[Morbidity, mortality and reliability of accounting of patients of different age groups with liver cancer in Russia.]

Liver cancer is a severe oncopathology. Mortality exceeds the number of primary-accounted patients in Russia on average. Every year in Russia more than eight thousand (8 810 in 2018) cases of liver cancer and more than 10 000 (10 018 in 2018) deaths from this cause are registered. Used Standard methods of medical statistics, all registered primary cases of liver cancer in Russia. In-depth development of the material was carried out on the basis of the database of the Population cancer register of the North-Western Federal district of the Russian Federation. The analysis of the data of the whole complex of available information in Russia as a whole is carried out. In-depth data development was carried out on the basis of the database of the Population cancer register of the North-Western Federal district of the Russian Federation. The increase in the incidence of liver cancer in Russia over 18 years in «rough¼ indicators and absolute numbers by 20% and in standardized by 1,22% was established. In women, there was a decrease in reported cases of liver cancer by 4,55%. The mortality rate of the Russian population in standardized indicators has decreased by almost 3% over 18 years. The excess of the number of deaths over those from liver cancer increases significantly in older age groups. The index of reliability of accounting is the ratio of absolute numbers or «rough¼ indicators of mortality to morbidity. For all malignant tumors, its value on average in Russia was 0,47, almost coinciding with the average European. The index of reliability of accounting for men is 0,55, higher than the calculated indicators for women - 0,40, which is primarily due to a more favorable structure of the incidence of malignant tumors in women. The median survival of primary liver cancer patients is a little more than three months. The five-year survival rate of patients with liver cancer even in the early stages is in the first among persons younger than 60 years - 25,3%, over 60 years - only 17,2%, in the second, respectively, 17,9 and 11%.

The influence of hepatocarcinogens on the central effects of phenobarbital an D-amphetamine.

The influence of two hepatotropic chemical carcinogens - 2-acetylaminofluorene (AAF) and N-nitrosodiethylamine (NDEA) on the processes of adrenergic activation of central synaptic structures and narcotic effect of phenobarbital was investigated. AAF and NDEA modified the stimulating effect of D-amphetamine which was demonstrated by the decrease of stereotype behavior interval and increase of its toxicity. Both carcinogens potentiated the narcotic effect of phenobarbital. The investigation of the terminal component of hepatic mixed-function oxidases system (cytochrome P-450) during carcinogen injections allows to exclude the great importance of D-amphetamine and phenobarbital metabolic variation in modification of their effects. The results of experiments assume the concept of chemical carcinogen effects on the functions of central and peripheral nervous system synaptic structures related to control of the proliferation and differentiation as initial step in hepatic carcinogenesis.

The role of central dopaminergic processes in chemical carcinogenesis.

The effect of chemical carcinogen N-nitrosodiethylamine (NDEA) was studied in white noninbred male rats in a series of experiments. The animals treated with dopamine receptor agonist (apomorphine) showed statistically significant inhibition of carcinogenesis. Dopamine receptor antagonist (haloperidol) showed a tendency to stimulate the carcinogenesis. Also, the modifying effect of NDEA on behavior stereotypy and aggressiveness of experimental animals was found following apomorphine injection at various dosages. The data obtained are discussed from the point of view of the leading role of ANS in homeostatic regulation of the organism and in carcinogenesis.

On participation of the autonomic nervous system in the mechanisms of chemical carcinogenesis.

With the view of studying the role of autonomic nervous system in chemical carcinogenesis mechanism in outbred white male rats, chronically treated with NDEA, there has been investigated the modifying effect of some neurotropic pharmacological drugs which cause either stimulation or inhibition of: 1. adrenergic processes (noradrenalin, isoproterenol, clonidine, pyrroxane and propranolol); 2. cholinergic processes (proserine and atropine); 3. the function of the central nervous system (CNS)--caffeine and ethanol. Pharmacological activation of alpha-adrenoreceptors or blocking of both beta-adrenoreceptors and cholinoreceptors has been revealed to stimulate hepatocarcinogenesis. On the contrary, the administration of alpha-adrenoreceptors antagonist or beta-adrenoreceptor and cholinoreceptors agonists inhibited the process of carcinogenic transformation. Caffeine, being the CNS stimulator, has significantly promoted carcinogenesis, while ethanol has practically prevented NDEA effect. Clonidine has also demonstrated its anticarcinogenic action. The obtained data are being discussed in connection with chemical carcinogenesis influence upon the CNS integrative function in control and regulation of tissue homeostasis.

[Primary mechanism of a reduction in the intensity of extremely weak mitochondrial luminescence in the process of chemical hepatic carcinogenesis]. / O pervichnom mekhanizme snizheniia intensivnosti sverkhslabogo svecheniia mitokhondrii v protsesse khimicheskogo gepatokantserogeneza.

The induced chemoluminescence in rat liver mitochondrial preparations was studied in the course of 2-acetylaminofluorene or N-nitrozodiethylamine induced hepatocarcinogenesis. As follows from the literature, the intensity of chemoluminescence is representative of catalase activity, i. e. of one of mitochondrial enzymes. Beginning from the stage of stimulation of pretumor cell proliferation, the course of carcinogenesis is caracterized by a progressive decrease in the intensity of chemoluminescence. An adrenomimetic noradrenaline induced a similar effect, whereas isoprenaline and alpha-adrenoblocator pirroxane stimulated chemoluminescence of mitochondria preparation in the intact rats. Ortobenzoquinone being oxidated with H2O2, noradrenaline and isoproteranol were deprived of oxidative activity. It is suggested that inhibition of mitochondrial catalase activity with endogeneous noradrenaline constitues a primary mechanism of the decrease in chemoluminescence intensity.

[Effects of apomorphine and haloperidol on experimental hepatocarcinogenesis]. / Vliianie apomorfina i galoperidola na éksperimental'nyi gepatokantserogenez.

The modifying effect of apomorphine and haloperidol - agonist and antagonist of dopamine receptors, respectively - on the development of N-nitrosodiethylamine (NDEA) - induced hepatic tumors was studied in 60 noninbred albino male rats. The study was concerned with an evaluation of the effect of the drugs on tumor frequency as well as on the neoplastic transformation of such cell elements as hepatocytes, cholangiolar epithelium and endothelium. It was found that apomorphine significantly inhibited the carcinogenic effect of NDEA and neoplastic transformation of hepatocytes. Haloperidol revealed a tendency of stimulating NDEA effect on cholangiolar epithelium. The results are discussed in the context of the considerable importance of the functional condition of the presynaptic receptors of catecholaminergic systems in the mechanism of carcinogenic chemical action.

[Influence of chemical carcinogens on the physiological effects of adrenomimetics]. / Vliianie khimicheskikh kantserogenov na fiziologicheskie éffekty adrenomimetikov.

The experiments on isolated atria of rats and guinea pigs have shown that chemical hepatotropic carcinogens (diethylnitrosoamine and 2-acetyl aminofluorene) modify the physiological effects of adrenomimetics. A correlation between the authors' findings and the literature data on application of adrenergic drugs in carcinogenesis allows a suggestion to be made on the possibility of a principally new aspect in the mechanism of action of chemical carcinogens related to their effect on adrenoreceptors of target-organs.

[Effect of chemical hepatic carcinogens and noradrenaline on the nucleoside phosphokinase activity of liver cells]. / Vliianie khimicheskikh gepatokantserogenov i noradrenalina na aktivnost' nukleozidfosfokinaz kletok pecheni.

Distinct increase in activity of uridine kinase and pronounced decrease in thymidine kinase activity were observed in cell-free extracts of rat liver tissue at early stages of hepatocarcinogenesis caused by administration of N-nitrose diethylamine and 2-acetyl aminofluorene. Exogenous noradrepaline did not affect the altered activity of thymidine kinase but stimulated the effect of N-nitrose diethylamine and lowered the effect of 2-acetyl aminofluorene on the urindine kinase activity. Adrenergic neurotransmitters appear to influence the cell proliferation due to modification of the enzymes participating in the synthesis of nucleic acid precursors.

[Changes in the activity of monoamine oxidase, adenylate cyclase and adenosine triphosphatase in liver cells during the process of hepatocarcinogenesis]. / Izmeneniia aktivnosti monoaminoksidazy, adenilattsiklazy i adenozintrifosfatazy mitokhondrii kletok pecheni v protsesse gepatokantserogeneza.

Activity of specific mitochondrial enzymes was studied in rat liver during 2-acetylamine fluorene or diethylnitrosamine-induced hepatocancerogenesis. The results of enzymatic activities studied correlated with morphological changes in cancerogenesis. Alterations in activity of monoamine oxidase, adenylate cyclase and adenosine triphosphatase depended on the step of cancerogenesis. Activity of adenylate cyclase in cell membranes decreased gradually during the impairment. Change in activity of the enzymes, observed at the step of enhanced liver cell proliferation, proceeded at further steps of cancerogenesis. The data obtained suggest that alterations in activity of mitochondrial enzymes are related to modified metabolism observed in the impaired cells.

[A method for making up the cost pricing of clinico-diagnostic studies in oncology]. / Metodika formirovaniia sebestoimosti klniko-diagnosticheskikh issledovanii v onkologii.

The functioning of the present-day system of public health is largely determined by the extent and effectiveness of the use of resources. The saving of resources is reflected in the costs. The research was concerned with development of methods of calculating the costs of clinical laboratory tests. Due account of costs offers means for evolving new patterns of self-reliance accounting and paid medical services.

[Assessment of degree of malignancy in non-Hodgkin B-cell lymphoma with immunophenotyping]. / Otsenka stepeni zlokachestvennosti B-kletochnykh nekhodzhinskikh zlokachestvennykh limfom metodom immunofenotipirovaniia.

Due to immunophenotypic examination of bioptic samples from 30 patients with non-Hodgkin's lymphoma (NHL), malignancy of B-cell NHL was identified at an early stage of diagnosis, before histological analysis yielded the results. Negative expression of T-cell antigens, monoclonal character of light-weight chains of immunoglobulins, positive expression of B-cell antigens and marked expression of CD5+ are immunologic markers of low-malignancy B-cell NHL. A similar immunophenotypic pattern, involving negative expression of CD5- and positive one for Calla-antigen as well as one identifiable by monoclonal non-cluster antibody IPO3, is a marker of highly-malignant B-cell NHL.

[Immunophenotyping in the differential diagnosis of malignant non-hodgkin's lymphomas]. / Immunofenotipirovanie v differentsial'noi diagnostike nekhodzhkinskikh zlokachestvennykh limfom.

Non-Hodgkin's malignant lymphoma was diagnosed in 66 patients by immunophenotype technique using a batch of 13 Russian-isolated monoclonal antibodies which help identify antigens of T- and B-lymphocyte surface membranes. Polyclonal light chains of immunoglobulins and T- and B-cell antigens were identified in the course of histological examination of biopsy material sampled from hyperplasia lymphoid tissue. B-cell lymphomas revealed monoclonal light chains of immunoglobulins and positive B-cell antigens. T-cell tumors had mostly T-cell antigens and no light chains of immunoglobulins. Neither common leukocyte antigen, nor panT- or panB-cell antigens were found in 7 cases of cancer metastasis to lymph nodes.

[Measurement of calcium content in the blood and other biological fluids by Arsenazo III complexone]. / Izmerenie soderzhaniia kal'tsiia v syvorotke krovi i drugikh biologicheskikh zhidkostiakh kompleksonom Arsenazo III.

A method of photometric measurement of total calcium in the serum and other biological liquids using Arsenazo III color complexone is offered. Physicochemical characteristics of Arsenazo III (mol extinction, affinity for other ions, spectral characteristics, and its complex with calcium) are described. Calcium was measured in 750 normal subjects, its reference value was 2.15-2.75 mmol/liter, the mean value 2.47 mmole/liter. In semiautomated measurement CV% was about 5%. The reagent is convenient, particularly for automated analyzers; no other reagent are needed, it can be stored for a long time at room temperature, and gives stable results.

[Neuropharmacologic regulation of the carcinogenic action of 1,2-dimethylhydrazine]. / Neirofarmakologicheskaia reguliatsiia kantserogennogo deistviia 1,2-dimetilgidrazina.

Chronic experiments were made on 100 male rats to examine the modifying effects of adrenergic and cholinergic agents that regulate homeostasis on 1,2-dimethylhydrazine-induced intestinal carcinogenesis. The sympatholytic guanethidine (5 mg/kg) and the alfa-adrenoblocker butyroxan (2.5 mg/kg) did not influence the carcinogenesis in the intestine. The noradrenaline- and atropine-induced (1 mg/kg and 10 mg/kg) increase in the adrenergic component of the vegetative nervous system led to the decrease in the number (by 2-3 times) and size of the tumor nodes in the intestine. The drugs did not affect the morphology of neoplasms. The results are discussed in terms of essential importance of the vegetative nervous system in the mechanism of chemical carcinogenesis.

Morphopharmacological analysis of the carcinogenic properties of N-methyl-N'-nitro-N-nitrosoguanidine.

The modifying influence of atropine and reserpine on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induction of stomach tumors was studied in experiments on 120 random-bred male white rats. At the same time, pharmacological analysis of the mechanism of the carcinogenic action of MNNG was carried out. Atropine stimulated and reserpine markedly inhibited the carcinogenic effect of MNNG. MNNG interference altered the specific effects of amphetamine and phenobarbital. These alterations are due to the MNNG damage of the permeability of the presynaptic membrane of the central adrenergic structures. The leading role of adrenergic influences on the presence of carcinogenic transformation of stomach cell processes is discussed.

Nicotine influence upon the development of experimental stomach tumors.

The study of nicotine action upon N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stomach cancer development was carried out in rats. As compared with control it was established that combined MNNG and nicotine long-term administration led to the occurrences: 1) stomach pretumorous changes of the whole mucous membrane; 2) earlier development of stomach cancer tumors and its frequency was doubled; 3) progressive decrease of acetylcholinesterase activity, especially expressed in homogenates of cerebrum hemispheres, hypothalamic region and medulla oblongata (where this activity is practically failed to be expressed). The obtained data are the witness of the nicotine ability to enhance the MNNG-stomach carcinogenesis in rats. The possible action of the autonomic nervous system in such nicotine effects is under discussion.

[Possible neuropharmacological regulation of chemical carcinogenesis caused by diethylnitrosamine]. / O vozmozhnosti neirofarmakologicheskoi reguliatsii khimicheskogo kantserogeneze, vyzvannogo diétilnitrozaminom.

The effect of a number of neurotropic drugs on diethylnitrosoamine (DENA)-induced chemical carcinogenesis was studied by applying pharmacological, morphological and biochemical techniques. Atropine stimulated significantly the rat liver and esophagus carcinogenesis, whereas the alpha-adrenoblocking agent, a pyrrhoxane analogue, and, particularly, proserine inhibited these processes. All animals treated with DENA demonstrated a significant increase of liver mitochondrial monoaminoxidase activity. These findings as well as the evidence of a stimulating effect of exogenous norepinephrine on carcionogenesis, together with the literature sources on carcinogenic and modifying carcinogenesis action of neurotropics allow the authors to formulate a concet of the trigger role played by catecholamines in the DENA-induced cell transformation and carcinogenesis.

[Adrenergic mechanisms of the regulation of stages of chemical carcinogenesis: role of presynaptic receptors]. / Adrenergicheskie mekhanizmy reguliatsii razlichnykh étapov khimicheskogo kantserogeneza: rol' presinapticheskikh retseptorov.

A modifying effect of a catecholamine precursor (L-DOPA, 20 mg/kg, intraperitoneally) on various stages (initiation and promotion) of hepatocarcinogenesis, induced by N-nitrosodiethylamine (NDEA, 85 mg per 1 litre of tap water) was studied in chronic experiments on 150 male rats. L-DOPA administration prior to NDEA (influence on initiation) stimulated hepatocarcinogenesis considerably, while its administration after NDEA (influence on promotion) inhibited the realization of a carcinogenic effect. A statistically significant decrease in noradrenaline hypothalamus content was identified during early stages of chemically induced neoplastic transformation of hepatic cellular elements (stages of diffuse and focal proliferation). The results are discussed in terms of the regulatory role of the tone of the adrenergic autonomous nervous system component at the level of presynaptic inhibitory receptors in realization of the chemical carcinogenic effect.

Central mechanism of vinblastine inhibitory effect on experimental carcinogenesis.

In the experiments carried out on white male rats the effect of vinblastine on the development of malignant stomach tumours induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has been studied. The combined administration of MNNG and vinblastine inhibits the experimental carcinogenesis at the stage of "intestinalization" and decreases the indicence of stomach adenocarcinomas by 3-fold. Pharmacological analysis using the application of apomorphine stereotypy showed the antagonism of MNNG and vinblastine at the level of central parts of the autonomic nervous system due to the inhibition of axoplasmic transport of catecholamines. These results confirm the earlier data on the essential role of catecholamines in the mechanisms of carcinogenic action of nitrosamines.