ANTINEOPLASTIC MEANS — the pharmaceuticals applied to treatment of tumors.
It is known apprx. 50 pharmaceuticals capable to destroy tumor cells (cytotoxic effect) or to oppress them proliferative activity (cytostatic effect). In this regard P. pages divide on cytotoxic and cytostatic (antimitotic and karioklastichesky).
However P. page have no sharp selectivity of action and along with tumoral damage cells of normal proliferating fabrics (cells of an adenoid tissue, marrow, went. - kish. path, gonads, skin, etc.).
For development and P.'s testing by the village use different models (fermental systems, cultures of bacteria, explants of tumoral and normal fabrics), but generally carry out selection of connections on experimental tumors (as a rule, on various strains of the intertwined tumors of mice or rats). Also attempts to use animals with the tumors caused by oncogenous agents and animals with spontaneous tumors are made. Accurate correlations in sensitivity to P. the page of experimental new growths and tumors of the person is not established. Therefore the question of a range of antineoplastic activity, i.e. a question of what tumors the village selected by P. will affect, finally is solved only in a wedge, conditions.
Some pharmaceuticals, napr, Befunginum (see) or Neocidum, have no antineoplastic activity, but are sometimes applied to symptomatic therapy onkol. patients for the purpose of decrease in the dispeptic phenomena and improvement of the general condition of the patient.
The Kliniko-pharmakologichesky characteristic of the fixed antineoplastic assets — see the table.
Pages divide all available P. into the following groups.
1. Synthetic Item of page: a) alkylating agents, b) antimetabolites; c) other synthetic drugs.
2. Antineoplastic means natural origin: a) alkaloids; b) antibiotics; c) enzymes; d) hormonal drugs.
Synthetic antineoplastic means
Alkylating agents represent substances which molecule contains chlorethylamine, etileniminny, epoxy groups or the remains metansulfonovy to - you, and make the most extensive group P. of page. Carry also derivative nitrozomochevina and some other drugs to them.
Biol. action of alkylating agents is caused by reaction of alkylation, the cut results a rupture of molecules DNA or cross binding between guanilny groups. Besides, they promote an inactivation of enzymes, structural change and function of cellular membranes. Their cytotoxic action is directed first of all to cells of quickly proliferating fabrics.
Some of alkylating agents, napr, Cyclophosphanum (see), are latent and need activation. Activation happens intracellularly to participation of microsomal oxidases preferential in a liver, to a lesser extent in other fabrics and in a tumor. The mechanism biol, actions of the activated Cyclophosphanum same, as well as at other alkylating agents.
For the purpose of creation of new, more perfect drugs as the carrier of the alkylating groups use various connections. In this work the big contribution was made by L. F. Larionov, under the direction of to-rogo such antineoplastic means as, e.g., sarcolysine (see) and to the sir are created on the basis of metabolites (see).
Most of alkylating agents is well soaked up in went. - kish. a path, however in connection with strong local irritative action many of them enter only intravenously. As a rule, in one days of connection are metabolized and brought out of an organism. Through a blood-brain barrier such alkylating agents as derivative nitrozomochevina and ours of paws get (see).
Alkylating agents have side effect on went. - kish. the path (the nausea, vomiting developing during the first hours after administration of drug), on a hemopoiesis (a leukopenia and thrombocytopenia), less often perhaps neurotoxic action, so, Prospidinum (see) causes dizziness and paresthesias. More or less expressed immunodepressive effect is characteristic of all drugs of this group. As indications to use of chlorethylamines and ethylene imines serve new growths of the hemopoietic bodies; some drugs are appointed at tumors of a mammary gland, ovary, a small egg.
Antimetabolites enter the competition to metabolites and lead to disturbance of life activity of tumor cells. The greatest interest is of: a methotrexate (see) — the antagonist folic to - you, being its chemical analog; Mercaptopurinum (see) — an analog of purine (see. Purine bases ); ftoruratsit (see), Phthorafurum (see) and Cytosarum (see) — analogs of a pyrimidine (see. Pirimidinovy bases ).
The methotrexate forms a strong complex from digidrofolatreduktazy (KF 126.96.36.199) and by that blocks recovery dihydrofolic to - you in its tetrahydroform and further turning into formid-tetrafolic to - that (leykovorin, a tsitrovorum-factor) and other metabolic active derivatives of folic acid (see) participating in synthesis of purines, thymidine, methionine, serine and a histidine. Earlier applied aminopterine also belongs to anti-folic drugs. Feature of antineoplastic action of other antimetabolites which are analogs of purines and pyrimidines consists that they turn into the abnormal biologically active nucleotides leading to disturbances of metabolism. Phthorafurum represents the transport form providing longer circulation ftoruratsit and in blood.
Antineoplastic means of a natural origin
Alkaloids. Derivatives a May apple linden (see), Vincristinum (see) and vinblastine entered practice of treatment of oncological patients Colchaminum (see), (see). Two last differ on chemical structure a little, have the similar mechanism of action, but various range of antineoplastic activity and give different side effects. Antineoplastic alkaloids belong to mitotic poisons; they denature tubulin — protein of microtubules of a spindle that leads to the block of a mitosis of cells at a stage of metaphase. Proliferating fabrics are sensitive to these drugs.
Antineoplastic antibiotics suppress synthesis nucleinic to - t, operating on the level of a DNA matrix. So, Dactinomycinum (see. Actinomycinums ), Olivomycinum (see) and anthracycline antibiotics (see) form the complexes interfering advance of enzymes along a DNA matrix with DNA, and Bruneomycinum (see) and Bleomycinum is caused by single ruptures of DNA.
Enzymes. Search of the enzymes possessing action on a tumor cell led to creation of drug of Crasnitinum representing enzyme L-asparaginase (see). It is applied at an acute lymphoblastoid leukosis. Cells of separate tumors do not synthesize asparagine and use the asparagine which is available in blood and a lymph. At introduction of Crasnitinum there is a destruction of asparagine, and the cells needing it, perish. It is established, however, that at the same time and some normal cells, napr, lymphocytes, cannot synthesize asparagine.
Hormonal drugs, their synthetic analogs, and also anti-hormonal means are widely used in onkol. to practice at hormonal and dependent tumors. Suggested to apply hormones at a prostate cancer for the first time in 1941 Ch. Haggins with sotr. Apply estrogen to hormonal therapy of malignant tumors (see), gestagena (see. Progestins ), androgens (see) and corticosteroids (see). From anti-hormones (see) use synthetic drugs hloditan, possessing property to reduce the level of corticosteroids, and Tamoxifenum having anti-oestrogenic effect.
Steroid hormones form complexes with proteinaceous molecules (receptors), contact chromatin and break synthesis nucleinic to - t in target cells (the cells sensitive to this hormone) and in certain doses proliferative processes in a mammary gland (androgens, are oestrogenic) oppress, to a prostate (are oestrogenic), the hemopoietic bodies (corticosteroids), an endometria (gestagena).
The general contraindications for antineoplastic means (except hormones) are: a leukopenia (it is less than 3000 leukocytes in 1 mkl of blood), thrombocytopenia (it is less than 100 000 thrombocytes in 1 mkl of blood), sharp exhaustion, an end-stage of a disease, serious associated diseases of cardiovascular system, lungs, a liver, kidneys, a nervous system, pregnancy.
Bibliography: Garin A. M. Facts, achievements and failures of modern oncology, Alma-Ata, 1980; Larionov L. F. Chemotherapy of malignant tumors, M., 1962, bibliogr.; Translator island and N. I. Clinical chemotherapy of tumoral diseases, M., 1976, bibliogr.; System of creation of antineoplastic drugs in the USSR and the USA, under the editorship of H. N. Blochina and Ch. G. Zubroda, M., 1977; Chemotherapy of malignant tumors, under the editorship of H. N. Blochina, M., 1977; Chernov V. A. Cytostatic substances in chemotherapy of malignant new growths, M., 1964, bibliogr.; Shelle To., Sh. and Nemet L Ekhardt. Medicinal treatment of tumoral diseases, the lane with Wenger., Buda - „pesht, 1975, bibliogr.; Experimental’ assessment of antineoplastic drugs in the USSR and the USA, under the editorship of 3. P. Sofyina, etc., M., 1980; Cancer medicine, ed. by J. P. Holland a. E. Frei, Philadelphia, 1982.
A. B. Syrkin.