Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Alkylating Agents: 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.Antineoplastic Agents, Alkylating: 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)Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Leukemia P388: An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.Amaryllidaceae Alkaloids: Alkaloids derived from TYRAMINE combined with 3,4-dihydroxybenzaldehyde via a norbelladine pathway, including GALANTAMINE, lycorine and crinine. They are found in the Amaryllidaceae (LILIACEAE) plant family.Narcissus: A plant genus of the family LILIACEAE. Members contain ungiminorine and LECTINS.Ellipticines: Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.Drug Screening Assays, Antitumor: 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.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Bibenzyls: Compounds with 1,2-diphenylethane. They are structurally like reduced STILBENES.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.ThiadiazinesBryostatins: A group of 20-member macrolactones in which there are three remotely substituted pyran rings that are linked by a methylene bridge and an E-disubstituted alkene, and have geminal dimethyls at C8 and C18 carbons. Some interact with PROTEIN KINASE C.Neoplasms: 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.Tumor Cells, Cultured: 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.Ancitabine: Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.Cisplatin: 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Cell Survival: 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.Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72.Alkylation: 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.Depsipeptides: Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized.Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Cell Line, Tumor: A cell line derived from cultured tumor cells.6-Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.Leukemia L1210Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.O(6)-Methylguanine-DNA Methyltransferase: 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.Aminoacridines: Acridines which are substituted in any position by one or more amino groups or substituted amino groups.Epothilones: A group of 16-member MACROLIDES which stabilize MICROTUBULES in a manner similar to PACLITAXEL. They were originally found in the myxobacterium Sorangium cellulosum, now renamed to Polyangium (MYXOCOCCALES).Sarcoma 180Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Drug Resistance: 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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.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.Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Lactones: Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.DNA Damage: 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.Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Cyclophosphamide: 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.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide 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 entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Carmustine: 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)Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.Nitrogen Mustard Compounds: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.Mechlorethamine: 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.Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Chlorambucil: 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)Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)Biotransformation: 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.Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.DNA: 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).Lung Neoplasms: Tumors or cancer of the LUNG.Kinetics: The rate dynamics in chemical or physical systems.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Dacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Melphalan: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ethyl Methanesulfonate: An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.Breast Neoplasms: Tumors or cancer of the human BREAST.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Leukemia: 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)DNA Repair: 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.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.Nitrosourea CompoundsStereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Colonic Neoplasms: Tumors or cancer of the COLON.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Taxoids: A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.GuanineMethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Mitomycin: 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.Triaziquone: Alkylating antineoplastic agent used mainly for ovarian tumors. It is toxic to skin, gastrointestinal tract, bone marrow and kidneys.Mitomycins: 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.Sulfuric Acid Esters: Organic esters of sulfuric acid.Phospholipid Ethers: Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues.Mutagens: 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.Thiotepa: 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).Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Gloves, Protective: Coverings for the hands, usually with separations for the fingers, made of various materials, for protection against infections, toxic substances, extremes of hot and cold, radiations, water immersion, etc. The gloves may be worn by patients, care givers, housewives, laboratory and industrial workers, police, etc.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Aziridines: Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms.Methyltransferases: 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.Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors.Mustard Gas: 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).Aster Plant: A plant genus of the family ASTERACEAE. This plant should not be confused with microtubule asters (MICROTUBULES) nor with aster yellows phytoplasma (mycoplasma-like organisms).Nylons: 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.Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation.Brain Neoplasms: 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.Glioma: 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)Olacaceae: A small plant family of the order Santalales, subclass Rosidae, class Magnoliopsida.Tumor Stem Cell Assay: 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.Topoisomerase II Inhibitors: 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.DNA, Neoplasm: DNA present in neoplastic tissue.Mutagenicity Tests: Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.Medical Secretaries: Individuals responsible for various duties pertaining to the medical office routine.DNA Modification Methylases: 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.Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.Oncology Nursing: A nursing specialty concerned with the care provided to cancer patients. It includes aspects of family functioning through education of both patient and family.Propiolactone: Disinfectant used in vapor form to sterilize vaccines, grafts, etc. The vapor is very irritating and the liquid form is carcinogenic.Comet Assay: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.LaunderingGlutathione: 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.Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.Protective Devices: Devices designed to provide personal protection against injury to individuals exposed to hazards in industry, sports, aviation, or daily activities.Carcinoma, Ehrlich Tumor: A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.Dental Physiological Processes: Functions and activities of DENTITION as a whole.HydrazinesEtanidazole: A nitroimidazole that sensitizes hypoxic tumor cells that are normally resistant to radiation therapy.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.DNA Glycosylases: 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.Glutathione Transferase: 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.Equipment and Supplies, Hospital: Any materials used in providing care specifically in the hospital.Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Poly(ADP-ribose) Polymerases: 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.Mesylates: Organic salts or esters of methanesulfonic acid.Ifosfamide: Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.Mutation: 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.Equipment Contamination: The presence of an infectious agent on instruments, prostheses, or other inanimate articles.Quinacrine Mustard: 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.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)Sister Chromatid Exchange: 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.Dicumarol: An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases.Sarcoma, YoshidaNimustine: 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.Methionine SulfoximineMolecular Sequence Data: 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.Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Radiotherapy: The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions.Combined Modality Therapy: 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.Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or CHEMICAL WARFARE AGENTS, from a person or object.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Neoplasms, Second Primary: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Vanadium Compounds: Inorganic compounds that contain vanadium as an integral part of the molecule.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Phlebitis: Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).Intercalating Agents: Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.Nursing Staff, Hospital: Personnel who provide nursing service to patients in a hospital.Distamycins: Oligopeptide antibiotics from Streptomyces distallicus. Their binding to DNA inhibits synthesis of nucleic acids.Iodoacetamide: An alkylating sulfhydryl reagent. Its actions are similar to those of iodoacetate.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Buthionine Sulfoximine: 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)DNA Topoisomerases, Type II: DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.Multiple Myeloma: 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.Leukemia L5178: An experimental lymphocytic leukemia of mice.Environmental Monitoring: The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment (soil, air, and water), workplace, or in the bodies of people and animals present in that environment.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.LeukopeniaCarcinogens: 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.Hazardous Substances: Elements, compounds, mixtures, or solutions that are considered severely harmful to human health and the environment. They include substances that are toxic, corrosive, flammable, or explosive.ThiosemicarbazonesPersonnel, Hospital: The individuals employed by the hospital.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.Porfiromycin: 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.Lethal Dose 50: The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.Mice, Inbred BALB CMustard Compounds: Strong alkylating and immunosuppressive agents whose biological activity is based on the presence of bis(2-chloroethyl)- groups. Although otherwise structurally diverse, the compounds have in common the capacity to contribute alkyl groups to DNA. They are generally highly toxic but include among their number many widely used and effective antineoplastic agents.Organoplatinum Compounds: Organic compounds which contain platinum as an integral part of the molecule.Cyclohexenes: 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.Netropsin: 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.Cross-Linking Reagents: 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.Drug Compounding: The preparation, mixing, and assembling of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814)Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Anthracyclines: Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.2-Propanol: An isomer of 1-PROPANOL. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Antineoplastic Protocols: Clinical protocols used to inhibit the growth or spread of NEOPLASMS.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.

L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. (1/1947)

PET with L-[1-11C]-tyrosine (TYR) was investigated in patients undergoing hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor alpha (rTNF-alpha) and melphalan for locally advanced soft-tissue sarcoma and skin cancer of the lower limb. METHODS: Seventeen patients (5 women, 12 men; age range 24-75 y; mean age 52 y) were studied. TYR PET studies were performed before HILP and 2 and 8 wk afterwards. The protein synthesis rates (PSRs) in nanomoles per milliliter per minute were calculated. After final PET studies, tumors were resected and pathologically examined. Patients with pathologically complete responses (pCR) showed no viable tumors after treatment. Those with pathologically partial responses (pPR) showed various amounts of viable tumors in the resected tumor specimens. RESULTS: Six patients (35%) showed a pCR and 11 patients (65%) showed a pPR. All tumors were depicted as hot spots on PET studies before HILP. The PSR in the pCR group at 2 and 8 wk after perfusion had decreased significantly (P < 0.05) in comparison to the PSR before HILP. A significant difference was found in PSR between the pCR and pPR groups at 2 and at 8 wk (P < 0.05). Median PSR in nonviable tumor tissue was 0.62 and ranged from 0.22 to 0.91. With a threshold PSR of 0.91, sensitivity and specificity of TYR PET were 82% and 100%, respectively. The predictive value of a PSR > 0.91 for having viable tumor after HILP was 100%, whereas the predictive value of a PSR < or = 0.91 for having nonviable tumor tissue after HILP was 75%. The 2 patients in the pPR groups with a PSR < 0.91 showed microscopic islets of tumor cells surrounded by extensive necrosis on pathological examination. CONCLUSION: Based on the calculated PSR after HILP, TYR PET gave a good indication of the pathological outcome. Inflammatory tissue after treatment did not interfere with viable tumor on the images, suggesting that it may be worthwhile to pursue TYR PET in other therapy evaluation settings.  (+info)

In vivo isolated kidney perfusion with tumour necrosis factor alpha (TNF-alpha) in tumour-bearing rats. (2/1947)

Isolated perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated kidney perfusion. We studied the feasibility of a perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated kidney perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the kidney to perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated kidney perfusion for human tumours seems, therefore, questionable.  (+info)

Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. (3/1947)

The purpose of this study is to characterize the absorption, metabolism, and excretion of carbon 14-labeled temozolomide (14C-TMZ) administered p.o. to adult patients with advanced solid malignancies. On day 1 of cycle 1, six patients received a single oral 200-mg dose of 14C-TMZ (70.2 microCi). Whole blood, plasma, urine, and feces were collected from days 1-8 and on day 14 of cycle 1. Total radioactivity was measured in all samples. TMZ, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) concentrations were determined in plasma, and urine and plasma samples were profiled for metabolite/degradation products. Maximum TMZ plasma concentrations were achieved between 0.33 to 2 h (mean, 1.2 h), and half-life, apparent volume of distribution, and oral clearance values averaged 1.9 h, 17 liters/m2, and 104 ml/min/m2, respectively. A first-order absorption, one-compartment linear model, which included first-order formation of MTIC from TMZ and elimination of MTIC via degradation to AIC, and a peripheral distribution compartment for AIC, adequately described the plasma TMZ, MTIC, and AIC concentrations. MTIC systemic clearance was estimated to be 5384 ml/min/m2, and the half-life was calculated to be 2.5 min. Metabolite profiles of plasma at 1 and 4 h after treatment showed that 14C-derived radioactivity was primarily associated with TMZ, and a smaller amount was attributed to AIC. Profiles of urine samples from 0-24 h revealed that 14C-TMZ-derived urinary radioactivity was primarily associated with unchanged drug (5.6%), AIC (12%), or 3-methyl-2,3-dihydro-4-oxoimidazo[5,1-d]tetrazine-8-carboxyl ic acid (2.3%). The recovered radioactive dose (39%) was principally eliminated in the urine (38%), and a small amount (0.8%) was excreted in the feces. TMZ exhibits rapid oral absorption and high systemic availability. The primary elimination pathway for TMZ is by pH-dependent degradation to MTIC and further degradation to AIC. Incomplete recovery of radioactivity may be explained by the incorporation of AIC into nucleic acids.  (+info)

The effect of fluconazole on cyclophosphamide metabolism in children. (4/1947)

Fluconazole is increasingly used in children receiving chemotherapy. Many of these patients are being treated with cyclophosphamide, which must undergo hepatic metabolism to produce active alkylating species. As a consequence of the cytochrome P-450 inhibitory properties of fluconazole, a potential interaction exists between these two agents that could influence the therapeutic effect of cyclophosphamide. To investigate this interaction, a retrospective case series of patients was chosen from a population of children with a previously established profile of cyclophosphamide metabolism. Twenty-two children who were not receiving other therapy known to influence drug metabolism were selected and analyzed in terms of fluconazole treatment; of these, nine were receiving fluconazole and thirteen were identified as controls. Study design was not randomized. The plasma clearance of cyclophosphamide was lower in patients receiving fluconazole [mean(SD) 2.4(0.71) versus 4.2(1.2) l/h/m2, p =.001]. In vitro studies were performed to characterize the interaction between fluconazole and cyclophosphamide in six human liver microsomes. The concentration of fluconazole required to reduce the production of 4-hydroxycyclophosphamide to 50% of control values (IC50) varied between 9 and 80 microM (median 38 microM). Further studies of the effect of fluconazole on 4-hydroxycyclophosphamide production in vivo are warranted to determine whether this interaction reduces the therapeutic effect of cyclophosphamide in clinical practice.  (+info)

Hprt mutant frequency and molecular analysis of Hprt mutations in Fischer 344 rats treated with thiotepa. (5/1947)

Thiotepa is a bifunctional alkylating anticancer drug that is a rodent carcinogen and a suspected human carcinogen. In order to determine the sensitivity of mutant induction in the Hprt lymphocyte assay for detecting tumorigenic doses of thiotepa, Fischer 344 rats were treated for 4 weeks with thiotepa using a procedure adapted from a carcinogenesis protocol. At various times after beginning the treatment regimen, rats were killed and the lymphocyte Hprt assay was performed on splenic lymphocytes isolated from the animals. The 6-thioguanine-resistant T lymphocyte mutant frequency increased with time during the period of thiotepa exposure and declined slightly thereafter. Significant dose-dependent increases in mutant frequency were found using concentrations of thiotepa that eventually result in lymphoproliferative tumors. Hprt mRNA from mutant lymphocytes was reverse transcribed to cDNA, amplified by PCR and examined for mutations by DNA sequencing. This analysis indicated that the major type of point mutation was G:C-->T:A transversion and that 33% of the mutants contained simple or complex frameshifts. Also, a multiplex PCR performed on DNA from mutant clones that were expanded in vitro indicated that 34% of the clones had deletions in the Hprt gene. These results indicate that the induction of lymphocyte Hprt mutants is a sensitive biomarker for the carcinogenicity of thiotepa and that the types of mutations found in the lymphocyte Hprt gene reflect the kinds of DNA damage produced by thiotepa.  (+info)

Therapy-related leukemia and myelodysplastic syndrome in breast cancer patients treated with cyclophosphamide or anthracyclines. (6/1947)

BACKGROUND: Accumulation of data regarding therapy-related leukemia (TRL) or myelodysplastic syndrome (t-MDS) is critical for assessing the risk of developing such diseases and for subsequent decision-making processes for better treatment. METHODS: We evaluated the clinical characteristics of patients with TRL/t-MDS diagnosed at the National Cancer Center Hospital between January 1989 and September 1997. This report is concerned with those patients who initially had been treated with chemotherapeutic agents for breast cancer. RESULTS: Thirteen patients (median age, 55 years) developed TRL (n = 4) or t-MDS (n = 9). The median interval between the development of TRL/t-MDS and initial treatment was 94 months (range 23-190 months). For the primary therapy, all patients had received intense and prolonged treatment with cyclophosphamide (CPA) and/or anthracyclines including doxorubicin (DOX), with a median cumulative dose of 55 g/body (range 16.4-288.5 g) for CPA and 480 mg/m2 (range 395-625.5 mg/m2) for DOX. Seven patients were subsequently treated by chemotherapy and one received an allogeneic bone marrow transplantation. CONCLUSIONS: Clinicians must remain alert to the risks associated with unproven medical practices which include long-term administration of alkylating agents. Selected patients with TRL/t-MDS may respond to intense salvage combination chemotherapy.  (+info)

Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer. (7/1947)

PURPOSE: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. PATIENTS AND METHODS: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. RESULTS: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (< 50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. CONCLUSIONS: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long-term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.  (+info)

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma. (8/1947)

PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2-4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/microliter to 141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.  (+info)

*Alkylating antineoplastic agent

An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to ... List of hormonal alkylating antineoplastic agents "Alkylating Agents". US National Library of Medicine. Retrieved 2 August 2014 ... University of Nebraska page on alkylating agent drugs Alkylating antineoplastic agents at the US National Library of Medicine ... alkylating agents are classified under L01A. Many of the agents are known as "Classical alkylating agents". These include true ...

*List of hormonal alkylating antineoplastic agents

This is a list of dual hormonal and alkylating antineoplastic agents. Estramustine phosphate (Emcyt, Estracyt; Leo 299, NSC- ...

*Cell-cycle nonspecific antineoplastic agents

Alkylating antineoplastic agent and anthracyclins are two examples. "Chemotherapy: The Basics". OncoLink. Archived from the ... Cell-cycle nonspecific antineoplastic agents (CCNS) refer to a class of pharmaceuticals that act as antitumor agents at all or ... "Cell killing action of cell cycle phase-non-specific antitumor agents is dependent on concentration--time product". Cancer ...

*EPOCH (chemotherapy)

... an alkylating antineoplastic agent; (H)ydroxydaunorubicin, also known as doxorubicin: an anthracycline antibiotic that is able ...

*CEPP

... 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 ...

*Hormonal therapy (oncology)

List of hormonal alkylating antineoplastic agents DeVita, Vincent T.; Hellman, Samuel; Rosenberg, Steven A., eds. (2005). ... It was previously used in the treatment of breast cancer, but has been replaced by more effective and less toxic agents. ... Selective estrogen receptor modulators (SERMs) are an important class of hormonal therapy agents which act as antagonists of ... although another class of hormonal agents, aromatase inhibitors, now have an expanding role in that disease. One effective ...

*Cytestrol acetate

List of hormonal alkylating antineoplastic agents Oborotov, A. V.; Smirnova, Z. S.; Osetrova, I. P.; Polozkova, A. P.; ... Cytestrol acetate is a steroidal antiestrogen and an alkylating antineoplastic agent (i.e., chemotherapeutic) which was ... having cytostatic actions via the alkylating nitrogen mustard moiety analogously to estramustine phosphate. The drug shows ...

*FCM (chemotherapy)

... an alkylating antineoplastic agent from the oxazafosforine group; (M)itoxantrone - a synthetic antracycline analogue ( ...

*ICE (chemotherapy)

... an alkylating antineoplastic agent of the oxazafosforine group; (C)arboplatin - a platinum based drug, also with an alkylating ...

*MINE (chemotherapy)

... an alkylating antineoplastic agent from oxazafosforine group; (N)ovantrone - a synthetic antracycline analogue (antraquinone) ...

*Alestramustine

List of hormonal alkylating antineoplastic agents List of estrogen esters NCI Thesaurus. "Alestramustine". Retrieved 24 June ... G. W. A. Milne (1 July 2000). Ashgate Handbook of Antineoplastic Agents. Wiley. p. 5. ISBN 978-0-566-08382-2. KD Tripathi (30 ... is a nitrogen mustard alkylating antineoplastic drug that was never marketed. It is the L-alanine ester of estramustine, which ...

*Distamycin

Derivates from distamycin are used as alkylating antineoplastic agents to combat tumours. Derivates with fluorophores are used ... Minor groove binders as anti-infective agents. In: Pharmacology & Therapeutics. 139(1), Juli 2013, 12-23. doi:10.1016/j. ... Hybrid molecules between distamycin A and active moieties of antitumor agents. In: Bioorganic & Medicinal Chemistry. Band 15, ...

*Alkylation

... is accomplished with the class of drugs called alkylating antineoplastic agents. Alkylating agents are classified ... for the ability of some alkylating agents to perform as anti-cancer drugs in the form of alkylating antineoplastic agents, and ... Alkylating agents Category:Ethylating agents Category:Methylating agents March Jerry; (1985). Advanced Organic Chemistry ... Thus, when an electrophilic alkylating agent is introduced to a primary amine, it will preferentially alkylate all the way to a ...

*GemOx

... a platinum-based antineoplastic agent with alkylating mechanism of action. GEMOX-R regimen is a highly effective salvage ...

*Estromustine

List of hormonal alkylating antineoplastic agents List of estrogen esters Bruce A. Chabner; Dan L. Longo (7 December 2011). ... is a major active metabolite of the cystotatic estrogen and nitrogen mustard alkylating antineoplastic agent estramustine ...

*DHAP (chemotherapy)

... a platinum-based antineoplastic agent with an alkylating mechanism; Effective salvage therapy for lymphoma with cisplatin in ...

*Dacarbazine

Melanoma Hodgkin disease ABVD History of cancer chemotherapy Alkylating antineoplastic agent "Dacarbazine". The American ... Dacarbazine is in the alkylating agent and purine analog families of medication. Dacarbazine was approved for medical use in ... Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane, which is an alkylating agent. ... As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of metastatic melanoma, and as part of the ABVD ...

*ICI-85966

List of hormonal alkylating antineoplastic agents List of estrogen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... nonsteroidal estrogen and alkylating antineoplastic agent of the stilbestrol group and a cytostatic nitrogen mustard ester of ...

*Estramustine

List of hormonal alkylating antineoplastic agents List of estrogen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... Estramustine (INN, USAN, BAN) is a synthetic, steroidal estrogen and alkylating antineoplastic agent which was never marketed. ...

*Estradiol mustard

List of hormonal alkylating antineoplastic agents List of estrogen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... steroidal estrogen and alkylating antineoplastic agent and a chlorphenacyl nitrogen mustard-coupled estrogen ester that was ... 898-. ISBN 978-1-4757-2085-3. Asai M, Takeuchi H, Okada H (1978). "In vivo interaction between steroidal alkylating agents and ... like estramustine phosphate have reduced toxicity relative to non-linked nitrogen mustard alkylating antineoplastic agents. ...

*Prednimustine

List of hormonal alkylating antineoplastic agents List of corticosteroid esters J. Elks (14 November 2014). The Dictionary of ... 868-. ISBN 978-3-88763-075-1. I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: ...

*Sturamustine

List of hormonal alkylating antineoplastic agents List of androgen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... that was developed as an alkylating antineoplastic agent (i.e., a chemotherapy drug) for the treatment of hormone-dependent ...

*Alkyl

Alkylating antineoplastic agents refer to a class of compounds that are used to treat cancer. In such case, the term alkyl is ... For example, nitrogen mustards are well-known alkylating agents, but they are more complex than a mere hydrocarbon. In ...

*Atrimustine

List of hormonal alkylating antineoplastic agents List of estrogen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... is a nitrogen mustard alkylating antineoplastic drug that was under development in Japan by Kureha Chemicals (now Kureha ... Ohsawa N, Yamazaki Z, Wagatsuma T, Isurugi K (1984). "[Bestrabacil: a possible target-oriented anticancer agent]". Gan to ... which results in targeted/site-directed DNA alkylating activity toward estrogen receptor-positive tissues such as breast and ...

*Phenestrol

List of hormonal alkylating antineoplastic agents List of estrogen esters J. Elks (14 November 2014). The Dictionary of Drugs: ... nonsteroidal estrogen and alkylating antineoplastic agent (i.e., chemotherapy drug) and a chlorphenacyl nitrogen mustard ester ... Lagova ND, Sof'ina ZP, Shkodinskaia EN, Kurdiumova KN, Valueva IM (1988). "[The antineoplastic activity of testiphenon]". Vopr ... Morozova TM, Merkulova TI, Martynov V, Iaguzhinskaia VP, Shkodinskaia EN (1984). "[Properties of alkylating derivatives of ...

*Cancer

... which are divided into broad categories such as alkylating agents and antimetabolites. Traditional chemotherapeutic agents act ... Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a ... Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and ... Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. ...
Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by radiation therapy ... read more and tamoxifen, or the same treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had HER2/ neu-negative disease, as determined by immunohistochemistry and chromogenic in situ hybridisation. Results: At a median follow-up of 84 months, a trend for a better relapse-free survival was observed in the high-dose arm: (hazard ratio (HR) 0.84, P = 0.076, two-sided). The 621 patients with HER2/neu-negative disease benefited from high-dose therapy, while patients with HER2/neu-positive disease did not (test for interaction, P = 0.006). ...
2. Molecular Subtyping of Brain Tumors - For example, determination of the presence of O(6)-methylguanine DNA methyltransferase (MGMT) activity as a prognosticator of response to alkylating chemotherapy in gliomas is becoming increasingly important to our clinical neuro-oncology colleagues. Other molecular tests that are gaining popularity include IDH1 and EGFR. Molecular profile panels will become the standard of practice in the coming decades ...
Introduction: After lymphoma the risk of secondary cancer namely lung cancer increases. Treatment (alkylating agents, radiotherapy) and smoking are known risk factors. Aims: To report on patients with lung cancer (LC) after lymphoma (LY), focusing on disease characteristics, detection methods and clinical outcomes. Methods: Retrospective study of patients diagnosed in a single institution with LC and previous LY from 1992 to 2012. Data regarding LY characteristics and treatment, smoking history and LC stage, histology and survival were obtained from medical records. Results: Of the 44 patients 43% had Hodgkin and 57% non Hodgkin lymphoma. All had known risk factors: 13 (30%) thoracic radiotherapy, 21 (48%) alkylating chemotherapy, 34 (75%) smoking habits. Median time between diagnoses was 9,5 years (±9.3).Thirteen were female (30%). Median age at LC diagnosis was 60 years (±13). Stage distribution was: 21(48%) IV, 10(23%) III; 13(30%) I/II. PS was 0/1 in 36(81%) patients. Diagnosis was ...
GyrI-like proteins are widely distributed in prokaryotes and eukaryotes, and recognized as small-molecule binding proteins. Here, we identify a subfamily of these proteins as cyclopropanoid cyclopropyl hydrolases (CCHs) that can catalyze the hydrolysis of the potent DNA-alkylating agents yatakemycin (YTM) and CC-1065. Co-crystallography and molecular dynamics simulation analyses reveal that these CCHs share a conserved aromatic cage for the hydrolytic activity. Subsequent cytotoxic assays confirm that CCHs are able to protect cells against YTM. Therefore, our findings suggest that the evolutionarily conserved GyrI-like proteins confer cellular protection against diverse xenobiotics via not only binding, but also catalysis.
Tumor recurrence after initial treatment with radiation and temozolomide is the major cause of mortality for patients with glioblastomas, yet recurrences are understudied because of the dearth of matched tumors samples. This is of particular concern because temozolomide treatment profoundly affects the tumors evolution as evidenced by dramatic alterations in the genomic landscape of recurrent tumors compared with their primary tumor counterparts (65). A big effort has been made recently to understand this evolutionary process by comparing the genomic and proteomic profiles of primary versus recurrent tumors and correlating these datasets with treatment regimens, radiologic data, and clinical history (65-67). However, in these studies, no functional assays were carried out to understand mechanisms of temozolomide resistance due to the lack of matching primary and recurrent cell lines. We developed an in vivo model of tumor recurrence in mice that allows us to understand temozolomide resistance ...
Tumor recurrence after initial treatment with radiation and temozolomide is the major cause of mortality for patients with glioblastomas, yet recurrences are understudied because of the dearth of matched tumors samples. This is of particular concern because temozolomide treatment profoundly affects the tumors evolution as evidenced by dramatic alterations in the genomic landscape of recurrent tumors compared with their primary tumor counterparts (65). A big effort has been made recently to understand this evolutionary process by comparing the genomic and proteomic profiles of primary versus recurrent tumors and correlating these datasets with treatment regimens, radiologic data, and clinical history (65-67). However, in these studies, no functional assays were carried out to understand mechanisms of temozolomide resistance due to the lack of matching primary and recurrent cell lines. We developed an in vivo model of tumor recurrence in mice that allows us to understand temozolomide resistance ...
2. Study activities and Population group: We will conduct a phase II single arm trial of Palonosetron (PALO) for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ). All eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks. Forty subjects with gliomas will participate.. 3. Data analysis and risk/safety issues: The frequency of toxicity will be summarized by type and the most severe grade experienced. The complete response rate, defined as the proportion of patients with no emetic episode or use of rescue medication while receiving radiation and concomitant temozolomide, will be estimated with a ...
Chemoresistance represents a major obstacle to successful treatment for malignant glioma with temozolomide. N (7)-methyl-G and N (3)-methyl-A adducts comprise more than 80 % of DNA lesions induced by temozolomide and are processed by the base excisi
To determine whether patients who receive radiotherapy with concomitant temozolomide followed by adjuvant temozolomide have a marginally better progression free
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.. Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.. After completion of combined modality therapy, patients will have 4 weeks without any therapy.. Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be ...
Purpose In this large cohort of Hodgkins lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment. Patients and Methods The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe dEtude des Lymphomes de lAdulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis. Results Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating ...
Single-agent docetaxel (Taxotere) has been shown to be highly active in metastatic breast cancer, with an overall response rate of 47%, median time to progression of 4 months, and survival of 10 months when administered as 1
Background: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of the Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months, making the development of combined therapies to treat GBM fundamental. One candidate for GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects. Methods: Glioma cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics, protein expression and phosphorylation status were measured. We ...
By sacrificing its only alkyl component to the TMZ-induced lethal depletion of alkyl products on tumoural DNA, MGMT serves as a suicidal DNA repair enzyme. Theoretically, this irreversible depletion of the MGMT protein could be exploited by increasing tumoural exposure to TMZ. The effect might be even more prominent when MGMT promoter is hypermethylated, although the impact of MGMT promoter methylation could not be demonstrated in the present study. Nonetheless this mechanism also accounts for myelosuppression, the main concern of long-term use of TMZ, since MGMT protein in normal cells can also be depleted by TMZ. It is more common in haematopoietic stem cells contributing to toxicity for patients using this alkylating agent.3 In a cohort that comprised 114 patients, 39 (34%) were observed to have CTCAE grade 3 haematological toxicity during administration of TMZ. The study included all patients who received 1 to 57 cycles of TMZ.8 The French SV3 Study also evaluated the effect of prolonged TMZ ...
A Randomized, Placebo Controlled Phase IIb/III Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)
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)
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, ...
Temozolomide is used in the treatment of brain tumor.get complete information about temozolomide including usage, side effects, drug interaction, expert advice along with medicines associated with temozolomide at 1mg.com
Clinical trial for Malignant neoplasm of brain , An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo for Newly Diagnosed Patients With Glioblastoma (GBM a Malignant Brain Cancer)
Clinical trial for Malignant neoplasm of brain , An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo for Newly Diagnosed Patients With Glioblastoma (GBM a Malignant Brain Cancer)
Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact [email protected] ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
This is a non-randomized two-part study of MK-4827 given with temozolomide in participants with advanced cancer. In Part A of the study, the dose-limiti
Research paper that shows Temozolomide coupled with transporter molecules for drug delivery results in increased efficiency in cancer cell lines and lower toxicity in normal cells. ...
A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase 1 of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting ...
Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the ...
... definition, any of various potentially cytotoxic, carcinogenic, and mutagenic substances: used therapeutically to destroy cells, especially proliferating cancer cells. See more.
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.
CAPTEM een combinatie behandeling van Xeloda - capecitabine met temozolomide - temodal zorgt voor spectaculaire resultaten - 97% bereikte minimaal duurzame stabiele ziekte - bij patiënten met alvleesklierkanker (NET tumoren), carcinoid, schildkliertumoren en hypofyse tumoren, ontstaan vanuit neuro endocriene afkomst, welke allemaal uitbehandeld waren. Nieuwe studies toegevoegd. Artikel update 22 december 2018
BACKGROUND. Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMThi). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome.. METHODS. We enrolled 7 newly diagnosed glioblastoma patients with MGMThi tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific ...
Enter Tumor Treating Fields (TTF): a little bit science fiction, a little bit science fact. I have to admit I was very skeptical when I first heard of the technology, and was even less enthused when I saw what a nuisance it is for patients - but it works. In 2015, investigator Roger Stupp (who developed temozolomide treatment in the first place) showed that adding TTF to standard treatment improved median overall survival from 16.6 to 19.6 months, and improved a patients chances of surviving 2 years from 29% to 43%3 - thats as big a step forward as adding temozolomide was in 2005.. Whats the magic? TTF subjects tumor cells to rapidly alternating electrical fields, disrupting cell division. And since its uncontrolled cell division that makes a cell cancerous in the first place, the TTF approach hits the cancer right where it hurts.. TTF doesnt cause nausea, or fatigue, or infections, or low blood counts. It doesnt even require patients come into the office for treatment- but there is a down ...
The purpose of this study is to treat metastatic melanoma with a combination of standard chemotherapy (decitabine and Temozolomide in a dose escalation
Hancock, E J. and Kilburn, D G., "The effects of cyclophosphamide on in vitro cytotoxic responses to a syngeneic tumour." (1982). Subject Strain Bibliography 1982. 988 ...
THE STUDYS invited discussant, Jordi Bruix, MD, PhD, of the University of Barcelona, Spain, said one of the benefits of the TACTICS study was to evaluate the use of the new unTACEable-based endpoint, which he favors. "The endpoint used in the trial is a good attempt to do something new that may.... ...
1.Polyfunctional alkylating agents 2.Other Alkylating Drugs 3.Antimetabolites 4.Purine antagonists 5.Pyrimidine antagonists 6.Plant alkaloids 7.Antibiotics 8.Monoclonal Antibodies, 9.Hormonal agents, 10.Miscellaneous anticancer drugs
Import Data And Price Of ifosfamide , www.eximpulse.com Eximpulse Services will provide you the latest and relevant market intelligence reports of ifosfamide Import Data. You can find live data of maximum number of ports of India which is based on updated shipment data of Indian Customs. Only previous two days data will be seen on website. You can use this ifosfamide import data for multiple kinds of analysis; lets say Import price, Quantity, market scenarios, Price trends, Duty optimization and many more. You can go through some of the sample shipment records for ifosfamide import data mentioned above. Here on Eximpulse Services you will get all kind of free sample as well as detailed reports of Export/ Import data as per your requirement. To get in touch for any kind of enquiry related to free sample or detailed report contact on +91-120-408-4957, +91-120-408-4958,+91-120-428-4019.. Data post 2012 as per Notification No.18/2012 - Customs(N.T.) and does not have names of Indian companies and ...
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 ...
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.
alkylating agent: Any highly reactive drug that binds to certain chemical groups (phosphate, amino, sulfhydryl, hydroxyl, and imidazole groups) commonly found in nucleic acids and other macromolecules,...
acheter du Chlorambucil ! Chlorambucil sans ordonnance commander Restinclières en France Chlorambucil Pharmacie en ligne || Achat
Professional guide for Trabectedin. Includes: pharmacology, pharmacokinetics, contraindications, interactions, adverse reactions and more.
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Ifosfamide- ന്റെ ഉപയോഗങ്ങൾ, ഡോസേജ്, പാർശ്വഫലങ്ങൾ, പ്രയോജനങ്ങൾ, പ്രതിപ്രവർത്തനങ്ങൾ, മുന്നറിയിപ്പ് എന്നിവ കണ്ടെത്തുക
TMZ has obtained the 911 call that was made after Nate Dogg -- cousin of Snoop Dogg -- suffered what was described as a heart attack ... and youre not…
Theres no telling (or understanding) what might happen when a supermodel and a horse meet.But luckily Karolina Kurkova used her supermodel powers to…
You do not have subscription access to this journal. Citation lists with outbound citation links are available to subscribers only. You may subscribe either as an OSA member, or as an authorized user of your institution. Contact your librarian or system administrator ...
In this case report we describe the management of a highly invasive multi-centric GBM in an older patient following partial tumor resection and treatment with a combination of standard therapy, fasting, and a R-KD. The patients response to this therapeutic approach was unusual, as no prior reports have appeared to our knowledge describing regression of GBM within 2.5 months from the time of diagnosis in either younger (, 50 yrs) or older (, 50 yrs) patients using standard radiation and temozolomide therapy alone. Although the patient in this study expressed hypermethylation of the MGMT gene promoter, which enhances the therapeutic action of temozolomide and is prognostic for increased survival [26], no prior cases of rapid GBM regression have been reported in patients with the MGMT hypermethylation phenotype to our knowledge. Temozolomide is an oral alkylating agent that damages DNA and is used as first and second line GBM treatment [2, 26, 29]. Continuous temozolomide administration depletes ...
Temozolomide (TMZ) is an alkylating chemotherapeutic agent that has recently been used in some cases as a new therapeutic tool for pituitary carcinomas and aggressive pituitary adenomas. In this report, we present the case of effective TMZ treatment
Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. Methods: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. Results: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. ...
Rare Cancer News & Clinical Trials » Trial - CNS Tumor » An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer ...
Oral alkylating drugs, alone and in combination therapy with steroids, have been extensively evaluated in the upfront treatment of WM. The greatest experience with oral alkylator therapy has been with chlorambucil, which has been administered on both a continuous (i.e. daily dose schedule) as well as an intermittent schedule. Patients receiving chlorambucil on a continuous schedule typically receive 0.1 mg/kg per day, whilst on the intermittent schedule patients will typically receive 0.3 mg/kg for 7 days, every 6 weeks. In a prospective randomized study, Kyle et al.109 reported no significant difference in the overall response rate between these schedules, although interestingly the median response duration was greater for patients receiving intermittent versus continuously dosed chlorambucil (46 vs. 26 months). Despite the favorable median response duration in this study for use of the intermittent schedule, no difference in the median overall survival was observed. Moreover, an increased ...
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.
Purpose Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG. Patients and Methods Four hundred forty-seven patients were randomly assigned to PCV (224 patients) or TMZ (sub-random assignment: TMZ-5 [200 mg/m(2) for 5 days, 112 patients] or TMZ-21 [100 mg/m(2) for 21 days, 111 patients]) for up to 9 months or until progression. The primary outcomes were survival (PCV v TMZ) and 12-week progression-free survival (PFS; TMZ-5 v TMZ-21). This study is registered as ISRCTN83176944. Results Percentages of patients completing 9 months of treatment in the PCV, TMZ-5, and TMZ-21 arms were 17%, 26%, and 13%, respectively. Major toxicity was similar across all three groups. With a median follow-up time of 12 months and 382 deaths, ...
Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12-14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.
TMZ, an imidazotetrazine derivative, is a new oral alkylating agent that has demonstrated promising antitumor activity in phase I and II trials (1, 2, 3, 4, 5, 6) , particularly in patients with advanced high-grade central nervous system malignancies and melanoma. Mechanistic and preclinical studies predicted a potential clinical advantage of TMZ based, in part, on the nonenzymatic, pH-dependent generation of the cytotoxic intermediate MTIC, which optimally occurs at physiological pH (7, 8, 9) . This clinical study provides evidence that the principal pathway for TMZ elimination is through the formation of MTIC. The observed low interpatient variability in TMZ clearance indicates that generation of MTIC is consistent between patients. These results, combined with the observed high systemic availability after oral administration, indicate that the clinical use of TMZ may lead to a significant therapeutic advantage over i.v. DTIC, which requires metabolic activation via cytochrome P450 ...
Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune
In the last figure of the paper, Johnson et al. investigate the effects of TMZ treatment on the mutational profiles of recurrent gliomas. For that purpose, the researchers classified a set of C,T/G,A recurrence-specific mutations in tumors subjected to TMZ treatment as "TMZ-associated." Panel A of the figure establishes that TMZ-associated somatic mutations comprise the better part (,98.7%) of the mutational profiles of tumor recurrences. TMZ is therefore a major mutation-inducing agent and likely contributes significantly to the malignant progression of initial gliomas to higher-grade recurrences. In order to identify TMZ-associated mutations which likely contribute to higher recurrence malignancy, the researchers then focused on the RB and Akt-mTOR signaling pathways that were previously known to be associated with proliferation regulation. Panel B demonstrates that mutations in either of those pathways were present almost exclusively in Grade IV, TMZ-treated tumors, thereby validating their ...
To determine safety and effectiveness of temozolomide, irinotecan and bevacizumab. All three of these agents have shown effectiveness in pediatric brain tumors.
Buy Temonat 250mg capsules online at lowest price in India by Natco Pharma. Find Temonat Temozolomide 250mg capsule MRP, uses, side effects, generic alternatives.
Interim results of the phase III CATNON trial (EORTC study 26053-22054) indicate a survival benefit of adjuvant temozolomide in 1p/19q non-codeleted anaplastic glioma. These findings were reported in The Lancet by van den Bent et al. Study Details In the open-label 2 x 2 factorial trial, 745.... ...
Synonyms for chlorambucil in Free Thesaurus. Antonyms for chlorambucil. 1 synonym for chlorambucil: Leukeran. What are synonyms for chlorambucil?
for use in conjunction with Aduro vaccines. GVAX vaccines are comprised of allogeneic malignancy cell lines which have been genetically-altered to secrete granulocyte-macrophage colony-stimulating element to stimulate the disease fighting capability and that have been treated to prevent cell division. GVAX Pancreas is administered with low-dose cyclophosphamide, which includes been shown to increase effectiveness. Sequential. Read More. ...
Carmustine belongs to the group of alkylating agents. It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by carmustine, other effects may occur. Some of these may be serious and must be reported to your doctor. Other effects (e.g., hair loss), may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used. Before you begin treatment with carmustine, you and your doctor should talk about the benefits this medicine will do as well as the risks. This medicine is to be administered only by or under the immediate supervision of your doctor. This product is available in the following dosage forms:. ...
Chlorambucil is used in the treatment of blood cancer,hodgkins disease.get complete information about chlorambucil including usage, side effects, drug interaction, expert advice along with medicines associated with chlorambucil at 1mg.com
View Notes - Lab Notes from BIOL 1208 at LSU. What Is An Enzyme? Organic catalyst o Most are proteins o Increases the rate of reaction o Not consumed Main function: to increase chemical reaction
Chlorambucil is helpful in multiple Chemotherapy protocols as well as Immune Mediated conditions. Chlorambucil is typically given daily or every other day or every third day.
Alkeran tablets and injection contain the active ingredient melphalan, which is a type of chemotherapy medicine to treat cancer called an alkylating agent.
Learn about BiCNU (Carmustine) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
This pill with imprint 5 mg 890 is White, Capsule-shape and has been identified as Temozolomide 5 mg. It is supplied by Sun Pharma Global FZE.
Alkeran: Melphalan belongs to the group of cancer-fighting medications known as antineoplastics, and specifically to the group of antineoplastics known as alkylating agents.
TY - JOUR. T1 - O6-methylguanine DNA methyltransferase repairs platinum-DNA adducts following cisplatin treatment and predicts prognoses of nasopharyngeal carcinoma. AU - Chen, Shang Hung. AU - Kuo, Ching Chuan. AU - Li, Chien Feng. AU - Cheung, Chun Hei Antonio. AU - Tsou, Tsui Chun. AU - Chiang, Huai Chih. AU - Yang, Yun Ning. AU - Chang, Shin Lun. AU - Lin, Li Ching. AU - Pan, Hsin Yi. AU - Chang, Kwang Yu. AU - Chang, Jang Yang. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Cisplatin (CDDP) is an important anti-cancer drug commonly used in various human cancers, including nasopharyngeal carcinoma (NPC). How to overcome the drug resistance of CDDP provides opportunities to improve clinical outcomes of NPC. O6-methylguanine-DNA methyltransferase (MGMT) has been well-characterized to be a therapeutic determinant of O6-alkylguanine alkylating drugs. However, the underlying mechanism and clinical relevance between MGMT and CDDP remain poorly defined in NPC. In this study, we showed that MGMT-proficient ...
Malignant gliomas are currently diagnosed based on morphological criteria and graded according to the World Health Organization classification of primary brain tumors. This algorithm of diagnosis and classification provides clinicians with an estimated prognosis of the natural course of the disease. It does not reflect the expected response to specific treatments beyond surgery (eg, radiotherapy or alkylating chemotherapy). Clinical experience has revealed that gliomas sharing similar histomorphological criteria might indeed have different clinical courses and exhibit highly heterogenous responses to treatments. This was very impressively demonstrated first for oligodendrogliomas. The presence or lack of combined deletions of the chromosomal segments 1p/19q was associated with different benefit from radiotherapy and chemotherapy. We review current molecular markers for malignant gliomas and discuss their current and future impact on clinical neuro-oncology. ...
TY - JOUR. T1 - Clinical and histological features of idiosyncratic acute liver injury caused by temozolomide. AU - Grant, Lafaine M.. AU - Kleiner, David E.. AU - Conjeevaram, Hari S.. AU - Vuppalanchi, Raj. AU - Lee, William M.. PY - 2013/5. Y1 - 2013/5. KW - Drug-induced liver injury. KW - Temozolomide hepatitis. KW - Temozolomide hepatotoxicity. KW - Temozolomide toxicity. UR - http://www.scopus.com/inward/record.url?scp=84878719823&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84878719823&partnerID=8YFLogxK. U2 - 10.1007/s10620-012-2493-9. DO - 10.1007/s10620-012-2493-9. M3 - Article. C2 - 23212393. AN - SCOPUS:84878719823. VL - 58. SP - 1415. EP - 1421. JO - Digestive Diseases and Sciences. JF - Digestive Diseases and Sciences. SN - 0163-2116. IS - 5. ER - ...
Kundu, Chanakya et al " Adenomatous polyposis coli (APC) protein causes hypersensitivity of mouse embryonic fibroblast cell lines to DNA-alkylating agent methylmethane sulfonate through base excision repair pathway ." Cancer Research 67.9 Supplement (2007): 1961. Web. 21 Feb. 2018. ...
Why does O6-methylguanine-DNA methyltransferase (MGMT), an indispensable DNA repair enzyme, have a mechanism which seems to run counter to its importance? This enzyme is key to the removal of detrimental alkyl adducts from guanine bases. Although the mechanism is well known, an unusual feature surrounds its mode of action, which is its so-called suicidal endpoint. In addition, induction of MGMT is highly variable and its kinetics is atypical. These features raise some questions on the seemingly paradoxical mechanism. In this manuscript we point out that, although there is ample literature regarding the "how" of the MGMT enzyme, we found a lack of information on "why" this specific mechanism is in place. We then ask whether we know all there is to know about MGMT, or if perhaps there is a further as yet unknown function for MGMT, or if the suicidal mechanism may play some kind of protective role in the cell ...
TY - JOUR. T1 - Quality of life in low-grade glioma patients receiving temozolomide. AU - Liu, Raymond. AU - Solheim, Karla. AU - Polley, Mei-Yin. AU - Lamborn, Kathleen R.. AU - Page, Margaretta. AU - Fedoroff, Anne. AU - Rabbitt, Jane. AU - Butowski, Nicholas. AU - Prados, Michael. AU - Chang, Susan M.. PY - 2009/2/1. Y1 - 2009/2/1. N2 - The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with his- tologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p , 0.01) but had lower reported emotional well-being scores (mean difference = ...
3209 The methylating agent temozolomide (TMZ) has demonstrated a significant cytotoxicity against glioma, and is currently used for initial treatment of glioblastoma (GBM). Over-expression of O6-methyguanine-DNA-methyltransferase (MGMT) is an important determinant of TMZ resistance but the expression of MGMT does not absolutely correlate with the TMZ response. We have developed a panel of GBM xenografts from patient tumors, and similar to clinical results, we have identified at least one xenograft line (GBM14) that is sensitive to TMZ despite the unmethylated MGMT promoter. To identify other gene products that are involved in TMZ resistance and sensitivity, we evaluated the gene expression in 2 xenograft lines that are sensitive to TMZ (GBM12 and 14) or resistant to TMZ (GBM 43 and 44) before and in after TMZ treatment. Global gene expression was analyzed with microarray technology using the Affymetrix Human Genome U133 2.0 Plus GeneChip Set, covering more than 54,000 gene transcripts, ...
A French team of investigators evaluated whether irinotecan and bevacizumab added to temozolomide-based chemoradiation would improve the prognosis of patients with unresectable glioblastoma. The study results show a trend towards improved progression-free survival and are presented by Dr B. Chauffert at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.. This phase II, randomized trial enrolled 120 patients, aged 18 to 70 years with de novo unresectable glioblastoma, Karnofsky performance status , 50 and recursive partitioning analysis (RPA) class 5. Patients were randomized, 60 patients per arm, to receive four cycles of neo-adjuvant bevacizumab plus irinotecan prior to radiotherapy with concurrent temozolomide and bevacizumab or to receive control treatment of concomitant temozolomide plus radiotherapy for 6 months.. Clinical factors were well balanced between arms and cross-over was allowed upon progression. An evaluation done at 16 months after the treatment ...
MONDAY, April 3, 2017 (HealthDay News) -- Adding tumor-treating fields (TTFields) to temozolomide (TMZ) is associated with improved progression-free and overall survival in glioblastoma (GBM), according to a study presented at the annual meeting of the American Association for Cancer Research, held from April 1 to 5 in Washington, D.C.. Roger Stupp, M.D., from the Northwestern University Feinberg School of Medicine in Chicago, and colleagues enrolled 695 patients with newly diagnosed GBM who were followed for a median of more than three years. Patients were randomized in a 1:2 ratio to either standard adjuvant TMZ alone or TMZ and TTFields within seven weeks after the end of concomitant chemoradiotherapy.. The researchers found that the median progression-free survival was 6.7 and 4.0 months for patients treated with TTFields/TMZ and TMZ alone, respectively (hazard ratio, 0.63; P = 0.00005). The median overall survival from randomization was 20.9 months for TTFields/TMZ versus 16 months for TMZ ...
BackgroundThis multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.MethodsPatients received temozolomide 100-125 mg/m2/day (days 1-5) and irinotecan 10 mg/m2/day (days 1-5 and 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.ResultsSixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration of response was 27.0 weeks ...
OBJECTIVE The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-l-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM). METHODS Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models. RESULTS Biological tumor volume before RCx (BTVpreRCx) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller ...
Background: TTFields is an established antimitotic treatment modality delivered to patients by a portable, home use, medical device. Here we evaluate whether this antimitotic effect can be translated into improved survival in a clinical setting. Based on a pre-specified interim analysis on 315 patients, the IDMC recommended early trial closure; we here report the first analysis of the full dataset of 700 randomized patients. Methods: This prospective phase 3 trial randomized patients with newly diagnosed glioblastoma, after completion of concomitant chemoradiotherapy, to receive either adjuvant temozolomide (TMZ) chemotherapy alone, or TMZ with TTFields (TTF/TMZ). The primary endpoint was progression-free survival, with overall survival, safety, cognitive function and quality of life as secondary endpoints. Results: (ITT) From 2009 to 2014, 700 Grade IV astrocytoma (glioblastoma) patients (68% male) were randomized 2:1. Patient characteristics were well balanced: median age was 56 and 57 years ...
Glioblastomas remain one of the most lethal of all tumors for which no effective treatment exists despite decades of research (1). Thus, there is an urgent need for the development of new therapeutic modalities for glioblastoma. The standard-of-care for glioblastoma is surgical resection followed by ionizing radiation and concomitant and adjuvant temozolomide (3). As both ionizing radiation and temozolomide induce DSBs (6, 38), blocking the DDR to these breaks is, in principle, a rational approach for sensitizing glioblastomas and other cancers (7-9). More than 10 years of research efforts focused on the development of potent DNA-PKcs and ATM inhibitors have yielded specific compounds, some of which are very useful in the laboratory for cell-based studies (12). Unfortunately, no single compound shows the necessary potency, bioavailability, and ability to cross the BBB that would allow their evaluation in preclinical mouse glioblastoma models. Against this backdrop, our results, demonstrating ...
The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.
A Phase II/III Randomized Trial of Veliparib or Placebo in Combination with Adjuvant Temozolomide in Newly Diagnosed Glioblastoma with Mgmt Promoter Hypermethylation. ...
The goal of this clinical research study is to find the highest tolerable dose of the combination of MK-4827 and temozolomide that can be given to patients with advanced solid cancers. The effects of the study drugs at different dose levels and the safety of the study drugs will also be studied. You are also being asked to take part in optional procedures, which are described in a separate consent form.
YONDELIS (Trabectedin) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
|p|This slideshow reviews drug information for YONDELIS (trabectedin). Click here for the complete |a href=http://www.empr.com/yondelis/drug/34614/ target=_blank|YONDELIS
Findings from a recent phase II study showed the PD-L1 inhibitor durvalumab generated durable responses in bevacizumab-naïve patients with recurrent glioblastoma multiforme (GBM).
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 ...
Although previous studies have investigated the mechanism(s) by which trabectedin inhibits cell growth (3, 9-13, 35, 36), the primary mechanism accounting for the potent antiproliferative effects of trabectedin in some cancer cell types is still poorly understood. A cancer cell line selected in vitro for its enhanced resistance to trabectedin (11) lacked a functional XPG (ERCC5), the structure-specific DNA endonuclease that makes the first 3′ incision on ssDNA during NER and transcription-coupled NER (39). Similarly, S. pombe cells deficient in rad13 (the yeast orthologue of XPG) also displayed increased resistance to trabectedin and underwent much less DNA damage than the corresponding isogenic WT strain. However, additional experiments showed that it is not the missing endonuclease activity of this protein that confers resistance to trabectedin but the lack of a highly conserved basic residue in the DNA-binding domain that can presumably stabilize a rad13/DNA/trabectedin ternary complex ...
The nitrosoureas are alkylating agents that are highly lipid soluble and share similar pharmacological and clinical properties. Carmustine (BCNU), lomustine
Learn about the veterinary topic of Alkylating Agents. Find specific details on this topic and related topics from the Merck Vet Manual.
Daniel RA, Rozanska AL, Mulligan EA, Drew Y, Thomas HD, Castelbuono DJ, Hostomsky Z, Plummer ER, Tweddle DA, Boddy AV, Clifford SC, Curtin ...
As described in this eMedTV article, ifosfamide is licensed to treat testicular cancer. This resource explains how this drug works and explores possible off-label uses. It also links to more details on this specific topic.
This study demonstrates the effects of the novel drug, NEO212 on GBM in vitro and in vivo. Our data show that NEO212, the conjugate of temozolomide and POH, is far more potent than each agent alone or the mixture of these agents (Fig. 2), indicating that NEO212 is a novel and powerful drug with unique characteristics. Previous studies from this laboratory had shown that POH was effective only at high doses, with an IC50 value ranging from 1.5 to 1.8 mmol/L for temozolomide-resistant cells (5), and required localized intranasal administration. In contrast, NEO212 is an effective cytotoxic agent with an IC50 of 40 to 50 μmol/L. Because only high doses of POH are effective for anticancer treatment, localized administration of POH (i.e., intranasal administration) is necessary. In contrast, NEO212 is effective at low, nontoxic doses and can be administered systemically that is, subcutaneously or by gavage. The NEO212 is a novel agent with activity different from the simple mixture of temozolomide ...
The tyrosine residue present at position 158 in the human O6-alkylguanine-DNA alkyltransferase is one of 22 amino acid residues that are conserved in all known alkyltransferase protein sequences. The importance of this amino acid in the reactions brought about by the alkyltransferase was studied by changing this residue to alanine or to phenylalanine. The control and mutant alkyltransferase proteins were expressed in an Escherichia coli strain lacking alkyltransferase activity and the proteins purified to near homogeneity and their activities measured using both methylated DNA and O6-benzylguanine (BG) as substrates. The alteration to alanine led to a very large decrease in activity towards both substrates but removal of O6-methylguanine from DNA and the conversion of BG to guanine could still be detected when large amounts of the protein were used. The activity of the Y158A mutant was at least 800 times less than that of the control alkyltransferase. The change of tyrosine-158 to phenylalanine reduced
The O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be , 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at , 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major ...
Tags:. cytoxan may side effects cyclophosphamide length treatment maximum lifetime dose of cyclophosphamide side effects of cyclophosphamide therapy cyclophosphamide epigastric pain cyclophosphamide pulse therapy in primary glomerulonephritis cyclophosphamide pretreatment cytoxan doxorubicin cyclophosphamide anemia oral cyclophosphamide lupus nephritis cytoxan ndc cyclophosphamide hair loss when cyclophosphamide histiocytosis cyclophosphamide excreted in urine cyclophosphamide versus azathioprine cyclophosphamide biocompare cytoxan chemotherapy bladder cancer cyclophosphamide cvp cyclophosphamide causes leukemia cytoxan side effects in canines cyclophosphamide haemophilia cyclophosphamide pathway cyclophosphamide pulmonary hemosiderosis cyclophosphamide pulse therapy dosage chemotherapy cyclophosphamide side effects long term cyclophosphamide renal cyclophosphamide recommended dose cyclophosphamide docetaxel combination cytoxan tooth decay cyclophosphamide and avastin ovarian cancer ...
While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wild-type genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSB) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks.

Alkylating antineoplastic agent - WikipediaAlkylating antineoplastic agent - Wikipedia

An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to ... List of hormonal alkylating antineoplastic agents "Alkylating Agents". US National Library of Medicine. Retrieved 2 August 2014 ... University of Nebraska page on alkylating agent drugs Alkylating antineoplastic agents at the US National Library of Medicine ... alkylating agents are classified under L01A. Many of the agents are known as "Classical alkylating agents". These include true ...
more infohttps://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent

List of hormonal alkylating antineoplastic agents - WikipediaList of hormonal alkylating antineoplastic agents - Wikipedia

This is a list of dual hormonal and alkylating antineoplastic agents. Estramustine phosphate (Emcyt, Estracyt; Leo 299, NSC- ...
more infohttps://en.wikipedia.org/wiki/List_of_hormonal_alkylating_antineoplastic_agents

Alkylating Antineoplastic Agents
     Summary Report | CureHunterAlkylating Antineoplastic Agents Summary Report | CureHunter

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, ... Alkylating Antineoplastic Drugs; Alkylating Antineoplastics; Alkylating Drugs, Antineoplastic; Antineoplastic Alkylating Agents ... Alkylating Antineoplastic Agents. Subscribe to New Research on Alkylating Antineoplastic Agents A class of drugs that differs ...
more infohttp://www.curehunter.com/public/keywordSummaryD018906-Alkylating-Antineoplastic-Agents.do

Search of: Testicular Leukemia | Antineoplastic Agents, Alkylating - List Results - ClinicalTrials.govSearch of: 'Testicular Leukemia' | 'Antineoplastic Agents, Alkylating' - List Results - ClinicalTrials.gov

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 ...
more infohttps://clinicaltrials.gov/ct2/results?cond=%22Testicular+Leukemia%22&intr=%22Antineoplastic+Agents%2C+Alkylating%22

Ethylene imines | Alkylating agents | Antineoplastic agentsEthylene imines | Alkylating agents | Antineoplastic agents

Antineoplastic agents Brokerage service for pharmaceutical and parapharmaceutical products active ingredients and precursors.. ... Agents acting on the renin-angiot.. Ace inhibitors, plain Ace inhibitors, plain ... Beta blocking agents Beta blocking agents Beta blocking agents, non-selecti.. Beta blocking agents, selective ...
more infohttps://goldpharma.com/article/11044/lang/ENGLISH/t/ethylene%20imines/

Misulban
        -
        Antineoplastic Agents,  Immunosuppressive Agents,  Alkylating Agents,  ATC:L01AB01Misulban - Antineoplastic Agents, Immunosuppressive Agents, Alkylating Agents, ATC:L01AB01

Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents ... Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the ...
more infohttp://pharmacycode.com/Misulban.html

Mitosan
        -
        Antineoplastic Agents,  Immunosuppressive Agents,  Alkylating Agents,  ATC:L01AB01Mitosan - Antineoplastic Agents, Immunosuppressive Agents, Alkylating Agents, ATC:L01AB01

Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents ... Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the ...
more infohttp://pharmacycode.com/Mitosan.html

Screening of natural products and alkylating agents for antineoplastic activityScreening of natural products and alkylating agents for antineoplastic activity

On the other hand, alkylating agents such as cisplatin, cis- [PtCl2 (NH3) 2] have been widely used as antineoplastic agents for ... Screening of natural products and alkylating agents for antineoplastic activity. dc.contributor.advisor. Rees, Jasper. ... Screening of natural products and alkylating agents for antineoplastic activity. en_US. ... However, the use of cisplatin as an anticancer agent is limited due to toxicity and resistance problems. The aim of this ...
more infohttp://etd.uwc.ac.za/xmlui/handle/11394/3162?show=full

Chemotherapy - WikipediaChemotherapy - Wikipedia

Alkylating agents[edit]. Main article: Alkylating antineoplastic agent. Alkylating agents are the oldest group of ... Available agents[edit]. Main article: List of antineoplastic agents. There is an extensive list of antineoplastic agents. ... 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.[1] They are so named because of their ability to alkylate many molecules ...
more infohttps://en.wikipedia.org/wiki/Chemotherapeutics

Allogeneic Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer - Full Text View - ClinicalTrials.govAllogeneic Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer - Full Text View - ClinicalTrials.gov

Antineoplastic Agents, Alkylating. Alkylating Agents. Molecular Mechanisms of Pharmacological Action. Antineoplastic Agents. ... Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. Antirheumatic Agents. ...
more infohttps://www.clinicaltrials.gov/ct2/show/NCT00056095?term=stem+cell+kidney&rank=39

Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell...Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell...

Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. Antineoplastic Agents, Alkylating. Alkylating ... Antineoplastic Agents. Antimetabolites, Antineoplastic. Antimetabolites. Molecular Mechanisms of Pharmacological Action. ...
more infohttps://www.clinicaltrials.gov/ct2/show/NCT01758328

Pseudoprogression and treatment effect.  - PubMed - NCBIPseudoprogression and treatment effect. - PubMed - NCBI

Antineoplastic Agents, Alkylating/therapeutic use. *Brain Neoplasms/drug therapy. *Brain Neoplasms/pathology* ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/22440871?dopt=Abstract

Acquired acute myelogenous leukemia after therapy for acute promyelocytic leukemia with t(15;17): a case report and review of...Acquired acute myelogenous leukemia after therapy for acute promyelocytic leukemia with t(15;17): a case report and review of...

The cumulative exposure to chemotherapy with alkylating agents and topoisomer ... Antineoplastic Agents, Alkylating / administration & dosage, adverse effects. Antineoplastic Combined Chemotherapy Protocols / ... The cumulative exposure to chemotherapy with alkylating agents and topoisomerase II inhibitors is associated with t-AML that ... 0/Antineoplastic Agents, Alkylating; 147-94-4/Cytarabine; 20830-81-3/Daunorubicin; 302-79-4/Tretinoin; 50-44-2/6-Mercaptopurine ...
more infohttp://www.biomedsearch.com/nih/Acquired-acute-myelogenous-leukemia-after/19530558.html

Evaluation of genotoxic effects of semicarbazide on cultured human lymphocytes and rat bone marrow.Evaluation of genotoxic effects of semicarbazide on cultured human lymphocytes and rat bone marrow.

Antineoplastic Agents, Alkylating / toxicity. Bone Marrow Cells / drug effects*. Cells, Cultured. Chromosomes / drug effects, ... 0/Antineoplastic Agents, Alkylating; 0/Mutagens; 0/Semicarbazides; 50-18-0/Cyclophosphamide ...
more infohttp://www.biomedsearch.com/nih/Evaluation-genotoxic-effects-semicarbazide-cultured/19819287.html

A Study of Trabectedin in Patients With Advanced Ovarian CancerA Study of Trabectedin in Patients With Advanced Ovarian Cancer

The purpose of this study is to test the safety and effectiveness of an investigational chemotherapy agent in patients with ... Antineoplastic Agents, Alkylating. *Alkylating Agents. *Adnexal Diseases. *Neoplasms. *Endocrine Gland Neoplasms. *Genital ...
more infohttp://www.knowcancer.com/cancer-trials/NCT00050414/

Malignant Giant Cell Tumor disease: Malacards - Research Articles, Drugs, Genes, Clinical TrialsMalignant Giant Cell Tumor disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

Alkylating Agents. Not Applicable. 20. Antineoplastic Agents, Alkylating. Not Applicable. 21. Antirheumatic Agents. Not ...
more infohttps://www.malacards.org/card/malignant_giant_cell_tumor?search=actc1

Ifosfamide / ifosfamide NDA 090181 global drug patent coverage, generic alternatives and suppliersIfosfamide / ifosfamide NDA 090181 global drug patent coverage, generic alternatives and suppliers

Antineoplastic Agents, Alkylating Profile for product number 001. Active Rx/OTC/Discontinued:. RX. Dosage:. INJECTABLE; ...
more infohttps://www.drugpatentwatch.com/p/NDA/090181

Dacarbazine / dacarbazine NDA 075940 global drug patent coverage, generic alternatives and suppliersDacarbazine / dacarbazine NDA 075940 global drug patent coverage, generic alternatives and suppliers

Alkylating Activity Medical Subject Heading (MeSH) Categories for 075940. Antineoplastic Agents, Alkylating ...
more infohttps://www.drugpatentwatch.com/p/NDA/075940

Alkylating Agents - Pharmacology - Merck Veterinary ManualAlkylating Agents - Pharmacology - Merck Veterinary Manual

Learn about the veterinary topic of Alkylating Agents. Find specific details on this topic and related topics from the Merck ... Antineoplastic Antibiotics. *Hormonal Agents. *Miscellaneous Antineoplastic Agents. *Ancillary Antineoplastic Agents. * ... 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 ...
more infohttp://www.merckvetmanual.com/en-pr/pharmacology/antineoplastic-agents/alkylating-agents

Alkeran | definition of Alkeran by Medical dictionaryAlkeran | definition of Alkeran by Medical dictionary

a trademark for an alkylating antineoplastic agent (melphalan). melphalan. An alkylating nitrogen mustard used to treat ovarian ...
more infohttps://medical-dictionary.thefreedictionary.com/Alkeran

Mycosis Fungoides (MF) - DrugBankMycosis Fungoides (MF) - DrugBank

A widely used local anesthetic agent. [PubChem]. DB00262. Carmustine. A cell-cycle phase nonspecific alkylating antineoplastic ... It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [PubChem]. ... This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby ... The hydrochloride is used as an antineoplastic in Hodgkins disease and lymphomas. It causes severe gastrointestinal and bone ...
more infohttps://www.drugbank.ca/indications/DBCOND0057197

Refractory Multiple Myeloma - DrugBankRefractory Multiple Myeloma - DrugBank

A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other ... Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog ... Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013. ... and it is the most potent DAC inhibiting agent available on the market. ...
more infohttps://www.drugbank.ca/indications/DBCOND0028542

Cyclophosphamide Versus Ifosfamide for Paediatric and Young Adult Bone and Soft Tissue Sarcoma Patients - PubMedCyclophosphamide Versus Ifosfamide for Paediatric and Young Adult Bone and Soft Tissue Sarcoma Patients - PubMed

Antineoplastic Agents, Alkylating / therapeutic use *. Actions. * Search in PubMed * Search in MeSH ... Background: Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children ... Secondary objectives were to determine effects of these agents on toxicities (including late effects) and quality of life. ...
more infohttps://pubmed.ncbi.nlm.nih.gov/26421585/

Alkylation - WikipediaAlkylation - Wikipedia

This mechanism of toxicity is relevant to the function of anti-cancer drugs in the form of alkylating antineoplastic agents. ... 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 + RX → ROR. When the alkylating agent is an alkyl halide, the conversion is called the ...
more infohttps://en.m.wikipedia.org/wiki/Alkylated
  • 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)