism;.

b) The tumour grasps from blood lots of amino acids ("a trap of nitrogen"). Plastic "robbing" of an organism occurs;

c) From perishing tumoral cells in blood toxic products - toxohormones flow. They cause the phenomena of the general intoxication;

d) Tumoral cells release a lot of unoxyfied substancies ? as a result develops non-gas acidosis;

e) As a result of an output of enzymes from the lost tumoral cells in blood develops enzymaemia;

f) During localization of a tumour in the digestive channel functions of digestive system are broken.

II. General displays are connected with local changes of tissues. Formation of ulcers, secondary infections, bleedings, a painful syndrome concern to this group.

III. Paraneoplastical syndromes. They are often accompanied by development of tumours, however their pathogenesis and connection with malignant tumoral growth are not found out.

To this group are concerned: endocrinopathia; hypercalcaemia; a nervously-muscular syndrome (myasthenia, violations of the central and peripheral nervous system); dermatological violations; defeats of bones and joints; vascular and haematological violations (thromboses, anaemia, leucomoid reaction).

The big contribution to studying complex mechanisms of influence of a tumour on an organism belongs to R.?. Kavetzky - a pupil of A.A. Bogomoletz.

16.43. What factors of an organism influence development of malignant tumours?

Development of a tumour is defined not only by properties of tumoral cells, but also influence of an organism on this process. The greatest value has:

a) Vascularisation of tumours. It is shown, that the maximal remoteness of tumoral cells from a gleam of blood vessels cannot be more than 1 - 2 mm. If the distance exceeds this size, cells of a tumour perish.

In a malignant tumour, as a rule, intensively sprout blood vessels. It is connected by that tumoral cells release so-called angiogenetical factor (angiogenine) which stimulates growth of capillaries and duplication of endothelial cells;

b) Hormones. Though tumoral process is independent, there are, however, tumours which show high hormonesensitiveness. It is, in particular, a cancer of mammary gland, uterus, ovaries, prostate. One hormone accelerate growth of the specified tumours, others slow down;

c) Condition of mechanisms of antineoplastic protection of an organism.

16.44. What mechanisms of antineoplastic protection exist in an organism?

I. Mechanisms of natural nonspecific resistance of an organism to tumours. Have no immunological specificity and do not demand preliminary immunization. They are carried out by the following cells:

a) N?-cells (natural killers). These are greater granular lymphocytes, being a version of 0- lymphocytes. They distinguish tumoral cells and destroy them;

b) LAK (the lymphokine-activated killers). They, as well as NK-cells, carry out cytolysis of tumoral cells;

c) Macrophages. Destruction of cells of a tumour by macrophages is carried out by phagocytosis and mechanisms of extracellular cytotoxicity.

Mechanisms of natural nonspecific antineoplastic protection are effective, if the quantity of tumoral cells in an organism does not exceed 10³.

II. Reactions of the acquired (specific) antineoplastic immunity are caused by specific tumoral antigens and include as cellular, connected with function ?-lymphocytes, and humoral, connected with formation of antibodies, immune reactions.

The specified reactions are effective, if the quantity of cells in a tumour is from 10³ up to 10⁶. If their quantity exceeds 10⁶ the condition of immunological depressions develops and the mechanisms of antineoplastic protection described above suppress.

Date: 2016-06-12; view: 100