Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.
An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC 2.1.1.63.
A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA.
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.
A group of alkylating agents derived from mustard gas, with the sulfur replaced by nitrogen. They were formerly used as toxicants and vesicants, but now function as antineoplastic agents. These compounds are also powerful mutagens, teratogens, immunosuppressants, and carcinogens.
An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
Organic esters of sulfuric acid.
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed).
A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
Alkylating antineoplastic agent used mainly for ovarian tumors. It is toxic to skin, gastrointestinal tract, bone marrow and kidneys.
A group of nitrogen mustard compounds which are substituted with a phosphoramide group or its derivatives. They are usually cytotoxic and used as antineoplastic agents.
Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed).
A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.
Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A nitroimidazole that sensitizes hypoxic tumor cells that are normally resistant to radiation therapy.
An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.
Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.
Disinfectant used in vapor form to sterilize vaccines, grafts, etc. The vapor is very irritating and the liquid form is carcinogenic.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A sulfhydryl reagent that is widely used in experimental biochemical studies.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
Polymers where the main polymer chain comprises recurring amide groups. These compounds are generally formed from combinations of diamines, diacids, and amino acids and yield fibers, sheeting, or extruded forms used in textiles, gels, filters, sutures, contact lenses, and other biomaterials.
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
An alkylating agent of value against both hematologic malignancies and solid tumors.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.
The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Toxic antibiotic of the mitomycin group, obtained from MITOMYCIN and also from Streptomyces ardus and other species. It is proposed as an antineoplastic agent, with some antibiotic properties.
Organic salts or esters of methanesulfonic acid.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Nitrogen mustard analog of quinacrine used primarily as a stain in the studies of chromosomes and chromatin. Fluoresces by reaction with nucleic acids in chromosomes.
An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.
A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7)
A potent mutagen and carcinogen. This compound and its metabolite 4-HYDROXYAMINOQUINOLINE-1-OXIDE bind to nucleic acids. It inactivates bacteria but not bacteriophage.
Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An experimental lymphocytic leukemia of mice.
An alkylating sulfhydryl reagent. Its actions are similar to those of iodoacetate.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Six-carbon alicyclic hydrocarbons which contain one or more double bonds in the ring. The cyclohexadienes are not aromatic, in contrast to BENZOQUINONES which are sometimes called 2,5-cyclohexadiene-1,4-diones.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
Established cell cultures that have the potential to propagate indefinitely.
A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.
Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions.
DNA present in neoplastic tissue.
A DNA repair enzyme that catalyses the excision of ribose residues at apurinic and apyrimidinic DNA sites that can result from the action of DNA GLYCOSYLASES. The enzyme catalyzes a beta-elimination reaction in which the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. This enzyme was previously listed under EC 3.1.25.2.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
The rate dynamics in chemical or physical systems.
A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A basic polypeptide isolated from Streptomyces netropsis. It is cytotoxic and its strong, specific binding to A-T areas of DNA is useful to genetics research.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Compounds containing the -SH radical.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)
Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.
Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.
Alkylating antineoplastic toxic to bone marrow; used in breast cancer, also in combination with other drugs.
Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.
Materials that add an electron to an element or compound, that is, decrease the positiveness of its valence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Oligopeptide antibiotics from Streptomyces distallicus. Their binding to DNA inhibits synthesis of nucleic acids.
An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)
Compounds that inhibit the activity of DNA TOPOISOMERASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Hydrolysate of DNA in which purine bases have been removed.
A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.
Alkylating anti-neoplastic agent.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.
A chlorinated epoxy compound used as an industrial solvent. It is a strong skin irritant and carcinogen.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Chemicals that are used to cause the disturbance, disease, or death of humans during WARFARE.
A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)
An enzyme which catalyzes the endonucleolytic cleavage of phosphodiester bonds at purinic or apyrimidinic sites (AP-sites) to produce 5'-Phosphooligonucleotide end products. The enzyme prefers single-stranded DNA (ssDNA) and was formerly classified as EC 3.1.4.30.
Enzymes that catalyze the cleavage of a carbon-oxygen bond by means other than hydrolysis or oxidation. EC 4.2.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
A cell line derived from cultured tumor cells.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.
A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.
A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.
One of the SCHISTOSOMICIDES, it has been replaced largely by HYCANTHONE and more recently PRAZIQUANTEL. (From Martindale The Extrapharmacopoeia, 30th ed., p46)
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
Elements of limited time intervals, contributing to particular results or situations.
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.

Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-iun expression. (1/1003)

Activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases is an early response of cells upon exposure to DNA-damaging agents. JNK-mediated phosphorylation of c-Jun is currently understood to stimulate the transactivating potency of AP-1 (e.g., c-Jun/c-Fos; c-Jun/ATF-2), thereby increasing the expression of AP-1 target genes. Here we show that stimulation of JNK1 activity is not a general early response of cells exposed to genotoxic agents. Treatment of NIH 3T3 cells with UV light (UV-C) as well as with methyl methanesulfonate (MMS) caused activation of JNK1 and an increase in c-Jun protein and AP-1 binding activity, whereas antineoplastic drugs such as mafosfamide, mitomycin C, N-hydroxyethyl-N-chloroethylnitrosourea, and treosulfan did not elicit this response. The phosphatidylinositol 3-kinase inhibitor wortmannin specifically blocked the UV-stimulated activation of JNK1 but did not affect UV-driven activation of extracellular regulated kinase 2 (ERK2). To investigate the significance of JNK1 for transactivation of c-jun, we analyzed the effect of UV irradiation on c-jun expression under conditions of wortmannin-mediated inhibition of UV-induced stimulation of JNK1. Neither the UV-induced increase in c-jun mRNA, c-Jun protein, and AP-1 binding nor the activation of the collagenase and c-jun promoters was affected by wortmannin. In contrast, the mitogen-activated protein kinase/ERK kinase inhibitor PD98056, which blocked ERK2 but not JNK1 activation by UV irradiation, impaired UV-driven c-Jun protein induction and AP-1 binding. Based on the data, we suggest that JNK1 stimulation is not essential for transactivation of c-jun after UV exposure, whereas activation of ERK2 is required for UV-induced signaling leading to elevated c-jun expression.  (+info)

The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis. (2/1003)

The recently sequenced Saccharomyces cerevisiae genome was searched for a gene with homology to the gene encoding the major human AP endonuclease, a component of the highly conserved DNA base excision repair pathway. An open reading frame was found to encode a putative protein (34% identical to the Schizosaccharomyces pombe eth1(+) [open reading frame SPBC3D6.10] gene product) with a 347-residue segment homologous to the exonuclease III family of AP endonucleases. Synthesis of mRNA from ETH1 in wild-type cells was induced sixfold relative to that in untreated cells after exposure to the alkylating agent methyl methanesulfonate (MMS). To investigate the function of ETH1, deletions of the open reading frame were made in a wild-type strain and a strain deficient in the known yeast AP endonuclease encoded by APN1. eth1 strains were not more sensitive to killing by MMS, hydrogen peroxide, or phleomycin D1, whereas apn1 strains were approximately 3-fold more sensitive to MMS and approximately 10-fold more sensitive to hydrogen peroxide than was the wild type. Double-mutant strains (apn1 eth1) were approximately 15-fold more sensitive to MMS and approximately 2- to 3-fold more sensitive to hydrogen peroxide and phleomycin D1 than were apn1 strains. Elimination of ETH1 in apn1 strains also increased spontaneous mutation rates 9- or 31-fold compared to the wild type as determined by reversion to adenine or lysine prototrophy, respectively. Transformation of apn1 eth1 cells with an expression vector containing ETH1 reversed the hypersensitivity to MMS and limited the rate of spontaneous mutagenesis. Expression of ETH1 in a dut-1 xthA3 Escherichia coli strain demonstrated that the gene product functionally complements the missing AP endonuclease activity. Thus, in apn1 cells where the major AP endonuclease activity is missing, ETH1 offers an alternate capacity for repair of spontaneous or induced damage to DNA that is normally repaired by Apn1 protein.  (+info)

Mismatch repair and differential sensitivity of mouse and human cells to methylating agents. (3/1003)

The long-patch mismatch repair pathway contributes to the cytotoxic effect of methylating agents and loss of this pathway confers tolerance to DNA methylation damage. Two methylation-tolerant mouse cell lines were identified and were shown to be defective in the MSH2 protein by in vitro mismatch repair assay. A normal copy of the human MSH2 gene, introduced by transfer of human chromosome 2, reversed the methylation tolerance. These mismatch repair defective mouse cells together with a fibroblast cell line derived from an MSH2-/- mouse, were all as resistant to N-methyl-N-nitrosourea as repair-defective human cells. Although long-patch mismatch repair-defective human cells were 50- to 100-fold more resistant to methylating agents than repair-proficient cells, loss of the same pathway from mouse cells conferred only a 3-fold increase. This discrepancy was accounted for by the intrinsic N-methyl-N-nitrosourea resistance of normal or transformed mouse cells compared with human cells. The >20-fold differential resistance between mouse and human cells could not be explained by the levels of either DNA methylation damage or the repair enzyme O6-methylguanine-DNA methyltransferase. The resistance of mouse cells to N-methyl-N-nitrosourea was selective and no cross-resistance to unrelated DNA damaging agents was observed. Pathways of apoptosis were apparently intact and functional after exposure to either N-methyl-N-nitrosourea or ultraviolet light. Extracts of mouse cells were found to perform 2-fold less long-patch mismatch repair. The reduced level of mismatch repair may contribute to their lack of sensitivity to DNA methylation damage.  (+info)

Tightly regulated and inducible expression of rabbit CYP2E1 using a tetracycline-controlled expression system. (4/1003)

A tetracycline (Tc)-controlled gene expression system that quantitatively controls gene expression in eukaryotic cells () was used to express cytochrome P-450 2E1 (CYP2E1) in HeLa cells in culture. The rabbit CYP2E1 cDNA was subcloned into the Tc-controlled expression vector (pUHD10-3) and transfected into a HeLa cell line constitutively expressing the Tc-controlled transactivator, a positive regulator of expression in the absence of Tc. The expression of CYP2E1 was tightly regulated. There was a time-dependent induction of CYP2E1 after removal of Tc. In the absence of Tc, the enzyme was induced more than 100-fold and expressed about 18 pmol of CYP2E1/mg microsomal protein. At maximal levels of expression the enzyme catalyzed the formation of 158 pmol 6-hydroxychlorzoxazone/min/mg total cellular protein. In addition, the level of the enzyme could be modulated by the concentration of Tc in the media. In the absence of Tc, exposure of cells to N-nitrosodimethylamine caused a significant dose-dependent decrease in cell viability. In contrast, menadione, a redox cycling toxicant, was less toxic to the cells after induction of CYP2E1 when compared with noninduced cells. Pulse-chase studies conducted 72 h after removal of Tc indicated a rapid turnover of CYP2E1 with a half-life of 3.9 h. Addition of the ligand, 4-methylpyrazole, and the suicide substrate, 1-aminobenzotrizole, decreased the degradation of CYP2E1. This cell line offers a useful system to examine the role of CYP2E1 in the cytotoxicity of xenobiotics and to investigate post-translational regulation of the enzyme.  (+info)

Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent-induced apoptosis and chromosomal breakage. (5/1003)

DNA polymerase beta (beta-pol), which is involved in base excision repair, was investigated for its role in protection of cells against various genotoxic agents and cytostatic drugs using beta-pol knockout mouse fibroblasts. We show that cells lacking beta-pol are highly sensitive to induction of apoptosis and chromosomal breakage by methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine and methyl methanesulfonate and the cross-linking antineoplastic drugs mitomycin C and mafosfamide. The cross-sensitivity between the agents observed suggests that beta-pol is involved in repair not only of DNA methylation lesions but also of other kinds of DNA damage induced by various cytostatic drugs. Cells deficient in beta-pol were not hypersensitive to cisplatin, melphalan, benzo(a)pyrene diol epoxide, chloroethylnitrosourea, or UV light. Because both established and primary beta-pol knockout fibroblasts displayed the hypersensitive phenotype, which, moreover, was complemented by transfection with a beta-pol expression vector, the alkylating agent hypersensitivity can clearly be attributed to the beta-pol deficiency. The results demonstrate that beta-pol-driven base excision repair is highly important for protection of cells against cell killing due to apoptosis and induced chromosomal breakage and suggest that incompletely repaired DNA damage causes chromosomal changes and may act as a trigger of DNA damage-induced apoptosis.  (+info)

Molecular analysis of mutants obtained by treatment with alkylating agents in a quadruplicated white-ivory strain of Drosophila melanogaster. (6/1003)

The use of a white-ivory (wi) strain of Drosophila melanogaster carrying four copies of this allele, (wi)4, has proved to be useful in detecting somatic mutation in genotoxicity testing. Nevertheless, until now very little information exists about the nature of the genetic effects detected in such a strain. This work presents molecular data on the changes that have taken place in different germinal mutants obtained after treatment with alkylating agents. Three different phenotypes were obtained: wild-type red eyes, dark red eyes and eyes lighter than (wi)4. Our results show that, in at least one of the four copies of the allele, the wild-type red eye phenotypes are due to a precise excision of the 2.96 kb duplicated region characteristic of the wi allele. These data agree with previous results obtained in a strain carrying only a single copy of the wi allele. The dark red eye mutants analysed seemed to be generated as a cluster and all proved to be caused by deletions at the 3'-end of the duplicated wi region in two of the copies of the (wi)4 genome. Finally, the light eye mutants (obtained at high frequencies) failed to show alterations at the molecular level, although we cannot discard the possibility that they might have originated by the loss of some of the wi copies of the (wi)4 strain.  (+info)

Alterations in Bacillus subtilis transforming DNA induced by beta-propiolactone and 1,3-propane sultone, two mutagenic and carcinogenic alkylating agents. (7/1003)

Transforming DNA was exposed to either beta-propiolactone or 1,3-propane sultone and then used for transformation of competent bacteria to nutritional independence from tyrosine and tryptophan (linked markers) and leucine (an unlinked marker). The ability to transform was progressively lost by the DNA during incubation with either of these two chemicals. For all three markers the inactivation curve was biphasic, with a short period of rapid inactivation followed by one characterized by a much slower rate. The overall rate of inactivation was different for all three markers and presumably was related to the size of the marker. The decrease in the transforming activity was in part due to the slower rate of penetration of alkylated DNA through the cellular membrane and its inability to enter the recipient bacteria. This decrease in the rate of cellular uptake, even for DNA eventually destined to enter the cell, began almost immediately after its exposure to the chemical and ended up with an almost complete lack of recognition of the heavily alkylated DNA by the specific surface receptors of competent cells. Such DNA attached to sites on the surface of competent bacteria which were different from receptors specific for the untreated nucleic acid. This attachment was not followed by uptake of the altered DNA. Presence of albumin during the incubation with a carcinogen further increased the degree of inactivation, indicating that the artificial nucleoproteins produced under such conditions were less efficient in the transformation assay than was the naked DNA. Cotransfomration of close markers progressively decreased, beginning immediately after the start of incubation of DNA with the chemicals. Extensively alkylated DNA fractionated by sedimentation through sucrose density gradients showed a peculiar distribution of cotransforming activity for such markers; namely, molecules larger than the bulk of DNA ("megamolecules") showed less ability to transform the second marker than did some of the apparently smaller molecules which sedimented more slowly through the gradient. An increase in cotransformation of distant markers was evident in DNA molecules after a short exposure to an alkylating agent, but cotransformation of such markers was absent in DNA treated for longer periods. The observed changes in the transforming and cotransforming activities of the alkylated DNA can be explained by what is known about the physicochemistry of such DNA and in particular about the propensity of the alkylated and broken molecules to form complexes with themselves and with other macromolecules.  (+info)

The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases. (8/1003)

Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC >1.0 x 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions.  (+info)

TY - JOUR. T1 - A phase I study of DMS612, a novel bifunctional alkylating agent. AU - Appleman, Leonard J.. AU - Balasubramaniam, Sanjeeve. AU - Parise, Robert A.. AU - Bryla, Christine. AU - Redon, Christophe E.. AU - Nakamura, Asako J.. AU - Bonner, William M.. AU - Wright, John J.. AU - Piekarz, Richard. AU - Kohler, David R.. AU - Jiang, Yixing. AU - Belani, Chandra P.. AU - Eiseman, Julie. AU - Chu, Edward. AU - Beumer, Jan H.. AU - Bates, Susan E.. PY - 2015/2/15. Y1 - 2015/2/15. N2 - Purpose: DMS612 is a dimethane sulfonate analog with bifunctional alkylating activity and preferential cytotoxicity to human renal cell carcinoma (RCC) in the NCI-60 cell panel. This first-in-human phase I study aimed to determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of DMS612 administered by 10-minute intravenous infusion on days 1, 8, and 15 of an every-28-day schedule. Experimental Design: Patients with advanced solid malignancies ...
Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKβ inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially ...
Title:A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents. VOLUME: 15 ISSUE: 5. Author(s):Pravin C. Patil, Vijay Satam and Moses Lee. Affiliation:Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.. Keywords:Antitumor-antibiotics, apoptosis, centanamycin, duocarmycins, tafuramycin A.. Abstract:The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, ...
Alkylating Antineoplastic Agents: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
Melflufen is designed for targeted delivery of alkylating moieties to tumor cells. In contrast to other alkylating agents that are hydrophilic, the lipophilicity of melflufen leads to rapid and extensive distribution into tissues and cells. Inside cells, melflufen may directly bind DNA or is readily metabolized by intracellular peptidases into the well-known antitumor compound melphalan, or by esterases into des-ethylmelflufen, which also has alkylating properties. Due to the high activity of peptidases and esterases in human tumor cells, the formation of melflufens metabolites is rapid in these cells with subsequent inflow of more melflufen. Since des-ethylmelflufen and melphalan are relatively hydrophilic, there is a possibility for intracellular trapping of these alkylators ...
The major alkylating agents are the nitrogen mustards and the nitrosoureas. These drugs covalently alkylate various cellular constituents. Most importantly for
Alkylating drug definition, any of various potentially cytotoxic, carcinogenic, and mutagenic substances: used therapeutically to destroy cells, especially proliferating cancer cells. See more.
Read The effect of the Primary Structure of DNA on Induction of Mutations by Alkylating Agents, Russian Journal of Genetics on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Fingerprint Dive into the research topics of Mechanisms of chemoresistance to alkylating agents in malignant glioma. Together they form a unique fingerprint. ...
Learn about the veterinary topic of Alkylating Agents. Find specific details on this topic and related topics from the Merck Vet Manual.
The relationships between DNA damage from UV radiation, alkylating drugs and the methylated xanthines (MX) have been studied in normal and malignant rodent and human cells. A comparison of the level of DNA excision repair (repair replication and unscheduled DNA synthesis) confirms that some forms of alkylating-agent damage (probably mono-filar DNA adducts) are less completely removed by both normal and malignant rodent cells than by their human counterparts, rendering rodent cells more susceptible to the toxic potential of unexcised lesions. The toxicity of alkylating agents can be increased by the presence of several MXs during the period of DNA replication which follows infliction of the damage. Human cells appear capable of excising more DNA damage, rendering them somewhat less susceptible to enhancement of cytotoxicity by MX. This resistance of human cells is only quantitative, however, since 2 human cancer cell lines (HeLa and HT-29) could be sensitized to a variety of alkylating agents by ...
Leukemia is not an important factor in the natural history of breast cancer, though its association with breast cancer therapy has frequently been reported. There are reports of therapy related hematological malignancies in breast cancer dated as early as 1980s describing the incidence as 1.68 ± .33% at 10 years with chemotherapy vis a vis 0.06% to 0.27% with surgery alone [1]. In 1992, a large case-control study of 82,700 women with breast cancer demonstrated a relative risk of developing AML as 2.4 for radiotherapy, 10 for therapy with alkylating agents and 17.4 when the two were used in combination [2] The chemotherapy regimens employed during these studies used mainly melphalan as alkylating agent and that for long durations (12 to 24 months) [1, 2]. Though over the last decade anthracyclines along with safer alkylating agents have formed the main core of the breast cancer therapy; the modern chemotherapy is not entirely safe. The more recent reports in the background of anthracycline and ...
Cisplatin is similar to the bifunctional alkylating agents. It covalently binds to DNA and disrupts DNA function. After cisplatin enters the cells, the chloride ligands are replaced by water molecules. This reaction results in the formation of positively charged platinum complexes that react with the nucleophilic sites on (...). ...
Melphalan is a DNA alkylating agent; induces cytotoxicity through the formation of stable interstrand and intrastrand crosslinks within DNA which inhibits growth of PC-3 cells (IC50 values are 0.074 and 0.77 μM for sequential dosing and single dosing respectively). Learn More ...
The preferred site of alkylation of diazine N-oxides by representative hard and soft alkylating agents was established conclusively using the 1H-15N HMBC NMR technique in combination with other NMR spectroscopic methods. Alkylation of pyrazine N-oxides (1 and 2) occurs preferentially on nitrogen regardless of the alkylating agent employed, while O-methylation of pyrimidine N-oxide (3) is favoured in its reaction with MeOTf. As these outcomes cannot be explained in the context of the hard/soft acid/base (HSAB) principle, we have instead turned to Marcus theory to rationalise these results. Marcus intrinsic barriers (∆G0‡) and ∆rG° values were calculated at the DLPNO-CCSD(T)/def2-TZVPPD/SMD//M06-2X-D3/6-311+G(d,p)/SMD level of theory for methylation reactions of 1 and 3 by MeI and MeOTf, and used to derive Gibbs energies of activation (∆G‡) for the processes of N- and O-methylation, respectively. These values, as well as those derived directly from the DFT calculations, closely reprod... ...
Reporting biases in published trials were first identified in 1986.1 Published randomized studies of combination chemotherapy compared with treatment with an alkylating agent as first line treatment for ovarian cancer showed a significant survival advantage for combination chemotherapy. Unpublished cancer trial registry data from the same studies, however, showed no such advantage.2 Similarly, in the treatment of multiple myeloma, registry data suggested a smaller survival advantage for combination chemotherapy (over prednisone and an alkylating agent) than the results of published studies. The author who reported the discrepancy concluded that his findings demonstrate the value and importance of an international registry of all clinical trials.1Subsequent evidence for biased and selective reporting included prompt or delayed publication depending on whether trial results were positive or negative3 and more favorable results and conclusions in published studies funded by industry than in those ...
Reporting biases in published trials were first identified in 1986.1 Published randomized studies of combination chemotherapy compared with treatment with an alkylating agent as first line treatment for ovarian cancer showed a significant survival advantage for combination chemotherapy. Unpublished cancer trial registry data from the same studies, however, showed no such advantage.2 Similarly, in the treatment of multiple myeloma, registry data suggested a smaller survival advantage for combination chemotherapy (over prednisone and an alkylating agent) than the results of published studies. The author who reported the discrepancy concluded that his findings demonstrate the value and importance of an international registry of all clinical trials.1Subsequent evidence for biased and selective reporting included prompt or delayed publication depending on whether trial results were positive or negative3 and more favorable results and conclusions in published studies funded by industry than in those ...
Reporting biases in published trials were first identified in 1986.1 Published randomized studies of combination chemotherapy compared with treatment with an alkylating agent as first line treatment for ovarian cancer showed a significant survival advantage for combination chemotherapy. Unpublished cancer trial registry data from the same studies, however, showed no such advantage.2 Similarly, in the treatment of multiple myeloma, registry data suggested a smaller survival advantage for combination chemotherapy (over prednisone and an alkylating agent) than the results of published studies. The author who reported the discrepancy concluded that his findings demonstrate the value and importance of an international registry of all clinical trials.1Subsequent evidence for biased and selective reporting included prompt or delayed publication depending on whether trial results were positive or negative3 and more favorable results and conclusions in published studies funded by industry than in those ...
S. B. J. Kan, H. Maruyama, M. Akakura, T. Kano, K. Maruoka, Angew. Chem. Int. Ed., 56, 9487-9491 (2017). (Highlighted in SYNFACTS, 2017, 985). Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines ...
O6-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the Mgmt gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. Mgmt-/- mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD50 values of Mgmt-/- and Mgmt+/+ mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of Mgmt-/- mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of Mgmt+/+ and Mgmt-/- mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ...
Many chemotherapeutic agents have been associated with pulmonary toxicities. Busulfan was the first chemotherapeutic drug with evidence of drug-induced lung disease 6. Other alkylating agents, such as cyclophophamide and chlorambucil have been clearly associated with pulmonary toxicity as well 7. Dacarbazine, which is closely related to temozolomide has been associated with pulmonary adverse effects only when used in combination with fotemustine, a nitrosourea agent 8.. Temozolomide is an imidazotetrazine compound and a derivative of the alkylating agent dacarbazine (second-generation oral alkylating agent). Temozolomide has proven activity against recurrent glioma 9. In a recent randomised trial, concomitant and adjuvant temozolomide chemotherapy with radiation significantly improved progression free survival and overall survival in glioblastoma multiforme patients 2.. Various adverse reactions have been reported, but they are usually mild to moderate and in the majority of cases do not require ...
Bendamustine has demonstrated clinical efficacy in the treatment of haematological malignancies and distinguish itself from other alkylating agents. The mechanistic and clinical differences associated with Bendamustine may be related to its structural features including a benzimidazole ring, although the mechanism of action is poorly understood. Understanding the molecular mechanism of Bendamustine could explain the therapeutic efficacy and identify potential biomarkers for response. The Bendamustine-DNA interaction in naked DNA, cytotoxicity, and ICL formation and repair (unhooking) in naked DNA or in cell lines and patient multiple myeloma cells by the single cell gel electrophoresis (comet) assay, were analyzed. DNA damage response (DDR) and potential mechanisms of acquired resistance to Bendamustine were also evaluated. Bendamustine alkylated DNA at guanine-N7 positions, produced ICLs in naked DNA and in cells, and demonstrated a cytotoxic effect comparable to conventional ICL drugs ...
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene (or their equivalents).[1] An alkyl group is a piece of a molecule with the general formula CnH2n+1, where n is the integer depicting the number of carbons linked together. For example, a methyl group (n = 1, CH3) is a fragment of a methane molecule (CH4). Alkylating agents use selective alkylation by adding the desired aliphatic carbon chain to the previously chosen starting molecule. This is one of many known chemical syntheses. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline.[2]. In medicine, alkylation of DNA is used in ...
DNA damaging alkylating agents are present abundantly in the environment and also produced endogenously.The majority of the DNA adducts caused by such alkylating agents would be in double-stranded DNA. However, single-strand- specific lesions canarise when DNA double helix is temporarily unwound during replication or recombination. The N1 position of purines and the N3 of pyrimidines, which are normally protected from alkylation by base pairing in duplex DNA, can be alkylated in single-stranded DNA. The Escherichia coliAlkB protein is an oxidative demethylase that repairs such alkylatedbases present in single stranded DNA. Although AlkB function was known in great detail, its regulation was poorly characterized. I hypothesized that some proteins might directly interact with AlkB to regulate its function.. ...
This trial is investigating the tolerability of irinotecan, temozolomide and bevacizumab in combination with existing high dose alkylator based chemotherapy for
The great diversity in sarcoma phenotypes and genotypes make this disease family exceptionally challenging. Phenotypically diverse human adult and pediatric sarcoma lines were screened with a defined set of drugs and compounds (22). Sarcoma genomics have been explored using cell lines and clinical specimens (12, 23). This study presents gene-expression data derived from exon array data as well as microRNA data, which are available in GEO.. One study goal was to identify small-molecule drugs for further examination in sarcoma. The constellation relational map provides visualization of the sarcoma screen for compounds with a dynamic range of at least one log in IC50 across the panel (Fig. 1). The clusters are compounds with similar patterns of response. Aurora kinase inhibitors form a distinct cluster adjacent to bifunctional alkylating agents, topoisomerase I and II inhibitors. Taxanes and microtubule fragmenters form a cluster adjacent to topoisomerase I and II inhibitors. The results are ...
Consistent results from three case-control studies and a pooled analysis, totaling 555 head and neck cancer cases and 792 controls, suggest that genetic variations in MGMT84, MGMT143, and XRCC1399 influence susceptibility to head and neck cancer. Moreover, the MGMT143 variant may modify alcohol-related risk.. MGMT encodes O6-alkylguanine DNA alkyltransferase, which preferentially removes O6-guanine alkyl adducts caused by carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone found in tobacco smoke (40), and the Val143 allele has previously been related to increased lung cancer risk in two small studies (each with ∼130 cases; refs. 28, 41). In our study, Val143 was associated with reduced head and neck cancer risk, particularly among heavy drinkers. In vivo and in vitro experiments show that MGMT-mediated repair of alkylated DNA is reduced by treatment with ethanol or its primary metabolite, acetaldehyde (42, 43), possibly due to MGMT inhibition (44). Although the functional ...
Anesthetic agent-induced liver damage information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
Failure to Diagnose Antituberculous agent-induced liver damage including overlooked symptoms and complications for under-diagnosed medical conditions.
Principal Investigator:SUGIYAMA Hiroshi, Project Period (FY):1997 - 1998, Research Category:Grant-in-Aid for Scientific Research (B), Section:展開研究, Research Field:Synthetic chemistry
At left, photoreceptor cells of the retina have undergone severe damage after treatment with an alkylating agent. This damage is exacerbated by the DNA repair
Generic name Melphalan hydrochloride Pronunciation MEL-fa-lan HIGH-droe-KLOR-ide Brand name(s), other common name(s) EvomelaTM Drug type Alkylating agent How the drug is given
Alkeran tablets and injection contain the active ingredient melphalan, which is a type of chemotherapy medicine to treat cancer called an alkylating agent.
In this article you will know all of the Main drugs used in cancer treatment. Know about Mitotic Inhibitors, Antibiotics, Antimetabolites and Alkylating
Diazomethane is toxic by inhalation or by contact with the skin or eyes (TLV 0.2ppm). Symptoms include chest discomfort, headache, weakness and, in severe cases, collapse.[14] Symptoms may be delayed. Deaths from diazomethane poisoning have been reported. In one instance a laboratory worker consumed a hamburger near a fumehood where he was generating a large quantity of diazomethane, and died four days later from fulminating pneumonia.[15] Like any other alkylating agent it is expected to be carcinogenic, but such concerns are overshadowed by its serious acute toxicity. CH2N2 may explode in contact with sharp edges, such as ground-glass joints, even scratches in glassware.[16] Glassware should be inspected before use and preparation should take place behind a blast shield. Specialized kits to prepare diazomethane with flame-polished joints are commercially available. The compound explodes when heated beyond 100 °C, exposed to intense light, alkali metals, or calcium sulfate. Use of a blast ...
Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[2] thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use, although it is also used to treat Hodgkin lymphoma as a second-line option.[3] Lomustine has a long time to nadir (the time when white blood cells reach their lowest number). Unlike carmustine, lomustine is administered orally. It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.[4] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[5] Lomustine is cell-cycle nonspecific. It has also been used in veterinary practice as a treatment for mast cell tumors in ...
TY - JOUR. T1 - Unraveling innate immunity using large scale N-ethyl-N-nitrosourea mutagenesis. AU - Hoebe, Kasper. AU - Beutler, B.. PY - 2005/5. Y1 - 2005/5. N2 - With the mouse genome almost entirely sequenced and readily accessible to all who wish to examine it, the challenge across most biological disciplines now lies in the decipherment of gene and protein function rather than in the realm of gene identification per se. In the field of innate immunity, forward genetic methods have repeatedly been applied to identify key sensors, adapters, and effector molecules. However, most spontaneous mutations that affect innate immune function have been mapped and cloned, and the need for new monogenic phenotypes has been felt evermore keenly. N-Ethyl-N-nitrosourea (ENU) mutagenesis is an efficient tool for the creation of aberrant monogenic innate immune response phenotypes. In this review, we will discuss the potential of the forward genetic approach and ENU mutagenesis to identify new genes and new ...
Introduction. High dose melphalan 200mg/m2 (MEL200) followed by autologous stem cell transplantation (ASCT) is the standard of care for fit patients with Multiple Myeloma (MM). Bendamustine has been shown to induce responses in MM resistant to other alkylating agents. Our prior Phase I trial, adding bendamustine to MEL200, demonstrated no additional toxicity above that expected with MEL200 alone (Mark et. al. BBMT 2013). A phase 2 trial of bendamustine/MEL200 conditioning was conducted to evaluate treatment efficacy. Objective and Methods. This single arm, open-label, phase II study was designed to establish the efficacy of Bendamustine (225 mg/m2) in combination with MEL200 in patients undergoing first ASCT for MM. Patients 18 to 75 years with confirmed MM, prior induction therapy, adequate mobilization (at least 2x106 of CD34+ hematopoietic stem cells), Karnofsky performance status ,70% and life expectancy ,12 weeks were eligible for screening. Major exclusion criteria included ...
After relapse or after early progression on first-line treatment, the prognosis of multiple myeloma (MM) patients is unfavourable, and the search for new treatment regimens, including drugs with novel mechanisms of action is essential.. Bendamustine and bortezomib have shown high activity boch in first-line regimens and pre-treated patients. The novel mechanism of action of the proteasome inhibitor and the non-cross resistance of bendamustine to other alkylating agents established in the first-line treatment of multiple myeloma seem to recommend a combination of the two drugs for salvage therapy (second-line regimen). Finally, the promising response data in a series of relapsing MM patients treated with bendamustine, bortezomib and prednisone support this assumption, as well as the feasibility and tolerability of the combination.. In summary, there is some evidence for a favorable risk/benefit ratio for the combination of bendamustine, bortezomib and a corticoid drug, warranting the exploration ...
TY - JOUR. T1 - Prevention of N-methyl-N-nitrosourea-induced breast cancer by α-fetoprotein (AFP)-derived peptide, a peptide derived from the active site of AFP. AU - Parikh, Rahul R.. AU - Gildener-Leapman, Neil. AU - Narendran, Amithi. AU - Lin, Hung Yun. AU - Lemanski, Nicole. AU - Bennett, James A.. AU - Jacobson, Herbert I.. AU - Andersen, Thomas T.. PY - 2005/12/1. Y1 - 2005/12/1. N2 - Purpose: α-Fetoprotein (AFP) is a protein of pregnancy associated with a decrease in lifetime risk of breast cancer in parous women. A synthetic, cyclic nonapeptide has been developed that mimics the antioncogenic active site of AFP. To test the hypothesis that the AFP-derived peptide (AFPep) can prevent breast cancer, the N-methyl-N-nitrosourea-induced breast cancer model was used in rats. Experimental Design: AFPep was given daily by injection beginning 10 days after N-methyl-N-nitrosourea treatment and continued for 23 days (a time designed to mimic pregnancy) or for other times to assess efficacy as a ...
Treg-cell function is compromised in rheumatoid arthritis (RA). As the master regulator of Treg cells, FOXP3 controls development and suppressive function. Stable Treg-cell FOXP3 expression is epigenetically regulated; constitutive expression requires a demethylated Treg-specific demethylated region. Here, we hypothesised that methylation of the FOXP3 locus is altered in Treg cells of established RA patients. Methylation analysis of key regulatory regions in the FOXP3 locus was performed on Treg cells from RA patients and healthy controls. The FOXP3 Treg-specific demethylated region and proximal promoter displayed comparable methylation profiles in RA and healthy-donor Treg cells. We identified a novel differentially methylated region (DMR) upstream of the FOXP3 promoter, with enhancer activity sensitive to methylation-induced silencing. In RA Treg cells we observed significantly reduced DMR methylation and lower DNA methyltransferase (DNMT1/3A) expression compared with healthy Treg cells. Furthermore,
A vesicant and necrotizing irritant destructive to mucous membranes, mechlorethamine is an alkylating drug. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkins disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [PubChem] The FDA granted marketing approval for the orphan drug Valchlor (mechlorethamine) gel on August 23, 2013 for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have received prior skin-directed therapy. Each tube of Valchlor contains 0.016% of mechlorethamine which is equivalent to 0.02% mechlorethamine HCL.
Mechanism: Valchlor is a gel formulation of mechlorethamine, an alkylating agent which inhibits rapidly proliferating cells. Valchlor is specifically indicated for the topical treatment of Stage IA and IB mycosisfungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. Valchlor is supplied as a gel for topical administration. The recommendation is to apply a thin film of Valchlor gel once daily to affected areas of the skin. Upon improvement, treatment with Valchlor can be restarted at a reduced frequency of once every 3 days. If reintroduction of treatment is tolerated for at least one week, the frequency of application can be increased to every other day for at least one week and then to once daily application if tolerated. Valchlor is a gel formulation of mechlorethamine, also known as nitrogen mustard, an alkylating agent which inhibits rapidly proliferating cells. ...
Epichlorohydrin (ECH) is a DNA bifunctional alkylating agent that has been shown to form DNA inter-strand cross-links in vitro at the N7 position of guanines at the 5-GNC and 5-GC consensus sequences. We used the quantitative polymerase chain reaction (QPCR) to monitor the formation of in vivo ECH lesions in 6C2 chicken erythroid progerutor cells. Three distinct loci were investigated in order to determine the effect of ECH reactivity in different levels of chromatin condensation. The sites consisted of an open locus of the nuclear genome, a closed locus of the nuclear genome, and a naked locus of the mitochondrial genome. We found that ECH alkylation was preferentially targeted towards the nuclear sites and that chromatin structure had no effect upon ECH reactivity. Repair assays of the three sites revealed that there appears to be no repair of ECH lesions in the nuclear genome.
The drug shows high potency and activity in various experimental models including P-gp- and MRP1-expressing multidrug resistant tumors as well as tumors resistant to platinum derivatives, alkylating agents and topoisomerase I and II inhibitors. Nemorubicin has a peculiar mechanism of action requiring NER activity for its full cytotoxicity. Cell lines defective in NER, which show an increased sensitivity to classical alkylating agents, display a three-four fold resistance to nemorubicin. Interestingly, L1210 murine leukemia cells selected for resistance to nemorubicin (L1210/MMDX) show a collateral sensitivity to both platinum derivatives and alkylating agents and are more sensitive (about 4-5 times) to UV light. In addition, these cells are not able to repair UV-induced damage on transfected DNA (host -cell reactivation assay), suggesting that the NER system might be involved in mediating the cytotoxic activity of nemorubicin. The aim of the present study was to evaluate the possible presence of ...
Consistent results from three case-control studies and a pooled analysis, totaling 555 head and neck cancer cases and 792 controls, suggest that genetic variations in MGMT84, MGMT143, and XRCC1399 influence susceptibility to head and neck cancer. Moreover, the MGMT143 variant may modify alcohol-related risk.. MGMT encodes O6-alkylguanine DNA alkyltransferase, which preferentially removes O6-guanine alkyl adducts caused by carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone found in tobacco smoke (40), and the Val143 allele has previously been related to increased lung cancer risk in two small studies (each with ∼130 cases; refs. 28, 41). In our study, Val143 was associated with reduced head and neck cancer risk, particularly among heavy drinkers. In vivo and in vitro experiments show that MGMT-mediated repair of alkylated DNA is reduced by treatment with ethanol or its primary metabolite, acetaldehyde (42, 43), possibly due to MGMT inhibition (44). Although the functional ...
When paternally transmitted, two independent ENU-induced mutations showed reduced whole body wet weight soon after birth. The mutations were mapped to Chromosome 9 (Chr 9) between the markers D9Mit208 and D9Mit215. Their map position and imprinted status suggested that they might alter RAS protein-specific guanine nucleotide releasing factor 1 expression. Both mutations introduced premature chain termination codons into the coding sequence of Rasgrf1, and no Ras-GRF1 protein was detected in the brain. The GENA53 line had a C to T transition at nucleotide 2137, and the line GENA37 had a T to A transversion at nucleotide 3552 of the cDNA sequence. Mutant mice had near normal body weight at birth, but their weight started to lag behind that of wild-type littermates during the first week, and they were about 15% lighter as adults.. ...
Mechlorethamine is used to treat the symptoms of several types of cancer. Mechlorethamine treats only the symptoms of cancer but does not treat the cancer itself. Mechlorethamine is also sometimes injected into body spaces around the heart, lungs, or stomach to treat fluid retention in these areas caused by cancer...
Medscape - Indication-specific dosing for Mustargen, mechlorethamine hcl (mechlorethamine), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy & lactation schedules, and cost information.
4.1 Polymorphisms and mutations are both variations in DNA sequence and can arise through the same mechanisms. We use the term polymorphism to refer to DNA variants that are relatively common in populations. Mutations affect the phenotype.. 4.2 Misreading of bases during replication can lead to substitution and can be caused by things like tautomerism, DNA alkylating agents, and irradiation.. 4.3 Looping out of DNA on the template strand during replication; strand breakage, due to radiation and other mutagens; and (discussed in earlier chapters) chromosomal aberrations such as deletions and translocations.. 4.4 Looping out of DNA on the growing strand during replication; transposition; and (discussed in earlier chapters) chromosomal aberrations such as duplications, insertions, and translocation.. 4.5 Benzopyrene is one of many hazardous compounds present in smoke. Benzopyrene is an intercalating agent, which slides between the bases of the DNA molecule, distorting the shape of the double helix, ...
Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells tre …
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In a phase II study reported in the Journal of Clinical Oncology, Chawla et al found that the combination of a hypoxia-activated alkylating prodrug (TH-302) and doxorubicin was active in first-line treatment of advanced soft-tissue sarcoma. TH-302 is a prodrug of the cytotoxic alkylating agent.... ...
Function: Corrects defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents ...
A catalyst composition that is the combination of or the reaction product of ingredients comprising (a) a nickel-containing compound, (b) an alkylating agent, (c) a fluorine-containing compound, and (d) a chlorine-containing compound.
Novel Heat shock 70 kDa protein 5 (HSPA5) inhibitor and ERCC1-XPF protein-protein interaction inhibitor, synergizing alkylating agents in cancer cells.; High Quality Biochemicals for Research Uses
Were found to alkylate all oxygens and nitrogens in nucleic acids , whereas a host of more moderately reactive electrophilic agents typically target nitrogens
AA-CW236 is a novel non-pseudosubstrate inhibitor of human O(6)-alkylguanine DNA methyltransferase (MGMT) by targeting MGMT active site Cys145 for covalent modification.
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An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect. . ...
Alkylating agents[edit]. Main article: Alkylating antineoplastic agent. Alkylating agents are the oldest group of ... Siddik ZH (2005). Mechanisms of Action of Cancer Chemotherapeutic Agents: DNA-Interactive Alkylating Agents and Antitumour ... Available agents[edit]. Main article: List of antineoplastic agents. There is an extensive list of antineoplastic agents. ... there are now many types of alkylating agents in use.[1] They are so named because of their ability to alkylate many molecules ...
Alkylating agents[edit]. The alkylating agents used in immunotherapy are nitrogen mustards (cyclophosphamide), nitrosoureas, ... Small biological agents[edit]. Fingolimod is a new synthetic immunosuppressant, currently in phase 3 of clinical trials. It ... Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications are drugs ... Immunosuppressive+Agents at the US National Library of Medicine Medical Subject Headings (MeSH) ...
Alkylating agents[edit]. The alkylating agents used in immunotherapy are nitrogen mustards (cyclophosphamide), nitrosoureas, ... Small biological agents[edit]. Fingolimod is a new synthetic immunosuppressant, currently in phase 3 of clinical trials. It ... Immunosuppressive drugs or immunosuppressive agents or antirejection medications are drugs that inhibit or prevent activity of ... Immunosuppressive+Agents at the US National Library of Medicine Medical Subject Headings (MeSH) ...
Gate, Laurent; Tew, Kenneth D. (2011). "Alkylating Agents". Cancer Management in Man: Chemotherapy, Biological Therapy, ... EMP is a dual cytostatic and hence chemotherapeutic agent and a hormonal anticancer agent of the estrogen type. It is a prodrug ... and hence was thought to be an alkylating antineoplastic agent. However, subsequent research has found that EMP is devoid of ... or other more marked toxicity associated with such agents. In contrast to most other cytostatic agents, which often cause ...
All are alkylating agents. A colorless solid, 2-chloromethylpyridine is a precursor to pyridine-containing ligands. 2- ...
It is an alkylating agent. It can react with DNA to form intrastrand crosslinks. Huang CH, Kuo HS, Liu JW, Lin YL (June 2009 ...
Alkylating agents such as cyclophosphamide and cisplatin, as well as intercalating agent such as daunorubicin and doxorubicin ... Alkylating agents such as ethylnitrosourea. The compounds transfer methyl or ethyl group to bases or the backbone phosphate ... Other alkylating agents include mustard gas and vinyl chloride. Aromatic amines and amides have been associated with ... 2016). "Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents". ...
... an alkylating antineoplastic agent; Hydroxydaunorubicin, also known as doxorubicin: an anthracycline antibiotic that is able to ...
They are strong alkylating agents. Aside from the BF− 4 salt, many related derivatives are available. Triethyloxonium ... Triethyloxonium tetrafluoroborate is a strong alkylating agent, although the hazards are diminished because it is non-volatile ...
Summary table of crosslinking agents[edit]. Crosslinking Agent Alkylating Agent Crosslink Structure Preferential Target ... Exogenous agents[edit]. *Nitrogen mustards are exogenous alkylating agents which react with the N7 position of guanine. These ... These agents differ from other crosslinkers as they alkylate O6 of guanine to form an O6-ethanoguanine. This intermediate ... Crosslinking agents[edit]. Many characterized crosslinking agents have two independently reactive groups within the same ...
The original reaction formed the alkylating agent using an alkene in the presence of a strong acid. The Ritter reaction ... Fernholz, H.; Schmidt, H. J. (1969). "Tert-Butyl Acetate as Alkylating Agent". Angewandte Chemie International Edition in ... Ritter reaction is a chemical reaction that transforms a nitrile into an N-alkyl amide using various electrophilic alkylating ...
Siddik ZH (2005). "Mechanisms of Action of Cancer Chemotherapeutic Agents: DNA-Interactive Alkylating Agents and Antitumour ... there are now many types of alkylating agents in use. They are so named because of their ability to alkylate many molecules, ... Alkylating agents will work at any point in the cell cycle and thus are known as cell cycle-independent drugs. For this reason ... Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of ...
Alkylating agents (e.g., N-ethyl-N-nitrosourea (ENU). These agents can mutate both replicating and non-replicating DNA. In ... Agents that form DNA adducts (e.g., ochratoxin A) DNA intercalating agents (e.g., ethidium bromide) DNA crosslinkers Oxidative ...
... is an alkylating agent. Indicative of its high reactivity (relative to alkyl chlorides), benzyl chloride reacts ...
It is incompatible with acids, bases, oxidizing agents, and reducing agents. Methyl bromoacetate is an alkylating agent. It has ... It reacts with conjugated base and produce alkylated carbene complexes. Methyl bromoacetate can be toxic by ingestion and ... been used to alkylate phenol and amino groups. Moreover, it can be used to make vitamins and pharmaceutical drugs. It is ...
Because HN1 is an alkylating agent, it damages DNA, causes immunosuppression, and causes injury to areas that come into contact ... HN1 is also an alkylating agent. Nitrogen mustards react via an initial cyclization to the corresponding aziridinium salt. The ... HN1 was developed in the 1920s and 1930s to remove warts and later as a military agent. Because of the latter use, it is a ... If HN1 has been ingested, emetics (agents that induce vomiting) and gastric lavage are contraindicated, and nothing should be ...
... an alkylating antineoplastic agent; (P)rednisone or (P)rednisolone - a glucocorticoid hormone that has the ability to cause ... an alkylating antineoplastic agent; (E)toposide - a topoisomerase inhibitor from the epipodophyllotoxin group; (P)rocarbazine ...
Treatment with alkylating agents gives organic polysulfides. In one commercial application, it is used to produce the cross- ... linking agent bis(triethoxysilylpropyl)tetrasulfide: Na2S4 + 2 ClC3H6Si(OEt)3 → S4[C3H6Si(OEt)3]2 + 2 NaCl Sometimes as a ...
These compounds are potentially dangerous alkylating agents. The reduction of sulfate in nature involves the formation of one ...
... (INN) is a nitrosourea alkylating agent. It is used to treat malignant brain tumors and has proven to be rather ...
Kang SI, Spears CP (January 1990). "Structure-activity studies on organoselenium alkylating agents". Journal of Pharmaceutical ... however it is still a potent alkylating agent and has potential uses in chemotherapy. Diethyl selenide O-Mustard Sesquimustard ... Selenium mustard is somewhat less toxic than its relatives and has not been used as a chemical warfare agent, ... Selenium mustard (Bis(2-chloroethyl) selenide) is a haloalkyl derivative of selenium, related to vesicant chemical agents such ...
... they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents. ... Brookes P, Lawley PD (September 1961). "The reaction of mono- and di-functional alkylating agents with nucleic acids". Biochem ... Note that the alkylating damage itself is not cytotoxic and does not directly cause cell death. Nitrogen mustards are powerful ... This aziridinium group then alkylates DNA once it is attacked by the N-7 nucleophilic center on the guanine base. A second ...
SAM is a weak DNA-alkylating agent. Another reported side effect of SAM is insomnia; therefore, the supplement is often taken ...
Tertiary alkyloxonium salts are useful alkylating agents. For example, triethyloxonium tetrafluoroborate (Et 3O+ )(BF− 4), a ...
It is used as an alkylating agent. Merck Index, 13th Edition, 1572. "1-iodobutane - Compound Summary". PubChem Compound. USA: ...
... an alkylating antineoplastic agent from oxazafosforine group; Mitoxantrone - a synthetic anthracycline analogue (anthraquinone ...
The resulting 1-bromoalkanes are versatile alkylating agents. By reaction with dimethyl amine, they are precursors to fatty ...
Dexter, Thomas Michael (1974). Leukaemogenesis by the alkylating agent methylnitrosourea (PhD thesis). University of Manchester ...
It is an alkylating agent that binds DNA. Brostallicin entry in the NCI Dictionary of Cancer Terms This article incorporates ...
... (INN) is a nitrogen mustard alkylating agent. It is sometimes abbreviated "TRO". It has been used in trials to ...
Prostate cancer may be treated by removing the major source of testosterone: testicle removal (orchiectomy); or agents which ... 17α-Alkylated 19-nortestosterone derivatives: Bolenol. *Dimethyltrienolone (7α-methylmetribolone, 7α,17α-dimethyltrenbolone) ...
However, sterilant alkylating agents such as ethylene oxide (ETO), and 10% bleach are effective against endospores. To kill ... Endospores are resistant to most agents that would normally kill the vegetative cells they formed from. Unlike persister cells ... Bacterial endospores are resistant to antibiotics, most disinfectants, and physical agents such as radiation, boiling, and ... Common anti-bacterial agents that work by destroying vegetative cell walls do not affect endospores. Endospores are commonly ...
... s are alkylated by alkyl halides. Acyl chlorides and acid anhydrides react with primary and secondary amines to form ... Either accomplished with reducing agents or by electrosynthesis Reduction of nitro compounds Nitro compounds Can be ... Important primary alkyl amines include, methylamine, most amino acids, and the buffering agent tris, while primary aromatic ... This reaction also takes place with a reducing agent such as lithium aluminium hydride. ...
Commonly, the phosphorus substrate is a phosphite ester (P(OR)3) and the alkylating agent is an alkyl iodide.[11] ... Phase-transfer catalysts and precipitating agentsEdit. Organic phosphonium cations are lipophilic and can be useful in phase ...
The alkylating agent affects more the upper parts of the respiratory tract, and only intensely exposed victims showed signs ... Sulfur mustard is a vesicant alkylating agent with strong cytotoxic, mutagenic, and carcinogenic properties. After exposure, ... followed by death allowing for evaluation of novel cytoprotective agents. Potential tissue reparative agents can be evaluated ... Other inhaled agents may be directly toxic (e.g. cyanide, carbon monoxide), or cause harm simply by displacing oxygen and ...
The aromatic ring in 6 is activated at positions ortho to the hydroxyl group, and is alkylated by 5, an alkylating agent. The ...
Intracellular chemotherapeutic agents / antineoplastic agents (L01). SPs/MIs. (M phase). Block microtubule assembly. *Vinca ... Alkylating. *Nitrogen mustards: Chlormethine. *Cyclophosphamide# (Ifosfamide#. *Trofosfamide). *Chlorambucil# (Melphalan. * ...
Cannabinoids are used in patients with cachexia, cytotoxic nausea, and vomiting, or who are unresponsive to other agents. These ...
For the intermolecular case, the reaction is limited to tertiary alkylating agents, some secondary alkylating agents (ones for ... or alkylating agents that yield stabilized carbocations (e.g., benzylic or allylic ones). In the case of primary alkyl halides ... The acylated reaction product can be converted into the alkylated product via a Clemmensen reduction.[17][18][19] ... Typical acylating agents are acyl chlorides. Typical Lewis acid catalysts are acids and aluminium trichloride. However, because ...
NaHOCH2SO2 reacts with alkylating agents to give sulfones. HO-CH2-SO2Na + 2 C6H5CH2Br → [C6H5CH2]2SO2 + NaBr + CH2O + HBr. ... The original use of the compound was as industrial bleaching agent and as a reducing agent for vat dyeing.[1] Another large- ... As such it is used both as a reducing agent and as a reagent to introduce SO2 groups into organic molecules. Treatment of ... scale use is as a reducing agent in redox-initiator systems for emulsion polymerization. One of the typical redox pair examples ...
Alkyl nitriles are sufficiently acidic to form nitrile anions, which alkylate a wide variety of electrophiles.[28] Key to the ... α-aminonitriles can be decyanated with other reducing agents such as lithium aluminium hydride.[31] ...
The alkylation process alkylates isobutane with isobutylene using a strong acid catalyst. In the NExOCTANE process, isobutylene ... Antiknock agents. References. *^ NExOCTANE - Neste Jacobs External links. *International Chemical Safety Card 0496 ...
Psychotropic agents[edit]. Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and ... Unselective agents Aceclofenac. Comes in betadex salt and free acid forms; practically insoluble in water, soluble in many ... Other agents directly potentiate the effects of analgesics, such as using hydroxyzine, promethazine, carisoprodol, or ... When choosing analgesics, the severity and response to other medication determines the choice of agent; the World Health ...
It may be used as a nasal/sinus decongestant, as a stimulant,[119] or as a wakefulness-promoting agent.[120] ... Tashkin, D. P. (1 March 2001). "Airway effects of marijuana, cocaine, and other inhaled illicit agents". Current Opinion in ... and anorectic agent.[112] It is commonly used in prescription and over-the-counter cough and cold preparations. In veterinary ... "Phenylisopropylamine stimulants: amphetamine-related agents". In Lemke TL, Williams DA, Roche VF, Zito W (eds.). Foye's ...
... , also known as Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell ... Alkylating. *Nitrogen mustards: Mechlorethamine. *Cyclophosphamide# (Ifosfamide#. *Trofosfamide). *Chlorambucil# (Melphalan. * ...
List of agents[edit]. Adrenaline releasing agents[edit]. Main article: Norepinephrine releasing agent ... 3 List of agents *3.1 Adrenaline releasing agents *3.1.1 Common or widely marketed ... since these agents lose effectiveness after a few days. ... Anticancer agents *Antimetabolites. *Alkylating. *Spindle ...
Nucleophilic alkylating agentsEdit. Nucleophilic alkylating agents deliver the equivalent of an alkyl anion (carbanion). The ... Electrophilic alkylating agentsEdit. Electrophilic alkylating agents deliver the equivalent of an alkyl cation. Alkyl halides ... Alcohols alkylate to give ethers: ROH + R'X → ROR'. When the alkylating agent is an alkyl halide, the conversion is called the ... Electrophilic, soluble alkylating agents are often toxic due to their tendency to alkylate DNA. This mechanism of toxicity is ...
These compounds are potentially dangerous alkylating agents. Natural sulfate esters[edit]. The reduction of sulfate in nature ...
On the other hand, methyl chloride and methyl bromide are gaseous, thus harder to handle, and are also weaker alkylating agents ... It is used for alkylating carbon, oxygen, sulfur, nitrogen, and phosphorus nucleophiles.[8] Unfortunately, it has a high ... "any anticipated scenario for the agricultural or structural fumigation use of this agent would result in exposures to a large ...
C)yclophosphamide, an alkylating agent which damages DNA by binding to it and causing the formation of cross-links ... H)ydroxydaunorubicin (also called doxorubicin or adriamycin), an intercalating agent which damages DNA by inserting itself ...
... which are divided into broad categories such as alkylating agents and antimetabolites.[144] Traditional chemotherapeutic agents ... Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and ... Physical agents. Some substances cause cancer primarily through their physical, rather than chemical, effects.[63] A prominent ... Agents (e.g. viruses) and events (e.g. mutations) that cause or facilitate genetic changes in cells destined to become cancer. ...
See also: Sex-hormonal agent and List of sex-hormonal medications available in the United States ... 17α-Alkylated 19-nortestosterone derivatives: Ethylestrenol. *Mibolerone. *Norethandrolone. *Normethandrone (methylestrenolone ... cholesterol-lowering agents and aspirin for cardiovascular disease, and vaginal estrogen for local symptoms. Observational ...
Like other alkylating agents, cyclophosphamide is teratogenic and contraindicated in pregnant women (pregnancy category D) ... Hall AG, Tilby MJ (September 1992). "Mechanisms of action of, and modes of resistance to, alkylating agents used in the ... Cyclophosphamide and the related nitrogen mustard-derived alkylating agent ifosfamide were developed by Norbert Brock and ASTA ... Cyclophosphamide is in the alkylating agent and nitrogen mustard family of medications.[4] It is believed to work by ...
To do this other anticancer drugs can be utilized such as alkylating drugs (cyclophosphamide), antimetabolites (5-fluorouracil ... result in the development of resistance to multiple drugs such as antibiotics and anti-cancer agents. Hundreds of ABC ... have gained extensive attention because they contribute to the resistance of cells to antibiotics and anticancer agents by ...
International Agency for Research on Cancer; World Health Organization (2001). Some Thyrotropic Agents. World Health ... 17α-Alkylated dihydrotestosterone derivatives: Androisoxazole. *Desoxymethyltestosterone. *Furazabol. *Mebolazine (dimethazine) ... Sica DA (2005). "Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium ...
Like many alkylating agents, chlorambucil has been associated with the development of other forms of cancer. ... In the 1950s, aromatic mustards like chlorambucil were introduced as less toxic alkylating agents than the aliphatic nitrogen ... Chlorambucil is in the alkylating agent family of medications.[2] It works by blocking the formation of DNA and RNA.[2] ... Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, inducing DNA damage via three different methods ...
Like PAH metabolites, acrolein is also an electrophilic alkylating agent and permanently binds to the DNA base guanine, by a ... Smoke, or any partially burnt organic matter, contains carcinogens (cancer-causing agents). The potential effects of smoking, ... because they can permanently alkylate DNA, similarly to mustard gas or aflatoxin. Acrolein is only one of them present in ... "Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA ...
Although not widely employed for esterifications, salts of carboxylate anions can be alkylating agent with alkyl halides to ... Using a dehydrating agent: sulfuric acid not only catalyzes the reaction but sequesters water (a reaction product). Other ... which involves treating a carboxylic acid with an alcohol in the presence of a dehydrating agent: RCO2H + R′OH ⇌ RCO2R′ + H2O. ... drying agents such as molecular sieves are also effective.. *Removal of water by physical means such as distillation as a low- ...
... an enzyme that has been implicated in the resistance of cancer cells against chemotherapeutic agents, especially alkylating ...
mitomycin C (CHEBI:27504) has role alkylating agent (CHEBI:22333). MTIC (CHEBI:72568) has role alkylating agent (CHEBI:22333). ... dimethylmyleran (CHEBI:67107) has role alkylating agent (CHEBI:22333). esperamicin A1 (CHEBI:53273) has role alkylating agent ( ... busulfan (CHEBI:28901) has role alkylating agent (CHEBI:22333). carmustine (CHEBI:3423) has role alkylating agent (CHEBI:22333) ... iodoacetic acid (CHEBI:74571) has role alkylating agent (CHEBI:22333). lomustine (CHEBI:6520) has role alkylating agent (CHEBI: ...
Members of alkylating agent Class. Download as Tab-delimited, XML, SDF 4-hydroperoxycyclophosphamide Mass :293.08500 Formula : ... CHEBI:22333 - alkylating agent. Main. ChEBI Ontology. Automatic Xrefs. Reactions. Pathways. Models. ... It could be used as an antineoplastic agent, but it might be very toxic, with carcinogenic, mutagenic, teratogenic, and ...
Alkylating agents synonyms, Alkylating agents pronunciation, Alkylating agents translation, English dictionary definition of ... Alkylating agents. tr.v. al·kyl·at·ed , al·kyl·at·ing , al·kyl·ates To add one or more alkyl groups to . al′kyl·a′tion n. n 1. ... Alkylating agents - definition of Alkylating agents by The Free Dictionary https://www.thefreedictionary.com/Alkylating+agents ... redirected from Alkylating agents). Also found in: Medical, Encyclopedia.. Related to Alkylating agents: Antimetabolites ...
Global response of Saccharomyces cerevisiae to an alkylating agent Message Subject (Your Name) has sent you a message from PNAS ... Global response of Saccharomyces cerevisiae to an alkylating agent. Scott A. Jelinsky and Leona D. Samson ... By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, ≈ ... Of the 21 genes that already were known to be induced by a DNA-damaging agent, 18 can be scored as inducible in this data set, ...
Antineoplastic Agent, Alkylating Agent. Class Summary. These agents inhibit cell growth and proliferation. ... Oral alkylating agent converted to MTIC at physiologic pH; 100% bioavailable; approximately 35% crosses the blood-brain barrier ... These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. ...
5-year DFS for favorable risk subset of NCI HR B-ALL (HR favorable) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of ...
PM00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA ... The compound has been proposed as a potential chemotherapeutic agent in the treatment of solid human tumors and hematological ... Petek, B.J.; Jones, R.L. PM00104 (Zalypsis®): A Marine Derived Alkylating Agent. Molecules 2014, 19, 12328-12335. ... "PM00104 (Zalypsis®): A Marine Derived Alkylating Agent." Molecules 19, no. 8: 12328-12335. ...
... agents [ref: 38], and combination regimens are less commonly used. Intensive combination therapy including alkylating agents ... INCLUDING ALKYLATING AGENTS (Group 1). For definition of Groups, see Preamble Evaluation. Supplement 7: (1987) (p. 254) A. ... MOPP and other combined chemotherapy including alkylating agents are carcinogenic to humans (Group 1).. For definition of the ... Combined chemotherapy containing alkylating agents for non-Hodgkins lymphoma may also lead to ANLL [ref: 34-37], although the ...
5 Studies found for: Churg-Strauss Syndrome , Antineoplastic Agents, Alkylating. Also searched for Churg strauss. See ...
Learn about the veterinary topic of Alkylating Agents. Find specific details on this topic and related topics from the Merck ... Other Alkylating Agents:. Of the other subgroups of alkylating agents, several have limited but specific uses. ... Alkylating Agents By Lisa G. Barber, DVM, Assistant Professor, Cummings School of Veterinary Medicine, Tufts University ... Resistance to one alkylating agent often implies resistance to other drugs in the same class and can be caused by increased ...
DNA alkylating and anticancer agent. Induces hepatotoxicity. Cell and blood-brain barrier permeable. Orally active. ... DNA alkylating and anticancer agent. Induces hepatotoxicity. Cell and blood-brain barrier permeable. Orally active. ...
Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and ... Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby ... Alkylating Agents. Subscribe to New Research on Alkylating Agents Highly reactive chemicals that introduce alkyl radicals into ... 01/01/2015 - "The treatment related factors like alkylating agents are usually taken as the responsible agents for therapy- ...
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to ... Alkylating; Antineoplastics, Alkylating; Antineoplastic Alkylating Drugs; Drugs, Antineoplastic Alkylating; Alkylating Agents, ... Antineoplastic Agents, Alkylating; Alkylating Antineoplastic Drugs; Alkylating Antineoplastics; Alkylating Drugs, ... Alkylating Antineoplastic Agents. Subscribe to New Research on Alkylating Antineoplastic Agents A class of drugs that differs ...
... cumulative doses of alkylating agent (AA) is associated with the risk of therapy-related acute myeloid leukemia/myelodysplastic ... HealthDay News) - For patients treated for Hodgkins lymphoma (HL), cumulative doses of alkylating agent (AA) is associated ...
... timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in ...
Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma ... We conclude that the bioreductive alkylating agent porfiromycin has demonstrated an acceptable toxicity profile to date. Final ... Further investigations, including large-scale multiinstitutional trials employing bioreductive alkylating agents or other ...
N-Nitroso Compounds and Alkylating Agents from Nitrosated Amino Acids, Gastric Juice and Foods. ...
The Use of Alkylating Agents in the Treatment of Wegeners Granulomatosis Annals of Internal Medicine; 67 (2): 393-398 ... Androgen Role in Erythroleukemia After Treatment with Alkylating Agents Annals of Internal Medicine; 81 (1): 118-119 ... We conclude that a response to an alkylating agent may be expected. Whether after treatment for 6 to 18 months most patients ... Five Year Study of Simultaneous Antimetabolites and Alkylating Agents in the Chemotherapy of Advanced Breast Carcinoma. Annals ...
The Reaction of Rat Glucokinase with Substrate-Based Alkylating Agents BERNARD A. CONNOLLY; BERNARD A. CONNOLLY ... BERNARD A. CONNOLLY, IAN P. TRAYER; The Reaction of Rat Glucokinase with Substrate-Based Alkylating Agents. Biochem Soc Trans 1 ...
Alkylating agents (ALKY) are one of the main systemic treatments used, at least for advanced duodeno-pancreatic NETs, with a ... Drug: Alkylating-based chemotherapy The alkylating-based group will receive CapTem regimen (capecitabine and temozolomide, /4 ... Drug: Alkylating-based chemotherapy The alkylating-based group will receive CapTem regimen (capecitabine and temozolomide, /4 ... Predictive Factor of Response to Alkylating Agents (MGMT-NET). The safety and scientific validity of this study is the ...
Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. Antineoplastic Agents, Alkylating. Antidotes. ... Antineoplastic Agents. Antiviral Agents. Anti-Infective Agents. Enzyme Inhibitors. ... Alkylating agents (ALKY) are one of the main systemic treatments used, at least for advanced duodeno-pancreatic NETs, with a ... Alkylating Agents. Antimetabolites, Antineoplastic. Antimetabolites. Molecular Mechanisms of Pharmacological Action. ...
... assessment of MGMT methylation for clinical purposes since it could refine prediction of response to alkylating agent … ... Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma ... Keywords: DNA methylation; MGMT; alkylating agent; cell free circulating DNA; digital PCR; metastatic colorectal cancer. ... silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide ...
GLB dosage sensitizes GC cells to the alkylating agents via arresting the cell cycle and enhancing cell death. This is of ... In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), ... These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. ... Sensitization of gastric cancer cells to alkylating agents by glaucocalyxin B via cell cycle arrest and enhanced cell death ...
ALKYLATING AGENTS AND THE EFFECTS OF ANTIDIURETIC HORMONE IN THE TOAD BLADDER. Robert Z. Gussin, Ulrike Miksche and Alfred ... ALKYLATING AGENTS AND THE EFFECTS OF ANTIDIURETIC HORMONE IN THE TOAD BLADDER. Robert Z. Gussin, Ulrike Miksche and Alfred ... ALKYLATING AGENTS AND THE EFFECTS OF ANTIDIURETIC HORMONE IN THE TOAD BLADDER. Robert Z. Gussin, Ulrike Miksche and Alfred ... Mechlorethamine, a potent alkylating agent of the nitrogen mustard class, can interfere with the ability of antidiuretic ...
Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science. 1990 Mar 23; 247(4949 Pt 1):1457 ... Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. ... Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. ...
... and bases that have been alkylated either from endogenous or exogenous alkylating agents, including some chemotherapeutic ... Temozolomide is an alkylating agent that creates DNA lesions, including N7-methylguanine and N3-methyladenine, which are ... Temozolomide is an alkylating agent that creates DNA lesions that are repaired by the BER pathway (14). Once administered, ... Manipulation of Base Excision Repair to Sensitize Ovarian Cancer Cells to Alkylating Agent Temozolomide. Melissa L. Fishel, ...
Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or ... as an antiadhesive agent, which also caused sensitization to alkylating agents (8, 9). Thus, some forms of both acquired and ... Generation of Alkylating Agent-Resistant Cell Lines. In vitro selected drug-resistant variants of murine EMT-6 and human H69 ... EMT-6 alkylating agent-resistant model (5) to be the result of an enrichment of a subpopulation with increased cell-cell ...
Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond ... Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and ... Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and ... Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and ...
  • Alkylation can result in miscoding of DNA strands, incomplete repair of alkylated segments (which leads to strand breakage or depurination), excessive cross-linking of DNA, and inhibition of strand separation at mitosis. (merckvetmanual.com)
  • Resistance to one alkylating agent often implies resistance to other drugs in the same class and can be caused by increased production of nucleophilic substances that compete with the target DNA for alkylation. (merckvetmanual.com)
  • That this effect is related to these compounds' ability to alkylate biologically active centers is further indicated by the fact that Dibenamine, a compound with a single moiety capable of alkylation, can also block the vasopressin-induced stimulation of short-circuit current. (aspetjournals.org)
  • Owing to the cytotoxic, teratogenic and carcinogenic effects that are caused by alkylation damage, alkylating agents pose considerable threats to human health. (axonmedchem.com)
  • High resolution denaturing gel electrophoresis indicated that 8a exclusively alkylated the A of the 5'-TGTAAAA-3' within a -400 bp DNA fragment Similarly, alkylation by 8b occurred exclusively at the G of the 5'-AGTCAGA-3' sequence with efficiency at nanomolar concentration. (nii.ac.jp)
  • In order to better understand the structure of the alkylated DNA by these conjugates, the alkylation of non-self complementary duplex decanucleotides, ODNl and ODN2, were investigated. (nii.ac.jp)
  • Alkylation of nucleic acids occurs both physiologically within living cells and after the administration of compounds that are either themselves direct chemical alkylating agents or are converted into alkylating agents by metabolic activation. (elsevier.com)
  • Carcinogenicity of these agents is due to the alkylation of certain cellular components because no other degradation product nor is the compound itself oncogenic. (elsevier.com)
  • It briefly discusses other alkylation reactions leading to the alkylphosphate triester production and alkylated pyrimidines. (elsevier.com)
  • Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones. (openrepository.com)
  • Alkylating agents use selective alkylation by adding the desired aliphatic carbon chain to the previously chosen starting molecule. (wikipedia.org)
  • Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents . (wikipedia.org)
  • Mice defective in the Mgmt gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. (oup.com)
  • The Measles vaccine is not recommended (contraindicated) for persons with congenital immunodeficiency, HIV infection, leukaemia, lymphoma or generalised malignancy or those who are currently receiving alkylating agents , antimetabolites, radiation or large doses of corticosteroids, in addition to pregnant women. (thefreedictionary.com)
  • Immunosuppressant drugs include antimetabolites, alkylating agents , some antibiotics and specific adjuvants. (thefreedictionary.com)
  • Besides corticosteroids, long-term treatment options for the treatment of JIA-associated uveitis include antimetabolites, alkylating agents and biologic agents. (thefreedictionary.com)
  • Five Year Study of Simultaneous Antimetabolites and Alkylating Agents in the Chemotherapy of Advanced Breast Carcinoma. (annals.org)
  • Individual alkylating agents are generally cell-cycle nonspecific and can be subgrouped according to chemical structure into nitrogen mustards, ethyleneamines, alkyl sulfonates, nitrosoureas, and triazene derivatives. (merckvetmanual.com)
  • The alkylating agents used in immunotherapy are nitrogen mustards ( cyclophosphamide ), nitrosoureas , platinum compounds, and others. (wikipedia.org)
  • The major alkylating agents are the nitrogen mustards and the nitrosoureas. (cynologist.com)
  • For example, many alkylating agents , such as cyclophosphamide and ifosfamide, are notorious for causing transient or permanent azoospermia. (thefreedictionary.com)
  • However, among the alkylating chemotherapy agents, the myelosuppressive effect of cyclophosphamide is considered relatively sparing of platelets and progenitor cells. (merckvetmanual.com)
  • In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), cisplatin (DDP), or cyclophosphamide (CTX) to treat GC cells. (dovepress.com)
  • In the FSaIIC murine fibrosarcoma system, 100 mg/kg of pentoxifylline i.p. immediately prior to the alkylating agent or 50 mg/kg x 5 of pentoxifylline over 24 h with the alkylating agent given immediately after the third dose increased the tumor cell kill achieved by CDDP, carboplatin, cyclophosphamide, and thiotepa. (nih.gov)
  • Cyclophosphamide is one of several types of alkylating agents. (lls.org)
  • Alkylating agents like cyclophosphamide alkylates and damages DNA. (greek.doctor)
  • Cyclophosphamide is the most commonly used alkylating agent. (greek.doctor)
  • Studies combining pentostatin with alkylating agents, including chlorambucil (Leukeran) and cyclophosphamide (Cytoxan, Neosar) in patients with chronic lymphocytic leukemia (CLL) have reported significant immunosuppression and have required dose modifications of one or both agents. (cancernetwork.com)
  • We conclude that the bioreductive alkylating agent porfiromycin has demonstrated an acceptable toxicity profile to date. (nih.gov)
  • Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. (aacrjournals.org)
  • Our results demonstrate that wild-type AGT plays an important role in protecting against the toxic and mutagenic effect of O 6 alkylating agents and that a mutant AGT resistant to inactivation by BG effectively prevents BG-enhanced toxicity and mutagenicity induced by these agents. (aacrjournals.org)
  • Preclinical evidence suggests that expression of BG-resistant AGTs in normal bone marrow results in protection against alkylating agent-induced toxicity and mutagenicity and may result in an increase in the therapeutic index for treatment of tumors that express wild-type AGT that is sensitive to inactivation by BG. (aacrjournals.org)
  • In efforts to determine the role of wild-type and mutant AGTs in protection against enhanced toxicity and mutagenicity induced by the combination of BG plus alkylating agents, we embarked on cell toxicity and mutagenicity studies of the combination in CHO cells and in CHO cells transfected with wild-type AGT (CHO WTAGT cells) and MIK (CHO MIK cells), a mutant AGT resistant to BG. (aacrjournals.org)
  • However, the use of cisplatin as an anticancer agent is limited due to toxicity and resistance problems. (uwc.ac.za)
  • Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: Secondary analysis of the Euro-Ewing99-R1 trial. (lu.se)
  • Combining multiple antitumor agents increases the cytotoxicity against cancer cells without necessarily increasing the general toxicity. (greek.doctor)
  • The 'alkylating-based' group will receive CapTem regimen (capecitabine and temozolomide, /4 week), alternatively LV5FU2 (folinic acid-5 fluorouracil)-dacarbazine (1x/2 week) or LV5FU2 (folinic acid-5-fluorouracil)-streptozotocine (1x/2 week). (clinicaltrials.gov)
  • O(6)-methyl-guanine-methyl-transferase (MGMT) silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide. (nih.gov)
  • To improve the treatment of women with ovarian cancer, we are investigating the modulation of a prominent DNA-damaging agent, temozolomide, by manipulating the DNA base excision repair (BER) pathway via BER inhibitor, methoxyamine, and overexpression of N -methylpurine DNA glycosylase (MPG). (aacrjournals.org)
  • Our data show that we can effectively modulate the activity of the chemotherapeutic agent, temozolomide, via modulator methoxyamine, in three ovarian cancer cell lines, SKOV-3x, Ovcar-3, and IGROV-1. (aacrjournals.org)
  • Our results show that MPG-overexpressing IGROV-1 and IGROV-1mp53 cells are significantly more sensitive to the clinical chemotherapeutic temozolomide in combination with methoxyamine as assayed by cytotoxicity, apoptosis, and levels of DNA damage than either agent alone. (aacrjournals.org)
  • These studies show that although clinical trials in ovarian cancer to determine temozolomide single-agent efficacy are in development, through manipulation of the BER pathway, an increase in response to temozolomide is achieved. (aacrjournals.org)
  • Methylating and chloroethylating agents ( i.e., temozolomide and BCNU 3 ) are known to produce a toxic/mutagenic lesion at the O 6 position of guanine. (aacrjournals.org)
  • We have examined the potential of pentoxifylline to augment the effects of antitumor alkylating agents in vitro and in vivo. (nih.gov)
  • Aziridinyl quinone antitumor agents based on indoles and cyclopent[b]indoles: structure-activity relationships for cytotoxicity and antitumor activity. (openrepository.com)
  • However, this agent also inhibits the generation of reactive oxygen species (ROS) and the c-Jun NH 2 -terminal kinase (JNK) pathway, and because many chemotherapeutic drugs generate ROS and activate JNK in the course of inducing apoptosis, we considered the possibility that curcumin might antagonize their antitumor efficacy. (aacrjournals.org)
  • Alkylating agents form highly reactive intermediate compounds that are able to transfer alkyl groups to DNA. (merckvetmanual.com)
  • Monofunctional alkylating agents transfer a single alkyl group and usually result in miscoding of DNA, strand breakage, or depurination. (merckvetmanual.com)
  • Alkylating agents are a ubiquitous family of reactive chemicals that transfer alkyl carbon groups onto a broad range of biological molecules, thereby altering their structure and potentially disrupting their function. (axonmedchem.com)
  • An alkylating antineoplastic agent is an alkylating agent that attaches an alkyl group to DNA . (chemeurope.com)
  • alkylating agent n a substance that causes replacement of hydrogen by an alkyl group esp. (en-academic.com)
  • alkylating agent - A reagent that places an alkyl group, eg. (en-academic.com)
  • Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. (pharmacycode.com)
  • Alkylating agents add an alkyl group to the cell's DNA molecule. (grayandwhitelaw.com)
  • Nucleophilic alkylating agents deliver the equivalent of an alkyl anion ( carbanion ). (wikipedia.org)
  • With a catalyst , they also alkylate alkyl and aryl halides, as exemplified by Suzuki couplings . (wikipedia.org)
  • Typical alkylating agents are alkyl halides. (wikipedia.org)
  • When the alkylating agent is an alkyl halide, the conversion is called the Williamson ether synthesis . (wikipedia.org)
  • Alkylating agent work by covalently binding alkyl chemical groups into DNA bases. (greek.doctor)
  • This study supports the quantitative assessment of MGMT methylation for clinical purposes since it could refine prediction of response to alkylating agents. (nih.gov)
  • By integrating genome-wide gene expression profiling, protein analysis, and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. (aacrjournals.org)
  • Molecular mechanisms of the adaptive response to alkylating agents]. (openrepository.com)
  • Inducible DNA repair enzymes involved in the adaptive response to alkylating agents. (ox.ac.uk)
  • NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. (aacrjournals.org)
  • Bendamustine received its first marketing approval in Germany, which is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited, which it is indicated as a single-agent or in combination with other anti-cancer agents for indolent NHL, multiple myeloma, and CLL. (medkoo.com)
  • A new generation of proteasome inhibitors, immunomodulatory agents, and deacetylase inhibitors are currently being investigated in clinical trials to treat patients with relapsed or refractory multiple myeloma. (onclive.com)
  • By removing O 6 adducts, the AGT protein limits the production of mutations and/or toxic lesions in response to carcinogenic and chemotherapeutic alkylating agents. (aacrjournals.org)
  • The attack on nucleic acids by carcinogenic alkylating agents is not entirely random and generally leads to the formation of alkylated nucleosides at many different sites distributed throughout the cellular nucleic acids. (elsevier.com)
  • Further investigations, including large-scale multiinstitutional trials employing bioreductive alkylating agents or other hypoxic cell cytotoxins as adjuncts to RT, are warranted. (nih.gov)
  • One- and two-electron reduction of 2-methyl-1,4-naphthoquinone bioreductive alkylating agents: kinetic studies, free-radical production, thiol oxidation and DNA-strand-break formation. (semanticscholar.org)
  • The one- and two-electron enzymic reduction of the bioreductive alkylating agents 2-methylmethoxynaphthoquinone (quinone I) and 2-chloromethylnaphthoquinone (quinone II) was studied with purified NADPH-cytochrome P-450 reductase and DT-diaphorase respectively, and characterized in terms of kinetic constants, oxyradical production, thiol oxidation and DNA-strand-break formation. (semanticscholar.org)
  • A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. (curehunter.com)
  • These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. (dovepress.com)
  • The severity of these side effects can be reduced by using sensitizing agents that have the effect of decreasing the overall dose of the drugs to reduce side effects while maintaining their therapeutic effects. (dovepress.com)
  • We report that GLB can markedly sensitize GC cells to the alkylating drugs. (dovepress.com)
  • However, in contrast to molecularly targeted drugs, similar mutational mechanisms that are unambiguously responsible for clinical forms of intrinsic or acquired resistance to conventional cytotoxic anticancer agents, such as DNA-damaging agents, have proven much more elusive to uncover and validate. (aacrjournals.org)
  • Alkylating agents are a commonly used cytotoxic class of anticancer drugs. (aacrjournals.org)
  • In KEAP1-mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. (aacrjournals.org)
  • In spite of this, certain toxic alkylating agents are commonly used systemically as chemotherapeutic drugs in cancer patients, with the goal of killing cancer cells. (axonmedchem.com)
  • Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. (eurekaselect.com)
  • They are called lipid lowering drugs (LLD) or agents. (en-academic.com)
  • Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx ) is a category of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents ) as part of a standardized chemotherapy regimen . (wikipedia.org)
  • Immunosuppressive drugs , also known as immunosuppressive agents , immunosuppressants and antirejection medications are drugs that inhibit or prevent activity of the immune system . (wikipedia.org)
  • These drugs covalently alkylate various cellular constituents. (cynologist.com)
  • therefore, these drugs are referred to as bifunctional alkylating agents. (cynologist.com)
  • Here, however, we will provide you with some general information about alkylating agents so that you can be aware of the drugs' potential benefits and risks. (grayandwhitelaw.com)
  • Chemotherapy drugs have side effects, and alkylating agents are no exception. (grayandwhitelaw.com)
  • Many alkylating agents are pro-drugs which are converted into an active metabolite in the body. (greek.doctor)
  • Drugs of this group are related to mustard gas, a chemical warfare agent. (greek.doctor)
  • Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. (pharmacycode.com)
  • Alkylating agents , for example, are more likely to contribute to the development of leukemia than cisplatin or carboplatin. (thefreedictionary.com)
  • Our preliminary study showed that glaucocalyxin B (GLB) may have the potential to be a sensitizing agent for GC cells to cisplatin treatment. (dovepress.com)
  • On the other hand, alkylating agents such as cisplatin, cis- [PtCl2 (NH3) 2] have been widely used as antineoplastic agents for a wide variety of cancers including testicular, ovarian, neck and head cancers, amongst others. (uwc.ac.za)
  • On the other hand the newly synthesized palladium complexes also need further evaluation to see if they can be used as anticancer agents that can overcome the problems associated with cisplatin. (uwc.ac.za)
  • To determine the efficacy of alkylating agents in multicentric reticulohistiocytosis. (annals.org)
  • Purpose: DMS612 is a dimethane sulfonate analog with bifunctional alkylating activity and preferential cytotoxicity to human renal cell carcinoma (RCC) in the NCI-60 cell panel. (elsevier.com)
  • Bifunctional alkylating agents are more cytotoxic and produce fewer drug-induced tumours than monofunctional agents. (cynologist.com)
  • The nitrogen mustards (bischloroethylamines) are a group of bifunctional alkylating agents that alkylate various macromolecules, but preferentially alkylate N-7 of the guanine base of DNA. (cynologist.com)
  • These active metabolites are often bifunctional , meaning that they can alkylate two guanine bases and not just one. (greek.doctor)
  • Prevention of hemorrhagic cystitis after high-dose alkylating agent chemotherapy and autologous bone marrow support. (duke.edu)
  • DT-diaphorase and cytochrome P450 reductase to form highly reactive DNA alkylating agents. (openrepository.com)
  • DNA alkylating and anticancer agent. (abcam.com)
  • Similar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. (aacrjournals.org)
  • This medication is an anticancer agent, prescribed for lymphoma. (medindia.net)
  • EMP is a dual cytostatic and hence chemotherapeutic agent and a hormonal anticancer agent of the estrogen type. (wikipedia.org)
  • Treatment of frequent relapse (2 relapses in 6 months or ≥4 relapses in 12 months): Continue infrequent relapse treatment for 3 months at the lowest dose to maintain remission or use corticosteroid-sparing agents, including alkylating agents, levamisole, calcineurin inhibitors, and mycophenolate mofetil . (medscape.com)
  • Pleuroparenchymal fibroelastosis as a late complication of chemotherapy agents. (pneumotox.com)
  • Decreased permeation of alkylating agents and increased activity of DNA repair systems are also common mechanisms of resistance. (merckvetmanual.com)
  • In the current work, we extensively investigated the effect and mechanisms for GLB as a sensitizing agent. (dovepress.com)
  • Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. (harvard.edu)
  • Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. (pharmacycode.com)
  • Using clinically relevant and experimental agents this review will describe many of these mechanisms. (openrepository.com)
  • HealthDay News) - For patients treated for Hodgkin's lymphoma (HL), cumulative doses of alkylating agent (AA) is associated with the risk of therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS), according to a study published online Jan. 7 in the Journal of Clinical Oncology . (empr.com)
  • The risk of leukemia from alkylating agents is "dose-dependent," meaning that the risk is small with lower doses, but goes up as the total amount of the drug used gets higher. (cancer.org)
  • Additionally, information from the National Institute of Diabetes and Digestive and Kidney Diseases indicates that some alkylating agents may also have significant impacts on the liver when given in high doses. (grayandwhitelaw.com)
  • Our data suggest that Ap endo activity mediates resistance to alkylating agents and radiation and may be a useful predictor of progression after adjuvant therapy in a subset of gliomas. (aacrjournals.org)
  • It also prevents the tumors from developing resistance to individual agents. (greek.doctor)
  • These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. (medscape.com)
  • Here we examine the association of glioma Ap endo activity with clinical response after alkylating agent-based chemotherapy or after radiotherapy. (aacrjournals.org)
  • Clinical applications of quinone-containing alkylating agents. (openrepository.com)
  • Pentostatin (Nipent) has demonstrated significant activity as a single agent in patients with low-grade B- and T-cell lymphomas, but thus far, clinical experience with combinations of pentostatin and other agents is limited. (cancernetwork.com)
  • Nonetheless, these reports are consistent in describing a strongly increased risk of ANLL after intensive treatment with combined chemotherapeutic regimens, particularly those containing alkylating agents. (inchem.org)
  • Newer agents such as bortezomib and lenalidomide in combination with lowdose steroids have replaced more toxic chemotherapeutic regimens for primary induction and have led to significant increases in progression-free survival. (onclive.com)
  • Some aromatic amines, hydrazine and related substances, N-nitroso compounds and miscellaneous alkylating agents. (ilo.org)
  • The DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT) has been shown to protect cells from the toxic and mutagenic effect of alkylating agents by removing lesions from the O 6 position of guanine. (aacrjournals.org)
  • Dialkylating agents can react with two different 7-N-guanine residues and if these are in different strands of DNA the result is cross-linkage of the DNA strands, which prevents uncoiling of the DNA double helix. (chemeurope.com)
  • Monoalkylating agents can react only with one 7-N of guanine. (chemeurope.com)
  • The alkylated guanine can be excised, paired with an A or T instead of the normal C or form cross-links with other alkylated guanine bases. (greek.doctor)
  • Polyfunctional alkylating agents typically cause strand cross-linking and inhibition of mitosis with consequent cell death. (merckvetmanual.com)
  • By common usage, the term chemotherapy has come to connote the use of rather non-specific intracellular poisons , especially related to inhibiting the process of cell division known as mitosis , and generally excludes agents that more selectively block extracellular growth signals (i.e. blockers of signal transduction ). (wikipedia.org)
  • Traditional chemotherapeutic agents are cytotoxic by means of interfering with cell division (mitosis) but cancer cells vary widely in their susceptibility to these agents. (wikipedia.org)
  • Alkylating agents are often classified according to their nucleophilic or electrophilic character. (wikipedia.org)
  • Nucleophilic alkylating agents can displace halide substituents on a carbon atom through the SN2 mechanism. (wikipedia.org)
  • The only specific drug combination that has been used with sufficient frequency that it can be clearly linked to ANLL is MOPP (nitrogen mustard, vincristine, procarbazine and prednisone), although several reports describe excess cases not attributable to MOPP [ref: 9,11,14,16], and excesses of ANLL have appeared after treatment with other alkylating agent-containing combinations. (inchem.org)
  • The most common subgroup of alkylating agents used is the nitrogen mustard group. (merckvetmanual.com)
  • Mechlorethamine, a potent alkylating agent of the nitrogen mustard class, can interfere with the ability of antidiuretic hormone to increase the short-circuit current, the oxygen consumption and the net movement of water across the isolated urinary bladder of the toad. (aspetjournals.org)
  • Medications known as alkylating agents help prevent cancer cell growth for patients with a variety of cancers. (grayandwhitelaw.com)
  • According to http://en.wikipedia.org/wiki/Bendamustine, bendamustine was first synthesized in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). (medkoo.com)
  • Exposure to multiagent chemotherapy, particularly alkylating agents , may potentiate the effect of previous radiation therapy in childhood and thus serve as another predisposing factor for the development of a postradiation sarcoma [12]. (thefreedictionary.com)
  • Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck. (nih.gov)
  • Contemporary postoperative care for high-grade gliomas usually includes radiation therapy (RT) followed by alkylating agent-based chemotherapy. (aacrjournals.org)
  • Patients will then receive consolidation therapy with three cycles of high-dose alkylating agents. (knowcancer.com)
  • The next cycle will consist of high-dose single agent thiotepa. (knowcancer.com)
  • Phenotypic expression of "quasi-Ada" is similar to the true Ada response, however in contrast it develops in the course of pretreatment of the cells by sublethal dose of non-alkylating agent, an NO-containing dinitrosyl iron complex with glutathione (DNICglu). (deepdyve.com)
  • The risk of developing leukemia from alkylating agents increases as the dose of alkylating agents increases. (grayandwhitelaw.com)
  • 1) Patients with therapy-related acute leukemias from alkylating agents generally show a latency of 3-7 years from exposure to the alkylating agent and often have an insidious course, with the development of MDS prior. (thefreedictionary.com)
  • By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, ≈325 gene transcript levels are increased and ≈76 are decreased. (pnas.org)
  • In this project, we wish to evaluate the contribution of the MGMT methylation, evaluated in the tumor , in predicting the Objective Response (OR) in patients treated with ALKY and to evaluate a treatment with alkylating agents versus Oxaliplatin in patients with a duodeno-pancreatic or lung or unknown primitive NET. (clinicaltrials.gov)
  • Patients with unmethylated MGMT NET will be randomly assigned (1:1) to either the alkylating-based chemotherapy arm or to the oxaliplatin-based chemotherapy arm. (clinicaltrials.gov)
  • Four of the SPM patients received either alkylating agents and/or immunomodulators during MM treatment, but the other two patients received only bortezomib plus dexamethasone (BD) therapy before SPM was diagnosed. (thefreedictionary.com)
  • The compound has been proposed as a potential chemotherapeutic agent in the treatment of solid human tumors and hematological malignancies. (mdpi.com)
  • Imbalance of the BER pathway via overexpression of MPG is detrimental to breast cancer cells following treatment with chemotherapeutic agents ( 3 , 4 ). (aacrjournals.org)
  • The observed down-regulation is in part reversible by treatment of tumor spheroids with the DNA-demethylating agent, 5-azacytidine. (aacrjournals.org)
  • The role of alkylating agents in the treatment of grade II gliomas is under active investigation. (aacrjournals.org)
  • alkylating agent - A drug that is used in the treatment of cancer. (en-academic.com)
  • Hypolipidemic agent - Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of hyperlipidemias. (en-academic.com)
  • The risk of leukemia after getting alkylating agents is highest about 5 to 10 years after treatment. (cancer.org)
  • When the amount of cytotoxic alkylating DNA lesions is increased by the treatment with chemical alkylating agents, PolIV is required for survival in an alkA tag -proficient genetic background as well. (genetics.org)
  • The main indication for the nervous system is treatment of central nervous system lymphoma and as an immunosuppressive agent in immune-mediated diseases. (cynologist.com)
  • In addition, the availability of orally active agents may decrease the need for outpatient infusions, thus decreasing the overall costs associated with treatment and improving patient satisfaction. (onclive.com)
  • Topics range from topical treatment, to locally administered therapy including drug-releasing implants, to systemic immunosuppressive treatments both tried and new, as well as surgical management, with each chapter highlighting important practice pearls as well as easy-reference dosing tables, side effects, and lab monitoring pertinent to the agents discussed. (springer.com)
  • Nevertheless, options for patients who experience an early relapse after frontline therapy should include different agents than those used for initial treatment, such as Dara or carfilzomib, both of which partner well with pomalidomide. (clinicaloptions.com)
  • Patients will receive induction therapy with antimetabolite agents (methotrexate, leucovorin and 5-fluorouracil) for four cycles. (knowcancer.com)
  • Pentostatin (Nipent) has shown single-agent activity in patients with low-grade T-cell and B-cell non-Hodgkin s lymphomas. (cancernetwork.com)
  • With the availability of newer agents for salvage therapies in refractory or relapsed patients, the reliance on HCT may decrease, potentially lowering healthcare costs. (onclive.com)
  • Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or preventing reduced DNA mismatch repair activity and that the chemosensitization properties of 5-azacytidine may conceivably reflect its role as a potential antiadhesive agent as well as reversal agent for MLH1 gene silencing in human tumors. (aacrjournals.org)
  • According to the American Cancer Society, developing a new cancer, specifically leukemia, is a rare risk of alkylating agents. (grayandwhitelaw.com)
  • The more alkylating agents you receive, the higher your risk of developing leukemia. (grayandwhitelaw.com)
  • If you received more alkylating agents than were necessary to treat your cancer and you developed leukemia, you need to know more about what happened to you and your legal rights. (grayandwhitelaw.com)
  • This medication is an alkylating agent, prescribed for chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). (medindia.net)
  • This medication is a synthetic anti-cancer agent, prescribed for hairy cell leukemia. (medindia.net)
  • This medication is an anti-cancer agent, prescribed for certain type of leukemia in people who are at least 60 years old. (medindia.net)
  • O 6 -Benzylguanine (BG) is a potent inactivator of AGT, resulting in an increase in the sensitivity of cells to the toxic effects of chemotherapeutic alkylating agents. (aacrjournals.org)
  • A new and emerging concept designed to sensitize cancer cells to DNA-damaging agents (i.e., chemotherapy and/or radiation) is inhibition of various proteins in the DNA repair pathways ( 1 ). (aacrjournals.org)
  • Pravin C. Patil, Vijay Satam and Moses Lee, "A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents", Anti-Cancer Agents in Medicinal Chemistry (2015) 15: 616. (eurekaselect.com)
  • More recently, we found that alkylating Py-Im polyamides that differ only in that the C-H bond is substituted by an N atom in the second ring showed significantly different cytotoxicities in 39 human cancer cell lines (4). (jbsdonline.com)
  • Since cancer cells generally proliferate unrestrictively more than do healthy cells they are more sensitive to DNA damage, and alkylating agents are used clinically to treat a variety of tumours. (chemeurope.com)
  • Your doctor should prescribe the right alkylating agent for your specific type of cancer. (grayandwhitelaw.com)
  • This medication is a chemotherapy agent, prescribed for non-small cell lung cancer. (medindia.net)
  • This medication is an alkylating agent, prescribed for certain types of cancer. (medindia.net)
  • This medication is an oral antineoplastic agent, prescribed for cutaneous T-cell lymphoma (CTCL, a type of skin cancer), lung cancer, breast cancer and Kaposi's sarcoma. (medindia.net)
  • This medication is an antineoplastic agent, prescribed for prostate cancer with prednisone. (medindia.net)
  • O 6 -methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. (oup.com)
  • These agents inhibit cell growth and proliferation. (medscape.com)
  • PM00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. (mdpi.com)
  • GLB dosage sensitizes GC cells to the alkylating agents via arresting the cell cycle and enhancing cell death. (dovepress.com)
  • Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N -acetylcysteine or glutathione-ethyl-ester, decreased ER stress and abrogated alkylating agents-induced cell death. (aacrjournals.org)
  • We demonstrated that alkylating Py-Im polyamides that recognized specific sites on the template strand effectively inhibit transcription in an in vitro transcription system (2) and induced sequence-specific gene silencing in human cell lines (3). (jbsdonline.com)
  • Such agents are cytotoxic, producing their effects by the scission and cross-linking of DNA chains, and are not cell cycleâ€"specific, but cell killing occurs primarily in rapidly proliferating tissues in which there is not time between mitoses for DNA repair systems to reverse the effects of the agent. (en-academic.com)
  • Hematopoietic, reproductive, and epithelial tissues are particularly sensitive to alkylating agents, and their use may cause depressed blood cell counts, amenorrhea or impaired spermatogenesis, damage to intestinal mucosa, alopecia, and increased risk of malignancy. (en-academic.com)
  • Alkylating agents keep the cell from reproducing by damaging its DNA. (cancer.org)
  • Alkylating agents cause side effects because they also interfere with cell division in certain healthy tissues where cell division is frequent, such as the gastrointestinal tract. (lls.org)
  • Alkylating agents are most active in the resting phase of the cell. (chemocare.com)
  • Alkylating agents are cell cycle-nonspecific. (pharmacycode.com)
  • In the Anatomical Therapeutic Chemical Classification System , alkylating agents are classified under L01A. (chemeurope.com)