RU2348435C2 - Method of treatment of malignant tumours in dogs - Google Patents

Abstract

FIELD: medicine; veterinary science.

SUBSTANCE: method involves diagnosis, electric magnetic field radiation of tumour to prepare for removal of malignant tumour, surgical removal of tumour and postoperative follow-up of animal. Herewith in preoperative period, animal is exposed to variable local alternating very-low-frequency pulsed electric magnetic field (AVP EMF) radiation of tumour at magnetic field induction B=(20÷80) mtesla, impulse time t_i=0.75 sec, pause time t_p=0.5 sec, exposure duration 30-60 minutes within 20-40 days. Surgical operation of malignant tumour removal is carried out 3-7 day AVP EMF exposure course.

EFFECT: high efficiency, low risk of recurrent tumour.

2 cl, 10 tbl, 2 dwg

Description

The invention relates to veterinary medicine, more specifically to oncology, and can be used in veterinary clinics in the treatment of animals with malignant tumors.

It is known to use ionizing radiation for the treatment of cancer by remote and intracavitary irradiation of neoplasms (see Lindenbraten L.D. Medical Radiology. - M .: Medicine, 2000, 672 p.).

The damaging effects of radiation therapy can effectively destroy their tissues. However, healthy tissues fall into the affected area. They are subject to the same lesion as the tumor. In radiation therapy, there is a limit when repeated irradiation of the same area is not permissible (according to the accumulated dose). After irradiation, as a rule, general (systemic) and local (local) negative reactions of the organism occur. In addition, radiation therapy requires expensive equipment and special training for staff.

It is known that non-ionizing electromagnetic radiation or electromagnetic fields (EMF) are used in oncology. Thermal effects of microwave fields are used for antitumor hyperthermia at temperatures above 43.5 ° C (see Dunchenko A.S. Microwave hyperthermia in oncology // Abstracts of reports "Medical Physics" - 95 - M .: 1995. - P.113 ) At the same time, denaturation processes are possible, leading to endoxicosis and irreversible damage to both healthy tissues and the body as a whole.

Investigations are made of the antistress and antitumor effects of a weak infra-low-frequency electromagnetic field for the slow growth of neoplasms in male rats, carcinogenesis of which was initiated by the introduction of benzoprene under the skin of the back. It was established that EMF, preventing the onset of oxidative stress and the functional integrity of the brain cell membranes, indirectly influenced the dynamics of the development of neoplasms (reduced the rate of their growth) (see A.с. No. 826587, A61 1/42, Publ. 30.08.90., Bull. No. 32).

Another method of indirect influence on neoplasms was used in the postoperative period in the treatment of the genitalized form of melanoma. Stimulation of the neuroendocrine system was achieved by synchronous exposure to the entire patient’s body with a low-frequency periodic EMF with an amplitude of ~ 3 mT. For exposure, a magnetotherapeutic apparatus was used, which ensures the rotation of the magnetic field in the working cavity with a frequency of (50-100) Hz. (see Bakhmutsky N.G. Treatment of the gendered form of skin melanoma by a vortex magnetic field. // Russian Oncological Journal. - 2000. No. 6. P.32-35). The author of the study concludes that there is a significant decrease in postoperative relapse of the disease under the condition of exposure to EMF compared to control.

The positive dynamics of the indirect effect of infra-low-frequency electromagnetic fields indicates the prospects of its use in oncopathologies.

Attempts to directly influence ifrano low-frequency EMF on tumor tissues began when a method for treating malignant neoplasms by applying an intermittent sinusoidal EMF (induction amplitude was 40 mT) was announced (see A.S. No. 522688, A61 No. 1/42, Publ. 05.03 .77. Bull. 9). According to the results of studies, softening of the tumor tissue was noted. However, the effectiveness of such exposure was low compared to radiation and chemotherapy used. As a result, the method has not received clinical use.

Currently, the search continues for more effective ways to influence intensive infra-low-frequency electromagnetic fields on malignant neoplasms. So, for this purpose, a short-term ~ 5 min pulsed exposure to EMF was used with an magnetic induction amplitude of up to 1.8 T, the intervals between pulses were 60 ms. The study was conducted on outbred rats with neoplasms of the soft tissues of the thigh (sarcomas). The effects of magnetotherapy were manifested in necrotic processes of varying intensity, which ultimately led to inhibition of tumor growth or complete regression of the tumor. This result allows us to search for optimal parameters and modes of influence of the low-frequency electromagnetic field on neoplasms (see Kaplan MA Prospects for the use of high-intensity pulsed magnetic fields in the treatment of malignant neoplasms. // Russian Oncological Journal. - 1998, No. 8, p. 34-37) .

The objective of the invention is to develop a method for the treatment of malignant tumors in animals by local exposure to neoplasms with intense infra-low-frequency electromagnetic fields. The parameters of the electromagnetic field, the method and modes of exposure should provide selectivity for exposure to malignant neoplasms. The consequences of such an effect on the tumor tissue are comparable to the consequences obtained after courses of polychemotherapy (carried out according to standard schemes) without damage to adjacent healthy tissues. This will allow preoperative irradiation of the animal on an outpatient basis with the use of medium-skilled personnel who do not require premises, with special protection, without unnecessary trauma and stress, with high treatment efficiency and ensuring the reduction of the risk of relapse in the future, using domestic equipment and devices - emitters of infra-low-frequency electromagnetic field.

The problem is solved in that after diagnosis, in the course of complex treatment, in the preoperative period, the detected malignant tumor is irradiated with a local alternating infra-low-frequency pulsed electromagnetic field (ZII EMF) with worked out and justified parameters: with a field induction amplitude of B = 20 ÷ 80 mT; with an electromagnetic pulse time t _imp = 0.75 sec, a pause time t _pauses = 0.5 sec, with a duration of a session of electromagnetic radiation of 30-60 minutes for 20-40 days daily, and a surgical operation to remove the irradiated ZII EMF of a malignant tumor is carried out 3-7 days after the end of the irradiation course. In cases of relapse after surgery, repeated irradiation with an infra-low-frequency pulsed electromagnetic field of the affected area is carried out in two courses of 15-20 sessions with an interval between courses of no more than 20 days. When irradiation, two coils are used, which are opposite to one axis along the same axis, emitting an electromagnetic field, while the axis of the ZII EMF coils is located in the center of the irradiated neoplasm, and the coils are located above and below the tumor at a distance of 2-5 cm from the animal, with an irradiation working area of ≈10 ÷ 30 cm ² .

The method is characterized in that in order to suppress the tumor cells, they are exposed to bipolar alternating infra-low-frequency pulsed electromagnetic fields with adjustable parameters formed in the space between two opposite directional solenoids along the same axis, which provides morphologically reversible and irreversible changes in malignant tissues that are selective with respect to healthy neoplasms.

To implement the method, an experimental magnetotherapeutic installation was designed and manufactured, one of the main elements of which is a generator of ZII EMF.

The exposure apparatus is a stationary installation with a radiator ZII EMF, which is made in the form of two toroidal solenoids.

The solenoid coils are made of non-magnetic material and are located on the upper and lower bases of the working rack, with the possible location of the object of influence between them. The design allows you to adjust the distance between the coils, as well as rotate the coils relative to the rack to change the position of the impact zone.

The unit is powered from an AC network with a frequency of 50 Hz. The power supply unit of the parallel connected coils of the magnetic field generator represents a step-down transformer, from the secondary winding of which voltage is supplied to the pulse forming unit. Pulse generation is performed using thyristors. The operation of the pulse forming unit is carried out through the start device from the control and monitoring system from a personal computer (Fig. 1). The need to include between the computer and the installation of the intermediate link of the control and monitoring system using the L-card is caused by the fact that the standard interfaces of the personal computer do not allow generating special signals that the trigger devices understand. A special control program is loaded into the memory of the L-card, which contains a number of functional blocks, which interacts with the installation by commands from a computer. The amplitude of EMF induction, the duration of the forward and reverse pulses and the subsequent pauses are individually regulated. Simultaneously with the operation of the control program, information on the exposure parameters and the image of the axial section of the distribution of the magnetic field induction (according to the amplitudes) is recorded on the computer display. The generated field is axisymmetric. It is mainly concentrated in the work area between the coils.

The temporal structure of the generated magnetic field is determined by the parameters of the electrical circuit of the coils, its resistance - R and inductance - L, which together determine its inertia. The change in the magnetic field of a pulse with an increase in its leading and falling edges is expressed by the relation B (t) = B _о · e ^{-t / m} , where m = L / R is the relaxation time. The amplitudes of pulsations of magnetic induction of ~ 1 mT with a frequency of 100 Hz per pulse allow the excitation of the action potential due to them. Thus, the efficiency of the pulse effect is increased.

The relaxation time of the rise and fall of the pulse fronts is ~ 50 ms. For a distance between coils of the order of 30 cm, the amplitude of magnetic induction on the axis in the planes of the ends of the coils is ~ 80 mT. For given parameters, the magnetic induction field depends on the distance between the coils and the magnitude of the current in the windings.

The characteristics of the experimental magnetic therapy unit used in the studies are shown in Table 1.

Table 1 Characteristics of a magnetotherapy unit Characteristics Values Magnetic field amplitude (V) up to 80 MT Coil Current (l) up to 27 A Coil spacing (h) (30-50) cm Sectional area of the working window (S) ~ 10 ÷ 30 cm ² Pulse Duration (t _AND ) from 0.01 s Duration of a pause (t _P ) from 0.05 s Power consumption (W) 1,5 kW

In the course of research, periodic monitoring of the operation of the magnetotherapy unit was carried out. Contactlessly measured the current in the coils. The magnetic field was monitored using a Hall sensor. The pulse parameters were reproduced on an oscilloscope at a given distance between the coils and the set time modes.

Outbred dogs were selected as material for conducting studies to substantiate the proposed method.

Before the experiment, about 150 animals (dogs) were examined. Of these, 54 animals were selected for the experiment. The object of the study was 44 outbred dogs with a spontaneous malignant tumor - according to the histological structure - highly and moderately differentiated ductal carcinoma of one or more mammary glands. Dogs were divided into groups. Animals in the amount of 10 dogs made up the control group. He did not conduct ZII EMF, and only surgical removal of neoplasms was carried out with subsequent histological examination of the material obtained. The time of tumor development (from the moment of detection to the start of treatment) ranged from 8 to 24 months. The size of the tumor at the beginning of treatment (exposure) ranged from 2.5 to 7 cm in diameter. The age of the dogs is from 6 to 13 years. The weight of the animals is from 7 to 25 kg.

Animals (depending on the results of histological examination) were divided into subgroups:

- Subgroup A - spent the number of sessions 20, the duration of the session 30 minutes

Subgroup A is divided by duty cycle:

- duty cycle t _and = (10-15) sec; t _p = (1-2) s;

- duty cycle t _and , = 0.75 sec; t _p = 0.5 sec.

Subgroup B - conducted the number of sessions 20, the duration of the session 45 min t _and = 0.75 seconds; t _p = 0.5 sec.

Subgroup C - behavioral number of sessions 40, session duration 30 min; t _And = 0.75 sec; t _p = 0.5 sec;

Sessions were held daily.

In the original version, B = (20-80), the duration of t _and and t _p were 15 seconds and 1 second, respectively. Subsequently, taking into account the results of preliminary studies, the parameters of the used ZII EMF were taken: t _and = 0.75 s, t _n = 0.5 s, V ~ 40 ÷ 80 mT.

In the process of irradiation, the animal was placed between the coils on a special table. The axis of the coils corresponded to the center of the irradiated neoplasm. During the procedure, the body temperature of the animals did not differ from the initial one and corresponded to 38-39 ° С.

All animals before, in the middle and after the course of exposure according to standard methods determined hematological, biochemical and immunological parameters. In individual animals, additional clinical and laboratory studies were carried out a month after the end of the course of exposure.

In hematological studies (erythrocytes, hemoglobin, leukocytes, eosinophils, neutrophils: young, stab, segmented; lymphocytes, monocytes, ESR) - the blood cells in the samples were counted in the Goryaev’s chamber, the leukocyte profile and the amount of hemoglobin were determined according to generally accepted methods.

A biochemical study of blood parameters (total protein, total bilirubin, sugar, urea, creatinine) was carried out using photospectrometry on the apparatus "Photometer photoelectric KFK-3".

The study of the immune status included the quantitative determination of T- (E-ROL) - and B- (M-ROL) - lymphocytes in the reaction of spontaneous rosette formation with sheep and mouse erythrocytes (number of leukocytes, number of Lymph, AKL, T / V, LTI, T- (E-ROL) -limph, B- (M-ROL) -limph). The phagocytic activity of neutrophils was determined by the opsonophagocytic reaction method, using the culture of Staphylococcus aureus (strain No. 209), the phagocytic index and phagocytic number were calculated.

Prior to the course of exposure, all animals underwent a puncture biopsy of the tumor formation, followed by histological and histostereometric examination of the obtained material. The preparations were stained using hematoxylin and eosin according to Romanovsky-Giemsa.

For (histostereometry) estimates of the volumetric ratios of the structural components of the studied tissues and their conditions, a grid containing 100 points was used. Separately, tumor cells in a stable state, as well as in a state of dystrophic changes and necrosis, lymphoid elements and stroma were counted. When calculating, the number of grid points randomly coinciding with each of the above types (states) of cells was taken into account. Counting results were expressed as a percentage. For each drug, to ensure the reliability of the result according to the specified methodology, the calculation was carried out ten times.

On 3-7 days after the end of the course of exposure to ZII EMF, the animals underwent surgical removal of the mammary glands affected by the tumor. The obtained surgical material was subjected to histological and histostereometric studies, and the studies were carried out in different areas of the tumor (to assess the effect of various values of magnetic field induction).

The effectiveness of the impact of ZII EMF on neoplasms was determined by comparing the results of histological studies and histostereometry of irradiated and non-irradiated tumor tissues. A comparison was also made of the effects on tumor and healthy tissues. Additionally, a qualitative comparison was made with the morphological consequences after chemotherapy.

The reliability of clinical, laboratory and histometric studies was evaluated by standard methods of mathematical statistics for each determined indicator (sign) with a confidence probability of P <0.05.

In dogs with spontaneous malignant neoplasms of the mammary glands, to substantiate this method, a dynamic study of hematological parameters was performed (before, in the middle and at the end of the course of exposure to ZII EMF) in comparison with similar indicators in the control group (dog health without a course of exposure). The data obtained are shown in table 2.

table 2 Characterization of hematological parameters under the influence of ZII EMF with parameters: B = (40 ÷ 80) mT; t _and = 0.75 sec; t _p = 0.5 sec; T _exposure = (30 min · 20 sessions) in dynamics; (M ± m) Indicator Control group Before the course of exposure Mid-course exposure After the course of exposure Red blood cells, mln / μl 4.19 ± 0.22 4.91 ± 0.48 4.99 ± 0.65 4.11 ± 0.55 Hemoglobin, g / l 133.69 ± 3.85 134.76 ± 7.14 139 ± 6.38 120.2 ± 9.07 White blood cells, thousand / μl 7.78 ± 0.36 8.95 ± 0.94 * 7.52 ± 1.06 * 6.47 ± 1.17 * Eosinophils, thousand / μl 0.48 ± 0.04 0.43 ± 0.12 0.42 ± 0.13 0.38 ± 0.10 Neutrophils n / a, thousand / μl 0.14 ± 0.03 0.12 ± 0.09 0.34 ± 0.13 0.10 ± 0.08 Agricultural neutrophils, thousand / μl 5.05 ± 0.11 6.33 ± 0.54 * 6.99 ± 0.65 * 4.92 ± 0.49 * Lymphocytes, thousand / μl 1.94 ± 0.11 1.99 ± 0.25 * 1.63 ± 0.27 * 1.21 ± 0.12 * Monocytes, thousand / μl 0.18 ± 0.03 0.08 ± 0.05 0.13 ± 0.06 0.09 ± 0.07 ESR, mm / hour 2-8 4.84 ± 1.47 6.33 ± 2.49 6.40 ± 2.37 * - p <0.05

From the presented table 2 shows that there are changes in a number of hematological parameters:

- a decrease in the number of leukocytes (thousand / μl) by the end of the course of exposure from (8.95 ± 0.94) to (6.47 ± 1.17), which is 28%;

- a decrease in the number of lymphocytes (thousand / μl) by the end of the course of exposure from (1.99 ± 0.25) to (1.21 ± 0.12), which amounted to 39%;

- a decrease in the number of neutrophils s / I (thousand / μl) by the end of the course of exposure from (6.33 ± 0.54) to (4.92 ± 0.49), which amounted to 22%.

Comparison of the biochemical blood parameters in dynamics in dogs with spontaneous malignant neoplasms of the mammary glands (before, in the middle and after the end of the course of exposure) with the same indicators in dogs (without exposure) are characterized by the following changes, presented in table 3.

Table 3 Characterization of blood biochemical parameters when exposed to ZII EMF with the following parameters: exposure B = (40 ÷ 80) mT; t _and = 0.75 sec; t _p = 0.5 sec; T _exposure = (30 min · 20 sessions) in the dynamics; (M ± m) Indicator Control group Malignant neoplasms Before the course of exposure After the course of exposure Total protein, g / l 55.00-75.00 79.48 ± 4.92 79.75 ± 3.43 Total bilirubin, µmol / l 0.90-10.60 5.5 ± 1.01 5.83 ± 0.57 Glucose, mol / L 3.40-6.00 4.43 ± 0.61 4.08 ± 0.82 Urea, mol / L 3.10-8.30 7.04 ± 1.24 6.63 ± 1.99 Creatinine, μmol / L 50.00-110.00 103.54 ± 9.31 * 117.97 ± 8.23 * * - p <0.05

From table 3 it is seen that the changes in the indicators are insignificant and are within normal limits, with the exception of values for creatinine. Its amount increased by the end of the course of exposure from (103.54 ± 9.50) μmol / L to (117.97 ± 8.23) μmol / L, which is 14%.

Dynamic monitoring of immunological parameters was also carried out in dogs with spontaneous malignant neoplasms of the mammary glands during the study (before and after exposure) in comparison with similar parameters in the control group (dogs without a course of exposure). The data are shown in table 4.

Table 4 Characterization of immunological parameters when exposed to ZII EMF with parameters: B = (40 ÷ 80) mT; t _and = 0.75 sec; t _p = 0.5 sec; T _exposure = (30 min · 20 sessions) in the dynamics; (M ± m) Indicator Control group Malignant neoplasms Before the course of exposure After the course of exposure The number of leukocytes, thousand / μl 7.78 ± 0.36 8.95 ± 0.94 * 6.47 ± 1.17 * The number of lymphocytes, thousand / μl 1.94 ± 0.11 1.99 ± 0.25 * 1.21 ± 0.12 * T / B 1.76 ± 0.14 1.71 ± 0.35 2.00 ± 0.28 LTI 17.60 ± 1.80 21.82 ± 2.14 23.10 ± 2.20 T- (E-ROL) lymphocytes, thousand / μl 0.53 ± 0.05 0.41 ± 0.09 * 0.28 ± 0.04 * B- (M-ROL) lymphocytes, thousand / μl 0.30 ± 0.02 0.24 ± 0.06 * 0.14 ± 0.02 * Phagocytic activity,% 26.88 ± 2.32 22.71 ± 3.68 22.57 ± 2.64 Phagocytic number, cu 1.68 ± 0.21 2.42 ± 0.61 1.62 ± 0.48 Phagocytic index 6.93 ± 1.07 10.65 ± 2.69 7.18 ± 2.12 * - p <0.95

From table 4 it is seen that:

- a decrease in the number of leukocytes (thousand / μl) by the end of the course of exposure from (8.95 ± 0.94) to (6.47 ± 1.17), which amounted to 28%;

- a decrease in the number of lymphocytes (thousand / μl) by the end of the course of exposure from (1.99 ± 0.25) to (1.21 ± 0.12), which is 39%;

- a decrease in T- (E-ROL) of lymphocytes (thousand / μl) by the end of the course of exposure from (0.41 ± 0.09) to (0.28: g0.04), which amounted to 51%;

- a decrease in B- (M-ROL) lymphocytes (thousand / μl) by the end of the course of exposure from (0.24 ± 0.06) to (0.14 ± 0.02), which amounted to 62%.

In animals subjected to a course of local exposure to ZII EMF, external changes were noted:

- an increase in the size of tumors due to the edematous component by the end of the course of exposure from (2.5 ÷ 7) cm to (3.5 ÷ 8.5) cm in diameter;

- to the touch, after a course of exposure, the tumors become softer;

- in tumors irradiated by animals outside the zone of exposure to ZII EMF, no such changes were observed over the period of the course of exposure.

In histological preparations of spontaneous malignant neoplasms of the mammary glands without the influence of ZII EMF (the diagnosis is high and moderately differentiated ductal carcinoma), glandular and glandular-cribrotic structures from polymorphic atypical cells with hyperchromic nuclei, single sections of dystrophies and foci of necrosis are determined among the stroma. There is a predominance of the epithelial tumor component under the stroma.

In a comparative study of histological preparations of spontaneous malignant neoplasms of the mammary glands (the diagnosis is moderate and highly differentiated ductal carcinoma) without exposure and after a course of exposure to ZII EMF with parameters and in the modes: B = (20 ÷ 40) mT; t _and = 0.75 sec; t _p = 0.75 sec; T _exposure = (30 min · 20 sessions) the following features are noted:

- dystrophic changes in epithelial cells in the form of focal diffuse karyopiknosis and karyorexis, vacuolization of the cytoplasm up to (25 ÷ 50)%;

- increase in the area of necrosis to (15 ÷ 25)%;

- change in the ratio of the stroma - epithelial tumor component in the direction of the stroma;

- moderate focal lymphoid infiltration of the stroma in the form of clusters of reactive lymphocytes;

- the appearance of areas of hyalinosis and fibrosis;

- the presence of hemosiderosis in the stroma.

The listed changes are more pronounced in the histological preparations of those neoplasms that were subjected to the course of exposure to ZII EMF with an amplitude of induction: B = (40 ÷ 80) mT and exposure T _exposure = (30 min ÷ 40 sessions), while therapeutic pathomorphism reaches I-II degrees. Dystrophic changes and necrosis increase and make up (40-60)% and (20-30)%, respectively.

At the same time, during histological examination of healthy mammary gland tissues, for all the parameters used for exposure to ZII EMF, dystrophic changes are (1-3)%, and no necrosis was detected.

The histostereomic treatment of histological preparations obtained after surgical removal of malignant neoplasms of the mammary glands in dogs was performed.

The effects of the course effect of ZII EMF on the tumor were evaluated according to histostereometry of histological preparations. The statistical reliability of the results was provided by:

- averaging the relative number of structural components and their conditions for each section of the tumor over its different sections;

- averaging the relative amount of structural components over the totality of the same type of tumor under the same exposure conditions.

Indicators of the structural components of spontaneous malignant neoplasms of the mammary glands of dogs without exposure and after a course of exposure to local ZII EMF with parameters B = (40 ÷ 80) mT; t _and = 0.75 sec; t _p = 0.5 sec; T _exposure = (30 min · 40 sessions), are selectively presented in tables 5-6.

Table 5 Indicators of the structural components of a spontaneous malignant breast tumor without exposure to ZII EMF Structural components and their condition Fields of view (in%) one 2 3 four 5 6 7 8 9 10 Tumor cells 28 26 29th 28 28 26 31 29th 31 25 Dystrophically altered cells 2 3 2 four 2 four four 5 2 ' 3 Necrosis. one 3 2 0 one one 2 one 0 one Lymphoid elements 3 one one 3 one 2 2 2 3 2 Stroma 66 67 66 65 68 67 61 63 64 69

Averaged over the fields of view, the ratio of structural components (table 5.) is characterized by the following indicators (figure 1):

- tumor cells - 28.1%;

- dystrophically altered cells - 3.1%;

- necrosis - 1.2%;

- lymphoid elements - 2.0%;

- stroma - 65.6%.

Table 6 Indices of the structural components of a spontaneous malignant breast tumor after a course of exposure to ZII EMF with exposure parameters B = (40 ÷ 80) mT; t _and = 0.75 sec .; t _p = 0.5 sec; T _exposure = (30 min · 40 sessions) Structural components and their condition Fields of view (in%) one 2 3 four 5 6 7 8 9 10 Tumor cells fifteen 12 eleven 9 10 12 eleven 12 12 10 Dystrophically altered cells one 2 one 2 one one 2 one one 2 Necrosis 0 one 0 0 0 0 0 one 0 0 Lymphoid elements 0 one 0 one 0 0 one 0 2 0 Stroma 84 84 88 88 89 87 86 86 85 88

Averaged over the fields of view, the ratio of structural components (table 6.) is characterized by the following indicators (figure 2):

- tumor cells - 11.2%;

- dystrophic altered cells - 1.4%;

- necrosis - 0.2%;

- lymphoid elements - 0.5%;

- stroma - 86.7%.

Histostereometric processing of histological preparations of spontaneous malignant neoplasms subjected to a course of exposure to local ZII EMF. The following structural changes occur as a result of the irradiation of ZII EMF, which are presented in tables 7-8.

Table 7 Characterization of the structural components of spontaneous malignant neoplasms of the mammary glands after a course of exposure at various amplitudes of MP induction (t _and = 0.75 sec; t _p = 0.5 sec; T _exposure = (30 min · 20 sessions); (M ± t) Structural components and their condition No effect (in%) After a course of exposure with MP induction (20 ÷ 40) mTl (in%) After a course of exposure with induction of MP (40 ÷ 80) mTl (in%) Tumor cells 28.49 ± 2.08 * 23.05 ± 2.47 * 18.58 ± 1.09 * Dystrophically altered cells 2.71 ± 0.67 2.97 ± 1.07 2.80 ± 0.59 Necrosis 0.80 ± 0.35 * 1.21 ± 0.41 * 1.46 ± 0.29 * Lymphoid elements 1.51 ± 0.42 1.64 ± 0.66 1.56 ± 0.31 Stroma 66.49 ± 2.16 * 71.13 ± 2.25 * 75.60 ± 3.27 * * - p <0.05

From table 7 it is seen that when exposed to an increase in the induction of MP in the tissues of malignant neoplasms, the following changes are determined:

- a significant decrease in tumor cells (in%) with (28.49 ± 2.08) - without exposure, up to (23.05 ± 2.47) and (18.58 ± 1.09) - with the induction of MP B = ( 20 ÷ 40) mT and B = (40 ÷ 80) mT after the course of exposure, respectively;

- increase in the number of necrosis (in%) with (0.80 ± 0.35) - without exposure, up to (1.21 ± 0.41) and (1.46 ± 0.29) mT - induction MP B = (20 ÷ 40) mT and B = (40 ÷ 80) mT after the course of exposure, respectively;

- a significant increase in the stroma (in%) from (66.49 ±, 16) - without exposure, to (71.13 ± 2.25) and (75.60 ± 3.27) - with the induction of magnetic field B = (20 ÷ 40) mTl and B = (40 ÷ 80) mTl after the course of exposure, respectively.

From table 8 it is seen that with an increase in exposure exposure in the tissues of malignant neoplasms, the following changes occur:

- a significant decrease in the number of tumor cells (in%) from (28.49 ± 2.08) - without exposure, to (18.58 ± 1.09) and (15.24 ± 1.33) - at T _exposure = ( 30 min · 20 sessions) and T _exposure = (45 min · 20 sessions), respectively; at T _exposure = (30 min · 40 sessions) the number of tumor cells decreases to (13.24 ± 3.19);

- a significant increase in stroma (in%) from (66.49 ± 2.16) - without exposure, to (75.60 ± 3.27) and (79.37 ± 3.91) - at T _exposure = (30 min · 20 sessions) and T _exposure = (45 min · 20 sessions), respectively; at T _exposure = (30 min · 40 sessions), the increase in stroma reaches (81.01 ± 8.79).

Table 9 Characterization of the structural components of spontaneous malignant neoplasms of the mammary glands after the course at different duty cycle (B = (40 ÷ 80) mT; T _exposure = (30 min · 20 sessions); (M ± m) Structural components and their condition No effect (in%) After the course of exposure with t _and = (10-15) sec. and t _n = (1-2) sec (in%) After the course of exposure with t _and = 0.75 sec. and t _n = 0.5 sec (in%) Tumor cells 28.49 ± 2.08 * 23.61 ± 4.57 18.58 ± 1.09 * Dystrophically altered cells 2.71 ± 0.67 3.10 ± 2.86 2.80 ± 0.59 Necrosis 0.80 ± 0.35 * 1.10 ± 2.58 1.46 ± 0.29 * Lymphoid elements 1.51 ± 0.42 1.71 ± 1.80 1.56 ± 0.31 Stroma 66.49 ± 2.16 * 70.48 ± 9.07 75.60 ± 3.27 * * - p <0.05

From table 9 it is seen that with a change in duty cycle in the structures of spontaneous malignant neoplasms of the mammary glands, the following changes occurred:

- reduction in the number of tumor cells (in%) from (28.49 ± 2.08) - without exposure, to (23.61 ± 4.57) and (18.58 ± 1.09) after the course of exposure with duty cycle (t _and = (10 ÷ 15) s; t _p = (1 ÷ 2) s) and (t _and = 0.75 s; t _p = 0.5 s), respectively;

- decrease in dystrophically altered cells (in%) from (2.71 ± 0.67) - without exposure, to (3.10 ± 2.86) and (2.80 ± 0.59) after the course of exposure with duty cycle (t _and = (10 ÷ 15) sec; t _p = (1 ÷ 2) sec and (t _and = 0.75 sec; t _p = 0.5 sec), respectively;

- increase in necrosis (in%) from (0.80 ± 0.35) - without exposure, to (1.10 ± 2.58) and (1.46 ± 0.29) after the course of exposure with duty cycle (t _and = (10 ÷ 15) sec; t _n = (1 ÷ 2) sec and (t _and = 0.75 sec; t _p = 0.5 sec, respectively;

- increase in stroma (in%) from (66.49 ± 2.16) - without exposure, to (70.48 ± 9.07) and (75.60 ± 3.27) after the course of exposure with duty cycle (t _and = (10 ÷ 15) sec; t _p = (1 ÷ 2) sec and (t _and = 0.75 sec; t _p = 0.5 sec, respectively.

An additional assessment of the effectiveness of the local ZII EMF effect on breast neoplasms was obtained by comparing the results of its consequences with the consequences after chemotherapy. An animal with a malignant tumor (histological diagnosis is highly differentiated ductal carcinoma) underwent a course of polychemotherapy according to the scheme (Cyclophosphamum - 100 mg intravenously every other day No. 7; Methotrexanate - 10 mg intravenously drop 1 and 8 days; Fluorouracil

- 500 mg intravenously on the 1st and 8th day).

Tables 6 and 10 show the corresponding histostereometric data for such a comparison.

The ratio of structural components, averaged over the fields of view, according to table 10 is characterized by indicators:

- tumor cells - 25.9%;

- dystrophically altered cells - 3.1%;

- necrosis - 1.1%;

- lymphoid elements - 1.9%;

- stroma - 68.0%.

Table 10 Characterization of the structural components of a malignant breast tumor exposed to a course of polychemotherapy according to the CMF scheme Structural components and their condition Fields of view (in%) one 2 3 four 5 6 7 8 9 10 Tumor cells 24 24 21 26 29th 24 26 28 thirty 27 Dystrophically altered cells 5 5 2 3 2 one 2 5 3 3 Necrosis 0 0 7 0 0 0 0 0 0 four Lymphoid elements one 2 0 2 3 one 3 3 one 3 Stroma 70 69 70 69 66 74 69 64 66 63

The results of numerous studies of the effects of ZII EMF with induction B = (20 ÷ 80) mTl allow us to draw the following conclusions:

1. Fundamentally significant are the first established selectivity and morphological irreversibility of the effects of exposure to tumor tissue in comparison with similar healthy ones. The determined therapeutic pathomorphism of malignant neoplasms according to their structural characteristics confirms the promise, non-obviousness and novelty of the use of ZII EMF in oncological practice.

2. The proposed modes of local ZII EMF exposure used reliably lead to therapeutic pathomorphosis of the I-II degree of severity of spontaneous malignant neoplasms in experimental animals, which corresponds to the consequences after one course of chemotherapy according to the standard method.

3. Local exposure to intense ZII EMF with the used parameters on animals with malignant neoplasms leads to significantly reversible changes in clinical and laboratory parameters. In total, the data of clinical and laboratory studies indicate the possibility of using ZII EMF for the effective treatment of malignant tumors in animals.

The proposed method and the realized conditions for exposure to alternating infra-low-frequency pulsed EMFs are promising for use in veterinary oncological practice, both independently and in combination with other treatment methods.

Claims (2)

1. A method of treating malignant tumors in dogs, including making a diagnosis, irradiating an EMF tumor in preparation for removing a malignant tumor, surgical removal of the tumor and postoperative observation of the animal, characterized in that the animal is irradiated with a regulated local alternating infrared low-frequency pulsed electromagnetic field in the preoperative period (FIL EMF) in the induction of the magnetic field B = (20 ÷ 80) mT pulse at time t = 0.75 _and s, the pause time t _n = 0.5, with prodolzhitelnos Strongly irradiation session 30-60 minutes for 20-40 days, and surgery to remove a malignant tumor was performed on day 3-7 after the end of the FIL EMF exposure. 2. A method for the treatment of malignant tumors in dogs according to claim 1, characterized in that in the event of a relapse after surgery, repeated irradiation of ZII EMF is performed on both sides of the affected area with an interval between courses of no more than 20 days.

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