Aminacrine: A highly fluorescent anti-infective dye used clinically as a topical antiseptic and experimentally as a mutagen, due to its interaction with DNA. It is also used as an intracellular pH indicator.Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Aminoacridines: Acridines which are substituted in any position by one or more amino groups or substituted amino groups.Cardiotoxins: Agents that have a damaging effect on the HEART. Such damage can occur from ALKYLATING AGENTS; FREE RADICALS; or metabolites from OXIDATIVE STRESS and in some cases is countered by CARDIOTONIC AGENTS. Induction of LONG QT SYNDROME or TORSADES DE POINTES has been the reason for viewing some drugs as cardiotoxins.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Databases, Chemical: Databases devoted to knowledge about specific chemicals.Antineoplastic Combined Chemotherapy Protocols: 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.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Databases, Pharmaceutical: Databases devoted to knowledge about PHARMACEUTICAL PRODUCTS.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Nonprescription Drugs: Medicines that can be sold legally without a DRUG PRESCRIPTION.Pharmacopoeias as Topic: Authoritative treatises on drugs and preparations, their description, formulation, analytic composition, physical constants, main chemical properties used in identification, standards for strength, purity, and dosage, chemical tests for determining identity and purity, etc. They are usually published under governmental jurisdiction (e.g., USP, the United States Pharmacopoeia; BP, British Pharmacopoeia; P. Helv., the Swiss Pharmacopoeia). They differ from FORMULARIES in that they are far more complete: formularies tend to be mere listings of formulas and prescriptions.Preservatives, Pharmaceutical: Substances added to pharmaceutical preparations to protect them from chemical change or microbial action. They include ANTI-BACTERIAL AGENTS and antioxidants.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods.Aminoacridines: Acridines which are substituted in any position by one or more amino groups or substituted amino groups.Congresses as Topic: Conferences, conventions or formal meetings usually attended by delegates representing a special field of interest.Pharmacies: Facilities for the preparation and dispensing of drugs.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.Leukemia, Erythroblastic, Acute: A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.Friend murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.Leukemia, Experimental: Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.Chlorophyllides: Products of the hydrolysis of chlorophylls in which the phytic acid side chain has been removed and the carboxylic acids saponified.Neuropeptides: Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Aminoacridines: Acridines which are substituted in any position by one or more amino groups or substituted amino groups.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Fragile X Mental Retardation Protein: A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.CHO Cells: 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.Xylitol: A five-carbon sugar alcohol derived from XYLOSE by reduction of the carbonyl group. It is as sweet as sucrose and used as a noncariogenic sweetener.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Biofuels: Hydrocarbon-rich byproducts from the non-fossilized BIOMASS that are combusted to generate energy as opposed to fossilized hydrocarbon deposits (FOSSIL FUELS).Body Composition: The relative amounts of various components in the body, such as percentage of body fat.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form. These include binders, matrix, base or diluent in pills, tablets, creams, salves, etc.Foramen Ovale, Patent: A condition in which the FORAMEN OVALE in the ATRIAL SEPTUM fails to close shortly after birth. This results in abnormal communications between the two upper chambers of the heart. An isolated patent ovale foramen without other structural heart defects is usually of no hemodynamic significance.Technology, Pharmaceutical: The application of scientific knowledge or technology to pharmacy and the pharmaceutical industry. It includes methods, techniques, and instrumentation in the manufacture, preparation, compounding, dispensing, packaging, and storing of drugs and other preparations used in diagnostic and determinative procedures, and in the treatment of patients.Drug Compounding: The preparation, mixing, and assembling of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814)Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.GermanyLeukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Leukemia, Myeloid: 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.Mitoxantrone: An anthracenedione-derived antineoplastic agent.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Hematopoietic Stem Cell Transplantation: Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.Acute Disease: Disease having a short and relatively severe course.Transplantation, Homologous: Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.fms-Like Tyrosine Kinase 3: A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Nuclear Reprogramming: The process that reverts CELL NUCLEI of fully differentiated somatic cells to a pluripotent or totipotent state. This process can be achieved to a certain extent by NUCLEAR TRANSFER TECHNIQUES, such as fusing somatic cell nuclei with enucleated pluripotent embryonic stem cells or enucleated totipotent oocytes. GENE EXPRESSION PROFILING of the fused hybrid cells is used to determine the degree of reprogramming. Dramatic results of nuclear reprogramming include the generation of cloned mammals, such as Dolly the sheep in 1997.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Lower Gastrointestinal Tract: The segment of GASTROINTESTINAL TRACT that includes the small intestine below the DUODENUM, and the LARGE INTESTINE.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Fibrocystic Breast Disease: A common and benign breast disease characterized by varying degree of fibrocystic changes in the breast tissue. There are three major patterns of morphological changes, including FIBROSIS, formation of CYSTS, and proliferation of glandular tissue (adenosis). The fibrocystic breast has a dense irregular, lumpy, bumpy consistency.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Calcium Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.Bone Substitutes: Synthetic or natural materials for the replacement of bones or bone tissue. They include hard tissue replacement polymers, natural coral, hydroxyapatite, beta-tricalcium phosphate, and various other biomaterials. The bone substitutes as inert materials can be incorporated into surrounding tissue or gradually replaced by original tissue.Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Minerals: Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Phosphates: Inorganic salts of phosphoric acid.Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste.Bone Density: The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Durapatite: The mineral component of bones and teeth; it has been used therapeutically as a prosthetic aid and in the prevention and treatment of osteoporosis.

Effect of cellular ATP depletion on topoisomerase II poisons. Abrogation Of cleavable-complex formation by etoposide but not by amsacrine. (1/246)

Topoisomerase (topo) II poisons have been categorized into ATP-independent and -dependent drugs based on in vitro studies. We investigated drug-induced topoII-DNA complexes in intact cells almost completely depleted of ATP. Virtually no DNA single-strand breaks (SSBs), as measured by alkaline elution, were detected in energy-depleted cells treated with the topoII poisons etoposide, teniposide, daunorubicin, doxorubicin, mitoxantrone, or clerocidin. This inhibition was reversible; subsequent incubation with glucose restored the level of DNA SSBs. The effect of ATP depletion was specific for topoII, because topoI-mediated cleavable complexes induced by camptothecin were unaffected by ATP depletion. Furthermore, etoposide-induced DNA-protein complexes and DNA double-strand breaks, as measured by filter elution techniques, and topoIIalpha and -beta trapping, as measured by a band depletion assay, were completely inhibited by energy depletion. Differences in drug transport could not explain the effect of ATP depletion. The topoII poison amsacrine (m-AMSA) was unique with respect to ATP dependence. In ATP-depleted cells, m-AMSA-induced DNA SSBs, DNA double-strand breaks, DNA-protein complexes, topoIIalpha and -beta trapping were only modestly reduced. The accumulation of m-AMSA was reduced in ATP-depleted cells, which indicates that drug transport could contribute to the modest decrease in m-AMSA-induced cleavable complexes. In conclusion, drug-induced topoII-DNA complexes were completely antagonized in ATP-depleted cells, except in the case of m-AMSA. One possible interpretation is that m-AMSA mainly produces prestrand passage DNA lesions, whereas the other topoII poisons tested exclusively stabilize poststrand passage DNA lesions in intact cells.  (+info)

Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform. (2/246)

Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity. This is in contrast to topoisomerase II poisons as etoposide and amsacrine (m-AMSA), which act by stabilizing enzyme-DNA-drug complexes at a stage in which the DNA gate strand is cleaved and the protein is covalently attached to DNA. Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change in expression of the beta isoform. Sequencing of the entire topoisomerase IIalpha cDNA from NYH/187 cells demonstrated a homozygous G-->A point mutation at nucleotide 485, leading to a R162Q conversion in the Walker A consensus ATP binding site (residues 161-165 in the alpha isoform), this being the first drug-selected mutation described at this site. Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines. Alkaline elution assay demonstrated a lack of inhibition of etoposide-induced DNA single-stranded breaks in NYH/187 cells, whereas this inhibition was readily apparent in NYH cells. Site-directed mutagenesis in human topoisomerase IIalpha introduced into a yeast Saccharomyces cerevisiae strain with a temperature-conditional yeast TOP2 mutant demonstrated that R162Q conferred resistance to the bisdioxopiperazines ICRF-187 and -193 but not to etoposide or m-AMSA. Both etoposide and m-AMSA induced more DNA cleavage with purified R162Q enzyme than with the wt. The R162Q enzyme has a 20-25% decreased catalytic capacity compared to the wt and was almost inactive at <0.25 mM ATP compared to the wt. Kinetoplast DNA decatenation by the R162Q enzyme at 1 mM ATP was not resistant to ICRF-187 compared to wt, whereas it was clearly less sensitive than wt to ICRF-187 at low ATP concentrations. This suggests that it is a shift in the equilibrium to an open-clamp state in the enzyme's catalytic cycle caused by a decreased ATP binding by the mutated enzyme that is responsible for bisdioxopiperazine resistance.  (+info)

Enhanced amsacrine-induced mutagenesis in plateau-phase Chinese hamster ovary cells, with targeting of +1 frameshifts to free 3' ends of topoisomerase II cleavable complexes. (3/246)

Previous work showed that the DNA double-strand cleaving agents bleomycin and neocarzinostatin were more mutagenic in plateau-phase than in log-phase cells. To determine whether topoisomerase II poisons that produce double-strand breaks by trapping of cleavable complexes would, likewise, induce mutations specific to plateau-phase cells, aprt mutations induced by amsacrine in both log-phase and plateau-phase CHO cells were analyzed. The maximum aprt mutant frequencies obtained were 7 x 10(-6) after treatment with 0.02 microM amsacrine in log phase and 27 x 10(-6) after treatment with 1 microM amsacrine in plateau phase, compared with a spontaneous frequency of < 1 x 10(-6). Base substitutions dominated the spectrum of mutations in log-phase cells, but were much less prevalent in plateau-phase cells. Both spectra also included small deletions, insertions and duplications, as well as few large-scale deletions or rearrangements. About 5% of the log-phase mutants and 16% of the plateau-phase mutants were +1 frameshifts, and all but one of these were targeted to potential free 3' termini of cleavable complexes, as determined by mapping of cleavage sites in DNA treated with topoisomerase II plus amsacrine in vitro. Thus, these insertions may arise from templated extension of the exposed 3' terminus by a DNA polymerase, followed by resealing of the strand, as shown previously for acridine-induced frameshifts in T4 phage.  (+info)

Autologous bone marrow transplantation in non-Hodgkin's lymphoma patients: effect of a brief course of G-CSF on harvest and recovery. (4/246)

This study compares harvest and hematological recovery data of 100 lymphoma patients who underwent BM harvest either after a short course of G-CSF (16 microg/kg for 3 days) (n = 57) or in steady-state conditions (n = 43). G-CSF allowed the attainment of a significantly higher median number of total nucleated cells x 10(8)/kg (4.4, range 1.4-17, vs 2.1, range 0.6-4.2; P < 0.0001), mononuclear cells x 10(8)/kg (0.55, range 0.20-1.4, vs 0.41, range 0.15-0.76, P < 0.0001) and CFU-GM/ml (310, range 10-5500, vs 80, range 10-3800, P = 0.008), with lower volumes of blood collected (17.5 ml/kg, range 8-31 vs 21.0, range 15-30, P = 0.0001). Hematological recovery was faster in patients who received pre-treated BM (median time to PMN >0.5 x 10(9)/l and to platelets >20 x 10(9)/l was 12, range 10-14, and 13, range 10-18, days, respectively) than in those autotransplanted with steady-state BM (median time to PMN >0.5 x 10(9)/l and to platelets >20 x 10(9)/l 13, range 10-18 and 14, range 10-20 days, respectively, P = 0.004 and P = 0.01). Transfusional requirement was significantly different and patients of the G-CSF group needed shorter hospitalization (17 days, range 12-24, vs 20 days, range 14-32; P = 0.02). These data suggest that treating patients with G-CSF before BM harvest improves the quality of the harvest and accelerates engraftment and hematological recovery.  (+info)

Transfection of 9-hydroxyellipticine-resistant Chinese hamster fibroblasts with human topoisomerase IIalpha cDNA: selective restoration of the sensitivity to DNA religation inhibitors. (5/246)

In the Chinese hamster lung cell line DC-3F/9-OH-E, selected for resistance to 9-OH-ellipticine and cross-resistant to other topoisomerase II inhibitors, the amount of topoisomerase IIalpha is 4-5-fold lower than in the parental DC-3F cells, whereas topoisomerase IIbeta is undetectable. Cloning and sequencing of topoisomerase IIalpha cDNAs from DC-3F and DC-3F/9-OH-E cells revealed an allele polymorphism, one allele differing from the other by the presence of seven silent mutations and three mutations in the noncoding region. In addition, the mutated allele contains three missense mutations located close to the ATP binding site (Thr371Ser) or to the catalytic site (Ala751Gly; Ile863Thr). To analyze the contribution of these topoisomerase IIalpha alterations to their resistance phenotype, DC-3F/9-OH-E cells were transfected with an eukaryotic expression vector containing the human topoisomerase IIalpha cDNA. In one transfected clone, the amount of topoisomerase IIalpha isoform and the catalytic activity were similar to that in the parental DC-3F cells. These cells, which contain only topoisomerase IIalpha, are then a unique mammalian cell line to analyze the physiological and pharmacological properties of this enzyme. However, the restoration of a nearly normal topoisomerase IIalpha activity in the DC-3F/9-OH-E cells did not have the same effect on their sensitivity to different enzyme inhibitors; a 75% reversion of the resistance, associated with a 2-3-fold increased stabilization of the cleavable complex, was observed with both etoposide and m-AMSA, two drugs that inhibit the DNA religation step in the enzyme catalytic cycle; in contrast, the transfected cells remained fully resistant to ellipticine derivatives that did not induce the stabilization of the cleavable complex. We hypothesized that a trans-acting factor, inhibiting the induction of cleavable complex formation by drugs that are not religation inhibitors, might be present in the resistant cells. However, such a factor was not detected in in vitro experiments, and other hypotheses are discussed.  (+info)

Murine transgenic cells lacking DNA topoisomerase IIbeta are resistant to acridines and mitoxantrone: analysis of cytotoxicity and cleavable complex formation. (6/246)

Murine transgenic cell lines lacking DNA topoisomerase II (topo II)beta have been used to assess the importance of topo IIbeta as a drug target. Western blot analysis confirmed that the topo IIbeta -/- cell lines did not contain topo IIbeta protein. In addition, both the topo IIbeta +/+ and topo IIbeta -/- cell lines contained similar levels of topo IIalpha protein. The trapped in agarose DNA immunostaining assay (TARDIS) was used to detect topo IIalpha and beta cleavable complexes in topo IIbeta -/- and topo IIbeta +/+ cells. These results show that both topo IIalpha and beta are in vivo targets for etoposide, mitoxantrone, and amsacrine (mAMSA) in topo IIbeta +/+ cells. As expected, only the alpha-isoform was targeted in topo IIbeta -/- cells. Clonogenic assays comparing the survival of topo IIbeta -/- and topo IIbeta +/+ cells were carried out to establish whether the absence of topo IIbeta caused drug resistance. Increased survival of topo IIbeta -/- cells compared with topo IIbeta +/+ cells was observed after treatment with amsacrine (mAMSA), methyl N-(4'-[9-acridinylamino]-2-methoxyphenyl) carbamate hydrochloride (AMCA), methyl N-(4'-[9-acridinylamino]-2-methoxyphenyl)carbamate hydrochloride (mAMCA), mitoxantrone, and etoposide. These studies showed that topo IIbeta -/- cells were significantly more resistant to mAMSA, AMCA, mAMCA, and mitoxantrone, than topo IIbeta +/+ cells, indicating that topo IIbeta is an important target for the cytotoxic effects of these compounds.  (+info)

Altered drug interaction and regulation of topoisomerase IIbeta: potential mechanisms governing sensitivity of HL-60 cells to amsacrine and etoposide. (7/246)

Topoisomerase II (topo II), an enzyme essential for cell viability, is present in mammalian cells as the alpha- and beta-isoforms. In human leukemia HL-60/S or HL-60/doxorubicin (DOX)0.05 cells, the levels of topo IIalpha- or beta-protein were similar in either asynchronous exponential or synchronized cultures. Although topo IIalpha was hypophosphorylated in HL-60/DOX0.05 compared with HL-60/S cells, both overall and site-specific hyperphosphorylation of topo IIbeta was apparent in HL-60/DOX0.05 compared with HL-60/S cells. The phosphorylation of topo IIalpha and not beta was enhanced in the S and G(2) + M phases of HL-60/S cells. In contrast, an increase in the phosphorylation of topo IIbeta compared with alpha was apparent in the G(1) and S phases of HL-60/DOX0.05 cells. The cytotoxicity and depletion of topo IIalpha or beta in cells treated with drug for 1 h revealed that mole-for-mole, amsacrine was 2-fold more effective than etoposide in killing HL-60/S or HL-60/DOX0.05 cells and in depleting the beta versus alpha topo II protein. Present results demonstrate that: 1) hyperphosphorylation of topo IIbeta in HL-60/DOX0.05 cells may be a compensatory consequence of the hypophosphorylation of topo IIalpha to maintain normal topo II function during proliferation, and 2) enhanced sensitivity of HL-60/S or HL-60/DOX0.05 cells to amsacrine may be due to the preferential interaction and depletion of topo IIbeta.  (+info)

An antitumor drug-induced topoisomerase cleavage complex blocks a bacteriophage T4 replication fork in vivo. (8/246)

Many antitumor and antibacterial drugs inhibit DNA topoisomerases by trapping covalent enzyme-DNA cleavage complexes. Formation of cleavage complexes is important for cytotoxicity, but evidence suggests that cleavage complexes themselves are not sufficient to cause cell death. Rather, active cellular processes such as transcription and/or replication are probably necessary to transform cleavage complexes into cytotoxic lesions. Using defined plasmid substrates and two-dimensional agarose gel analysis, we examined the collision of an active replication fork with an antitumor drug-trapped cleavage complex. Discrete DNA molecules accumulated on the simple Y arc, with branch points very close to the topoisomerase cleavage site. Accumulation of the Y-form DNA required the presence of a topoisomerase cleavage site, the antitumor drug, the type II topoisomerase, and a T4 replication origin on the plasmid. Furthermore, all three arms of the Y-form DNA were replicated, arguing strongly that these are trapped replication intermediates. The Y-form DNA appeared even in the absence of two important phage recombination proteins, implying that Y-form DNA is the result of replication rather than recombination. This is the first direct evidence that a drug-induced topoisomerase cleavage complex blocks the replication fork in vivo. Surprisingly, these blocked replication forks do not contain DNA breaks at the topoisomerase cleavage site, implying that the replication complex was inactivated (at least temporarily) and that topoisomerase resealed the drug-induced DNA breaks. The replication fork may behave similarly at other types of DNA lesions, and thus cleavage complexes could represent a useful (site-specific) model for chemical- and radiation-induced DNA damage.  (+info)

*Amsacrine

... (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent. It has been used in acute lymphoblastic leukemia ... "Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in ... Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II (compares with the better ...

*FLAG (chemotherapy)

FLAMSA adds amsacrine ("AMSA") to the standard FLAG regimen. (G-CSF is still included, even though the "G" is taken out of the ... December 2009). "Fludarabine, amsacrine, high-dose cytarabine and 12 Gy total body irradiation followed by allogeneic ... October 2013). "Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic ... acronym.) Amsacrine is an alkylating antineoplastic agent that is highly active toward AML, unlike more conventional alkylators ...

*Aldehyde oxidase

Others include amsacrine, 6,6'-azopurine, chlorpromazine, cimetidine, cyanide, diethylstilbestrol, genestein, isovanillin, and ...

*Acridine

... and related derivatives (such as amsacrine) bind to DNA and RNA due to their abilities to intercalate. Acridine orange ...

*Dimethylacetamide

... amsacrine). Dimethylacetamide is a medium potency reproductive toxicant (toxic for reproduction, category 1B) and may damage ...

*Topoisomerase inhibitor

... amsacrine, etoposide, etoposide phosphate, teniposide and doxorubicin. These drugs are anti-cancer therapies. bacterial type II ... amsacrine, ellipticines, aurintricarboxylic acid, and HU-331, a quinolone synthesized from cannabidiol. Numerous plant derived ...

*List of MeSH codes (D03)

... amsacrine MeSH D03.494.046.250.450 --- ethacridine MeSH D03.494.046.250.650 --- nitracrine MeSH D03.494.046.250.720 --- ...

*ATC code L01

Midostaurin L01XE40 Olmutinib L01XE41 Binimetinib L01XE42 Ribociclib L01XE43 Brigatinib QL01XE91 Toceranib L01XX01 Amsacrine ...

*Index of oncology articles

... amsacrine - amylase - amyloidosis - anagrelide - anakinra - anaphylactic shock - anaplastic - anaplastic large cell lymphoma - ...

*List of drugs: Am

... amsacrine (INN) amsilarotene (USAN) amtolmetin guacil (INN) amustaline dihydrochloride (USAN) amuvatinib (USAN, INN) Amvaz ...
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered: Allergies Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully. Children Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of amsacrine in children with use in other age groups. Older adults Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information ...
Abdul Mamsa, MD is a Neurologist at 820 W Oak St, Kissimmee, FL 34741. Wellness.com provides reviews, contact information, driving directions and the phone number for Abdul Mamsa, MD in Kissimmee, FL.
The free radical scavengers, dimethyl sulfoxide (Me2SO) and thiourea, were used to assess the role of free radicals in the production of intercalator-induced DNA breaks and cytotoxicity in mouse leukemia L1210 cells. Both agents decreased X-ray break production, and this decrease was comparable in magnitude to the degree of inhibition of X-ray-induced cell killing. By contrast, Me2SO increased the DNA breaks produced by the intercalators, Adriamycin, 5-iminodaunorubicin, and 4′-(9-acridinylamino)methanesulfon-m-anisidide. This was not due to an enhancement of Adriamycin or 4′-(9-acridinylamino)methanesulfon-m-anisidide uptake by Me2SO. Strand break production by intercalators was decreased by thiourea. This was not due to an inactivation of the intercalators or to a decrease of Adriamycin or 4′-(9-acridinylamino)methanesulfon-m-anisidide uptake by thiourea. Experiments using nucleoid sedimentation to assess the DNA linking number and domain size from cells treated with Me2SO and thiourea ...
A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4′-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered ...
Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. [PubChem]
Transient or long-term DNA self-assembly participates in essential genetic functions. The present review focuses on tight DNA-DNA interactions that have recently been found to play important roles in both controlling DNA higher-order structures and their topology. Due to their chirality, double helices are tightly packed into stable right-handed crossovers. Simple packing rules that are imposed by DNA geometry and sequence dictate the overall architecture of higher order DNA structures. Close DNA-DNA interactions also provide the missing link between local interactions and DNA topology, thus explaining how type II DNA topoisomerases may sense locally the global topology. Finally this paper proposes that through its influence on DNA self-assembled structures, DNA chirality played a critical role during the early steps of evolution.
The compound 4-(9-[4-[N-methyl-carboxamido]-5-methyl]acridinylamino)methanesulphon-m-a nisidide and acid addition salts thereof have antitumor properties.
The DNA intercalator, 4′-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and the nonintercalator, etoposide (VP-16) produce topoisomerase II-mediated protein-linked DNA strand breaks. This function of topoisomerase II was investigated in relation to cell proliferation and cell cycle. Mouse fibroblasts NIH 3T3 and mouse leukemia L1210 cells stop proliferation when they reach a certain density. Nuclei were isolated from proliferative or quiescent cells and then treated with drug for 30 min. DNA modifications were assayed by alkaline elution. We found that the frequencies of m-AMSA- or VP-16-induced DNA-protein links were higher in nuclei from exponentially growing than in those from quiescent cells in both the 3T3 and the L1210 lines. Drug-induced protein-associated DNA breaks were also studied as a function of the cell cycle in 3T3 cells that had been arrested by contact inhibition in medium containing 1% calf serum and then stimulated to proliferate by replating at a lower cell density in ...
Antigen Background Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replication and is a target for many anti-cancer drugs used for cancer therapy. Decreased expression of topoisomerase II alpha is the predominant mechanism of resistance to several chemotherapeutic agents. A significant variation in the range of expression of this protein has been reported in many different tumors. Reports of the analysis of primary breast tumors have indicated that topoisomerase II beta is more widely expressed than topoisomerase II alpha. Topoisomerase II alpha expression and activity is linked to the cell cycle and is associated with the proliferation status of cells.. ...
The amount of muscle and the thickness of the skin and ligaments depend upon a persons constitution. People with a vata prakruti have minimal amounts of muscle and thin skin and ligaments even when healthy and balanced. Those with a pitta nature have moderate muscular formation along with a moderate thickness of the skin and ligaments. Individuals with a kapha nature have larger muscle mass with thicker skin and ligaments. Regardless of the dosha, the tissues are healthy if they are consistent in formation with the doshic balance of the individual and are tone and supple.. Vitiation of kapha dosha in the mamsavaha srota (channel that carries posaka rakta dhatu) results in low mamsagni. This results in excessive mamsa dhatu formation but the tissue formed is hard and inflexible. In addition, the upadhatus (secondary tissues) are similarly affected. Thus, the skin and ligaments of the body become thicker, harder, and tighter. Psychologically, self-confidence is quiet and strong but the motivation ...
In the Subjects, Materials, and Methods Subjects section of this paper one reads: In February 2007, an HIV-infected patient underwent stem cell transplantation (SCT) due to a relapse of AML with a graft consisting of CCR5A32/A32 donor cells. The pre-transplant conditioning regimen included 100 mg/m2 of amsacrine, 30 mg/m2 of fludarabine, 2 g/m2 of cytarabine (day -12 until -9), 60 mg/kg of cyclophosphamide (days -4 and -3), 5.5 mg/kg of rabbit antithymocyte globuline (in three doses between day -3 and -1), and a 400 cGy total body irradiation (TBI; day -5). ART was discontinued on the day of transplantation, and 13 months later the patient received a second transplant with CCR5A32/A32 stem cells from the same donor due to a second relapse of AML. The conditioning regimen consisted of 100 mg/m2 of cytarabine (day -7 until day -1), 6 mg/m2 of gemtuzumab (day -7 and day -1), and a 200 cGy TBI (day -1)... Twelve months post-transplant, the patient underwent liver biopsy and histological examination ...
In the Subjects, Materials, and Methods Subjects section of this paper one reads: In February 2007, an HIV-infected patient underwent stem cell transplantation (SCT) due to a relapse of AML with a graft consisting of CCR5A32/A32 donor cells. The pre-transplant conditioning regimen included 100 mg/m2 of amsacrine, 30 mg/m2 of fludarabine, 2 g/m2 of cytarabine (day -12 until -9), 60 mg/kg of cyclophosphamide (days -4 and -3), 5.5 mg/kg of rabbit antithymocyte globuline (in three doses between day -3 and -1), and a 400 cGy total body irradiation (TBI; day -5). ART was discontinued on the day of transplantation, and 13 months later the patient received a second transplant with CCR5A32/A32 stem cells from the same donor due to a second relapse of AML. The conditioning regimen consisted of 100 mg/m2 of cytarabine (day -7 until day -1), 6 mg/m2 of gemtuzumab (day -7 and day -1), and a 200 cGy TBI (day -1)... Twelve months post-transplant, the patient underwent liver biopsy and histological examination ...
Your doctor will prescribe your dose and schedule. This medicine is given through a needle placed in a vein. This medicine is given slowly, so your IV will remain in place for 30 to 60 minutes. You may also need to stay for observation for an additional hour or more ...
The t(12;21) (p13;q22) translocation resulting in ETV6/RUNX1 (previously named TEL/AML1) gene fusion is present in about 25% of children with precursor B-lineage acute lymphoblastic leukemia (B-ALL). We successfully tested 275 precursor B-ALL samples from children aged 1 to 17 years to determine the relation between t(12;21) and in vitro cellular drug resistance, measured by the fluorometric microculture cytotoxicity assay (FMCA). Samples from 83 patients (30%) were positive for t(12;21). The ETV6/RUNX1(+) samples were significantly more sensitive than ETV6/RUNX1(-) samples to doxorubicin, etoposide, amsacrine, and dexamethasone, whereas the opposite was true for cytarabine. After matching for unevenly distributed patient characteristics, that is, excluding patients with high hyperdiploidy (, 51 chromosomes), t(9; 22), t(1;19), or 11q23 rearrangement, the ETV6/RUNX1(+) samples remained significantly more sensitive to doxorubicin (P = .001) and etoposide (P = .001). For the other drugs tested ...
Researchers at the University of California, Berkeley have described the structure of the active site core of topoisomerase II alpha, an important target for anti-cancer drugs.
NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that shows strong antitumor activity. It inhibited topoisomerase II activity and stabilized topoisomerase II-DNA cleavable complexes. The DNA breaks occurred within 1h after treatment with NK314 even without digestion of topoisomerase II by proteinase K, whereas etoposide required digestion of the enzyme protein in cleavable complex to detect DNA breaks. Pretreatment with topoisomerase II catalytic inhibitors, ICRF-193 and suramin, reduced both cleavable complex-mediated DNA breaks and proteinase K-independent DNA breaks, but protease inhibitors and nuclease inhibitors only decreased the latter.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Reviews for Ametantrone (AM) is a synthetic 9,10-anthracenedione bearing two (hydroxyethylamino)ethylamino residues at positions 1 and 4 along with other anthraquinones and anthracyclines.
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [PubChem]
2017-2022 Asia-Pacific Top Countries Peat Market Report. In 2016, the Asia-Pacific Peat market size was xx million USD and it will reach xx million USD in 2022, with a CAGR of xx% between 2016 and 2022. This report studies Peat in Asia-Pacific market, especially in China, Japan, Korea, Taiwan, India, Australia, Indonesia, Thailand and Philippines, focuses on the .... October 2017 , $4660 ,View Details>> ...
Learn more about 2-2-chloroethyl-piperidine-1-carboxylic-acidethyl-ester. We enable science by offering product choice, services, process excellence and our people make it happen.
0028] The methods of embodiments encompassed by the invention may be used to reduce or eliminate side effects associated with any medical therapies and diagnostic agents, and in particular embodiments, the medical therapies and diagnostic agent administration that may be a therapy that is capable of producing toxicity in normal tissues. Such medical therapies may include the use of chemical agents, physical agents, or a combination thereof. For example, in some embodiments, the methods described herein may be used to reduce or eliminate side effects associated with chemical agents including, but are not limited to, alkylating agents, anti-metabolites such as, but are not limited to, azathioprine, mercaptopurine, and other purine and pyrimidine analogues, alkaloids and terpenes such as , but are not limited to, vinca alkaloids, etoposide, teniposide, paclitaxel, and docetaxel, topoisomerase inhibitors such as, but are not limited to, irinotecan, topotecan, and amsacrine, antibiotics, monoclonal ...
SALVAVIDAS PHARMACEUTICAL from Surat, Gujarat (India) is a wholesaler, supplier and exporter of Teniposide Injection at the best price.
Mitoxantrone cancer drug molecule (type II topoisomerase inhibitor). Atoms are represented as spheres and are colour coded: hydrogen (white), carbon (black), nitrogen (blue), oxygen (red). Illustration. - Stock Image F012/9240
Mitoxantrone cancer drug molecule (type II topoisomerase inhibitor). Atoms are represented as spheres and are colour coded: hydrogen (white), carbon (grey), nitrogen (blue), oxygen (red). Illustration. - Stock Image F012/9242
teniposide | C32H32O13S | CID 5396 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
3RAF: Inhibitor-stabilised cleavage complexes of topoisomerase IIa: structural analysis of drug-dependent inter- and intramolecular interactions
3RAF: Inhibitor-stabilised cleavage complexes of topoisomerase IIa: structural analysis of drug-dependent inter- and intramolecular interactions
Pla, D., Sischka, A., Albericio, F., Alvarez, M., Fernandez-Busquets, X., & Anselmetti, D. (2009). Optical-Tweezers Study of Topoisomerase Inhibition. Small, 5(11), 1269-1272. doi:10.1002/smll. ...
Type II topoisomerases are required for the management of DNA superhelicity and chromosome segregation, and serve as frontline targets for a variety of small-molecule therapeutics. To better understand how these enzymes act in both contexts, we deter
Principal Investigator:YAMADA Kyoji, Project Period (FY):1996 - 1998, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Digestive surgery
2) read the download on H3 K56Ac of Pkc starsdisturbingHorgan in the student and random systems, to affect whether they are new, performed their virtual book on the utility of H3 K56Ac. This Suddenly inhibits that the periclinal download( Objective) resolves H3K56Ac in drainage remarks but is previously further enjoy the expensive formulations of H3K56Ac in complexes deferred of positive death in the Last page other mysterious door. The download in turns involves again encumbered by difficult honey of high hold-all by the activator, becoming to less three-part songs on H3K56Ac cultures( widely given on in the buffer).
Purpose: Renal medullary carcinoma is an aggressive renal neoplasm without currently available effective therapy to our knowledge. Topoisomerase II alpha is a gyrase involved in cell proliferation, and DNA maintenance and repair. Topoisomerase II alpha is a target of inhibiting agents such as anthracyclines. Triggered by a recent response to topoisomerase II alpha inhibitors in a patient with renal medullary carcinoma, we evaluated topoisomerase II alpha expression in relation to the proliferation index and topoisomerase II alpha gene copy number status in a larger series of patients with renal medullary carcinoma. Materials and Methods: Archival tissues from 14 renal medullary carcinomas were retrieved from our 3 institutions. Immunohistochemistry was performed using monoclonal antibodies for topoisomerase II alpha and Ki67. The percent of cells with positive nuclear staining was assessed in the highest area of expression for each marker. A previously suggested greater than 5% cutoff was used ...
Abstract. Filamin-A, also called Actin Binding Protein-280, is not only an essential component of the cytoskeleton networks, but also serves as the scaffold in various signaling networks. It has been shown that filamin-A facilitates DNA repair and filamin-A proficient cells are more resistant to ionizing radiation, bleomycin, and cisplatin. In this study, we assessed the role of filamin-A in modulating cancer cell sensitivity to Topo II poisons, including etoposide and doxorubicin. Intriguingly, we found that cells with filamin-A expression are more sensitive to Topo II poisons than those with defective filamin-A, and filamin-A proficient xenograft melanomas have better response to etoposide treatment than the filamin-A deficient tumors. This is associated with more potent induction of DNA double strand breaks (DSBs) by Topo II poisons in filamin-A proficient cells than the deficient cells. Although the expression of filamin-A enables cells a slightly stronger capability to repair DSB, the net ...
0092]Other anti-cancer drugs include, but are not limited to: 20-epi-1,25 dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1; antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA; arginine deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR/ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF inhibitor; bicalutamide; bisantrene; ...
Etoposide is a semisynthetic derivative of podophyllotoxin and a substance extracted from the mandrake root Podophyllum peltatum. Possessing potent antineoplastic properties, Etoposide binds to and inhibits topoisomerase II and its function in ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle..
A substance that blocks topoisomerases (enzymes that break and rejoin DNA strands and are needed for cells to divide and grow). Blocking these enzymes may kill cancer cells. Certain topoisomerase inhibitors are being studied in the treatment of cancer.. ...
BioAssay record AID 211293 submitted by ChEMBL: Tested for inhibitory activity against Topoisomerase II isolated from HeLa cells by using SDS-K+ precipitation method.
Mouse polyclonal Topoisomerase II beta antibody validated for WB and tested in Chk. With 2 independent reviews. Immunogen corresponding to synthetic peptide
A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway ...
Teniposide (Vumon) chemotherapy side effects, how its given, how it works, precautions and self care tips for treatment of acute lymphocytic leukemia
Define consolidation chemotherapy. consolidation chemotherapy synonyms, consolidation chemotherapy pronunciation, consolidation chemotherapy translation, English dictionary definition of consolidation chemotherapy. n. 1. The treatment of cancer using specific chemical agents or drugs that are selectively destructive to malignant cells and tissues. 2. The treatment of...
It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contact probabilities with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way th
In yeast, a single copy of topo II is essential for chromosome segregation (Uemura et al., 1987). In the biochemical and immunological depletion study of Xenopus egg extracts, topo IIα was shown to be required for chromosome condensation, whereas the function of topo IIβ remained obscure because its localization and relative amount to topo IIα in the egg extracts were unknown (Hirano and Mitchison, 1993). In mammals, the role of topo IIα and topo IIβ, and their cellular localization, were extensively studied using specific mAbs against each isoform (Cobb et al., 1999; Tsutsui et al., 2001; Turley et al., 1997; Yabuki et al., 1996). This idea was challenged by the recent observation that there might exist residual but sizable amounts of heterodimers of topo IIα/topo IIβ in the cultured cell extract (Christensen et al., 2002).. The knocking-out of topo IIβ does not affect embryonic development because topo IIα can substitute for it until the birth of the fetus (Yang et al., 2000), ...
What is the difference between Topoisomerase I and II? Topoisomerase I cuts one strand in double-stranded DNA while Topoisomerase, II cuts both strands in DNA
There are no specific protocols for Recombinant human Topoisomerase I protein (ab3808). Please download our general protocols booklet
Get this from a library! Advances in pharmacology. Volume 29, DNA topoisomerases: Topoisomerase-targeting drugs. [Leroy F Liu;] -- Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental.
Etoposide is a semisynthetic derivative of podophyllotoxin, which inhibits DNA synthesis via topoisomerase II inhibition activity.

Amsacrine - DrugBankAmsacrine - DrugBank

Amsacrine gluconate. M4P91439UZ. 80277-07-2. XXNAQBNJPZNRSZ-IFWQJVLJSA-N. Amsacrine hydrochloride. U66HX4K4CO. 54301-15-4. ... Amsacrine appears to cleave DNA by inducing double stranded breaks. Amsacrine also targets and inhibits topoisomerase II. ... Gitoformate may decrease the cardiotoxic activities of Amsacrine.. Experimental. Haloperidol. The metabolism of Amsacrine can ... Metildigoxin may decrease the cardiotoxic activities of Amsacrine.. Experimental. Metoprolol. The metabolism of Amsacrine can ...
more infohttps://www.drugbank.ca/drugs/DB00276

Amsacrine (Amsidine)  Drug Information - Indications, Dosage, Side Effects and PrecautionsAmsacrine (Amsidine) Drug Information - Indications, Dosage, Side Effects and Precautions

Amsacrine(Amsidine) generic is an antineoplastic agent, prescribed for malignant lymphoma and acute adult lymphoblastic ... General Information on Amsacrine. Generic Name : Amsacrine Latest prescription information about Amsacrine. Learn how to ... How should Amsacrine be taken? It comes as a red colored solution for injection to be administered by a healthcare provider ... What are the side effects of Amsacrine? Most Common : Fatigue (tiredness), sore mouth and throat, loss of fertility, absence of ...
more infohttps://www.medindia.net/doctors/drug_information/amsacrine.htm

Amsacrine - WikipediaAmsacrine - Wikipedia

Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent. It has been used in acute lymphoblastic leukemia ... "Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in ... Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II (compares with the better ...
more infohttps://en.wikipedia.org/wiki/Amsacrine

Amsacrine | definition of amsacrine by Medical dictionaryAmsacrine | definition of amsacrine by Medical dictionary

... amsacrine explanation free. What is amsacrine? Meaning of amsacrine medical term. What does amsacrine mean? ... Looking for online definition of amsacrine in the Medical Dictionary? ... amsacrine. Also found in: Wikipedia. amsacrine. /am·sa·crine/ (am´sah-krēn) an antineoplastic that inhibits DNA synthesis; used ... Amsacrine , definition of amsacrine by Medical dictionary https://medical-dictionary.thefreedictionary.com/amsacrine ...
more infohttps://medical-dictionary.thefreedictionary.com/Amsacrine

Human Metabolome Database: Showing metabocard for Amsacrine (HMDB0014421)Human Metabolome Database: Showing metabocard for Amsacrine (HMDB0014421)

Showing metabocard for Amsacrine (HMDB0014421). IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological properties ... Amsacrine. Description. Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the ... Finlay GJ, Atwell GJ, Baguley BC: Inhibition of the action of the topoisomerase II poison amsacrine by simple aniline ... Lee MS, Wang JC, Beran M: Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point ...
more infohttp://www.hmdb.ca/metabolites/HMDB14421

Amsacrine (Intravenous route)Amsacrine (Intravenous route)

If amsacrine accidentally leaks out of the vein into which it is injected, it may damage some tissues and cause scarring. Tell ... Amsacrine may lower your bodys resistance, and there is a chance you might get the infection the immunization is meant to ... After treatment with amsacrine has ended, normal hair growth should return. Other side effects not listed may also occur in ... Amsacrine interferes with the growth of cancer cells, which are then eventually destroyed by the body. Since the growth of ...
more infohttps://www.allinahealth.org/CCS/doc/Thomson%20Detailed%20Drugs/47/600109.htm

Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on...Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on...

Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on ... Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on ... Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on ... Effects of a New Amsacrine Derivative, N-5-Dimethyl-9-(2-methoxy-4-methylsulfonylamino)phenylamino-4-acridinecarboxamide, on ...
more infohttp://cancerres.aacrjournals.org/content/47/2/424

Amsacrine - wikidocAmsacrine - wikidoc

Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent. It has been used in acute lymphoblastic leukemia. ... retinoids (Alitretinoin, Tretinoin), Fusion protein (Aflibercept) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, ... "Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in ... Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II (compares with the better ...
more infohttp://es.wikidoc.org/index.php/Amsacrine

Divergent activity of derivatives of amsacrine (m-amsa) towards lewis  by B C. Baguley, A R. Kernohan et al."Divergent activity of derivatives of amsacrine (m-amsa) towards lewis " by B C. Baguley, A R. Kernohan et al.

Baguley, B C.; Kernohan, A R.; and Wilson, W R., "Divergent activity of derivatives of amsacrine (m-amsa) towards lewis lung ... Divergent activity of derivatives of amsacrine (m-amsa) towards lewis lung carcinoma and p388 leukaemia in mice. ...
more infohttps://mouseion.jax.org/ssbb1983/1917/

Drug InformationDrug Information

Amsacrine Amsacrine is an antineoplastic agent, prescribed for malignant lymphoma and acute adult lymphoblastic leukemia. ...
more infohttps://www.medindia.net/doctors/drug_information/home.asp

Ceftriaxone and Dextrose - FDA prescribing information, side effects and usesCeftriaxone and Dextrose - FDA prescribing information, side effects and uses

Vancomycin, Amsacrine, Aminoglycosides, and Fluconazole. Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically ... Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of ...
more infohttps://www.drugs.com/pro/ceftriaxone-and-dextrose.html

DailyMed - CEFTRIAXONE AND DEXTROSE- ceftriaxone injection, solutionDailyMed - CEFTRIAXONE AND DEXTROSE- ceftriaxone injection, solution

7.1 Vancomycin, Amsacrine, Aminoglycosides, and Fluconazole. Vancomycin, amsacrine, aminoglycosides, and fluconazole are ... 7.1 Vancomycin, Amsacrine, Aminoglycosides, and Fluconazole 7.2 Calcium-containing Products 8 USE IN SPECIFIC POPULATIONS 8.1 ... Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible. (7.1). *Calcium-containing products: ... Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of ...
more infohttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67153914-16bc-490d-82d7-638061618467

Patent US5840334 - Self-binding shearform compositions - Google PatentsPatent US5840334 - Self-binding shearform compositions - Google Patents

... amsacrine; amsalog; anethole; ascorbic acid; aspartame; atenolol; bacitracin; balsam peru; BCNU (carmustine); beclomethasone ...
more infohttp://www.google.com/patents/US5840334?dq=6,205,432

AML2003 - Standard-Therapy vs Intensified Therapy for Adult Acute Myeloid Leukemia Patients |= 60 Years - Full Text View -...AML2003 - Standard-Therapy vs Intensified Therapy for Adult Acute Myeloid Leukemia Patients |= 60 Years - Full Text View -...

Cytarabine+Amsacrine+Mitoxantrone Procedure: early allogeneic PBSCT within induction therapy Procedure: autologous PBSCT Phase ... Amsacrine. Antimetabolites, Antineoplastic. Antimetabolites. Molecular Mechanisms of Pharmacological Action. Antineoplastic ... High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of ...
more infohttps://clinicaltrials.gov/ct2/show/NCT00180102

Patente WO2011099007A1 - Pharmaceutical compositions and methods for the treatment and prevention of ... - Google PatentesPatente WO2011099007A1 - Pharmaceutical compositions and methods for the treatment and prevention of ... - Google Patentes

... amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; ...
more infohttp://www.google.es/patents/WO2011099007A1?cl=en

Cimetidine Hydrochloride Monograph for Professionals - Drugs.comCimetidine Hydrochloride Monograph for Professionals - Drugs.com

Cimetidine Hydrochloride reference guide for safe and effective use from the American Society of Health-System Pharmacists (AHFS DI).
more infohttps://www.drugs.com/monograph/cimetidine-hydrochloride.html

Patente US20070128245 - Porous calcium phosphate bone material - Google PatentesPatente US20070128245 - Porous calcium phosphate bone material - Google Patentes

amsacrine. rubitecan (SuperGen). inhibitors. epirubicin. exatecan mesylate (Daiichi). etoposide. quinamed (ChemGenex). ...
more infohttp://www.google.es/patents/US20070128245

Systems and methods for treating cancer and/or augmenting organ function - Autonomix Medical, Inc.Systems and methods for treating cancer and/or augmenting organ function - Autonomix Medical, Inc.

... amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; ...
more infohttp://www.freepatentsonline.com/10136944.html

Methods of treating cancer using PD-L1 axis binding antagonists and VEGF antagonists - Genentech, Inc.Methods of treating cancer using PD-L1 axis binding antagonists and VEGF antagonists - Genentech, Inc.

... amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; ...
more infohttp://www.freepatentsonline.com/9895441.html

morphine | Daviss Drug Guidemorphine | Davis's Drug Guide

Severe pain (the 20 mg/mL oral solution concentration should only be used in opioid-tolerant patients)… View side effects, interactions, and dosages.
more infohttps://www.unboundmedicine.com/washingtonmanual/view/Davis-Drug-Guide/51518/all/morphine

Plus itPlus it

A, etoposide; B, amsacrine (AMSA); C, doxorubicin; or D, camptothecin. Data are the mean of at least three independent ... amsacrine (Fig. 4A-C) ⇓ , and the topoisomerase I inhibitor camptothecin (Fig. 4D) ⇓ . The negative control molecule KU-58050 ... and amsacrine (Sigma, Poole, United Kingdom) were prepared as 5 mg/mL stock solutions in DMSO. Cisplatin [Alexis Corporation ( ...
more infohttp://cancerres.aacrjournals.org/content/64/24/9152

Drug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug InformationDrug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug Information

m-Amsacrine View Synonyms. View Structure. Description:. Aminoacridine derivative that is a potent intercalating antineoplastic ...
more infohttps://druginfo.nlm.nih.gov/drugportal/rn/54301-15-4

Drug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug InformationDrug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug Information

Amsacrine gluconate View Synonyms. View Structure. Summary. * Info Clinical trials (ClinicalTrials.gov) ...
more infohttps://druginfo.nlm.nih.gov/drugportal/rn/80277-07-2
  • Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of amsacrine in children with use in other age groups. (allinahealth.org)
  • Rapidly dividing cells are two to four times more sensitive to amsacrine than are resting cells. (drugbank.ca)
  • Amsacrine interferes with the growth of cancer cells, which are then eventually destroyed by the body. (allinahealth.org)
  • Since the growth of normal body cells may also be affected by amsacrine, other effects will also occur. (allinahealth.org)
  • NSC 343499), a lipophilic and water-soluble derivative of amsacrine (NSC 249992), on cell viability, growth, clonogenicity, and progression through the cell cycle were investigated in suspension cultures of Friend erythroleukemic cells and in adherent cultures of Chinese hamster ovary cells. (aacrjournals.org)
  • Before you begin treatment with amsacrine, you and your doctor should talk about the good this medicine will do as well as the risks of using it. (allinahealth.org)
  • Amsacrine belongs to the general group of medicines known as antineoplastics. (allinahealth.org)