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Description
The main agents of this group are vinblastine, vincristine, vinorelbine, docetaxel, irinotecan, paclitaxel, teniposide, topotecan, etoposide, etc.
According to D.A. Kharkevich, antitumor agents of plant origin can be represented by the following groups:
1. Vinca pink alkaloids - vinblastine, vincristine.
2. Yew tree alkaloids (taxanes) - paclitaxel, docetaxel.
3. Podophyllotoxins secreted from thyroid podophyll are etoposide, teniposide.
4. Colchicum alkaloids magnificent - demecolcin (colhamin), colchicine.
Most alkaloids are phase-specific antitumor agents, i.e. effective in certain phases of the cell cycle.
Alkaloids can be divided into two groups according to the point of application of action:
Cells acting on microtubules (colchicine, vinca alkaloids, taxanes);
Topoisomerase inhibitors (etoposide, teniposide, irinotecan, topotecan).
Vinca alkaloids- structurally related substances, in the chemical structure of which there are two polycyclic units - vindoline and kataranthin. Vinca alkaloids include vinblastine and vincristine, alkaloids isolated from the rose periwinkle plant. (Vinca rosea L.), as well as vindesine and vinorelbine - semi-synthetic derivatives of vinblastine. Vinorelbine differs in structure from other vinca alkaloids by having an 8-membered cataranthin ring (instead of a 9-membered one). The antitumor effect of these alkaloids is due to the effect on cells in the M-phase of the cell cycle (mitosis phase).
In the normal (correct) course of mitosis, the formation of the achromatin spindle begins at the prophase stage and ends at the metaphase stage. Towards the end of cell division, the spindle breaks down (the mitotic spindle is formed at each division of a eukaryotic cell and regulates the orientation and distribution of chromosomes in two daughter cells). The cytoplasmic globular protein tubulin is involved in the construction of the fission spindle filaments (microtubules).
Tubulin is a dimeric protein composed of two similar but not identical subunits, alpha-tubulin and beta-tubulin. Both subunits have a molecular weight of about 50 kDa each (53 kDa and 55 kDa) and differ somewhat in isoelectric point. Under certain conditions, depending on the needs of the cell, tubulin dimers polymerize and form linear chains consisting of alternating alpha-tubulin and beta-tubulin molecules (protofilaments), from which microtubules are formed.
Microtubules form the basis of the mitotic apparatus (mitotic spindle) during cell division, and are also an important component of the cell cytoskeleton. They are necessary for the implementation of many cellular functions in the interphase, incl. to maintain the spatial shape of cells, intracellular transport of organelles. In neurons, bundles of microtubules are involved in the transmission of nerve impulses.
Each microtubule is a cylinder with an outer diameter of about 24 nm and an inner channel of about 15 nm in diameter, the length of a microtubule is several microns. The walls are built of 13 protofilaments arranged in a spiral around the central cavity. Microtubules are dynamic polar structures with (+)- and (-)-ends. Both polymerization and depolymerization of tubulin occur at the ends of microtubules, with the greatest changes occurring at the (+) end.
The antimitotic effect of vinca alkaloids is mediated mainly by their action on microtubules: by binding to tubulin molecules of microtubules (due to their pronounced affinity), they prevent the polymerization of this protein, inhibit the formation of the fission spindle (assembly of microtubules), and stop mitosis at the metaphase stage. Vinca alkaloids can also change the metabolism of amino acids, cAMP, glutathione, the activity of calmodulin-dependent Ca 2+ transport ATPase, cellular respiration, the biosynthesis of nucleic acids and lipids.
It is believed that there are some differences in the mechanism of action of different vinca alkaloids, which may be due to differences in their chemical structure, interaction with different parts of the tubulin molecule, and different interactions with microtubule-associated proteins. These proteins can change the nature of the interaction of alkaloids with the tubulin of microtubules, which, as a result, also determines some nuances in the action of different alkaloids. Yes, under the conditions in vitro, vinblastine, vincristine and vinorelbine have approximately similar activity in terms of the assembly of tubulin into microtubules, however, vinorelbine does not have a specific effect in terms of inducing the formation of spirals.
An experimental comparative study of the effects of vinblastine, vincristine, and vinorelbine on mitotic spindle microtubules and axon microtubules in mouse embryos at an early stage of neuronal development showed that vinorelbine had a more selective effect on mitotic spindle microtubules.
Natural vinca alkaloids (vincristine, vinblastine) are used to treat rapidly proliferating neoplasms. One of the widely used vinca alkaloids, vincristine, is mainly used in combined chemotherapy for acute leukemia, lymphogranulomatosis, and other tumor diseases (introduced intravenously once a week). The neurotoxic effect of vincristine can be manifested by impaired neuromuscular transmission, neurological complications, incl. paresthesia, motor disorders, prolapse of tendon reflexes, intestinal paresis with the occurrence of constipation, up to paralytic ileus, etc.
Unlike vincristine, another vinca alkaloid, vinblastine, is a less neurotoxic drug, but causes myelosuppression, has a pronounced irritant effect with a risk of developing phlebitis, necrosis (with extravasal contact). Like vincristine, vinblastine is used in the complex therapy of a number of tumor diseases, including Hodgkin's disease, lympho- and reticulosarcomas.
TO alkaloids of Colchicum splendid (Colchicum speciosum Stev.) lily family (Liliaceae) include demecolcin (colhamin) and colchicine, which is close to it in structure, contained in the corms of the plant.
In the Middle Ages, an infusion of colchicum seeds and tubers was used as a remedy for gout, rheumatism, and neuralgia. Currently, demecolcin and colchicine are used to a limited extent.
Both alkaloids have antimitotic activity. The mechanism of action of colchicine is primarily due to the fact that, by binding to tubulin, it leads to disaggregation of the mitotic apparatus and causes the so-called. K-mitosis (colchicine mitosis) - cell division is disturbed at the stage of metaphase and subsequent anaphase, while the chromosomes cannot disperse to the poles of the cell, resulting in the formation of polyploid cells. Colchicine is widely used in experimental studies as a mutagen, as well as for obtaining polyploid forms of plants.
Demecolcin, which is 7-8 times less toxic than colchicine, is used mainly as an external agent (in the form of an ointment) for skin tumors (it inhibits the growth of tumor tissue, causes the death of tumor cells upon direct contact). Colchicine is used to treat and prevent gout attacks. Colchicine, along with antimitotic activity, has the ability to prevent the formation of amyloid fibrils and block amyloidosis, has a uricosuric effect, prevents the development of the inflammatory process (it inhibits the mitotic division of granulocytes and other mobile cells, reduces their migration to the focus of inflammation). Assign colchicine for gout, mainly with the ineffectiveness of NSAIDs or contraindications to them.
In addition to vinca alkaloids and alkaloids of colchicum splendid, a new group of alkaloids, taxanes, are among the agents whose antimitotic activity is mainly due to their action on cell microtubules.
Taxanes— chemotherapeutic agents that became widespread in clinical practice in the 1990s.
Paclitaxel, the first taxane derivative with antitumor activity, was isolated in 1967 from the bark of the Pacific yew. (Taxus brevifolia), in 1971 its chemical structure was deciphered (it is a diterpenoid taxane). Currently, paclitaxel is also produced semi-synthetically and synthetically.
Docetaxel, close to paclitaxel in structure and mechanism of action, is obtained by chemical synthesis from natural raw materials - European yew needles. (Taxus baccata).
Taxanes belong to a class of drugs that act on microtubules. Unlike vinca alkaloids, which inhibit the formation of the mitotic spindle, taxanes, by binding to free tubulin, increase the rate and degree of its polymerization, stimulate the assembly of microtubules, stabilize the formed microtubules, and prevent tubulin depolymerization and microtubule breakdown. Taxanes disrupt the functioning of the cell during mitosis (M-phase) and in interphase.
The formation of an excessive number of microtubules and their stabilization leads to inhibition of the dynamic reorganization of the microtubule network, which ultimately leads to disruption of the formation of the mitotic spindle and inhibition of the cell cycle in G 2 and M phases. Changes in cell functioning in interphase, incl. violation of intracellular transport, transmission of transmembrane signals, etc. is also a consequence of a violation of the microtubular network.
Paclitaxel and docetaxel have a similar mechanism of action. However, differences in the chemical structure determine some of the nuances in the mechanism of action of these substances found in the experiment. For example, docetaxel has a more pronounced effect in terms of activating the polymerization of tubulin and inhibiting its depolymerization (about two times). Under the action of paclitaxel on the cell, some changes in the structure of microtubules are characteristic, which were not detected under the action of docetaxel. Thus, experimental studies have shown that microtubules formed in the presence of paclitaxel contain only 12 protofilaments (instead of 13 in the norm) and have a diameter of 22 nM (in contrast to 24 in the norm).
In addition, paclitaxel induces an abnormal arrangement of microtubules in bundles throughout the cell cycle and the formation of multiple stellate clumps (asters) during mitosis.
The mechanisms of action of various drugs that affect microtubules remain not fully understood, despite the large amount of accumulated information. It has been established that the sites of binding to tubulin are different for natural vinca alkaloids, vinorelbine, colchicine, and taxanes. Thus, in experimental studies of paclitaxel, it was shown that it predominantly binds to the beta subunit of tubulin, while its ability to bind to microtubules is higher than that of tubulin dimers.
Taxanes are effective in breast cancer, ovarian cancer, non-small cell lung cancer, head and neck tumors, etc.
Podophyllotoxins. Antitumor agents of plant origin include podophyllin (a mixture of natural substances isolated from rhizomes with roots of podophyllum thyroid (Podophyllum peltatum L.) barberry family (Berberidaceae). Podophyllin contains at least 40% podophyllotoxin, alpha and beta peltatins. An extract from the rhizomes of podophyllum has long been used in folk medicine as a laxative for chronic constipation, as an emetic and antihelminthic. Later, its cytostatic activity was discovered, manifested by the blockade of mitosis at the metaphase stage (it resembles colchicine in action). Podophyllotoxin is used topically in the treatment of papillomas and other skin neoplasms.
In clinical practice, semi-synthetic derivatives of podophyllotoxin are widely used - epipodophyllotoxins(etoposide and teniposide), according to the mechanism of action related to inhibitors of topoisomerases.
Topoisomerases are enzymes directly involved in the process of DNA replication. These enzymes change the topological state of DNA: by carrying out short-term breaks and reunions of DNA sections, they contribute to the rapid unwinding and twisting of DNA during replication. At the same time, the integrity of the circuits is preserved.
Topoisomerase inhibitors, by binding to the topoisomerase-DNA complex, affect the spatial (topological) structure of the enzyme, reduce its activity and thereby disrupt the process of DNA replication, inhibit the cell cycle, delaying cell proliferation.
Topoisomerase inhibitors have a phase-specific cytotoxic effect (during the S and G 2 phases of the cell cycle).
Etoposide and teniposide are topoisomerase II inhibitors.
Camptothecins- semi-synthetic derivatives of the alkaloid camptothecin, isolated from the stems of the shrub Camptotheca acuminata, represented by irinotecan and topotecan. According to the mechanism of action, they belong to the group of topoisomerase inhibitors. Unlike epipodophyllotoxins, camptothecins are topoisomerase I inhibitors. Irinotecan is currently the first-line drug for the treatment of colon cancer. Topotecan is widely used in the treatment of lung and ovarian cancer.
Preparations
Preparations - 1733 ; Trade names - 97 ; Active ingredients - 14
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Anticancer drugs are drugs used to treat cancer. Drug therapy does not replace surgical and radiation methods of treatment, but complements them, and only for some tumor diseases can be used as the only method of treatment, for example, for leukemia, lymphogranulomatosis, reticulosarcomatosis, multiple myeloma, uterus.
Anticancer drugs that have received practical application in oncology are usually divided into the following groups: 1) hormonal drugs (, corticosteroids);
2) alkylating agents - chlorethylamines (embihin, novembihin, dopan, degranol, novembitol,), ethyleneimines (, dipin, benzotef, fluorobenzotef), methanesulfonides (myelosan), epoxides;
3) antimetabolites - purine antagonists (6-mercaptopurine), pyrimidine antagonists (), antagonists (methotrexate); 4) substances of plant origin - vinca alkaloids (vinblastine, vincristine), colhamine; 5) antitumor antibiotics (actiaomycins C and D, olivomycin, bruneomycin, rubomycin); 6) other drugs (natulan, orthopara DDD).
The main condition that provides an antitumor effect is the accumulation of drugs (except hormones) in the tumor preferential compared to normal tissues.
Modern antitumor agents do not have sufficient selectivity and therefore it is necessary to administer them in large doses, despite the fact that the difference between their maximum therapeutic and minimum toxic doses is less than that of most other drugs. In this regard, with antitumor drug therapy, side effects and complications often occur. They are expressed in a depressant effect on the hematopoietic tissue (leukopenia,), damage to the mucous membranes of the digestive tract (,), vomiting, dermatitis, inhibition of spermatogenesis, disruption of the ovulatory cycle, etc.
Given the high toxicity of anticancer drugs, a prerequisite for their use is strict adherence to the instructions for use and constant monitoring of their tolerance, dynamic monitoring of the readings of the number of leukocytes in peripheral blood, detection of the first signs of damage to the mucous membranes of the digestive tract, etc.
Contraindications to the use of antitumor drugs: leukocytopenia and thrombocytopenia, severe insufficiency of the function of parenchymal organs (liver, kidneys), etc.
Methods of administration of anticancer drugs are different. Substances that are administered only intravascularly cause necrosis when they enter the skin (embihin, novembihin, vinblastine). Other drugs can be administered intravenously and intramuscularly (cyclophosphamide, thiophosfamide).
There are drugs that are used orally (mercaptopurine), as well as those that are used parenterally and orally (sarcolysin, cyclophosphamide, methotrexate).
As a rule, the use of anticancer drugs is carried out according to the prescription of a specialist doctor and under his control.
Anticancer drugs - drugs used for the drug treatment of malignant tumors. Antitumor agents belong to different classes of chemical compounds and have different mechanisms of action.
The largest group is made up of drugs with an alkylating action, which consists in attaching a substance at the site of the released valency of the carbon atom to the most important components of the cell - DNA, RNA, proteins and phospholipids. It is assumed that due to the addition of the drug to two nearby DNA points, the high-polymer molecule breaks into smaller parts, as a result of which DNA cannot perform its functions during mitosis, the transfer of genetic information, and as a regulator of protein synthesis. As a result of this, as well as due to energy disturbances, tumor cells lose their viability. The side effect of alkylating substances consists mainly in the inhibition of hematopoiesis, which is based on the same process of a chemical reaction with the DNA of undifferentiated cells of the myeloid and lymphoid series. Nevertheless, many alkylating substances have a known selective effect on certain malignant tumors, i.e., they affect them more strongly than they do on hematopoietic tissues.
The first alkylating agent was embihin, methyl-di-(2-chloroethyl)amine hydrochloride (synonym: HN 2 , Dichloren, Mustargen, dimitan). Its therapeutic effect in Hodgkin's disease, chronic leukemia, reticulosarcoma was first established by American authors. In the USSR, embikhin was replaced by a drug close to it, novembihin (see), which has the same therapeutic effect, but milder side effects. The drug is still used in the treatment of lymphogranulomatosis and chronic lymphocytic leukemia.
Japanese authors have proposed the drug nitromin, which is an oxide of embichin. The drug is used in Japan and some European countries. Austrian scientists have shown that with the systematic use of nitromin after surgical removal of lung cancer, the percentage of relapses decreases.
With lymphogranulomatosis, chronic leukemia and reticulosarcoma, chlorbutine (chlorambucil), dopan, degranol are also effective. The first two are convenient in that they are taken orally in tablets.
Dopan is a domestic original drug, which is 4-methyl-5-di-(2-chloroethyl) aminouracil. It is used in a single dose of 8-10 mg (4-5 tablets) once every 5 days. The total dose is 50-80 mg. Side effects were noted - nausea, sometimes vomiting, oppression of hematopoiesis. The course of treatment ends when the number of leukocytes in the blood drops to 3000. To prevent nausea and vomiting, it is recommended to use dopan after dinner and give Nembutal or chlorpromazine at night.
Degranol was proposed in Hungary and is 1,6-di-(chloroethyl)-amino-1,6-deoxymannitol dihydrochloride. It is used intravenously in a single dose of 100 mg every other day. The total dose per course is 500-1000 mg.
It has been proven that with the help of novembihin and dopan, with proper and persistent treatment, started in the early stages of lymphogranulomatosis, positive long-term results of treatment (life expectancy of 5 and 10 years from the start of treatment) can be obtained.
In the USSR, the drug sarcolysin (a chloroethylamine derivative of phenylalanine) was proposed, also synthesized in England. Sarcolysin (see) was the first drug of a new group in which the metabolite (essential amino acid) is the carrier of the alkylating (chlorethylamine) group. The spectrum of action of sarcolysin differs from that of its predecessors. Sarcolysin is effective in seminoma metastases, multiple myeloma, soft tissue and bone reticulosarcomas, esophageal cancer (together with kolhamin), melanoma (perfusion application), ovarian cancer (with intra-abdominal injections). In Germany, the drug endoxan (cyclophosphamide) was invented, which also has a fairly wide spectrum of action; the drug itself is inactive, but is converted to the active compound in the body. Endoxan is activated mainly in the liver. It is used for lymphogranulomatosis, chronic and acute leukemia, lymphoreticulosarcomas, lung, breast and ovarian cancer. Cyclophosphamide has a relatively weak side effect and is well tolerated by patients.
A group of alkylating agents close to di-(2-chloroethyl)amines in terms of the mechanism of action is ethyleneimines. These include the drug TEM (TET), which is triethylenemelamine. It has an effect in chronic lymphocytic leukemia, lymphogranulomatosis, ovarian and lung cancer. In the USSR, TEM was not put into practice due to the presence of side effects. Etimidine (see), proposed in the USSR, is used mainly for ovarian cancer. In Germany, ethyleneimine derivatives of benzoquinone have been developed - E-39, A-139 and trenimone. They give an effect in chronic leukemia, lymphogranulomatosis and some other tumors.
A special group of ethyleneimines are ethylenephosphoramides. The main representative is TIO-TEF [thiophosfamide (see)], which is used in breast cancer, ovarian cancer and some other tumors (for example, in combination with surgical treatment of lung cancer). In the USSR, ethyleneimines are also proposed and used: benzotef (see) - mainly for ovarian cancer, dipine and thiodipine (see) - for lymphocytic leukemia.
Dipin is an original domestic drug, which is 1,4-dipiperazine. It is used intravenously in a single dose of 10-15 mg every other day with a total dose of up to 200 mg. The therapeutic effect of dipin is described not only in lymphocytic leukemia, but also in hypernephroma metastases to the lungs.
Myelosan belongs to the class of alkylating substances (see), otherwise mileran, the representative of sulfonoxy compounds proposed in England. Myelosan has earned general recognition as the drug most effective in chronic myelogenous leukemia.
The second important group of anticancer drugs are the so-called antimetabolites - compounds involved in the metabolism due to their similarity with normal participants in the exchange - metabolites. Due to this similarity, antimetabolites can occupy the sites intended for metabolites on the active sites of enzymes and form a more or less stable complex with an apoenzyme or coenzyme. As a result, the corresponding enzymatic reaction is inhibited (at one stage or another). The strength of the antimetabolite bond with the enzyme determines the nature of its action.
The first antimetabolite to find practical use was aminopterin (4-amino derivative of folic acid).
Later, a more effective amethopterin (methotrexate) was obtained. These drugs inhibit the synthesis of nucleic acids in cells. Initially, their effectiveness was established in acute leukemia in children. Later, the effect of methotrexate was found in metastases of chorionepithelioma of the uterus to the lungs. With prolonged intra-arterial infusion, methotrexate can cause regression of squamous cell carcinomas (cervix, head and neck tumors). The second drug of the antimetabolite group - 6-mercaptopurine - is the most effective in the treatment of acute leukemia and can cause remission of the disease not only in children, but also in adults. 6-Mercantopurine is administered orally in tablets daily at 2.5 mg/kg for 3-8 weeks or more until remission occurs. If after 4 weeks from the start of treatment there is no improvement and there are no side effects, the dose is gradually increased to 0.5 mg / kg. In the treatment of acute leukemia, 6-mercaptopurine is used in combination with other anticancer drugs and prednisolone. The third antimetabolite, 5-fluorouracil, has a wide spectrum of antitumor activity. It inhibits the synthesis of deoxyribonucleic acid and, being included in ribonucleic acid, makes it "fake". As a result, tumor cells lose their viability.
Unlike alkylating agents, 5-fluorouracil can be effective in primary adenocarcinomas of a number of organs: stomach, pancreas, liver, colon and rectum, breast, ovaries. Fluorouracil enhances the effect of ionizing radiation on tumors and therefore, in combination with radiation treatment, it has an effect in lung cancer. Fluorouracil is a very important antitumor drug, as it can give a therapeutic effect in the most common tumors (stomach cancer, etc.).
The third group of drugs - antitumor antibiotics. Of these, actinomycins were used (see) Cu D. The first gives an effect in the early stages of lymphogranulomatosis. The domestic version is called aurantina. Actinomycin D is effective in uterine chorionepithelioma (especially in combination with methotrexate), in metastases of the kidney tumor (Wilms), and in children in combination with radiation treatment and in some other tumors. With chorionepithelioma, the domestic antibiotic chrysomallin is very active.
Antibiotic mitomycin C containing an alkylating group, according to Japanese authors, has a positive effect on breast, stomach and lung cancer, metastases of osteosarcoma. Domestic drugs close to antibiotics (crucine and neocid) are used in the treatment of advanced stages of malignant tumors as symptomatic agents.
A group of herbal preparations are colhamine and vinblastine. Kolkhamin is isolated from Colchicum by domestic authors. It is deacetylmethylcolchicine. When used orally, a single dose is 4-5 mg every other day. Kolhamin when applied externally (in ointment) can cure skin cancer only at an early stage. In combination with sarcolysin, it has an effect on esophageal cancer. Vinblastine and vincristine close to it have a positive effect on lymphogranulomatosis, acute leukemia, chorionepithelioma and some other tumors. The drug from the birch fungus "chaga" is used for various tumors as a symptomatic remedy.
The last group of anticancer drugs are hormones and hormone-like substances. Hormonal drugs act on tumors mainly not directly, but by influencing the endocrine organs and some aspects of the metabolism in the body. The first group of hormonal drugs are, i.e., substances with the action of the female sex hormone (see). These include sinestrol, diethylstilbestrol, estradiol, hongvan (fosfestrol), estradurine, etc. They are used to treat prostate cancer and breast cancer (in older women). It is believed that the action of estrogens is carried out through inhibition of the secretion of follicle-stimulating hormone from the pituitary gland. The second group is androgens (substances with the action of the male sex hormone). These include testosterone propionate (for intramuscular injection), methyltestosterone, methylandrostenediol, 2a-methyldihydrotestosterone. They are used for breast cancer in relatively young women. The corpus luteum hormones progesterone and oxyprogesterone capronate (delalutin) can be used in the treatment of breast and uterine cancer. The third group of hormonal drugs are corticosteroids (see), cortisone, prednisone, prednisolone, fluorohydrocortisone, etc. Corticosteroids are used in the treatment of acute leukemia, chronic lymphocytic leukemia, lymphogranulomatosis and breast cancer.
The effect produced by antitumor drugs depends on the sensitivity of a given tumor to a particular drug, the stage of the disease, in particular on the volume of tumor tissue, on whether there is only a primary tumor or metastases, or both, on the general condition of the body, and also on the applied treatment methods. In some patients, the effect is only subjective and is expressed in an improvement in the general condition, pain relief, in others the temperature decreases, cough decreases, the patency of the esophagus improves (for example, with cancer of the esophagus and stomach), but the objective indicators of the tumor state remain the same (symptomatic effect). In the third group of patients, there is a decrease in the size (regression) of tumors until complete disappearance (objective effect).
Most drugs that have an objective effect give it only for tumors of a certain localization and histological structure, and not in all patients, which depends on the biochemical characteristics of different tumors of the same organ. In some cases, the drug has a better effect on metastases than on primary tumors (for example, sarcolysin with seminoma), in others, the primary tumor reacts more strongly (for example, gastric cancer with 5-fluorouracil). The resulting objective effect can be very short-lived, especially with a slight regression of tumors, and lasts from several weeks to several months. With complete regression of some tumors, a lasting effect can be obtained for a period of 3-5 years or more. This kind of result, conventionally referred to as a clinical cure, was obtained, for example, as a result of the use of colhamin in skin cancer, sarcolysin in seminoma, multiple myeloma, bone reticulosarcomas, dopan in lymphogranulomatosis, methotrexate in chorionepithelioma metastases. Antitumor agents are used both alone and in combination with surgical and radiation treatment. It has been established that actinomycin D (chrysomallin) and 5-fluorouraccl potentiate the effect of ionizing radiation on some tumors. There is evidence that the use of certain drugs (Nitromin, Endoxan, THIO-TEF) after surgical removal of lung cancer reduces the percentage of relapses and metastases. Postoperative chemotherapy for other malignant tumors is not well developed.
To obtain the greatest therapeutic effect, the method of using anticancer drugs is essential. Due to the insufficiently high selectivity of the action of existing drugs, in most cases it is necessary to use the maximum tolerated dose, the achievement of which is determined by the appearance of side effects (decrease in the number of leukocytes and platelets with alkylating agents, phenomena from the oral cavity and gastrointestinal tract with antimetabolites, etc.). To increase the therapeutic effect and reduce side effects, in some cases, regional administration of drugs is used - intracavitary, intra-arterial infusion and perfusion (see Perfusion of isolated organs). Currently, intensive work is underway to create new anticancer drugs. with higher selectivity and a different spectrum of antitumor activity.
Oncology treatment is based on the use of three methods of therapy: surgery, radiation therapy and chemotherapy (pharmacotherapy) or their combinations. Chemotherapy uses various anticancer drugs.
What are anticancer drugs and how do they work
The bulk of tumors arise due to the uncontrolled reproduction of just one type of cell. The reason for this uncontrolled division is considered to be genetic changes in the structure of the human body. Cancer cells not only have a hostile effect on the tissues of the organ where they were formed, but are also transferred by the fluids of the affected organ to other organs.
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Anticancer drugs are chemicals that can be in different forms - tablets, solutions for injections intravenously and intramuscularly, substances for oral use. All of these medicines are used to:
- slowing down the development of malignant tumors;
- check the level of maturation and growth of abnormal cells;
- attract the main agent influencing tumor formations.
Anticancer (antiblastoma) drugs act on cancer cells without affecting healthy, dormant ones. Most drugs prevent the growth of cancer cells by slowing down the production of deoxyribonucleic acid.
The action of anti-blastoma drugs is directed only at active (dividing) cancer cells. If at the time of therapy, tumor cells are in a "sleeping" state (do not multiply), drugs may not work on them. This is due to the relapse of the disease - when favorable conditions arise for the development of tumor cells, they begin to multiply again.
Need to know! A feature of antitumor drugs is that they cannot distinguish between harmful and harmless cells, but affect those that are in active reproduction.
You can use anticancer drugs as directed by an oncologist. Depending on the course of the disease, the tolerability of chemotherapy, a treatment regimen, doses, and a combination of one drug with others are established.
Classification of anticancer drugs
The pharmacological group of antitumor drugs (cytostatics) is divided into several main groups depending on the mechanism of action on the tumor:
- anticancer antibiotics;
- antimetabolites;
- alkylating antineoplastic agents;
- hormones;
- herbal preparations.
The main list of cytostatic drugs:
- Alkylating antineoplastic agents. All these drugs interfere with the DNA copying process (mix with them), preventing the copying of the cell genome during division. The result - the production of elements is interrupted, and the cell dies. Medicines of this group effectively affect all multiplying cells. This group includes:
- ethyleneimines ("Thiotepa");
- alkylsulfonates ("Treosulfan", "Busulfan");
- nitrosourea derivatives ("Nimustine", "Carmustine");
- chlorethylamines ("Trophosphamide", "Chlorambucil", "Ifosfamide", "Cyclophosphamide").
- plant alkaloids. Anti-cancer substances of plant origin are not very effective in the later stages of the disease. Such remedies have much fewer side effects than non-natural antibiotics. They should be administered carefully to older patients. In pregnancy, they are prescribed when the maternal health benefit of such drugs is greater than the risk to the fetus. These include:
- Antimetabolites. These drugs interfere with the compounds needed for cell division, and they also prevent the tumor cell from completing its metabolic process. Some of these drugs can replace key metabolites, preventing cancer cells from functioning, while others slow down protein production. Antimetabolites include:
- folic acid antagonists ("Methotrexate");
- purine antagonists (Pentostatin, Cladribine, Thioguanine);
- pyrimidine antagonists (Gemcitabine, Cytarabine)
- anthracyclines ("Daunorubicin", "Doxorubicin", "Mitoxantrone", "Epirubicin");
- other antitumor antibiotics ("Mitomycin", "Bleomycin").
- Other cytostatics:
- derivatives of camptothecin ("Topotecan");
- platinum derivatives ("Oxaliplatin", "Cisplatin", "Carboplatin");
- others ("L-asparaginase", "Temozolomide", "Amsakrin", "Estramustine", "Dacarbazine", "Hydroxycarbamide").
- Monoclonal antibodies(Rituximab, Trastuzumab).
- Cytostatic hormones. These anticancer drugs create an unfavorable environment for the development of cancer cells. Medicines of this group are used to treat tumors of certain organs. The principle of action of these antitumor drugs is the use of hormones of the opposite sex - men are prescribed estrogens, women - androgens. This kind of therapy prevents the spread of tumor cells throughout the body and inhibits the growth of neoplasms. This group includes the following drugs:
- Immunomodulators. These funds increase the effectiveness of antiblastoma antibiotics and cytostatics ("Derinat").
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Anticancer drugs of plant origin
To date, medicinal plants with antitumor activity have become widespread in the treatment of cancer. The list of medicinal plants that have antitumor properties:
- ginger;
- turmeric;
- Ginkgo tree;
- ginseng;
- milk thistle;
- hemlock spotted;
- Jungar aconite;
- elecampane;
- celandine.
Often, patients with oncological problems use herbal preparations in therapy. In the treatment of skin cancer, when the tumor is quite close to the skin, an antitumor ointment (gel), hemlock oil is used.
Traditional medicine allows the treatment of tumors with tinctures:
- fly agaric;
- chaga;
- geisha mushroom.
Neoplasms in folk medicine are treated mainly with poisonous plants. Because of this, the side effects can be quite unpleasant.
New generation anticancer drugs
Recently, a substance has been discovered that effectively fights pathology - this is vitamin B17. Once in a diseased organism, it is attracted to neoplasms and destroys them, killing tumor cells completely. Healthy particles are not affected by this vitamin, since B17 "distinguishes" affected cells from healthy ones. In the later stages, this modern medicine greatly reduces the volume of the tumor and prevents the formation of metastases. In addition, B17 includes benzoic acid, which is an antiseptic, the vitamin has analgesic and antirheumatic properties. 
Side effects
Cancer drugs used in cancer therapy are usually highly toxic. Anticancer drugs can provoke adverse reactions in a patient:
- nausea, vomiting, anorexia are side effects of the use of alkylating agents, antibiotics and metabolites;
- stomatitis, diarrhea may occur with antimetabolic therapy;
- increases susceptibility to infections with the use of drugs that suppress bone marrow function;
- bleeding occurs due to the effect of drugs on platelet count;
- fluid retention occurs due to hormone therapy;
- neurological disorders - due to the use of plant alkaloids;
- hair loss, nail problems can occur due to the effect of anticancer drugs on the hair follicles.
Medicinal methods have been developed to increase the tolerability of anticancer drugs. Highly effective can reduce the feeling of nausea, get rid of the urge to vomit, "colony-stimulating factors" (filgrastim, etc.) - reduce the risk of developing neutropenia.
Question answer
Peptides, or short proteins, are found in many foods - meat, fish, and some plants. When we eat a piece of meat, the protein is broken down during digestion into short peptides; they are absorbed into the stomach, small intestine, enter the blood, cells, then into DNA and regulate the activity of genes.What is the difference between cytotoxic drugs and cytostatic drugs?
Cytotoxins (Citoxine) cause necrosis of tumor cells, and cytostatics trigger a self-destruction mechanism inside the cancer cell.
It is advisable to periodically use the listed drugs for all people after 40 years for prevention 1-2 times a year, after 50 years - 2-3 times a year. Other drugs - as needed.
How to take peptides
Since the restoration of the functional ability of cells occurs gradually and depends on the level of their existing damage, the effect can occur both 1-2 weeks after the start of taking peptides, and 1-2 months later. It is recommended to conduct a course within 1-3 months. It is important to take into account that a three-month intake of natural peptide bioregulators has a prolonged effect, i.e. works in the body for another 2-3 months. The effect obtained lasts for six months, and each subsequent course of administration has a potentiating effect, i.e. amplification effect already obtained.Since each peptide bioregulator has a focus on a specific organ and does not affect other organs and tissues in any way, the simultaneous administration of drugs with different effects is not only not contraindicated, but is often recommended (up to 6-7 drugs at the same time).
Peptides are compatible with any drugs and biological supplements. Against the background of taking peptides, it is advisable to gradually reduce the doses of simultaneously taken drugs, which will positively affect the patient's body.
Short regulatory peptides do not undergo transformation in the gastrointestinal tract, so they can be safely, easily and simply used in encapsulated form by almost everyone.
Peptides in the gastrointestinal tract decompose to di- and tri-peptides. Further breakdown to amino acids occurs in the intestine. This means that peptides can be taken even without a capsule. This is very important when a person for some reason cannot swallow capsules. The same applies to severely weakened people or children, when the dosage needs to be reduced.
Peptide bioregulators can be taken both prophylactically and therapeutically.
Efficiency natural(PC) 2-2.5 times lower than encapsulated. Therefore, their intake for medicinal purposes should be longer (up to six months). Liquid peptide complexes are applied to the inner surface of the forearm in the projection of the course of the veins or on the wrist and rubbed until completely absorbed. After 7-15 minutes, the peptides bind to dendritic cells, which carry out their further transport to the lymph nodes, where the peptides make a “transplant” and are sent with the bloodstream to the desired organs and tissues. Although peptides are protein substances, their molecular weight is much smaller than that of proteins, so they easily penetrate the skin. The penetration of peptide preparations is further improved by their lipophilization, that is, the connection with a fatty base, which is why almost all peptide complexes for external use contain fatty acids.
Not so long ago, the world's first series of peptide drugs appeared for sublingual use—
A fundamentally new method of application and the presence of a number of peptides in each of the preparations provide them with the fastest and most effective action. This drug, getting into the sublingual space with a dense network of capillaries, is able to penetrate directly into the bloodstream, bypassing absorption through the mucosa of the digestive tract and metabolic primary deactivation of the liver. Taking into account direct entry into the systemic circulation, the rate of onset of the effect is several times higher than the rate when the drug is taken orally.
Revilab SL Line- these are complex synthesized preparations containing 3-4 components of very short chains (2-3 amino acids each). In terms of peptide concentration, this is the average between encapsulated peptides and PC in solution. In terms of speed of action, it occupies a leading position, because. absorbed and hits the target very quickly.
It makes sense to introduce this line of peptides into the course at the initial stage, and then switch to natural peptides.
Another innovative series is a line of multicomponent peptide preparations. The line includes 9 preparations, each of which contains a range of short peptides, as well as antioxidants and building materials for cells. An ideal option for those who do not like to take many drugs, but prefer to get everything in one capsule.
The action of these new generation bioregulators is aimed at slowing down the aging process, maintaining a normal level of metabolic processes, preventing and correcting various conditions; rehabilitation after serious illnesses, injuries and operations.
Peptides in cosmetology
Peptides can be included not only in drugs, but also in other products. For example, Russian scientists have developed excellent cellular cosmetics with natural and synthesized peptides that affect the deep layers of the skin.External aging of the skin depends on many factors: lifestyle, stress, sunlight, mechanical stimuli, climatic fluctuations, dieting hobbies, etc. With age, the skin becomes dehydrated, loses its elasticity, becomes rough, and a network of wrinkles and deep grooves appears on it. We all know that the process of natural aging is natural and irreversible. It is impossible to resist it, but it can be slowed down thanks to the revolutionary ingredients of cosmetology - low molecular weight peptides.
The uniqueness of peptides lies in the fact that they freely pass through the stratum corneum into the dermis to the level of living cells and capillaries. Restoration of the skin goes deep from the inside and, as a result, the skin retains its freshness for a long time. There is no addiction to peptide cosmetics - even if you stop using it, the skin will simply age physiologically.
Cosmetic giants create more and more "miraculous" means. We trustfully buy, use, but a miracle does not happen. We blindly believe the inscriptions on the banks, not suspecting that this is often just a marketing ploy.
For example, most cosmetic companies are in full production and advertising anti-wrinkle creams with collagen as the main ingredient. Meanwhile, scientists have come to the conclusion that collagen molecules are so large that they simply cannot penetrate the skin. They settle on the surface of the epidermis, and then washed off with water. That is, when buying creams with collagen, we are literally throwing money down the drain.
As another popular active ingredient in anti-aging cosmetics, it is used resveratrol. It really is a powerful antioxidant and immunostimulant, but only in the form of microinjections. If you rub it into the skin, a miracle will not happen. It has been experimentally proven that creams with resveratrol practically do not affect the production of collagen.
NPCRIZ (now Peptides), in collaboration with scientists from the St. Petersburg Institute of Bioregulation and Gerontology, has developed a unique peptide series of cellular cosmetics (based on natural peptides) and a series (based on synthesized peptides).
They are based on a group of peptide complexes with different application points that have a powerful and visible rejuvenating effect on the skin. As a result of application, skin cell regeneration, blood circulation and microcirculation are stimulated, as well as the synthesis of collagen-elastin skin skeleton. All this manifests itself in lifting, as well as improving the texture, color and moisture of the skin.
Currently, 16 types of creams have been developed, incl. rejuvenating and for problematic skin (with thymus peptides), for the face against wrinkles and for the body against stretch marks and scars (with bone and cartilage tissue peptides), against spider veins (with vascular peptides), anti-cellulite (with liver peptides), for eyelids from edema and dark circles (with peptides of the pancreas, blood vessels, bone and cartilage tissue and thymus), against varicose veins (with peptides of blood vessels and bone and cartilage tissue), etc. All creams, in addition to peptide complexes, contain other powerful active ingredients. It is important that the creams do not contain chemical components (preservatives, etc.).
The effectiveness of peptides has been proven in numerous experimental and clinical studies. Of course, to look beautiful, some creams are not enough. You need to rejuvenate your body from the inside, using from time to time various complexes of peptide bioregulators and micronutrients.
The line of cosmetic products with peptides, in addition to creams, also includes shampoo, mask and hair balm, decorative cosmetics, tonics, serums for the skin of the face, neck and décolleté, etc.
It should also be borne in mind that the appearance is significantly affected by the sugar consumed.
Through a process called glycation, sugar is destructive to the skin. Excess sugar increases the rate of collagen degradation, leading to wrinkles.
Glycation - the interaction of sugars with proteins, primarily collagen, with the formation of cross-links - is a natural for our body, permanent irreversible process in our body and skin, leading to hardening of the connective tissue.
Glycation products - A.G.E particles. (Advanced Glycation Endproducts) - settle in cells, accumulate in our body and lead to many negative effects.
As a result of glycation, the skin loses its tone and becomes dull, it sags and looks old. This is directly related to lifestyle: reduce your intake of sugar and flour (which is good for normal weight) and take care of your skin every day!
To counter glycation, inhibit protein degradation and age-related skin changes, the company has developed an anti-aging drug with a powerful deglycing and antioxidant effect. The action of this product is based on stimulating the deglycation process, which affects the deep processes of skin aging and helps to smooth out wrinkles and increase its elasticity. The drug includes a powerful complex to combat glycation - rosemary extract, carnosine, taurine, astaxanthin and alpha-lipoic acid.
Peptides - a panacea for old age?
According to the creator of peptide preparations V. Khavinson, aging largely depends on lifestyle: “No drugs will save if a person does not have a set of knowledge and the right behavior - this is the observance of biorhythms, proper nutrition, physical education and the intake of certain bioregulators.” As for the genetic predisposition to aging, according to him, we depend on genes by only 25 percent.The scientist claims that peptide complexes have a huge reduction potential. But to elevate them to the rank of panacea, to attribute non-existent properties to peptides (most likely for commercial reasons) is categorically wrong!
Taking care of your health today means giving yourself a chance to live tomorrow. We ourselves must improve our lifestyle - play sports, give up bad habits, eat better. And of course, to the extent possible, use peptide bioregulators that help maintain health and increase life expectancy.
Peptide bioregulators, developed by Russian scientists several decades ago, became available to the general public only in 2010. Gradually, more and more people around the world learn about them. The secret to maintaining the health and youthfulness of many famous politicians, artists, scientists lies in the use of peptides. Here are just a few of them:
UAE Minister of Energy Sheikh Saeed,
President of Belarus Lukashenko,
Former President of Kazakhstan Nazarbayev,
King of Thailand
pilot-cosmonaut G.M. Grechko and his wife L.K. Grechko,
artists: V. Leontiev, E. Stepanenko and E. Petrosyan, L. Izmailov, T. Povaliy, I. Kornelyuk, I. Viner (rhythmic gymnastics coach) and many, many others...
Peptide bioregulators are used by athletes of 2 Russian Olympic teams - in rhythmic gymnastics and rowing. The use of drugs allows us to increase the stress resistance of our gymnasts and contributes to the success of the national team at international championships.
If in youth we can afford to do health prevention periodically, when we want, then with age, unfortunately, we do not have such a luxury. And if you don’t want to be in such a state tomorrow that your loved ones will be exhausted with you and will wait impatiently for your death, if you don’t want to die among strangers, because you don’t remember anything and everything around you seems to be strangers in fact, you should take action from today and take care not so much about themselves as about their loved ones.
The Bible says, "Seek and you will find." Perhaps you have found your own way of healing and rejuvenation.
Everything is in our hands, and only we can take care of ourselves. No one will do this for us!
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Summary of the article:
1) Antitumor ointments,
2) Antitumor plants,
3) Antitumor mushrooms,
4) Anticancer teas,
5) Antitumor tinctures,
6) Antitumor dietary supplements,
7) Antitumor agents of plant origin.
Antitumor ointments
And so very often I advise people who are faced with oncology antitumor ointments based on plant poisons. In this situation, a very good ointment from herb hemlock spotted. This article will also write about this plant as the main antitumor folk remedy in the CIS. In some European countries, this drug is officially used in the treatment of cancer, but so far this is not the case in our country, it is most likely not profitable for pharmaceutical companies to produce a drug that in many cases helps patients. It's not for me to judge them.
Hemlock-based antitumor ointment is used in the treatment of skin cancer, breast cancer and other types of cancer, when the tumor is close to the skin and alkaloids can easily penetrate the skin to the formation.
Second, anticancer folk remedy on the basis of hemlock, you can make an oil that, like an ointment, is used to treat cancer. In order to prepare such oil on hemlock, we need to take dry hemlock, pour it into a glass jar and pour oil over it. Put in a dark place for six months, after which it can be used for treatment.
Anticancer plants
On the territory of Russia and the CIS, many medicinal plants grow that can be used as antitumor plants. These plants include:
Herbs Jungar aconite, collected in Central Asia high in the mountains;
Spotted hemlock, also desirable when collected high in the mountains;
Grass cocklebur;
Grass elecampane;
Grass celandine.
It makes no sense to write a lot of herbs, otherwise you will get even more confused, but these are the main antitumor plants that can be used in the treatment of cancer.
Why is the article focused on collecting herbs high in the mountains? It's no secret that plants that grow in difficult conditions are much stronger and more hardy than plants that grow, say, on the plains. You can also say about people, the same highlanders who live longer. Therefore, the medicinal properties of such antitumor plants are much better. Let's talk about Dzungarian aconite. There are many types of aconite, and the aconite itself is used as a garden plant because of its beauty, but again, it should not be confused with the Dzungarian aconite. Jungar aconite itself is very poisonous, this poison is its medicinal property, therefore, before buying on the Internet, always ask where the raw material comes from and how it was collected. I collect Jungar aconite high in the mountains.
You can also say about grass hemlock spotted. If it is collected high in the mountains, then the healing properties are also better. More about the antitumor folk remedy hemlock tincture can be found in the article below.
Grass celandine, cocklebur is also an antitumor plant and is often used in the treatment of oncology. Articles about them below.
Anticancer mushrooms
There is a so-called fungotherapy, that is, treatment with mushrooms. Yes, in my healing practice I use mushroom tinctures and advise people to drink this or that tincture for treatment. Anticancer fungi include:
Mushroom Amanita;
Birch mushroom (chaga);
Reishi mushroom.
I can say about the fly agaric mushroom that by its action it behaves like Dzhungarian aconite and like hemlock, since these plants and the fungus are united by the presence of poisonous alkaloids, which give these plants and the fungus poisonous properties. I’ll tell you about fly agaric tincture in the topic anticancer tinctures.
antitumor fungus- birch fungus, often used in folk medicine for treatment.
First, soften the birch mushroom (chaga) (you can use warm water), then pass it through a blender or meat grinder, pour warm water in a ratio of 1 to 2 and insist for two days. Drink 600 gr. per day, that is, three times a day, 200 ml. Continue like this for 3 months
Preparation of a birch alkaline solution according to the following recipe: we take birch ash and place it in water (1: 5 ash / water ratio) and boil for 10 minutes in a glass or enamel bowl. After that, cool and strain. Method of treatment: dose: 50 g (8 tsp) solution mixed with milk or fruit juice, 3 times a day.
Diet, as with the above appointments, vegetable, dairy (you must use sour milk); eliminate meat from the diet completely (in any form).
anticancer reishi mushroom. The composition of the fungus is quite complex. It contains trace elements: a high level of germanium, coumarins, vitamins, organic acids, polysaccharides. The most important fungal compounds are triterpenes, polysaccharides, ganoderm acids and germanium. It is these compounds that determine the medicinal properties of the fungus.
Medicinal properties of reishi: immunomodulatory, soothing, antiallergic, antispasmodic, lowering blood pressure, antitumor (due to activation of the immune system), expectorant, hypoglycemic, antimicrobial, anti-inflammatory.
Mushroom applications. Make a tincture according to this method: 10 grams of chopped mushroom are infused in 400 ml. vodka for 2 weeks. Take 1 tbsp. l. 2-3 times a day 30 minutes before meals.
Reishi mushroom infusion should be made according to the following recipe: 1 tbsp. l. crushed mushroom per 700 ml. water, simmer for 60 minutes. Strain. Take 200 ml. decoction 3 times a day 30 minutes before meals.
Anticancer teas
To antitumor teas, I include herbal preparations that can be drunk as infusions or as teas.
Here I will write you one of the anticancer teas that you need to drink to prevent cancer. Take 1 tablespoon of pine needles, 1 tablespoon of young sea buckthorn leaves, 1 teaspoon of crushed milk thistle fruit. All herbs pour three cups of boiling water and boil for 18-20 minutes over low heat. Then strain the broth. Take 0.5 cup instead of tea.
Second anticancer tea: Burdock roots - 30 g, Burnet roots - 30 g, Marsh cinquefoil roots - 30 g, Rhizome of evading peony - 30 g, Bedstraw herb - 20 g, Dioecious nettle leaves - 20 g, Common agrimony grass - 20 g. Take one dessert spoon of a well-mixed collection of herbs and pour boiling water over it, leave for 30 minutes. Drink like tea with honey, 2-3 times a day. A month later, the fee is changed.
Antitumor tinctures
I already wrote in a paragraph about antitumor plants, those plants that are used in the treatment of oncology. Antitumor tinctures are made from these plants.
Antitumor tinctures include tinctures:
Tincture of hemlock spotted;
Tincture of Dzungarian aconite;
Tincture of celandine;
Cocklebur tincture;
Fly agaric tincture;
Reishi mushroom tincture;
Chaga tincture,
Basically, poisonous tinctures are used in the treatment of oncology. Why poisonous? As they say: poison is also a medicine, and if it is used in moderation, it has a beneficial effect on the body. The main toxic substance in poisonous tinctures is alkaloids. These are organic nitrogen-containing substances, which in their pure form are poison. Each plant or fungus has its own alkaloid. In hemlock it is coniine, in aconite it is aconitine, in fly agaric it is muscarine. They are different. That is why they say that it is better to drink poisonous tincture up to a maximum of 8 months? The body gets used to the poison, that is, the use of poison in the first month and in the tenth has a different effectiveness. Why is it necessary to drink another poison in between, say, if you take hemlock tincture, then you need to drink aconite during the break, because, so that the body does not lose the immunity reserve that it received from hemlock tincture, another poison, another alkaloid, another effect. You also need to look at which poison is best for the patient. When taking hemlock, there can be zero effect, since the body is like that, well, it does not perceive this poison, then we change it to aconite, if it does not perceive it, then we switch to fly agaric tincture.
Anticancer agents of plant origin
To antitumor agents of plant origin, I refer to agents that are made from natural material. I can refer Flaraxin to such means.
Flaraxin is an anticancer agent of plant origin, which is used in the treatment of oncology.
Other herbal antitumor agents:
Befungin
Vinblastine
Vincristine
Vinorelbine
Docetaxel
Irinotecan
Paclitaxel
Teniposide
Topotecan
Ukraine
etoposide
Summing up this, a large article, you learned that treatment with folk remedies is a complex treatment that is complex. Just taking one tincture is good, but you still need to work with other herbs and tinctures from herbal preparations.
Be healthy!
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