TUMOURS

From Big Medical Encyclopedia

TUMOURS (tumores; synonym: blastomas, new growths) — the excessive pathological growth of fabrics, in-coordinate with an organism, continuing after cancellation of the reasons which caused it; consist of qualitatively changed cells become atypical concerning a differentiation and the nature of growth transferring these properties to the descendants. The lake arises from appearance of small group of atypical cells, due to reproduction to-rykh there is its growth. The main signs of O. are its atypia (on a structure, an arrangement and relationship of cells of O. differ in various degree from initial fabric), autonomous growth (see) and progression of a tumor (see). Researches in the field of a carcinogenesis, diagnosis, treatment and O.'s prevention are a subject oncology (see).

Fig. 1. An endoscopic picture of the lipoma (is specified by an arrow) which is located under a mucous membrane of a stomach, hemorrhage in a tumor. Fig. 2. Macrodrug of the lipoma of a stomach removed in the operational way, hemorrhage in a tumor. Fig. 3. Macrodrug of a knotty form of a fleecy tumor of a large intestine. Fig. 4. An endoscopic picture of the leiomyosarcoma (is specified by an arrow) which is located under a mucous membrane of a large intestine. Fig. 5. Macrodrug of the same tumor removed in the operational way. Fig. 6. Microdrug of the same tumor: tumor cells of a polimorfna, with large hyperchromic kernels, are located in the form of the bunches intertwining in various directions; coloring hematoxylin-eosine.

Distinguish high-quality and malignant Lakes. High-quality O., napr, lipoma (color. fig. 1 — 2), have expansive growth, as a result to-rogo surrounding fabrics are removed or moved apart, sometimes are squeezed and exposed to atrophic changes. A clear boundary between O. and the fabrics surrounding it with an expansive growth is imitated by formation of the capsule though true capsules, napr, organ, O. do not have similar. Malignant O. infiltrirut and destroy surrounding fabrics. Infiltrative (invasive) growth is the main criterion distinguishing malignant O. from high-quality. Also ability is characteristic of malignant O. to to innidiation (see).

There are also so-called locally destruiruyushchy O. having infiltrative growth, but, as a rule, without tendency to innidiation.

Distribution in the nature

O. are described at all classes and animal species, and also at plants. Growths of a parenchyma of plants can remind O. animals. Nek-rye O. of plants, napr, so-called koronchaty Gauls, consist from with firmness the changed cells similar on biol, to features with O.'s cells of animals. At insects the melanoma of a fruit fly of a drosophila is most known. This tumor occasionally arises spontaneously, but can be caused also in an experiment as a result of ionizing radiation. Lakes occur in many families of fishes, apparently, most often at bony. At fishes tumors are described high-quality (fibroma, a lipoma, a myxoma, a chondroma, an osteoma) and malignant (various types of sarcomas). Adenomas and an adenocarcinoma of a thyroid gland occur at the trout living in reservoirs of Switzerland and New Zealand. O.'s emergence at fishes can serve as the indicator of pollution of reservoirs oncogenous substances. Considerable concentration in a stern of an aflatoxin of V or DDT leads to emergence at O.'s trout of a liver. Aquarian small fishes of the guppy can serve as an object for experimental studying of oncogenous action of a number of nitroso compounds. H. F. Stich in 1975 in the water area of the port of Vancouver which is strongly contaminated by benzpyrene found a significant amount of O. (papillomas) in a flounder. Such O. practically do not occur at the fishes caught in less contaminated reservoirs.

Spontaneous O. of various localization occur at amphibians. Most often find epithelial O. in frogs, napr, multiple adenomas of glands of skin and a tumor of urinogenital system. The melanoma, an epithelioma, a neuroepithelioma and an adenocarcinoma occur at an axolotl.

Among reptiles there is fibroma of a stomach and ovarian cancer the pancreatic cancer and a malignant melanoma — at pine snakes, a fibroadenoma of lungs — at turtles are described at a python.

Practically all types O. known in pathology of mammals occur at birds. At the same time their frequency at birds of different types is not identical; e.g., at geese and O.'s ducks occurs less than at hens. From the birds living in zoos O. at wavy parrots are especially frequent and various. By data I. I. Kasyanenko (1964, 1978), 75% of all O. at hens make hemoblastoses, and from total number of other O. of St. 59% it is the share of O. of urinogenital system. Also fibromas and various sarcomas meet. Nek-rye from sarcomas, napr, so-called sarcoma of Raus, have ability to be intertwined with filtrates. Various forms, many from to-rykh, napr occur among hemoblastoses of hens, Marek's disease, are viral diseases. O.'s frequency of the hemopoietic system at hens as show data of nek-ry researchers, increases at introduction to a food allowance of such products as bone and fish meal, to-rye may contain Oncogenous nitroso compounds.

High-quality and malignant O. occur at all species of mammals. At the same time O. of the same name at different animals are morphologically usually similar among themselves and their frequency increases with age. In the frequency of emergence of O. in general and in the frequency of emergence of O. of separate localizations there are specific differences. E.g., cancer of a lung, stomach, large intestine are frequent malignant O. of the person and seldom occur at the majority of species of mammals. About 90% of all malignant O. of the person have an epithelial origin while at nek-ry animal species the most frequent malignant O. are hemoblastoses (at cattle, horses and pigs — apprx. 80% of all O., and at sheep — apprx. 90%). At dogs about 50% of all malignant O. make sarcomas, among to-rykh so-called transmissible sarcoma of external genitals, sexually transmitted is of special interest. At females of dogs the most frequent are O. of mammary glands which quite often have a structure of carcinosarcomas. O.'s frequency at dogs of different breeds is various; e.g., according to N. A. Krayevsky and V. I. Ponomarkov (1979), hemoblastoses are observed at boxers by 6 times more often than at other breeds, and osteosarcomas occur almost only at large dogs. The melanoma of skin often occurs at horses of light color. At cats lymphosarcomas of the virus nature are of the greatest interest. At mice and rats spontaneous O.' frequency considerably is defined by their belonging to these or those closed lines. At one lines of mice hemoblastoses, at others — an adenocarcinoma of mammary glands, at the third — adenoma of lungs, at the fourth — a gepatoma prevail. Fibroadenomas of mammary glands, O. of a hypophysis, a uterus, sebaceous glands of outside acoustical pass, hemoblastoses most often occur at rats; O. of adrenal glands and a prestomach often are found in golden hamsters. At rabbits of the most frequent the adenocarcinoma of a uterus is, O. of kidneys, mammary glands, etc. meet less often. Spontaneous O. (easy, generative organs, mammary glands) seldom occur at Guinea pigs and are induced also hardly (as a rule, only very high doses of oncogenous substances). O. of a mammary gland at a rainbow trout, spontaneous ferruterous O. of a stomach like carcinoids, and also O. of a liver, kidneys, the hemopoietic fabric at the South African rodent of a ma-stomis are described. Occur at O.'s monkeys practically in all bodies and fabrics, at females O. of mammary glands and ovaries are rather frequent.

Statistics

the First observations about malignant O.' distribution appeared in 15 century when in Shneeberg (Saxony) more frequent emergence of O. at miners, than at working other specialties was noted. In 1728 in London the first attempt of registration of cancer patients was made. In 19 century the results of researches characterizing mortality from malignant by O. Odnako the insufficient account are published did not give the chance to draw any conclusions on features of distribution

of O. Zabolevayemost and began to study mortality from malignant O. in Russia at the beginning of 20 century. The first works on malignant O.' statistics were carried out by L. L. Levshin, S. A. New rural, A. V. Govorov, I. E. Gagen-Thorn, N. A. Velyaminov. The data on registration of patients with malignant O. prepared in 1913 by P. Geynats for the All-Russian hygienic exhibition were added with H. N. Petrov in his report at the III International conference of oncologists in Brussels. However these data did not give an idea of true distribution of O. in 90 provinces and 7 large cities of Russia where they were brought together. Only after the victory of Great October socialist revolution along with the organization oncological service (see) the state system of actions for in-depth statistical studies in the field of oncology gained development. In 1932 in the Ukrainian SSR the system of the special accounting of patients with malignant O. S of 1939 in all cities having onkol, institutions is entered, obligatory registration of patients with for the first time began the established malignant O.'s diagnosis, the expert of 1953 such registration began to be carried out everywhere. Within the 70th in the USSR events for improvement onkol, statistics, to transition to system of the centralized accounting of patients with malignant O. with data processing by means of the COMPUTER are held.

At malignant O.'s detection the doctor fills in the special notice on the patient with for the first time in life the established diagnosis of cancer or another malignant the Lake. At the same time in onkol, institutions fill in «The control map of dispensary observation» behind a sick malignant new growth. Statistical data collect in an organizational me-todicheskikh departments onkol, clinics, statistical bureaus of bodies of health care and are generalized by Management of medical statistics and computer facilities of M3 of the USSR together with scientific research institute of oncology of H. N. Petrova of M3 of the USSR. In a number of the countries it is accepted to conduct selective researches with extrapolation of data on all population of the country. There are population and hospital registers O. Data of hospital registers cover only a part of the patients with malignant O. who are subject to hospitalization. In GDR, Denmark, Norway, Finland and Sweden there are population registers of cancer. In the USSR and nek-ry other member countries of SEV this function is performed by registers onkol, clinics and scientific research institute of oncology.

In economically developed O.'s countries take the second place (15 — 23%, according to WHO data) in the general structure of mortality, conceding to cardiovascular diseases mortality. Rates of mortality from malignant O. on 100 000 population in 1950 and 1976 made to the USA respectively 141,2 and 175,8, in England — 197,0 and 255,4, Japan — 78,9 and 125,3.

Around the world annually the St. 6,3 million people gets sick with malignant O., and not less than 4,3 million the persons die of them. Growth of mortality comes from malignant O. generally at the expense of cancer of a lung, a mammary gland and a rectum. The number onkol, patients in the USSR, as well as in many other economically developed countries, keeps a tendency to growth, especially among men. Men on average in 1V2 of time more often than women, O. of lymphatic and hemopoietic fabric get sick, are twice more often — O. than a stomach and a gullet and in 4kh/2 time to a thicket — O. of lungs. The tendency to decrease in incidence in the USSR by malignant O. of a gullet, a stomach, a neck of uterus is noted, however indicators of incidence of malignant O. of lungs, a mammary gland and rectum (tab. 1) accrue.

Growth of mortality from malignant O. first of all can be caused by falloff of mortality from infectious, parasitic and other diseases, and also a postareniye of the population. In studying of rates of mortality the features of its dynamics, general for many countries, are of great importance. The analysis of rates of mortality from onkol, diseases from 1960 for 1978 demonstrates that rates of its growth in the USSR were significantly slowed down. In the 70th rates of mortality from O. of a gullet and a stomach whereas mortality from O. of lungs, a mammary gland, a rectum increased (tab. 2) considerably decreased.

In the USSR it is accepted the information about all dead from O. which were not staying during lifetime on the registry in onkol, institutions, to include in data on for the first time diseased in the current year. Specific weight of posthumously registered patients with malignant O. among all patients with for the first time the established diagnosis of a malignant tumor averages 2,3% (1977). Decrease in indicators of incidence and mortality from O. of a number of localizations is noted that it is connected with improvement of quality of diagnosis, development and implementation in practice of complex methods of treatment.

The epidemiology of malignant tumors

the Subject of epidemiology of O. is studying of origins and patterns of distribution of O. depending on biological and natural factors, conditions of the social circle of separate groups of the population. The main objective of epidemiology of O. consists in accumulation and the analysis of materials on an etiology and O.'s pathogeny, on the basis to-rykh it is possible to develop rational methods of prevention and treatment. Complex influence of professional and household factors, specific features of an organism (taking into account the combined influence of these factors) create conditions, at to-rykh one groups of the population get into so-called risk groups, and others avoid this danger. According to Doll (R. Doll) and J. Higginson, low indicators of incidence of O. testify to the so-called natural, usual level of tumoral diseases, and increase in these indicators indicates a role of these or those environmental factors. According to Committee on prevention of cancer of WHO, to 90% of tumors it is connected with influence of external factors, and 10% depend on genetic factors and viruses.

In O.'s epidemiology use generally the methods standard in epidemiology, social hygiene and medical geography.

L. A. Zilber considered that carrying out epidemiol, researches O. can promote establishment of a virusogenetichesky origin of nek-ry forms malignant O. Eto justified itself on the example of studying of epidemiology of a disease of Berkitt, and allocation of a virus of Epstayn — Barre was an important link in a chain of these researches. Allocation of a virus of a leukosis of cats, overseeing by Marek's disease at hens and leukoses of a cattle caused the necessity of in-depth studies of incidence of O. at domestic animals. In this plan studying of a role of viruses of domestic animals is of interest to the person and vice versa, a possibility of infection in an experiment of monkeys the material taken from patients with a leukosis. Pilot studies showed a possibility of receiving in the way inbreeding (see) high-cancer lines lab. animals. Domestic animals, napr, at dogs, in breeds, small on number, have certain forms of malignant O. more often that is explained with closely related crossings. Similar observations are noted in small nationalities, at inhabitants of certain islands, etc.

The complex of researches of epidemiology of O. includes studying of production, household and klimatogeografichesky factors, assessment of adaptive mechanisms of an organism, frequency of emergence of separate O. in various areas taking into account migration, an ethnic origin and extent of adaptation; roles of hereditary factors, and also values of disturbances of hormonal, exchange and other functions of an organism.

In O.'s epidemiology demographic data, materials a dignity are widely used. statistics, results social, including forwarding, inspections of various groups of the population. Besides, are exposed to the analysis and data of the clinicodiagnostic examinations conducted with the preventive purpose are used. The complex of studying of O. includes the analysis of dynamics of incidence, and also in-depth studies of O. in selective groups of the population in certain territories. The large role is played by the unified criteria for evaluation of results of researches using mathematical methods. Development of automatic systems of collection of information expands opportunities epidemiol. researches. A special role epidemiol, researches play during the studying of the production factors important for developing of tumors. In a complex with pilot studies they give the chance to define risk groups and to develop system of preventive actions. Epidemiol. observations specify the possible directions of pilot studies of a carcinogenesis. At the same time experimental data prompt need of epidemiological researches not only for the production sphere, but also during the studying of influence of household factors on emergence of the Lake.

The main stages of researches are: definition of features of distribution of O. in the studied territory or in the separate elected groups of the population; development of a working hypothesis, on a basis a cut assessment, group and selection of possible causative factors for drawing up the programmed card of inspection is carried out; a special analytical research on the basis of information collected according to the programmed cards of inspection; experimental check of results of analytical inspection; development of preventive measures.

Important sources of data for epidemiol, O.'s analysis are the demographic indicators characterizing extent of migration and population density, and also data on economy of districts of accommodation of the studied groups. Here a number of the indicators concerning not only smoke, impurities of the environment, availability of household and production allergens, but also sots enters. - a gigabyte. the conditions influencing the state of health of the population. So, the geological and geographical characteristic of the area, assessment of chemical structure of soils and water, climatic and meteorol, factors, features of food and the nature of its preparation shall be made.

The complex of organized researches includes also use of a method of mapping of O. with drawing up atlases for certain territories, comparison with geological, me lo to a gicha remove Teo Ro also other parameters of the same territories.

The significant role in O.'s epidemiology belongs to the retrospective researches based on comparison of groups of ill and healthy faces concerning exposure to their influence of a complex of the studied factors, and also genetic predisposition to O. Izvestno's emergence of St. 100 hereditary syndromes, napr, multiple polyposes of a large intestine with tendency to a malignancy (Gardner's syndrome), Peyt-ts's syndrome — Egersa, extended polyposes went. - kish. path, especially small bowel, retinoblastoma, Vilms's tumor, pigmental xeroderma, neurofibromatosis and some other. Nek-ry malignant O.' frequency in population often affects in increase of emergence them in separate families, and only by means of special researches there can be an otdifferentsirovana at the same time a role of genetic factors. Definition of degree of predisposition to malignant O.' development in families, in to-rykh were observed onkol. diseases, it is made by means of population and genetic and epidemiol, researches. Kliniko-ge a nealogichesky method gives the chance to reveal by poll and studying of registration documents malignant O.' frequency in family trees and to establish separate O.' frequency in families. Families with rather high frequency of malignant O. in several generations are described. At the same time family predisposition to a carcinoma of the stomach, a mammary gland, to leukoses and a melanoma is noted. By data A. I. Ariona (1978), cancer cases of a stomach at men of the first degree of relationship was 1,9 times higher, and at relatives of women — is 2,3 times higher, than in control group. The breast cancer at relatives of the first degree of relationship also meets more often, and at relatives in a climacteric it is observed more often by 5,2 times. Preferential defeat of nek-ry ethnic groups of the population tumors of a gullet (Kazakhs, Tatars, Mongols, etc.) can testify to a role of a genetic factor also.

The etiology and a pathogeny

In O.'s etiology attach great value to action ionizing radiation (see), oncogenous substances (see) and viruses (see. Oncogenous viruses ), a cut in some cases can be combined. At the same time the oncogenous effect can be strengthened by not oncogenous agents and is modified by various factors. In these or those O.' etiology factors can prevail various etiol. So, e.g., among the reasons of a carcinoma cutaneum Uv-radiation, among the reasons of cancer of lung is of great importance, and it is probable also throats, the greatest significance is attached to inhalation of oncogenous substances from the free air contaminated by them, e.g. during the smoking. The disturbances of process of self-cleaning of lungs connected, e.g., with hron, bronchitis and other diseases can play an important role to-rye promote a delay and deposition in lungs of oncogenous substances. Etiol, Oncogenous cyclic amines, in others — endogenous blastomogenic derivatives of tryptophane or tyrosine can appear the factors leading to development of cancer of bladder in one cases. Disturbances of exchange of endogenous metabolites, damages of fermental systems, stagnation of urine, etc. can promote effect of oncogenous substances on a mucous membrane of a bladder. Many O.' etiology, napr, a hysterocarcinoma, and partly and necks of uterus, tumors of milk, prostatic, thyroid glands, a hypophysis, adrenal glands, etc., is based on dishormonal shifts in an organism. The facts, to-rye, undoubtedly, roles of oncogenous viruses at the most often found malignant O. would demonstrate about etiol, of the person, it is not received. Idea that Oncogenous agents affect those macromolecules of a cell is standard, to-rye define synthesis of protein and consequently, growth, reproduction, a differentiation and behavior of cells. As a result of, apparently, multistage process there are clones of the cells which are exposed to a malignancy (see. Carcinogenesis ).

The biology of tumoral growth

is the cornerstone of O.'s emergence emergence and reproduction in an organism of the tumor cells capable to transfer the properties acquired by them in an infinite series of generations (see. Carcinogenesis ). Therefore tumor cells consider as genetically changed. Division of the preexisting tumor cells — the main and in most cases the only way of growth of the Lake. Primary nodes of many O. of the person and animals represent clones, i.e. consist of cells, being descendants of one tumor cell. At malignant O. transfer and reproduction of tumor cells in other fabrics leads to formation of metastasises. In experimental conditions tumor cells can be transplanted from one organism to another, and also to grow up and it is long to brown in cellular cultures (see. Cultures of cells and fabrics, in oncology ). In the course of O.'s growth properties of neoplastic population can change, apparently, because the arising new options of tumor cells can gain the separate properties other than parent. In cultures of cells it is possible to create special conditions, at to-rykh in them the options of tumor cells less different from normal cells, than the majority of cells of culture collect.

Distinctions between normal and tumor cells arise in connection with the changes of a genome leading to emergence in a cell of tumoral properties and the nature of phenotypical structural changes and functions of a cell. There are several types of the changes of a genome leading to emergence of tumor cells: 1) the integration of a genome of an oncogenous virus with a genome of a cell which is a basis of the tumoral transformation caused by oncogenous viruses; 2) a mutation of a cellular genome (the question of the specific genovariations distinguishing tumor cells from normal is not clear so far; there are data on characteristic restructurings of chromosomes in cells of nek-ry types O. and leukoses); 3) epigenomny changes — the permanent changes of genetic properties accompanying a differentiation of cells in their embryonic development. Change of a differentiation is characteristic feature of many tumor cells, however there are no proofs that genetic distinctions between tumor and similar normal cells come down only to epigenomny changes. At O.'s development, and also at different stages of a progression of the same tumor the role of different types of genetic changes can be various.

Disturbances of reaction to action of factors of the microenvironment surrounding cells in an organism are characteristic of tumor cells (humoral factors, the next cells, collagenic fibers, basal membranes, etc.). The most characteristic of them are disturbances of regulation of reproduction, a differentiation and formation of contacts of a cell with various surfaces, e.g. with a bottom of a cultural vessel. Disturbances of regulation of reproduction at tumor cells consist in disappearance of ability to change a reproductive rate depending on influence of control factors of a microenvironment. Decrease in hormonal dependence of growth at many types of tumor cells belongs to manifestations of disturbance of reaction to humoral factors: such cells gain ability to a mitosis for lack of hormones, to-rye were necessary for reproduction of stem normal cells. In culture of cells the minimum concentration of serum, calcium and the nek-ry other components of a microenvironment necessary for their reproduction are quite often lower for tumor cells, than for initial normal.

During O.'s progression many signs of a differentiation of tumor cells can be lost that is one of manifestations anaplaziya (see). However at the majority of types of tumor cells these or those signs of a fabric differentiation remain, to-rye are characteristic of stem normal cells. The special form of disturbances of a differentiation of tumoral fabric can be considered emergence of ability to synthesis of embriospetsifichesky proteins, i.e. proteins, to-rye similar normal fabric synthesizes only in the embryonal period, napr, embriospetsifichesky hepatic protein of alpha-fetoprotein. Degree of a differentiation of tumoral fabric sometimes can be raised significantly, having changed conditions, in to-rykh tumor cells grow. E.g., to A. D. Ti-mofeevsky (1946) was succeeded to achieve increase in degree of a differentiation of cells of a rabdomioblastoma in culture of fabric; Mintts (V. Mintz) with sotr. (1976 — 1977) received similar results at change of cells of a mouse teratoblastoma in an environment of normal embryonic cells.

the Scanning diffraction pattern of normal and tumoral fibroblasts: and — the normal fibroblast has a smooth surface and is spread on a substrate; — the tumoral fibroblast has a fleecy surface and is badly spread on a substrate; X 2500.

Reproduction of tumor cells in culture can become independent of contact with a substrate — a bottom of a cultural vessel and to take place in not attached suspenzirovanny state whereas fibroblasts are normal and epithelial cells breed only after an attachment to takop to a substrate. At cultivation of cells find also disturbances of dependence of reproduction on contacts with other cells: at achievement of critical density of cell population (a certain number of cells per acre of a substrate) reproduction of normal cells stops whereas reproduction of tumor cells can continue. Disturbance of formation of contacts of a tumor cell with various surfaces consists that they in culture of fabric are weaker, than normal, are attached to noncellular substrates (e.g., to walls of a cultural vessel), less spread on such substrates and worse form intercellular contacts (fig). It probably is the reason of many disturbances of structure of tumoral fabric in an organism.

Tumor cells are capable to grow and extend selectively in fabrics because they are less dependent on control factors of a microenvironment, than homologous normal cells. At early stages of a progression of O. such distribution can be limited to the territory specific to cells of this fabric type; e.g., epithelial tumor cells of carcinomas of in situ can extend within epithelial layer, without sprouting a basal membrane. At later stages of a progression of a tumor its growth can become invasive, i.e. tumor cells begin to extend in surrounding fabric. To growth and distribution of tumor cells in an organism the fact that many of them are capable to induce reproduction of connective tissue cells and capillaries (stromato-gene and angiogenic action of tumor cells) in surrounding normal fabric that provides creation in tumoral fabric of network of the vessels feeding it is essential. Induction of such proliferation is connected with allocation by tumor cells of the angiogenic factors, apparently, having the proteinaceous nature.

In the course of innidiation there can be a selection of special options of the tumor cells differing on the properties from the ground mass of primary O. V an experiment by selection it was succeeded to receive from one tumoral strain several various sublines which are sharply differing on extent of innidiation and localization of metastasises, napr, selectively metastasizing in lungs, a brain and other bodies. It proves that distinctions in the nature of innidiation can be connected with elective affinity of nek-ry types of tumor cells to certain fabrics.

The nature of changes of the cellular structures and functions defining the broken reaction of tumor cells to influence of factors of a microenvironment remains not quite clear. The central role in interactions of a tumor cell with a microenvironment is played it an outer membrane with molecules receptors, and also the cortical layer responsible for the movements of a membrane and number of intracellular structures located under an outer membrane of a cell. Molecules receptors of an outer membrane of a tumor cell can interact, e.g., with molecules of hormones or surfaces, with to-rymi the tumor cell contacts. It in some cases is followed by complex reorganization of a cellular membrane with change of its permeability (e.g., for calcium, sodium, sugars), activities of membrane enzymes (e.g., the adenyl cyclase catalyzing education cyclic 3-5 adenosinemonophosphates), and also components of a cortical layer. These shifts can serve as the initial stages of various regulatory reorganizations of a cell. According to many researchers, changes of their surface are the cornerstone of the broken reactivity of tumor cells. So, on a surface of many tumor cells to an ots! stvut protein the fibronekting to-ry is available on Nosta of stem normal cells outside atop. Also changes chemical sost a tava of the carbohydrate chains which are attached outside to a nek-eye to proteins and lipids of an outer membrane of a tumor cell are described. At interaction with a substrate under a membrane of normal cells characteristic change of a cortical layer is observed, in Krom bunches of octynic microfilaments appear. At many types of tumor cells such bunches are not formed that can demonstrate disturbances of structure of a cortical layer. Remains not clear, surfaces of cells, what of changes, are most specific to tumoral transformation and are important for disturbances of reactivity of cells.

Kinetics of tumoral growth.

Growth rate of O. depends on several kinetic characteristics of tumoral fabric: durations of a mitotic cycle of tumor cells, sizes of growth fraction (proliferative pool) and speed of death of tumor cells. A mitotic cycle of tumor cells as well as normal cells, consists of several phases: phases Gx (prereplikativny), phases S (synthesis of DNA), phases G2 (post-synthetic) and phases M (actually mitosis). In usual conditions of neoplastic population are asynchronous, i.e. in each timepoint of a cell of population are distributed evenly on different phases of a cycle. The average duration of a mitotic cycle (an interval from a mitosis to the following mitosis, or time of generation) different O.' cells fluctuates within 16 — 60 hours that usually it is not less, than at intensively breeding normal cells of an adult organism. Growth fraction call the part of the cells of tumoral population participating in a mitotic cycle expressed as a percentage. The growth fraction only in nek-ry O. approaches 100%; in the majority of the animals investigated by O. and the person it makes lower figure (30 — 70%). Thus, in O. there is a considerable fraction of not breeding cells that can be result of an irreversible differentiation of cells (e.g., keratinizations of cells in planocellular cancer); damages of cells (e.g., as a result of a lack of nutrients); reversible transition of cells from a mitotic cycle in a so-called resting phase (phase Go).

As an indicator of intensity of death of tumor cells use a factor of loss of cells — a percentage ratio of number of the perishing cells to total number of the cells which increased in population as a result of cellular division during one cycle. In nek-ry experimental O. and new growths of the person the factor of loss of cells makes 80 — 90%. Death of tumor cells most often, apparently, is result of a lack of nutrients in growing at the Lake.

Change of each kinetic indicator of tumoral growth can lead to changes of growth rate of a tumoral node; e.g., delay of growth of O. can be result not only increases in duration of a mitotic cycle, but also reduction of growth fraction, and also increase in number of the perishing tumor cells. Growth rate of O. is usually determined by repeated measurements of diameter of a tumoral node. Growth of a number of tumoral nodes can be described as exponential function, at the same time time of doubling of number of tumor cells in a node in process of its growth remains to constants. However many O.' growth considerably deviates exponential; most often in these cases time of doubling of number of tumor cells increases in process of growth of a node.

For definition of kinetic indicators of tumoral fabric usually use autoradiographic methods using thymidine, marked hyzone; for assessment of distribution of cells on phases of a mitotic cycle it is possible to use also a method of flowing tsitospektro-photometry. The available methods of definition of growth fraction and a factor of loss of cells are insufficiently exact.

Biochemistry

Biol, properties of a tumor cell are not caused by proteins, enzymes, specific to O., or the general for all O. in the metabolic ways which are absent in normal cells of an organism during this or that period of its ontogeny. Only in O. induced by DNA - the containing oncogenous viruses, the specific squirrels participating in transformation of these cells are found. So-called opukholespetsifichesky antigens in many cases were proteins of an embryonal origin or components of an oncogenous virus. Lakes are capable to synthesize embryonal proteins, napr, alpha-fetoprotein, and also embryonal isoforms of many enzymes of carbohydrate, nitrogen and phosphoric metabolism, e.g., of a pyruvatekinase, thymidinekinases, an alkaline phosphatase. In gepatoma of experimental animals there is highly active ^-gluta-mit the transpeptidase synthesized also by a liver of an embryo. Nek-rye O. is synthesized sometimes by ectopic hormones not inherent to homologous fabrics; e.g., planocellular cancer of a lung in some cases produces parathyroid hormone, ovsyanokletochny cancer of a lung — adrenocorticotropic hormone, etc. It is undoubted that in a tumor cell regulation of processes of life activity, and first of all a metabolism is broken. However it is not established what deviation biochemical, processes causes a nekontro-liruyemost of growth

of O. O. Warburg opened feature of energy balance of a tumor cell — intensive anaerobic glycolysis (see) what promotes to as later it became clear, repeated increase in activity of enzymes of a hexokinase, fosfofruktokinaza and pyruvatekinase, and also sharply increased permeability for glucose of outer membranes of tumor cells. However blast cells at an acute lymphoid leukosis keep the aerobic type of exchange inherent in their normal analogs. The ability described also by Warburg tumoral kletkd to aerobic glycolysis was not specific and is not shown with O.'s growth in an organism.

The lake is characterized by potentially full breath though absolute activity in its cells of nek-ry enzymes of a respiratory chain (cytochrome oxydase, a suktsinoksidaza) and contents tsitokhroma-S are lowered. Lakes oxidize fat to - you and proteins, and also glucose at its surplus. O.'s breath in an organism is weakened because of its poor supply by oxygen, and for it anaerobic glycolysis is the main source of energy. As a result of sharp lag of speed of intake of glucose from the speed of its exchange in fabric O. it is supported low, almost imperceptible, the content of glucose that causes essential shifts in a homeostasis. The lake realizes only a small share of the potential ability to exchange of glucose in an organism and therefore can absorb in addition its huge quantities entered from the outside until the level of glucose in it is not balanced with that in other fabrics. Lakes have the lowered ability to synthesis fat to - t from glucose and acetate. She receives the main number of necessary O. of lipids from an organism in the form of lipoproteids of very low density and free fat to - t in a complex with albumine.

Processes of protein synthesis and nucleinic to - t in O. prevail over processes of their disintegration. Though this feature is inherent also in the normal growing fabrics, but unlike them in tumor cells intensity of disintegration of proteins, amino acids and nucleinic to - the t is insignificant. The island receives ready amino acids from an organism. Her need for a glutamine and asparagine is especially big. In tumoral fabric repeated increase in activity of the enzymes participating in synthesis of purine and pirimidinovy nucleotide predecessors nucleinic to - t with simultaneous easing of activity of enzymes of their disintegration is noted.

The lake, as well as any growing fabric, strenuously synthesizes polyamines — putrestsin, from Perm of dynes, spermine. In a blood plasma and urine of a considerable part onkol, patients the content of polyamines is increased, a cut sharply decreases after operational removal of the Lake. Reduction of content of polyamines in a blood plasma and urine and the relations can indicate spermidine/spermine positive effect of treatment by antineoplastic means or radiation therapy.

The despetsialization, disturbance of a differentiation and the perverted reaction (resistance or, on the contrary, supersensitivity) to the factors, in particular hormones controlling biochemical, processes is characteristic of tumoral fabric biochemical. These lines, however, are rather secondary sign, result of a progression of O. and are almost not characteristic of high-quality

O. V of the intertwined O., especially in malignant gepatoma, alignment phospholipid-nogo of structure of plasma, mik-rosomny and mitochondrial membranes is observed. Each of the specified types of membranes contains phospholipids, specific to it, in normal hepatocytes. In malignant O. of the person, except acute leukoses, there comes unification an isoenzyme-nogo of a range of a lactate dehydrogenase towards increase in a share of V and reduction of a share of the I isoenzymes. Sharp falling of activity of an isoenzyme of the I lactate dehydrogenase is characteristic also of high-quality O. and blast cells at an acute lympho-and miyeloblastny leukosis. The last feature is universal for any O. though biol, the sense of the phenomenon remains not clear. In gepatoma nek-ry enzymes of a gluconeogenesis, specific to a liver, disappear, ability to form acetoacetate from fat to - t sharply decreases. Normal in a liver and leukocytes synthesis of cholesterol at its surplus in blood is suppressed. In tumor cells of a liver and blood this mechanism of regulation is, as a rule, lost. The carcinoma of a mammary gland can be a rezistentna to estrogen and in case of preservation of cytosolic receptors to these hormones. The carcinoma of a mammary gland of a rat induced by dimethylbenzanthracene gains dependence on insulin: at an animal with experimental diabetes growth of a tumor stops, homologous normal cells are not sensitive to insulin.

In a tumor cell selectivity of transfer of information RNA from a kernel in cytoplasm is weakened, in to-ruyu their richer set, than in the based normal cell gets. The similar phenomenon is observed also in actively proliferating normal fabrics.

It is obvious that O.'s adaptability to unfavorable conditions of internal environment of an organism (the low oxygen content, metabolites, ions, etc.) which are not interfering its growth shall be caused by the corresponding shifts in the fermental and receptor device O.

the Physical and chemical characteristic of growth of tumors

Among physical. - chemical characteristics of growth of O. the greatest value has studying of ranges of the electronic paramagnetic resonance (EPR) of tumoral fabrics.

H. M. Emanuel and sotr., A. N. Sap-rin, Shvartts (S. The lake of Schwartz), is established by P. Y. Duchesne, Mylay that tumor cells are characterized by signals electronic paramagnetic resonance (see), other than those in homologous normal fabrics. There is a certain pattern in change of intensity of signals of EPR of a tumor and normal fabrics. The influences leading to O.'s regression or braking of its growth are followed by normalization of ranges of EPR of tumor cells. In O.'s most of animals and the person are found unusual for biol, objects signals of EPR with triplet structure, to-rye are caused by the nitrozilny complexes of haemo proteins localized in mitochondrions and microsomes. Formation of these complexes is accompanied by development of a hypoxia in tumor cells and recovery of nitrates. However it turned out that the signal of EPR is not specific to O. since it is found at nek-ry influences in normal fabrics and is connected with development in them necrotic changes.

In the course of O.'s growth intensity of signals of EPR in tumor cells changes. Concentration of free radicals (see), measured by the EPR method, in a row O., napr, a rhabdomyosarcoma, a lymphosarcoma, above, than for homologous normal fabrics, in other O., napr, a gepatoma — below. The kinetics of change of radical concentration in O. is connected with patterns of tumoral growth.

The maximum of radical concentration always on time precedes achievement of the maximum growth rate

of O. V a tumor cell other interrelation between biophysical, characteristics, than in healthy cells is observed that can be essential in change of sensitivity of tumor cells to regulatory influences. Changes of lipidobelkovy relationship in membranes of tumor cells, increase in membrane potential of rest, a negative charge of tumor cells are important. Increase in viscosity of membrane components, change of structure of gangliosides and glycolipids can be one of the reasons of change of contact interaction, recognition of cells, sensitivity of receptors to factors, growth-regulating.

Immunology

Immunol, O.'s relation and an organism include natural resistance of an organism to O., reaction of the acquired (specific) immunity and an immunodepressive effect of O. on an organism.

Natural resistance of an organism to O. does not possess immunol, specificity and does not demand preliminary immunization. By means of pilot studies it is established that recognition and rejection of single tumor cells is carried out immunol, system of natural resistance. The special kind of the lymphocytes having cytotoxic effect on various Lakes is found in animals and the person. Such lymphocytes received the name of NK cells or natural killers. The nature of their antigensvyazyvayushchy receptors and the mechanism of recognition of tumor cells by them are not found out. These lymphocytes are present at an organism normal and do not belong to T - or to V-lymphocytes, quantity they do not increase with a growth of the Lake. Other important factor of natural resistance of an organism to O. are macrophages (see). Activation of macrophages, apparently, generally caused a favorable effect of intra tumoral introduction of BTsZh.

Reactions of the acquired (specific) atrepsy (see. atrepsy ) are caused by the specific tumoral antigens which are present at a row O. At the same time O.'s immunogenicity significantly depends on its etiology. Most immuno O. induced by exogenous oncogenous viruses are gene. A genome of these viruses, being built in a genome of a cell, induces in it protein synthesis and glycoproteins — actually virus or not entering into structure of a virus. These proteins are alien for an organism and therefore immunogens. If they are present at a cellular membrane, then immunol, reaction is directed not only against a virus, but also against a tumor cell and is capable to suppress its growth. Immunity is carried out in this case by immune lymphocytes together with macrophages, the special lymphocytes distinguishing the target cells covered with antibodies, and humoral antibodys with participation of a complement. In different systems this or that type immunol, impacts on O. Podobnye immunol prevails. O.'s relation and an organism are widespread, e.g., at O. caused by viruses of papilloma and on-liomy in different animals, a viral leukosis and sarcoma of cats, leukoses and sarcomas of the mice and rats called a lab. strains of the corresponding viruses, viral leukoses and sarcomas of hens, Marek's disease of hens, epizootic leukosis of cattle, viral leukoses and sarcomas of monkeys. At the person Berkitt's lymphoma and a so-called nasopharyngeal carcinoma can be carried to this group. The virus of group of herpes takes part in these O.' education (Epstayn's virus — Barre), a genome to-rogo

is present at cells of these O. Meney the immunogens O. caused by the viruses getting to an organism with gametes in shape about a virus (endogenous viruses) or with milk of mother as, e.g., viruses of cancer of mammary glands of mice. Antigens of these viruses induce in an organism partial or full immunol, tolerance (see. unresponsiveness ), specifically suppressing an immune response on these antigens.

At similar O.' development even immunostimulation — strengthening of their growth at suppression of immune system is found.

The special type of atrepsy is revealed at O. of the animals induced by strong oncogenous substances, napr, metilkholantreny. These O., as a rule, immunogens, but immunity to them is individually specific, i.e. is sent against this tumor with slight cross-reactions in relation to others to O. Immunitet the hl is carried out. obr. immune lymphocytes — so-called. T-killers. The nature and an origin of antigens of such O. are not established.

The most extensive group are the spontaneous O. of an unspecified etiology arising out of explicit dependence on virus or other oncogenous factors, which are characterized by very low immunogenicity or even its absence. In spontaneous O. embryonic antigens, slaboimmunogenny in vivo, but revealed by means of reactions of cellular immunity of in vitro most often are found. These antigens define cross immunol, between various spontaneous O. Priroda of immunogene spontaneous O.' antigens is not established to reaction. The exception is made by cells of germinal embryonal carcinomas of mice, in to-rykh the membrane antigen, immunogene in singenny system is identified.

At plasmacytomas and V-lymphocytic lymphoma there can be monoclonal immunoglobulins connected with a cellular membrane. Each clone normal and according to tumoral V-lymphocytes produces the immunoglobulin containing unique determinant group (an idiotypic determinant) which is as if specific immunol, a marker of this clone. Idiotypic determinants of immunoglobulins immunogens in singenny system can also cause effective specific atrepsy.

In some cases, napr, at a melanoma, find the antibodies reacting with O. and specific reactivity of lymphocytes of in vitro with cells of autologous Lakes in patients. These reactions and a possibility of their use for the diagnostic purposes or O.'s immunotherapy it is strenuously studied.

O.'s progression, as a rule, is followed by immunodepressive effect — weakening of hypersensitivity reactions of the slowed-down type, decrease in number of T lymphocytes or them funkts, activities. In onkol, practice are used immunol, tests for hypersensitivity of the slowed-down type and T lymphocytes, to-rye, in addition to the general assessment immunol, the status of the patient, have also a nek-swarm predictive value.

The antigens associated about O., in particular tumoral embryonic antigens are used for immunol, diagnoses and estimates of efficiency of treatment of a row O. So, at hepatocellular cancer of a liver, teratoblastomas of a small egg and an ovary define alpha fetoprote-in, at tumors of intestines — a cancer embryonic antigen, trophoblastic tumors — a horio-gene gonadotrophin and trophoblastic beta globulin. Specific antigens of T - and V-lymphocytes use for differentiation of lymphoma.

Influence of malignant tumors on an organism

two main interconnected forms of systemic action on an organism Distinguish, the general for all malignant O.: the competition to body tissues for the vital metabolites and trophic factors, and also O.'s influence on biol, the characteristics of various fabrics leading to disturbance of their differentiation and weakening of the regulating influence from an organism.

The shifts caused by O. in carbohydrate metabolism are especially essential. In malignant O. of the person unlike healthy fabrics glucose is not found. Thanks to this feature of O. are capable «to nasasyvat» glucose from blood. In these conditions compensatory opportunities of an organism will be mobilized — first of all stocks of a glycogen of a liver and muscles are spent. As the main process allowing an organism to cover in most cases a decrease of the glucose absorbed by O. serves the gluconeogenesis, endogenous formation of glucose in a liver and kidneys from not carbohydrate predecessors and in particular glucogenic amino acids and glycerin. When the gluconeogenesis is not stimulated or O. have the big sizes, there can come deep hypoglycemia (see). It is described apprx. 150 cases of falling of a sugar content in blood to 6 — 15 mg on 100 ml against the background of the normal or lowered level of insulin in blood. Hypoglycemic influence of O. can be revealed by means of special receptions even in the organism supporting a normoglikemiya on tension of compensatory processes of a gluconeogenesis and an expenditure of a glycogen. It is known that the gluconeogenesis is stimulated by a glucagon, a growth hormone and especially glucocorticoids. According to many researchers, the maintenance of glucocorticoids in blood and urine of patients increases during intensive growth of O. Vozmozhno that the shift serves in hormonal balance of an organism to one of the reasons immunodepressive) influences of the Lake. Increase in level of fibrinogen in blood onkol, patients it is possible to explain with action of the glucocorticoids stimulating synthesis of fibrinogen in a liver.

Tumoral fabric is a peculiar trap of nitrogen, both the alimentary, and released at disintegration proteins and nucleinic to - t. Introduction to an organism of glucose preserves nitrogen, prevents emergence of negative nitrogenous balance, weakens a catabolism of fabric, in particular muscular, proteins. These facts testify to a role of hypoglycemic influence of O. as the factor causing shifts of a nitrogen metabolism. A part of amino acids distracts in a bed of carbohydrate metabolism (gluconeogenesis), and synthesis of fabric proteins as a result shall be weakened. At the same time their disintegration amplifies thanks to hyperfunction of bark of adrenal glands that promotes formation of free amino acids as material for a gluconeogenesis.

the Scheme of the frustration of a homeostasis arising in an organism with a tumoral growth.

O.'s growth leads to the strengthened mobilization of lipids of fat depos and muscles. This process is followed by a lipidemia (see. Lipemia ). A part of lipids assimilates O. for formation of membranes proliferating tumor cells. Mobilization of lipids is considered first of all as the compensatory reaction of an organism to hypoglycemic influence of O. allowing fabrics to use at a lack of glucose oxidation fat to - t as an additional energy source. So, the induced hyperglycemia stops mobilization of lipids at a lab. animals with experimental O., at the same time it it is possible to call in healthy animals introduction to an organism of a neassnmiliruye-my structural analog of glucose of a 2-dezoksiglyukoza. Thus, many forms of frustration of a homeostasis of an organism (disturbance of carbohydrate, nitrogen, lipidic metabolism and function of nek-ry endocrine systems) can be considered not as the separate phenomena, and as a chain of the interconnected consecutive events induced by the same starting link — the hypoglycemic influence of O. creating some kind of vicious circle (see the scheme).

At O. disturbances biol, characteristics of various fabrics are noted. In a liver synthesis of a water-soluble catalase is suppressed, activity of tkanespetsifichesky enzyme of a glucokinase, glyukozo-6-phosphatase, a glutaminsintetaza decreases and activity of thymidinekina-zy, an isoenzyme geksokinazy-Sh, glyukozo-6-fosfatdegidrogenazy increases. In lysosomes of a liver activity increases (3 galactosidases, arylsulphatases, R-glucuronidases, cathepsine and acid ribonuclease. In likhmfoidny fabric a lab. animals with experimental O., in lymphocytes onkol, patients hypoactivity of an adenosinedeaminase that is followed by accumulation of dezoksi-adenosinetriphosphate, extremely toxic for lymphocytes.

In microsomes a lab. animals with experimental O. the indutsiruyemost is sharply weakened by alien compounds of enzymes. As a result such animals become more sensitive to action nek-ry pharmakol, agents. In microsomes and mitochondrions of these animals peroxide oxidation unsaturated fat to - t as result of depletion of a liver by antioxidant (and-tokofe a beater) and an imbalance between the enzymes generating peroxides of lipids (NAD P • H-dependent dioxygenase) and the enzymes inhibiting this process (02 dismutase) and utilizing peroxide (glutathione peroxidase) is strengthened. In the isolated mitochondrions of cells of a liver a lab. animals with quickly growing malignant O. breath and phosphorylation is partially separated, but normal respiratory phosphorylation can be recovered by addition on Wednesday of albumine. This fact indicates accumulation in mitochondrions of the highest unsaturated fat to - t, to-rye are effective razobshchitel and easily contact albumine. In a liver a lab. animals with nek-ry intertwined by O. considerably limit of sensibility to glucocorticoids is increased. E.g., at mice with Ehrlich's carcinoma, at to-rykh there comes the hypoglycemia, the gluconeogenesis remains at a low level and is stimulated only with considerable doses of glucocorticoids.

As a starting link in the frustration of a homeostasis arising in an organism with a tumoral growth serves hypoglycemic influence of a tumor. It causes hypofunction of the insulyarny device and stimulates the compensatory mechanisms providing, as a rule, a normoglipemiya by means of hyperproduction of glucocorticoids to-rye stimulate endogenous formation of glucose (gluconeogenesis) from not carbohydrate connections (products of the strengthened disintegration of proteins of muscular tissue — glucogenic amino acids) and mobilization of lipids with release of glycerin. Hyperproduction of glucocorticoids causes also an immunosuppression. Derivation of a part of amino acids in a bed of carbohydrate metabolism breaks protein synthesis of muscular tissue that along with other changes leads to muscular dystrophy.


At patients with cancer of a stomach, lung, mammary gland in process of distribution of process the progressing decrease in level of immunoreactive insulin in blood serum and disturbance of dependence between products of an anterior pituitary hormone and hormones of other hemadens is observed. In particular, falloff of content of triiodothyronine happens against the background of the increased level of content in blood of thyritropic hormone. At a hysterocarcinoma, a mammary gland and a rectum loading glucose does not reduce the level of maintenance of a growth hormone in blood, and in nek-ry cases this loading causes even paradoxical reaction — hyperproduction of a growth hormone. At patients with malignant O. of various localization the limit of sensibility of gipotalamogipofizarny system regulating secretion of adrenalosteroid is increased.

The nomenclature, a structure, classification

a large number of separate forms O. (in the guide to pathoanatomical diagnosis of O. under N. A. Krayevsky and A. V. Smolyannikov's edition, 1976, it is mentioned apprx. 500 various forms O.) Is allocated. The gistogenetichesky and histologic principles in this connection in names their cellular and fabric accessory is reflected are put in a basis of the nomenclature and O.'s classification. Despite significant progress of the equipment, morfol. researches, gisto-and nek-ry O.' morphogenesis remains unsolved that complicates their classification.

Names of most of O. consist of two parts: the first part contains the instruction on a source of development of a tumor (cells, fabric, body), the second part is the suffix of «ohm» meaning a tumor. E.g., the tumor developing from fatty tissue is called a lipoma, from cartilaginous tissue — a chondroma, muscular tissue — myoma, etc.

In the name O., in addition to its gistogenetichesky features, point to its communication with this or that body (e.g., adenoma of a thyroid gland), or anatomic area (e.g., a lipoma of a hip), etc. In creation of names of a row O. deviations from the specified principle meet; e.g., the epithelial tumor of a liver is called ge-patomy, a tumor of a meninx — a meningioma, a tumor of a thymus — a thymoma, etc. Quite often in the name O. its cellular structure is emphasized; e.g., the tumor from histiocytes is called a histiocytoma, from cells of Leydiga — a leydigoma, from Sertoli's cells — serto-liomy.

The tumors arising from elements of the hemopoietic system received special names — lymphoma, leukoses, etc. O.'s structure can remind fabrics or bodies and then speak about histoid or organoid Lakes. In some cases in O. find elements of embryonal fabrics that allows to designate them as embryonal and teratoid O., or teratomas. A question of such O.' zlokachestvennost on morfol, given to solve sometimes very difficult. In the presence of signs of a zlokachestvennost of epithelial and mesenchymal components O. use the term «teratoblastoma».

Proceeding from ideas of possible sources of development, O. distribute on main types of fabrics: epithelial, connective tissue, muscular and neurogenic. Similar communication is reflected in the majority of names O., but there are also deviations from this rule. E.g., malignant connective tissue O. received the general name sarcoma (see) owing to external similarity of their fabric to fish meat. This term is applied also to malignant O.' designation muscular and nervous fabrics, however their similarity to fish meat is observed not always. The term «sarcoma» is, as a rule, supplemented with the instruction on its fabric a source, napr, a liposarcoma, a chondrosarcoma, etc. If a fabric source of sarcoma is muscular tissue, then depending on its character (smooth or cross-striped) speak respectively about a leiomyosarcoma or a rhabdomyosarcoma (tsvetn. fig. 5 — 6). Terminological designation O., coming from epithelium, very variously. So, in high-quality epithelial O.' names consider not only an initial epithelium, but also features of a structure of tumoral fabric. E.g., papillomas call O. with formation of papillary structures developing from a multilayer flat or transitional epithelium, polyps and adenomas — O. with formation of zhelezistopodobny structures, coming from a cylindrical epithelium. Also the combined names, napr, a glandular polyp can be applied. The malignant O. developing from an epithelium are called cancer (see).

The macroscopic type of O. is various. They can have the form of a roundish or oval node, an ulcer, to remind a mushroom or a cauliflower. Their surface happens smooth, hilly, rough, etc. In relation to a gleam of hollow body O.'s growth can be endo-and exophytic. Endophytic growth is directed to depth of a wall, and exophytic — to a gleam of a cavity, napr, a stomach, a bladder, a throat. In nek-ry cases of O. as if diffuzno infiltrirut all body. Macroscopically the border between O. and surrounding fabrics is distinguishable not always. When this border is accurately distinguishable, tell about existence of the capsule O. though do not possess true capsules O.

The basis for establishment of the diagnosis of O. at gistol, its research is existence of a structural atipizm of the cells creating it and all education in general. The structural features inherent only to O.'s cells, by means of modern methods morfol, the research is not revealed. At the same time the tumoral atipizm really exists, however degree of its expressiveness fluctuates over a wide range. As a standard of definition of degree of an atipizm for comparison serve normal cells and fabrics, to-rye as it is peculiar also to tumor cells, breed, grow, create these or those structures. Not accidentally especially often O. compare to the embryonal or regenerating fabrics, and one of the main signs of an atipizm of tumoral fabric is lack of standard completeness of development cycles of cells and fabrics that is shown in formation, e.g., of ferruterous educations without output channels, etc. The cellular atipizm of kernels and cytoplasm can be expressed in other nuclear and cyto plasmatic ratios, features of kernels and cytoplasms, and also extracellular formations. Microscopic examination of O. shows degree of their difference from initial fabrics, gives an idea of mature and unripe O., degrees of their differentiation, an anaplaziya and a cataplasia. By comparison of structure of O. from them biol, features and a wedge, a picture it turned out that, as a rule, less mature and more kataplazirovanny O. differ in a bigger zlokachestvennost. Criterion of a zlokachestvennost is also O.'s ability to innidiation. Metastasises usually repeat a structure of an initial tumor, but can and differ considerably from it, napr, on degree of a differentiation. Therefore establishment of primary center at morfol, a research of metastasises not always perhaps.

The structural atipizm of O. extends to all its components — both the main cellular (parenchyma), and a stroma (connecting fabric, including interstitial substance, vessels and even nervous elements). Proceeding from relationship of a stroma and parenchyma, napr, in epithelial O., there were ideas of cancer-mozgovike (poor in a stroma) and a scirrhus with sharp dominance of a connective tissue stroma over a parenchyma. Stroma of an epithelial tumor (tsvetn. fig. 9) form elements of connecting fabric, development and a structure the cut can be caused by O. Kolichestvo of vessels in O. various, and their structure atypical with existence thin-walled, sinusoidny, irregular shape of vessels. The general very tectonics of vessels in O. differs from their structure in normal fabrics markedly that the wedge helps, to diagnosis, napr, by means of an angiography. Nervous elements O. can form secondary atypical structures. Various deviations in formation of interstitial substance are noted by hl. obr. in sarcomas, they are expressed as excess formation of collagen or osteoid, their wrong distribution, accumulation of mucopolysaccharides, formation of the centers of calcification, etc. In epithelial O. it is possible to observe excess and atypical secretion of slime and even hormones.

Uniform comprehensive classification of O. does not exist. Numerous private classifications are quite often difficult comparable among themselves. At the same time such classifications and the nomenclature are necessary for the statistical account and O.'s analysis, to-rye would allow to obtain comparable aggregated data on institutions, bodies and geographical regions. For the purpose of elimination of the specified difficulties of WHO started the edition international gistol, O.'s classifications, and in 1967 the first of them «Histologic types of tumors of lungs» was let out. By 1981 it is published twenty two gistol, classifications.

There is a number patol, processes, boundary with O., for designation to-rykh instead of a suffix a noma» use a suffix «оз», «napr, a fibromatosis, adenomatosis, etc.

the Diagnosis

the Basis of O.'s diagnosis makes their timely recognition at early stages of a disease when use of radical methods of treatment is the most effective. As onkol, patients ask for the help doctors of different specialties, each doctor shall be O., competent of questions of timely diagnosis, and pretumor diseases. In early recognition of O. the vigilance of the doctor including not only knowledge of symptoms onkol, diseases, especially in initial stages, but also careful inspection of the patient, irrespective of character of the complaints shown them, and also joint decision of questions in cases, difficult for diagnosis, is of great importance onkol. It is especially important onkol, vigilance of the doctor at inspection of persons is more senior than 40 years when the risk of a disease of malignant O. increases. A wedge, displays of tumoral and pretumor diseases are often a little expressed therefore active inspection of the patient is necessary. Use a wedge, methods (survey, a palpation, percussion, auscultation) gives the chance to consistently reveal a number of details, to-rye sometimes have crucial importance for establishment of the diagnosis of the Lake.

O.'s diagnosis is divided on primary, carried out usually in the conditions of polyclinic inspection or during the carrying out routine maintenances, and specifying, to-ruyu, as a rule, out in a hospital. In O.'s diagnosis are of great importance clinical (the anamnesis and an objective research) and tool (radiological, endoscopic, morphological and radio isotope methods of a research. At primary diagnosis of O. the wedge, methods of inspection allow to suspect or diagnose O. and to draw up the rational plan of use of tool methods of a research. For recognition of early forms of cancer of lung use large picture frame fluorography of bodies of a thorax (see. Fluorography ), a carcinoma of the stomach and a colon — the fibrogastroscopy (see. Gastroscopy ) and koloposkopiya (see) from aim biopsy (see), cancer of a neck of uterus — cytologic research (see). Initial shapes O. of a mammary gland in some cases come to light at survey and a palpation, and also with the help rentgenol, and morfol, methods of a research.

The specifying diagnosis at patients from already revealed malignant O. or with suspicion on it is directed to assessment of specific features of a disease and a condition of the patient for the choice of the most rational type of treatment. At the same time it is necessary to reveal local and general criteria of a disease. Refer the specified primary O.'s localization, anatomic features of its growth to local criteria, gistol, a structure, degree of its differentiation and a stage of a disease; to the general — genetic predisposition of the patient to these or those O., it immunol, the status, a condition of a metabolism and a hormonal profile. Local criteria onkol, diseases in a wedge, medicine use long ago. Its general criteria are actively studied and gained practical value at a breast cancer, a retinoblastoma, a pigmental xeroderma, a neuroblastoma, a pheochromocytoma, a paraganglioma, Vilms's tumor and at other tumors.

Along with assessment of local and general criteria in a hospital find out specific features of a disease, specify degree of operational risk. At the same time consider associated diseases, funkts, indicators and age of the patient. For detection of specific features of a disease use various diagnostic methods. The most widespread is rentgenol, the research allowing to establish localization and borders of the Lake. It включает^ non-contrast и^шщщщые methods issledo-Beskontrastnye methods rentgenol. researches (raying, a X-ray analysis and a tomography) use hl. obr. for assessment of a condition of bodies of an abdominal cavity chest less often, extremities, a neck. Multiaxial raying with use funkts, tests allows to make the plan more difficult rentgenol, inspections. X-ray films carry out at different rigidity of x-ray emission that allows to study structure patol, shadows, to receive the enlarged image small patol. center, etc. At a X-ray analysis of nek-ry bodies use natural contrast — the air promoting more accurate identification of borders and structures patol, the center, napr in a throat, hollow bodies, etc. Great practical value for establishment of the preliminary diagnosis has the analysis flyuorogramm lungs and a mammary gland. The tomography (layer-by-layer rentgenol, a research) is often used for O.'s identification lungs. More difficult contrast methods rentgenol, apply researches on special indications, a thicket to O.'s diagnosis of bodies went. - kish. path. For this purpose use liquid contrast agents, napr, a baric suspension and the high-concentrated water solutions of organic compounds of iodine (for contrasting of vessels, krovosnabzhayushchy O. or adjacent to it, and nek-ry bodies, napr, a thyroid gland). Apply to contrasting also gaseous fluids, hl. obr. oxygen, to-ry enter into a mediastinum, retroperitoneal space, a stomach, intestines, etc. Quite often at the same time use liquid contrast agents and gaseous fluids, napr, at so-called double or triple contrast study (tsvetn. fig. 7).

Fig. 7. The roentgenogram of a hepatic corner of a large intestine in the conditions of a double contrast study air and barium sulfate at a colon cancer: not finishing circular narrowing of a gut (it is specified by shooters) with uneven contours is visible. Fig. 8. Endoscopic picture of the same tumor: the edge of the tumoral education (is specified by an arrow) which is sharply narrowing a gleam of a gut is visible. Fig. 9. Microdrug of the same tumor (adenocarcinoma): atypical glands in moderately developed fibrous stroma; coloring hematoxylin-eosine. Fig. 10. Cytologic picture of the same tumor: the group of atypical tumor cells is visible. Fig. 11. An endoscopic picture of a carcinoma of the stomach at the time of capture from a tumor (it is specified by shooters) scraping for a cytologic research. Fig. 12. Cytologic picture of the same tumor (undifferentiated cancer): tumor cells with large hyperchromic kernels are visible.

Endoscopic methods (see. Endoscopy ) allow to inspect hollow bodies by means of special tools endoscopes (tsvetn. fig. 1,4), belly and chest cavities, interfabric spaces to make at the same time a biopsy or to take material for tsitol. researches (tsvetn. fig. 8, 10—12). Use of endoscopic methods of a research allows to diagnose small O., including preinvazivny cancer.

In each case of O. or at suspicion on it use morfol, diagnostic methods, most often a biopsy. However the biopsy is not made at suspicion of a melanoma since the injury can accelerate its growth. The biopsy of osteosarcomas is made only according to absolute indications.

Tracer techniques of a research are based on many O.' ability and their metastasises to accumulate radioactive nuclides and are used for definition of localization of O., its borders, existence of metastasises, assessment of results of treatment, and also identification funkts, shifts in the bodies and systems caused by O. and its metastasises. With the diagnostic purpose to the patient enter the radioactive nuclide possessing short half-life, distribution to-rogo in an organism it is caught by special counters (see. Radio isotope diagnosis ).

Laboratory diagnostic methods of malignant O. are less informative, i.e. special a lab. tests for each type of O. are absent. Use shdmutuod. tests, with the help to-rykh come to light embryonal. antigens, harakternyedlya nek-ry O., napr, alpha fetoprote-in — at primary cancer of a liver and a teratoblastoma of a small egg and ovaries, carcinoembryonic antigen — at cancer of intestines, a2n-fetoprotein — at lymphoma. Lake of a brain and neuroblastoma. Lab. researches (clinical, biochemical, immunological) are of great importance for assessment of the general state onkol, the patient, and their results often serve as indirect confirmation of presence of O. and changes in an organism caused by it.

When the complex of methods of the specifying diagnosis is insufficient, use of diagnostic operation is shown. Such operations apply at suspicion on O. of abdominal organs more often.

Treatment

high-quality O.' Treatment generally operational though in some cases apply methods of radiation therapy, a cryolysis and other methods. High-quality O. shall be exposed to radical treatment, especially when there is a risk of their malignancy. Malignant O.' treatment is performed having distinguished methods depending on the nature of growth and gistol, forms O., its localizations, a wedge, stages, age of the patient, existence of associated diseases, etc. Treatment onkol, patients can be radical, at Krom it is possible to count on full treatment, palliative, usually directed to extension of life of the patient, and symptomatic. Due to the constant growth of number of the patients receiving radical treatment gains great value the organization of their medical rehabilitation, carrying out about-tivoretsidivnoy and fortifying therapy. The main methods of treatment of O. are operational treatment, radiation therapy and medicinal treatment using antineoplastic means, antibiotics and hormonal drugs. Possibilities of an immunotherapy of cancer are intensively studied. Progress modern a wedge, oncology is considerably connected with development and deployment in broad practice of the combined and complex methods of treatment of malignant O., in particular combinations of operational treatment and radiation therapy, addition of an operational method of treatment with purpose of antineoplastic means, combinations of beam and medicinal methods of treatment. In this regard need of hospitalization of the majority onkol, patients in specialized onkol increases. the institutions having the relevant technical base and qualified personnel.

Operational treatment is the basic at the majority of the Lake. It is applied independently or in a combination with other methods of treatment at a carcinoma of the stomach, a lung, colonic and a rectum, a mammary gland, at various forms of sarcomas of bones and soft tissues, etc. At an operative measure concerning malignant O. it is important to specify extent of distribution of tumoral process for the solution of a question of the rational volume of operation and need of use of additional methods of treatment. An operative measure can appear (at far come process), radical go palliative. To O.'s occasion refer imposing of a bypass anastomosis at O. to palliative oneratsiyampyu, to-rye cannot be removed and threaten to close or already closed a gleam went. - kish. path; a gastroenterostomy in similar cases at cancer of a pylorus, gastrostomy) at cancer of a gullet, etc.

A radical operative measure concerning malignant O. is based on the principle of full removal of O. within healthy fabrics. At considerable defeat of any body by malignant O. often there is necessary its full removal or an extensive resection. Use of so-called economical operations is allowed only in early stages of O. and at an isiolzovaniye ^ругпх-^эффективных methods of treatment, in chakhshshst of radiation therapy. During operations for malignant O. adhere to the principle of an ablastika, i.e. such performing surgery when the possibility of leaving in a surgery field of tumor cells is excluded. Standard schemes of operations for O. of various localizations are for this purpose developed. In most cases consider necessary not only removal of the body affected with a tumor, but also excision regional limf, the device where there can already be metastasises or tumor cells capable in the subsequent it to be a source of innidiation. So, at a total or subtotal resection of a stomach concerning cancer excise the uniform block big and small epiploons, a gastropancreatic sheaf and cellulose, in to-rykh nodes are located regional limf (see. Gastrectomy ). At cancer of a uterus make its extirpation and removal by the uniform block of both ovaries together with uterine tubes and wide ligaments of a uterus, and if necessary — is the parameter of l ny cellulose (see. Hysterectomy ). At a breast cancer it is deleted, as a rule, together with big and small pectoral muscles, and also a fatty tissue and limf, nodes axillary, infrascapular, subclavial (and sometimes and parasternal) areas (see. Mastectomy ).

In some cases it is considered the so-called combined operations when together with the struck body the partial resection of the next bodies is made justified to make. So, at a carcinoma of the stomach the splenectomy, a resection of a liver, a pancreas, a colon or its mesentery can be made, at cancer of a lung — a resection of a chest wall etc. The combined operative measure is made usually in cases of germination or a metastayairo-vaniye of a tumor in the next bodies and in the absence of signs of the remote innidiation i.e. when it is possible to expect radicalism of operation. Nek-ry surgeons are supporters of expanded operative measures, napr, removals of a spleen at a carcinoma of the stomach that allows to excise cellulose with limf, the nodes located in her leg. The expanded radical mastectomy when typical operation is supplemented with opening of a thorax and removal of cellulose of a front mediastinum belongs to the same operations.

Carry to special methods of operational treatment of malignant O. electrosurgery (see), a kriodaskhruktion (see. Cryosurgery ) and destruction of a tumor beams laser (see). Apply the alternating currents of high frequency causing the local heat effect used for a section and coagulation of fabrics to an electrosurgery. This method is quite widely applied for the purpose of ablastichny performing surgeries, napr, resections of a stomach, a large intestine, excision of tumors of skin, etc. The cryolysis is carried out by the special device, with the help to-rogo to O. liquid nitrogen moves. This method gained distribution at treatment of outside forms of cancer, especially skin, and is shown when an operative measure can result in cosmetic defects. The cryolysis is applied with the palliative purpose to recovery of passability at cancer of a rectum and gullet, removal of pains, stops of bleeding, etc.

Results of operational treatment of O. depend on many factors, and first of all on a stage of a disease, localization, degree of a maturity and gistol, structures of the Lake. Existence or lack of metastasises in regional limf, nodes is of great importance. Optimum results of treatment are received at a carcinoma cutaneum (5-year survival more than 90% of patients). At a carcinoma of the stomach and cancer of a lung 5-year survival after radical operations makes no more than 30 — 35%.

Radiation therapy consists in use of impact of ionizing radiation on the tumoral center. For radiation therapy (see) apply different types of electromagnetic or corpuscular ionizing radiation: x-ray, gamma, brake (megavoltny) radiations, cathode rayss, neutrons, protons, etc.

The therapeutic effect at radiation therapy of malignant O. is caused by consecutive development in their fabric of the changes of physical, physical and chemical, chemical and biochemical character which are coming to the end with lethal or sublethal damage of tumor cells. As a result of radiation breakdowns of DNA and RNA, an inactivation of a number of enzymes, damages of cellular membranes arise difficult disturbances during exchange processes of a cell owing to what there occurs her death in the period of interphase or during other phases of a mitosis. Along with development in O. of necrotic and necrobiotic processes regeneration of connective tissue elements is observed, leads edges to substitution of destructive sites O. cicatricial fabric.

The effect of damage of tumor cells depends on the size of an absorbed dose of radiation, a time factor (in cases of the fractioned or continuous radiation), conditions of oxygenation of O., its reproductive ability and degree of a cellular anaplaziya, and also on a phase of a mitotic cycle. So, it is established that the cells which are in the phase G1? G2 or M, are characterized by higher degree of radio sensitivity. At the same time the cells staying in a phase S have resistance to ionizing radiation.

The existing distinction in radio-sensitivity (radioporazhayemost) of O. and normal fabric which received the name radiotherapeutic interval (see), causes development after radiation of more expressed destructive changes in O. in comparison with normal fabrics. This phenomenon is explained partially by the fact that in normal fabrics under the influence of the regulating systems there comes fuller and bystry reparation of radiation breakdowns of cellular structures. For the purpose of expansion of a radiotherapeutic interval use various means possessing the radio sensibilizing action (O.'s radiation in the conditions of hyperbaric oxygenation, a hyperthermia, use of elektronaktseptorny connections) or causing the inhibiting effect concerning recovery of beam damages of tumor cells. Researches on synchronization of division of tumor cells and their radiation in radio sensitive phases of a cellular cycle are of also interest.

Radiation therapy of malignant O. is applied as an independent method of treatment or in a combination with others, napr, operational treatment or purpose of antineoplastic means. According to statistical data, in the USSR radiation therapy is applied more than at 70% onkol, patients. Depending on the purpose radiation therapy as an independent method of treatment is subdivided on radical, palliative and symptomatic. Radical radiation therapy provides radiation of a zone of an arrangement of primary O. and its regional metastasises in to lay down. doses. Palliative radiation therapy is carried out for the purpose of partial destruction of O. and stabilization of process. At the same time focal doses are lower, than at radical treatment. Symptomatic radiation therapy is applied at nszdny stages of development of tumoral process and is directed to elimination of the separate symptoms dominating in a wedge, a picture of a disease (pain, a compression syndrome, etc.). The effect reached as a result of symptomatic radiation therapy is temporary.

Various ways of radiation are developed, to-rye depending on an arrangement (orientation) of a source of ionizing radiation in relation to O. call outside (remote), application, intracavitary and interstitial (intra tumoral). Tele-irradiation is carried out by means of gamma and therapeutic installations, roentgenotherapeutic devices, linear or cyclic accelerators and is the most frequent option of radiation therapy. At deeply located O. use multifield cross or mobile radiation. Use of megavoltny radiation (gamma, a bremsstrahlung) allows to lower sharply beam load of skin in the field of the entrance field and to avoid its beam damages. Application radiation is carried out by means of applicators, on a surface to-rykh radioactive drugs 60Co, 224Ra, 137Cs, 90Sr, etc. are placed. It is shown at rather superficially located O., napr, skin, an under lip, an eye. Intracavitary radiation is used at O. of hollow bodies, napr, a uterus, a rectum, etc., and carries out by introduction to cavities of these bodies of special endostat with radioactive nuclides (b0so, 224Ra, 13‘Cs, 252Cf). Intracavitary radiation is often combined with remote radiation therapy — the so-called combined radiation. Interstitial or intra tumoral radiation is carried out by implementation in fabric of a tumor of radioactive needles, naylo-new hollow tubes with granules 60so, 182 That, 192Ir, 252Cf, and also granules 198ai. O.'s radiation in some cases can be carried out by infiltration by its colloid solutions or by endolymphatic administration of solutions of radio headlights-matsevtichesky drugs. At nek-ry O., napr, a thyroid gland, their properties to selectively accumulate radioactive compounds of iodine are used.

Beam methods of treatment can be a part of the combined or complex treatment onkol, patients. Preoperative radiation therapy is shown at O., the most often recurrent and metastasizing, napr, at a melanoma, sarcoma of soft tissues, cancer of an upper jaw, language, a mammary gland, bladder. The main objective at the same time comes down to decline in the ability of tumor cells to implantation in normal fabrics and to development of metastasises or a recurrence of the Lake. Postoperative radiation therapy is directed to destruction of tumor cells both in primary tumor, and in limf, nodes in case of insufficiently radical operative measure.

c make Radiation therapy of O.! by continuous radiation (at low dosage rate) or by means of leading of separate fractions (at high dosage rate). Depending on the size O., it gistol, a structure and radio sensitivity for final fracture it is necessary to bring to O. a dose 5000 — 7500 I am glad (50 — 75 Gr) on condition of radiation "Tpggv — weekly during 5 — 8 weeks. At the same time tolerance of normal fabrics is of great importance, edges is defined by many factors, and first of all a condition of the patient, prevalence of tumoral process, weight of complications and existence of associated diseases. The insufficient accounting of these factors can be an origin beam damages (see).

Use of megavoltny radiation therapy allowed to improve results of treatment of many Lakes. Five-year survival after radiation therapy of cancer of neck of uterus (T1_2N0M0) is observed at 80 — 90% of patients, throat cancer (TjNqMq) — at 80 — 85%, a carcinoma cutaneum (Ti_2N0) — at 96 — 97%, a lymphogranulomatosis — at 60 — 70% of patients in the I—II stage of a disease. Unsatisfactory are results of cancer therapy of a gullet, lung. Five-year survival at these localizations of tumors at T2_3N1M0 does not exceed 3 — 5%.

Medicinal treatment, or chemotherapy — use of the pharmaceuticals having the damaging effect on tumoral fabric. In most cases the chemotherapy is one of components of complex treatment and is used at a certain stage of a disease, supplementing and expanding possibilities of operational treatment and radiation therapy. At nek-ry malignant O. (is more often at hemoblastoses) the chemotherapy is applied as the only method of treatment.

Various O.' sensitivity to separate antineoplastic means is various and therefore special value has a right choice of a method of treatment, especially because antineoplastic means (see) have a certain toxicity, in a varying degree damaging normal bodies and body tissues. Medicinal antineoplastic means of hormonal type were (estrogen) for the first time with success are applied in 1941 by Ch. Haggins and sotr. for cancer therapy of a prostate. In 1942 Goodman, Gilmen and Phillips (L. S. Goodman, A. Gilman, Phillips) found antineoplastic action of nitrogenous analogs of yperite, or Aether chloratus of amin derivatives that was an incitement to active studying of drugs of this group from the point of view of their antineoplastic action. In the USSR researches on O.'s chemotherapy were begun in 1952 by L. F. Larionov and sotr., studying generally drugs of the alkylating action. Works on creation of new antineoplastic means and their approbation are actively conducted in many countries of the world.

All means used for medicinal treatment of O. can be divided into two groups — gormonalnya-lshkarstvenny means and actually antineoplastic means synthetic and natural proiskho zhdyon1shg ~ Rermonadny pharmaceuticals generally use for O.'s treatment which to some extent kept ability of initial fabrics to react to the hormones normal regulating their growth i.e. at so-called hormonedependent O., napr, a prostate cancer, a mammary gland, a body of the womb, a thyroid gland. Nek-ry hormonal drugs, napr, corticosteroids, apply also at treatment of hemoblastoses. Anti-estrogen — derivatives of a-phenyl stilbene is close to hormonal means, one of the main mechanisms of antineoplastic action to-rykh is blocking of receptors of steroid hormones.

The therapeutic effect of the majority of the antineoplastic means possessing cytostatic action is connected with suppression of exchange by them nucleinic to - t, first of all in tumor cells. At the same time they usually exert impact and on exchange nucleinic to - t in quickly breeding populations of cells of marrow, went. - kish. a path, etc. what their side effect is connected with. It is known that antineoplastic means can directly work on nucleinic to - you, breaking their ability to function normally, and also can interact with the enzymes participating in biosynthesis and function nucleinic to - t. The alkylating antineoplastic means directly interact with the nucleinic bases of DNA. Nek-ry antineoplastic antibiotics and alkaloids block a DNA matrix and complicate activity of polymerases. Function nucleinic to - t is broken also if as a result of influence of antineoplastic means the natural component of a chain of DNA or RNA is replaced with modified. The inclusion (intercalation) of drug between the nucleinic bases in a chain of DNA or RNA which is also interfering normal processes of replication and a transcription is possible.

Action of many antineoplastic means from group of antimetabolites is based on interaction with the enzymes which are participating in biosynthesis of predecessors of components of molecules DNA or RNA, carrying out their catabolic transformations, and also synthesis of biopolymers from these components. Inhibitor can interact’ with an active center of enzyme, and the type of interaction can be various.

Effect of antineoplastic medicines of a plant origin is connected with suppression by them лроцессой^шюза. The greatest value in the mechanism of action of similar means has interaction with tubuliny — protein of microtubules, i.e. the structures forming a spindle in the course of mitotic division. Apparently, the antineoplastic effect shown by nek-ry alkaloids — inhibitors of a mitosis, depends also on suppression by them nek-ry others biochemical, processes.

Intensive search of the antineoplastic means capable to selectively destroy substances is conducted, in to-rykh a tumor cell especially needs. The enzymes destroying amino acids are in this respect especially interesting. An example of such enzyme which received practical application as antineoplastic means is L-asparaginase.

Many patterns of action of antineoplastic funds for malignant O.' growth, according to Skipper (H. E. Skipper) and sotr., are explained by features of kinetics of their clonogenic cells. Tumor cells as well as cells of normal proliferating fabrics, pass phases of a mitotic cycle, in different degree sensitive to influence of various antineoplastic means. It is active the sharing cells are most sensitive to chemotherapeutic influences. Temporarily or constantly based cells to them are almost insensitive. Studying of kinetics of cell populations allowed to find out a number of patterns of action of antineoplastic means. All tumoral diseases, highly sensitive to chemotherapeutic influences, napr, leukoses, a lymphosarcoma, a reticulosarcoma, horionepitelioma, are among fast-growing O., i.e. tumors, in to-rykh the most part of cells is in a condition of active growth. In these O. with big fraction of growth during a unit of time the considerable number of tumor cells enters a phase of synthesis of DNA and therefore use of inhibitors of synthesis of DNA can render considerable effect. Contrary to it slowly growing O., napr, the differentiated forms of cancer of lung, a stomach, a large intestine, in to-rykh fraction of growth it is small, are insensitive to the substances influencing synthesis of DNA. Normal fabrics with big fraction of growth, napr, marrow, are also highly sensitive to DNA inhibitors. At the same time in fast-growing O. the fraction of growth is more, than the fraction of growth of stem cells of marrow, and at such tumoral diseases carrying out intensive discontinuous courses of chemotherapy allows to gain the expressed wedge, effect, giving at the same time the chance of a reparation of the injured marrow. For slowly growing O. use of longer modes with big intervals between repeated courses of treatment is more perspective. It is obvious that even at highly sensitive O. results of use of chemotherapy it is better for those, than less total quantity of tumor cells in an organism. Therefore teoretchesk are justified palliative operations in a combination with chemotherapy at Lakes, sensitive to it. Radiation therapy of radio sensitive O. can also reduce number of tumor cells in an organism, increasing thereby chances of effect of chemotherapy.

The idea of synchronization of cells of O. usually by means of the means operating on a cell in a phase of a mitosis gained recognition. Such antineoplastic means as Vincristinum, vinblastine, Colchaminum, blocking on a certain time term tumor cells in a phase M of a mitosis, promote that after their use the most part of tumor cells synchronously enters the following phases of a cellular cycle and, therefore, appointment through a certain time term of the drugs operating on cells in phases S or a mitosis it appears more effective. Possibility of synchronization of tumor cells as well as expediency of simultaneous use of the antineoplastic means operating on different phases of a cellular cycle is one of justifications of the combined chemotherapy of malignant Lakes. Other its justification is expediency of use of drugs with various mechanism of action. At the same time proceed from idea that disturbances various biochemical, processes in O. reduce chances that resistant clones of tumor cells will escape. The rational combination of drugs with various toxicity allows to sum up antineoplastic effect of drug without increase in toxic manifestations. The drugs which are not oppressing a hemogenesis are in this respect especially perspective for use in combinations. The combined chemotherapy which was repaid in treatment of general diseases of the hemopoietic fabric allowed to take a step forward and in treatment of solid Lakes. Use of combinations of antineoplastic means allowed to achieve expressed a wedge, effect at O. which were considered steady against chemotherapeutic influences such, e.g., as t; eratoblastoma of a small egg. However simultaneous use of various antineoplastic means as showed A. Goldin's researches, can lead not only to strengthening of antineoplastic effect, but also to its reduction. In this regard it is very important to estimate efficiency of the combination of antineoplastic means planned for use in iredklini-chesky researches.

Efficiency of antineoplastic means considerably depends on the optimum mode of its use (a dose, a rhythm of introduction). Use of data of pharmacokinetics is important for the choice of optimum doses and intervals between introduction of antineoplastic means. The issue of a possibility of use of antineoplastic means is resolved individually. This decision first of all is defined by the exact diagnosis since different O. show various sensitivity to antineoplastic means, and nek-ry of them a rezistentna to all existing antineoplastic pharmaceuticals. It is necessary to consider prevalence of process, the general condition of the patient, existence or absence of associated diseases, i.e. indications and contraindications to chemotherapy shall be weighed. Conditionally taking into account modern opportunities himioterashsh all tumoral diseases can be subdivided into four groups: The lake, at to-rykh essentially possibly treatment by means of medicinal methods of treatment (a horionepite-lioma of a uterus, Berkitt's lymphoma, an acute leukosis at children, a lymphogranulomatosis, a seminoma of a small egg); The lake, at to-rykh chemotherapy gives the expressed wedge, effect (an acute leukosis at adults, chronic leukoses, a lymphosarcoma, a reticulosarcoma, a multiple myeloma, an Osler's disease, Ewing's tumor and a bone reticulosarcoma, a breast cancer, a prostate, a throat, small-celled cancer of a lung, ovarian cancer, bodies of the womb, teratoblastomas of a small egg, Vilms's tumor, a neuroblastoma at children, an embryonal rhabdomyosarcoma, angiogenic sarcomas, a carcinoma cutaneum, cancer of a penis, a kortikosterom); The Lake with low sensitivity to a himiota to rapevtichesky influences (crayfish went. - kish. path, melanoma, planocellular carcinoma cutaneum of the head and neck, glioblastom, retinoblastoma, cancer of a bladder, insuloma, cancer of a vagina, synovial sarcoma and leiomyosarcoma, osteosarcoma); The Lake, almost insensitive to modern antineoplastic means (e.g., the differentiated forms of cancer of lung, cancer of a neck of uterus, a fibrosarcoma).

Modern the wedge, chemotherapy most often is under construction on use of repeated courses of combinations of antineoplastic means for preservation a wedge, effect (support of remission). At emergence of resistance resort to change of the therapeutic modes with use of the means which do not have cross stability. In some cases introduction of high doses of antineoplastic means is justified.

Rehabilitation of oncological patients

Rehabilitation of oncological patients — the multi-stage process allowing to restore patients to full-fledged life and work. Whenever possible early initiation of treatment, its continuity, succession, complex character, staging and individual approach for the purpose of recovery of the lost functions and return to active socially useful work are philosophy of recovery treatment onkol, patients. In scoping rehabilitations, as a rule, are also more whole various specialists — doctors, psychologists, sociologists, lawyers, employees of bodies of social security, etc. take part. Individually the program of recovery treatment is developed for each patient, edges depends on the general condition of the patient, his age, a condition of the psychological sphere, a profession, a stage of development, localization and gistol, O.'s structures, estimated methods of treatment, the forecast, etc. This program provides the maximum recovery of working capacity, including physical, psychological, social and professional adaptation. The doctor provides the possible reasons of disability, to-rye can appear as a result of a disease or the carried-out treatment to manage to reduce them or to prevent.

For the purpose of professional rehabilitation vrachebnotrudovy examination, vocational education of patients, their rational employment, including and at the specialized enterprises are carried out. The beginning of professional rehabilitation is definition of individual opportunities of socially useful activity for each patient. This task is assigned on medical and consulting commissions (see) and vrachebnotrudovy commissions of experts (see).

At employment consider not only the state of health, but also a profession, qualification, level of the general and vocational education of the patient. Rational employment completes rehabilitation onkol, the patient.

Prevention

Modern data on an etiology and O.'s pathogeny allow to plan two ways of their prevention: prevention of emergence of O., or so-called primary, hygienic, prevention, and prevention of their development, or secondary, clinical, prevention.

Philosophy primary gigabyte. O.'s prevention are: the termination of contact with oncogenous substances by their withdrawal from industrial production and replacement with harmless substances (or processes), introduction of wasteless technology or establishment of the marginal emissions (ME) of harmful connections, a gigabyte. limitation (establishment of maximum allowable concentration) of those oncogenous substances, to-rye are everywhere widespread and cannot be completely withdrawn from the environment surrounding the person; creation gigabyte. working conditions and respect for personal hygiene working. Primary gigabyte. O.'s prevention is based on idea of oncogenous agents, first of all oncogenous substances (see) and ionizing radiation (see). The oncogenous effect, as a rule, depends on a dose and time of contact with the oncogenous agent. The dose and the period of its influence are less, the, as a rule, more rare and later there are Lakes. Elimination or decrease in number of harmful effects and reduction of contact with them promote prevention of emergence of the Lake. Improvement of working conditions, implementation of new technology, in particular sealing of dangerous processes of manufacture, implementation of protective measures, observance the gigabyte governed. situations at the enterprises and personal hygiene, promote elimination of action on an organism of oncogenous agents.

Systematic work on professional O.' prevention of a bladder is carried out to the USSR (e.g., production 2 naphthylamines and 3,3 '-dikhlorbenzi-dyne is stopped, the pressurized method of receiving benzidine is implemented, the method of synthesis of aminotobias-acid is developed, at Krom there is no oncogenous 2 naphthylamine, etc.). Striking example of a possibility of primary prevention of lung cancer is fight against smoking since smoking cessation leads to decrease in risk onkol, diseases.

The substances possessing oncogenous action can occur among the dyes and preservatives used at production of foodstuff. E.g., in the nek-ry capitalist countries as dye for oil, margarine, flour, etc. used oncogenous substance of dimethylamine azobenzene (Buttergelb, or butter-yellow). Oncogenous substances, in particular the polycyclic aromatic hydrocarbons (PAH), can get to foodstuff at them about a job of t napr, during the smoking or drying. Change of technology of smoking, in particular use of so-called smoking liquids, can reduce considerably quantity of PAU in products.

A necessary link in a chain of actions for prevention of cancer is environmental control (see). The oncogenous substances which are contained, e.g., in smoke of heating systems, emissions of the industrial enterprises and internal combustion engines contaminate reservoirs and the soil, can pass into plants, get to forages, foodstuff and a human body. Decrease in pollution of free air oncogenous substances is possible by selection of fuel, improvement of the mode of its burning, improvement of methods and the equipment of catching of smokes and exhausts. In the USSR active fight for decrease in pollution of free air by reconstruction of the old industrial enterprises, introductions of wasteless technology, rational planning of the cities etc. is conducted.

Clinical prevention of O. is based on knowledge of patterns of development pretumor diseases (see). Their early detection and effective treatment are a basis a wedge, prevention of the Lake. Importance their reversibility in the early periods of development have ideas of staging of development of pretumor diseases. Knowledge a wedge, manifestations of phases of a diffusion or focal hyperplasia of high-quality O. in various bodies and fabrics allows to reveal timely them and by means of rational influence to prevent development malignant the Lake. On it it is based a wedge, prevention of a breast cancer, a stomach, neck of uterus and other bodies. So, at the diffusion forms of a fibrosing adenosis of a mammary gland and mastopathies corresponding to a phase of a diffusion hyperplasia in development of pretumor states, rational hormonal therapy in some cases allows to liquidate patol.proyavleniye and to prevent development of the Lake. At nodal forms of the dishormonal giperplaziya corresponding to a phase of development of focal proliferat with the preventive purpose most often apply operational treatment.

For O.'s prevention data on the factors promoting malignant O.' development against the background of pretumor diseases have essential value. For the purpose of their elimination, napr, at the pigmental xeroderma which is an obligate precancer along with use of photoprotective ointments make excision of the changed sites of skin with plastics of defects.

In malignant O.' prevention early detection of patients with pretumor diseases or states, napr is important, at routine maintenances. In identification of pretumor states and rational a wedge, O.'s prevention endoscopic methods, especially in combination with morfol, methods of a research are of great importance. They allow to establish character and extent of pretumor changes in upper respiratory tracts, a gullet, a stomach, intestines, etc. and to carry out treatment, napr, to remove polyps of a stomach or intestines by means of the endoscope.

Good results are yielded by a wedge, such O.' prevention, pretumor changes at to-rykh are timely distinguished, e.g. O. of skin, lips, oral cavities, throats, necks of uterus, a mammary gland, etc.

Tumours at children

the Decrease in child mortality in economically developed countries which is especially connected with sharp reduction of a lethality from inf. diseases, led to the fact that on the foreground mortality from malignant Lakes acts. According to WHO data (1976), in 23 economically developed countries mortality of children from malignant O. takes the second place, conceding only to mortality from accidents. The selective statistical researches (WHO, 1978) conducted in the nek-ry countries of Europe showed that annually zlokachestvennyma get sick with tumors 15 — 16 children on 100 000 children's population. In structure of incidence of malignant O. at children, according to Blum (N. of Bloom, 1975), Jones, Campbell (P. Jones, P. Campbell, 1976), 31% occupy leukoses, 18% — tumors of c. the N of page, 11% — malignant lymphoma, 7% — tumors of kidneys (Vilms's tumor), on 6% is the share of a neuroblastoma, tumors of bones, eyes and an orbit, soft tissues, 9% make other O., among to-rykh extremely seldom occur at children a carcinoma of the stomach, a gullet, a mammary gland, a uterus, a rectum, skin.

In O.'s emergence at children, according to most of researchers, diseases of mother and various adverse effects transferred it during pregnancy including frequent rentgenol matter. the researches conducted during pregnancy increase further risk of emergence of O. at the child. Much attention is paid to studying transplapentarno-go a carcinogenesis — transfer to a fruit che-pel? — to a goshtsshtt of oncogenous substances. Lakes at children are quite often combined with various malformations. So, at Vilms's tumor the hemihypertrophy, an ani-ridiya, malformations of urinogenital system often meet; lymphoma are combined quite often with an inborn agammaglobulinemia; tumors of bones — with exostoses, enchondromas, imperfect bone formation; a leukosis — with a Down syndrome. Genetically caused syndromes are known, to-rye contribute to O.'s development at children's age. O.'s emergence at children is also connected with the uneven growth of nek-ry bodies and fabrics during certain age periods, sharply expressed proliferative reaction of cells and fabrics to influence, e.g., of such factor as ionizing radiation.

In morfol, O.'s relation at children hl are. obr. sarcomas and only approximately in 2% of cases — crayfish. Criteria of a zlokachestvennost of O. at children are very relative. So, malignant O., napr, Vilms's tumor and a neuroblastoma, a long time behave as high-quality (are surrounded with the capsule, do not burgeon in surrounding bodies and fabrics), and high-quality O., napr, hemangiomas, quite often have local infiltriruyushchy growth.

Clinically O. are found in children aged from two up to five years more often, however at careful studying of the anamnesis quite often it turns out that they arose much earlier. O.'s development happens against the background of process fiziol, growth of the child what a number of features a wedge, O.'s currents at children is connected with. At the sick child the behavior changes, slackness, weakness, a loss of appetite, pallor of skin, subfebrile temperature, pains of various localization is noted. Nek-rye O. at children proceed clinically as acute inf. diseases.

O.'s recognition at children is complicated, and, according to a number of researchers, the St. 75% of patients arrive on hospitalization in late stages of a disease. It is explained, in particular, with the fact that at children's age O. of visually observed localizations meet less often, there is a set of «masks», for to-rymi they disappear, napr, children's infections and a number of children's diseases. At O.'s diagnosis at children pay attention to symptoms, to-rye it is impossible to explain with other diseases, napr, increase limf, nodes in the absence of regional defeats. In all cases at survey of the child, including and preventive, the palpation of a stomach for the purpose of O.'s exception of retroperitoneal space shall be carried out. Urography, angiography and other methods rentgenol. researches allow to distinguish the most often found O. at children. O.'s diagnosis at children by means of tracer techniques of a research is perspective.

O.'s treatment at children of hl. obr. complex. Operational treatment lazinesses, and also makstshalyshgsgtets” a zheniya carry out taking into account ab erasers 1^radik I Doctordss ( discussion ) ttshtey7 — Mefoda the obezeoliva-niya and corrections of a homeostasis allow to make if necessary expanded operations, and ability to bystry regeneration of the resected bodies, napr, a liver, gives the chance to receive the encouraging results. Radiation therapy is used in some cases as an independent method of treatment, napr, at a lymphogranulomatosis, and also for the combined treatment, in the preoperative and postoperative period. Especially often radiation therapy is used in the postoperative period in combination with purpose of antineoplastic means. Lakes at children are, as a rule, sensitive to treatment by antineoplastic means, from to-rykh Cyclophosphanum, Vincristinum and Actinomycinum of D are most effective.

Results of treatment of malignant O. at children are more favorable, than at adults. Treatment of a tumor of Vilms in the I—II stage leads to recovery St. 80% of children, in the III—IV stages — apprx. 20%.

Tables

Table 1. INCIDENCE of the POPULATION of the USSR of MALIGNANT TUMOURS of SEPARATE LOCALIZATIONS in 1970, 1975 and 1977 (on 100 000 inhabitants)


Table 2. MORTALITY of the POPULATION of the USSR FROM MALIGNANT TUMOURS of SEPARATE LOCALIZATIONS in 1970, 1975 and 1977 (on 100 000 inhabitants)





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H. H. Blochin (head of group of authors); G. I. Abelev (of), E. B. Burlakova (physical. - the chemical characteristic of growth of tumors), Yu. M. Vasilyev (biol.), V. N. Gerasimenko (rehabilitation onkol, patients), L. A. Durnov (ped.), N. A. Kra-evsky (stalemate. An.), V. M. Merabishvili (the medical Art.), A.S. Pavlov (I am glad.), N. I. Perevodchi-kova (medicinal treatment), B. E. Peterson (diagn.), H. N. Trapeznikov (hir.), G. V. Falileev (profit.), A. V. Chaklin (epid., gen.), L. M. Shabad (etiol., patog., profit.), V. S. Shapot (biochemical, influence on an organism).

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