Chemotherapeutic agents can be classified based on the following criteria: chemical properties or mechanism of action; source e. Based on the modality in which they are obtained, their mechanism of action and their biochemical structure, chemotherapeutic agents are divided into several classes.
Alkylating agents Alkylating agents are a diverse group of chemical compounds capable of forming molecular bonds with nucleic acids, proteins, and many other low weight molecules.
These compounds are electrophilic avid for electrons or generate electrophilic radicals in vivo that form covalent bonds with the molecule regions that have a positive charge. Alkylating agents have the ability of forming compounds attached to DNA DNA adducts by covalent bonds via an alkyl group.
The cytotoxic effect occurs due to the interaction between electrophilic radicals and DNA, by substitution reactions, interstrand bonds or strand breaking, eventually with inhibition or inadequate replication, alteration of information coded in DNA, and cell death. The alkylating agents more frequently used in the present are: cyclophosphamide, ifosphamide, dacarbazine, temozolomide, trabectedin, and others 4,5. Platinum salts platinum analogues Besides the ability to form G-G intrastrand DNA links adducts like classic alkylating agents do, platinum salts also have the ability to form intrastrand crosslinks, affecting replication and transcription.
Recent studies highlighted the repair mechanisms involved in the DNA lesions after chemotherapy with platinum salts. Among the substances of current therapeutic use in this category we note: cisplatin, carboplatin, and oxaliplatin 3,4,5.
Antimetabolites Antimetabolites are a group of compounds with low molecular weight that perform their function sarcoma cancer lungs stage 4 to their structural or functional similarity with the natural metabolites involved in nucleic acid synthesis.
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As structural analogues of metabolites involved in DNA and RNA synthesis, they act by competition with these for a catalytic site or regulator of certain key enzymes or by sarcoma cancer lungs stage 4 substitution and incorporation in DNA or RNA, in the synthesis S phase of the cell cycle. By inhibiting critical enzymes involved in nucleic acid synthesis or by becoming incorporated in the nucleic acid, they cause incorrect coding. Both mechanisms cause cell death via inhibition of the DNA synthesis.
Blocking the DNA synthesis, antimetabolites are very active on cells with a rapid growth, and they are all considered S cell cycle-phase specific. Frequently used antimetabolites are: methotrexate, pemetrexed, 5-fluorouracil, capecitabine oral fluoropyrimidinegemcitabine.
Natural derivatives Natural products are grouped together as they are derived from natural sources. The group includes usual cytostatic agents, products of vegetal extraction, fermentation products of various Streptomyces fungi species, and bacterial products 9. Three subgroups are included: antitumor antibiotics topoisomerase I and II inhibitors cytostatic agents that act on the microtubules of the division spindle. Sarcoma cancer lungs stage 4 antibiotics a. Anthracyclines: doxorubicin Adriamicin®epirubicin Farmorubicin®daunorubicin, idarubicin.
The mechanism of action of anthracyclines is complex, and it involves: intercalation between the base pairs of the DNA alkylating-like topoisomerase II inhibitors: anthracyclines form a ternary cleavable complex with DNA-topoisomerase II, that grasps the DNA chains generation of free oxygen radicals that damage the macromolecules via REDOX oxidation cycles with peroxidation of membrane lipids, which explains the cardiotoxicity of these compounds.
Non-anthracyclines: mitomycin C, mitoxantrone Sarcoma cancer lungs stage 4actinomycin D dactinomycinbleomycin 4,5.
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Topoisomerase inhibitors Topoisomerase I is a nuclear enzyme that acts sarcoma cancer lungs stage 4 a single DNA strand, counteracting the additional torsion that occurs during replication. In a first step it sections a strand, thus allowing the rotation of the other strand and the detensioning of the chain. Subsequently, the same enzyme is responsible for the reverse process, reconstructing the sectioned area.
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Topoisomerase II acts on both strands by sectioning them and creating a breach that allows the passing of an intact double-strand fragment, and detensioning of the chain, and then the same enzyme reestablished the continuity. Among the representatives of topoisomerase I inhibitors sarcoma cancer lungs stage 4 note: irinotecan, topotecan, camptothecin, and lamellarin D, and among those of topoisomerase II inhibitors: etoposide VP16teniposide Sarcoma cancer lungs stage 4and, respectively, anthracyclines doxorubicin, epirubicin 4,5.
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Cytostatic agents that act on the division spindle. These include antimitotic agents they act on the division spindle via binding to the microtubule proteins, preventing cell division in the M phase of the cell cycle.
They are classified into Vinca derivatives and taxanes. Vinca rosea alkaloid derivatives are: vincristine vinorelbine vindesine. The cytotoxicity of Vinca alkaloids is mainly related to depolymerization of the microtubules, causing the blockage of the cells in the G and M phases of the cell cycle.
Vinca derivatives prevent the forming of microtubules by depolymerization.
Возвращаясь в свою зону, Ричард разговаривал с Арчи, демонстрируя, как хорошо работает теперь его транслятор в реальном времени.
Microtubules are integral components of the mitotic spindle during the metaphase of cell mitosis that contain polymers of tubulin a contractile protein. Taxanes: paclitaxel, docetaxel, cabazitaxel, nab-paclitaxel 3,4,5.
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Enzymes, retinoids and other compounds These are represented, for example, by L-asparaginase which decomposes the L-asparagine from the blood, therefore preventing proliferation of lymphoblastsretinoids e.
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Classification of cytostatic agents currently used in oncology 5 Chemotherapy has two major disadvantages in clinical practice: the secondary toxicity the chemoresistance phenomenon 6. Toxicity Cytotoxic chemotherapeutic agents have one of the most important toxicities among human medications.
Normal tissues undergoing division are particularly vulnerable, including cells of the hematopoietic bone marrow, of the hair follicle and mucosal cells. Other sarcoma cancer lungs stage 4 of toxicity occur non-related sarcoma cancer lungs stage 4 cell growth and are specific to the cytostatic agent.
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Side effects can be subdivided in acute, subacute and chronic. Knowing and treating these is preceded by a methodical approach of assessment of each patient. Before initiating treatment, it is cervical cancer metastasis sites to perform an assessment of the risk factors and an individualization of the therapeutic scheme which is adapted to the stage of the disease.
И тут же поняла, насколько устала.
These toxic effects are limiting both the dose and the administration rhythm of the cytostatic agents and can compromise their efficacy 7. Figure 1.