The modern period of development of medicine is characterized by significant achievements in the field of creation of medicines based on peptides, to study their clinical efficacy and rationale for use in complex therapy of various diseases and pathological conditions. Investigation of the mechanisms of action of the peptides is of particular importance in connection with the development of biological tumor therapy aimed at enhancing immune function.
To assess the influence of natural and synthetic peptides on carcinogenesis studied the effect of these peptide drugs on the growth of spontaneous, induced, and transplantable tumors in experimental animals.
The research results indicate that peptides have a pronounced protective effect in experimental carcinogenesis and have a modulating effect on the immune and neuroendocrine systems of the body involved in the tumor process.
The use of natural peptides in mice and rats has contributed to a significant decrease in the incidence of spontaneous tumors in 1.5-2.5 times and increase the life expectancy of animals by 30-40%. It was also observed the increase of cellular immunity.
In studying the effect of natural peptide induced radiation effects carcinogenesis was found distinct inhibitory effect of drugs on tumor growth. The number of rats who developed malignant tumors in the experimental group was 1.9-2.7 times less than in control. The average latent period of tumours in the group of rats receiving the natural peptides were on average 2 months more compared to the control.
In irradiated mice, which were injected with natural peptides, the frequency of all tumors was 28 %, whereas in the irradiated animals in control the figure was 92 %. The number of malignant tumours was reduced by administration of drugs 10 times.
The influence of natural peptides for chemical carcinogenesis was studied on the model of adenocarcinomas of the mammary gland of rats induced by 7,12 introduction–dimethylbenz(a)anthracene. In the control animals under effect of the carcinogen of adenocarcinoma of the breast developed in 80% of cases, and the introduction of the peptide only in 25 %. Up to 3 times decreased the multiplicity of occurrence of adenocarcinomas.
Important to assess the antimutagenic and anticarcinogenic properties of peptide drugs are the results obtained from the study of their impact on transplacental carcinogenesis in rats, which were exposed during pregnancy effects of nitrozomocevina. As you know, with the introduction of nitrozomocevina rats–females in offspring with high frequency develop glial tumors of the Central nervous system and neuromas of the peripheral nerves. Introduction natural peptides contributed to the increase in the latent period of tumor development by an average of 2 months, the index decreased the multiplicity of tumors was 1.4 times, reducing the frequency of tumors of the spinal cord and kidneys and increase lifespan of animals.
Evidence that natural peptides cause inhibition of carcinogenesis and increase the lifetimes of laboratory animals, was the basis to study the effect of synthetic peptides (analogs endogenous) of these indicators.
The use of di - and tetrapeptides had a dampening effect on spontaneous carcinogenesis in mice, which was reflected in the decrease in 1.5 times the incidence of all tumors and 1.9 times the multiplicity of tumors. The dynamics of survival in all studied groups of animals were not significantly different until the age of 22 months, and then observed a distinct decrease of mortality under the influence of the peptides.
With the introduction of dipeptide rats exposed to radiation from a mixture of 90Sr and 137Cs was observed in the inhibition of malignant tumors, in particular, the reduction in the incidence of adenocarcinomas of the mammary gland. It was noted the increase of maximum life span by 4.6 months compared to control group animals.
It is established that the tetrapeptide inhibited the growth of colon tumors induced by 1,2–dimethylhydrazine. The effect of this drug was reflected in a decrease in the multiplicity of tumors and their size.
In studying the effect of synthetic peptides on the occurrence and development of bladder cancer induced by carcinogen selective action of N-butyl-N-(4-hydroxybutyl)nitrosamines, found that the introduction of dipeptide tumor appeared in 56% of animals, while in the control group at 75.5% of cases. Under the action of the drug is marked reduction in 2 times the development preneoplastic and early neoplastic changes in the bladder mucosa and significant inhibition of carcinogenesis. The effect of the dipeptide resulted in inhibition as the process of initiation of carcinogenesis, and promotion, i.e. the implementation of the neoplastic process.
Synthetic di - and tetrapeptide when administered to animals with transplanted hepatomas provided reliable inhibitory effect in the early stages after inoculation of tumor cells. In the study of the influence of the peptide on tumor growth ACETOL was established also their inhibitory effect. The use of synthetic peptides for the latent period led to a significant slowdown in the growth of transplantable sarcoma M-1. The inhibitory effect was evident 2 weeks after completion of the injection of peptide, and persisted throughout the observation period. In addition, it was found that after application of the peptides increased the level of apoptotic death of tumor cells.
The effect of synthetic peptides on carcinogenesis were examined in female transgenic mice carrying gene for breast cancer. The number of animals whose breast tumor did not develop in the group that received the tetrapeptide, was 1.6 times more than in controls. The maximum size of adenocarcinomas of the mammary gland in mice treated with this peptide, was 33% less than in control. Expression of the oncogene in mammary tumors of mice that received the tetrapeptide, were reduced by 3.7 times in comparison with the same indicator in tumors of control mice.
Experimental study of antitumor action of natural and synthetic peptides indicate the influence of these drugs on the mechanisms of carcinogenesis and prospects for their application in cancer patients.
Due to the fact that the natural peptides contribute to the restoration of cellular immunity and hormonal regulation, as well as have anti-tumor activity, these drugs used in cancer patients mainly with hormone-dependent tumours (breast cancer, of the body or the cervix of the uterus, ovaries and other sites). All patients had histological verification of tumor process. The majority of the subjects were subjected to the combined or complex treatment.
The natural peptides used in patients with breast cancer stage II-III, during radiation therapy. Drugs were administered on different circuits: after completion of radiotherapy, in the middle of the course and in the last 5-10 days of preoperative radiotherapy. Some patients peptides used in the remote terms after radiation therapy (after 2-6 months) in connection with the development of persistent leukopenia and lymphopenia that are not amenable to correction with other drugs. Introduction peptides with cancer of the breast contributed to the increase in the number of lymphocytes and T-lymphocytes in the blood. In addition, in patients after immune improved functional activity of T-cells and recovered the intensity of reactions of cellular immunity. Administration of drugs to patients in the remote terms after irradiation caused an increase in the number of leukocytes in the blood. Indicators of cellular immunity after administration of preparations is almost normal.
In clinical studies conducted in patients with cervical cancer treated with natural peptides marked increase in the number and functional activity of T-lymphocytes in the peripheral blood. Prescriptions for patients with cervical cancer who received radiation therapy or chemotherapy, had a pronounced protective effect on haematopoiesis, warned the development of leukopenia, thrombocytopenia, and inflammatory postoperative complications.
The research results indicate the prospects of application of combined projectnature and immunotherapy in patients with primary endometrial cancer. The study of the influence of natural peptides on immunological parameters in patients with endometrial cancer after preoperative course of hormone therapy showed that the treatment leads to a significant increase in the absolute number of lymphocytes and T-lymphocytes. Simultaneously, we observed recovery of the functional activity of T-lymphocytes.
The results of experimental study of influence of synthetic peptides on the growth of spontaneous, induced and transplanted tumors has also led to the use of these drugs in cancer patients.
Application of the dipeptide in patients with colorectal cancer aged over 50 years in surgical and complex treatment, and the use of it in the background of the generalization of cancer developed after the previously performed radical treatment helps to normalize the immune status of patients, reduce adverse and toxic effects of chemotherapy. Use 3 courses of the drug in patients of this category in the first 6 months after radical treatment caused a significant decrease in the incidence of relapses and generalization of the tumor in the next 2 years.
A dipeptide used in patients with breast cancer on the background of high-dose chemotherapy. In the process of observation (22 months) noted positive results in 100% of patients, there were recurrences and metastases. At the same time, during this period in the control group with traditional treatment regimens have to 35.2% of patients with the revealed distant metastases. The use of the drug has improved the tolerability of chemotherapy (decreased frequency of vomiting, nausea) were noted more rapid recovery of leukocyte count, lymphocytes of different subpopulations and platelets. Decreased length of stay of patients in hospital on average for eight days.
Ontomodificationdate properties of the dipeptide were evaluated in the complex treatment of patients with inoperable forms of cancer of the breast and ovaries. While all patients noted reduction of pain, restoration of appetite and weight gain.
A dipeptide used in patients with dysplasia or pre-invasive carcinoma of the cervix in the process of surgical conization of the cervix. In the study it was found that the drug helped restore the number of T-lymphocytes, phagocytosis, and a significant increase in the level of natural killer cells. 90% of the patients after treatment noted morphological signs of regeneration in the remote cone of the cervix. This was not observed amplification of the morphological signs of malignancy of the cervical epithelium, on the contrary, in many patients, the severity of the neoplastic transformation of cervical epithelium after treatment is reduced. The average time to the exclusion of burn eschar in patients who received the dipeptide was 5±1.6 days in patients of the control group and 11±2.0 days. The reduction in the time to rejection of scab was observed in 55% patients of the main group. Inflammatory complications (necrosis with purulent discharge) were noted in 10% of patients of the main group and 70% in the control group. Postoperative period with application of the dipeptide had fast loosening and rejection of the scab and the absence of pronounced necrosis in the area of the burn eschar. The average period of complete epithelialization of surgical wounds in patients of the main group was 29±2.4 days in patients of the control group and 48±7.2 days.
In conclusion, we must admit that the main focus of anticancer therapy is the destruction of tumor mass. However, the development of molecular genetic studies in recent years have opened a new intracellular interaction and communication of tumor cells with the microenvironment, immune and vascular system, with normal tissues. Prospects for application and further development of methods of biological therapy of cancer in the light of new scientific knowledge is no longer in doubt. Our clinical experience suggests that the use of peptides to patients regardless of the stage of the cancer and treatment not only enhances efficiency but also significantly improves the quality of life of this category of patients.